to finalize the fifth edition of the Medical eligibility criteria for contraceptive use. All members of the Guideline Development Group and the Evidence Secretariat participated in at least one of the three consultations. WHO is very grateful for the suggestions provided by colleagues who peer-reviewed the earlier drafts of the guideline as members of the External Peer Review Group. The names of the participants in each group are listed below.# Executive summary
This document is part of the process for improving the quality of care in family planning. Medical eligibility criteria for contraceptive use (MEC), the first edition of which was published in 1996, presents current World Health Organization (WHO) guidance on the safety of various contraceptive methods for use in the context of specific health conditions and characteristics. This is the fifth edition of the MEC -the latest in the series of periodic updates.
In the MEC, the safety of each contraceptive method is determined by several considerations in the context of the medical condition or medically relevant characterstics; primarily, whether the contraceptive method worsens the medical condition or creates additional health risks, and secondarily, whether the medical circumstance makes the contraceptive method less effective. The safety of the method should be weighed along with the benefits of preventing unintended pregnancy. This fifth edition of the MEC is divided into two parts. Part I describes how the recommendations were developed and Part II contains the recommendations and describes how to use them. The recommendations contained within this document are based on the latest clinical and epidemiological data. Several tools and job aids are available from WHO and other sources to help providers use these recommendations in practice.
This document covers the following family planning methods: low-dose ( 35 mcg ethinyl estradiol) combined 1 oral contraceptives (COCs), combined patch (P), combined vaginal ring (CVR), combined injectable contraceptives (CICs), progestogen-only pills (POPs), depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), levonorgestrel (LNG) and etonogestrel (ETG) implants, emergency contraceptive pills (ECPs), copper-bearing intrauterine devices (Cu-IUDs), levonorgestrel-releasing IUDs (LNG-IUDs), copper-IUD for emergency contraception (E-IUD), progesterone-releasing vaginal ring (PVR), barrier methods (BARR), fertility awareness-based methods (FAB), lactational amenorrhoea method (LAM), coitus interruptus (CI), and female and male sterilization (STER).
For each medical condition or medically relevant characteristic, contraceptive methods are placed into one of four numbered categories. Depending upon the individual, more than one condition may need to be considered together to determine contraceptive eligibility. These conditions and characteristics include, among others: age, weeks/months postpartum, breastfeeding status, venous thromboembolism, superficial venous disorders, dyslipidaemias, puerperal sepsis, past ectopic pregnancy, history of severe cardiovascular disease, migraines, severe liver disease, use of CYP3A4 inducer, repeat use of ECPs, rape, obesity, increased risk of sexually transmitted infections, high risk of HIV infection, living with HIV, use of antiretroviral therapy.

# MEC categories for contraceptive eligibility
1 A condition for which there is no restriction for the use of the contraceptive method 2 A condition where the advantages of using the method generally outweigh the theoretical or proven risks 3 A condition where the theoretical or proven risks usually outweigh the advantages of using the method 4 A condition which represents an unacceptable health risk if the contraceptive method is used.

# Target audience
The intended audience for this publication includes policymakers, family planning programme managers and the scientific community. The MEC aims to provide guidance to national family planning and reproductive health programmes in the preparation of guidelines for delivery of contraceptive services. It is not meant to serve as the actual guidelines but rather as a reference.
The guidance in this document is intended for interpretation at country and programme levels, in a manner that reflects the diversity of situations and settings in which contraceptives are provided. While it is unlikely that the classification of categories in this document would change during this process, it is very likely that the application of these categories at country level will vary. In particular, the level of clinical knowledge and experience of various types of providers and the resources available at the service delivery point will have to be taken into consideration.

# Guideline development methods
The Guideline Development Group (GDG), convened by WHO on 14-15 May 2013, 9-12 March 2014 and 24-25 September 2014, consisted of 68 individuals representing a wide range of stakeholders. Their mandate was to review and, where appropriate, revise the guidance in the fourth edition of the MEC to develop the fifth edition.
For this revision process, the GDG prioritized the review of: (a) six topics identified as important to the field and/or those topics with new evidence that may warrant a change in the existing recommendation; (b) two topics for which interim guidance was issued following the publication of the fourth edition; (c) contraceptive eligibility recommendations for the inclusion of four new contraceptive methods in the fifth edition; and (d) two topics to provide greater clarity for the recommendations in the fourth edition relating to these topics, at the request of the Guidelines Review Committee. Therefore, recommendations for a total of 14 topics were reviewed for the fifth edition of the MEC.
The GDG considered the overall quality of the available scientific evidence, paying particular attention to the strength and consistency of the data, according to the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach to evidence review. 2 To formulate recommendations using the four MEC categories for contraceptive eligibility, the GDG considered potential harms related to contraceptive use, the GRADE evidence profiles, the benefits of preventing unintended pregnancy, and applied an approach towards values and preferences that prioritized the availability of a wide range of contraceptive options. The GDG reached its decisions through consensus, which entailed discussion, debate and consultation with experts to reconcile any disagreements. For certain recommendations, the GDG added clarification statements to provide further explanation or guidance on interpretation of the numerical classification.
For each contraceptive method, the GDG considered the potential benefits and risks of its use with respect to each of the medical conditions or medically relevant physiologic or personal characteristics assessed (such as age, breastfeeding, smoking status).
Updated evidence. In many instances, either no new evidence has been identified since the publication of the fourth edition of the MEC (2009), or evidence emerging since that publication confirms previous research findings. Therefore, in many cases the recommendations that were published in the fourth edition have been reviewed and confirmed by the GDG with no changes made. For such recommendations that remained unchanged, the WHO Secretariat updated the evidence statements, references and citations that appear in the contraceptive method tables in Part II.
WHO will initiate a review of the recommendations in this document in four years. In the interim, WHO will continue to monitor the body of evidence informing these recommendations and will convene additional consultations, as needed, should new evidence necessitate reconsideration of existing recommendations. Such updates may be particularly warranted for issues where the evidence base may change rapidly. These interim recommendations will be made available on the WHO's web pages for sexual and reproductive health. WHO encourages research to address key unresolved issues related to establishing medical eligibility criteria for contraceptive use. WHO also invites comments and suggestions for improving this guidance.

# Summary of reviewed recommendations
Fourteen topics (encompassing over 575 recommendations) were reviewed by the GDG during the 2014 revision of the MEC (see Table 1). The GRADE approach was applied to assess the quality of the available evidence, and this provided the basis for the formulation of recommendations (see central column). For some topics, multiple outcomes of interest and/or contraceptive methods were examined. For these topics, GRADE assessments of the quality of evidence are presented, either a single assessment or a range (see final column). An explanation of the process followed to select and prioritize these topics is included in Part I of the document, section 1.2: Methods, pp. 3-7 (Table 1.1). Other than the recommendations shown in Table 1, all other recommendations were confirmed by the GDG and did not undergo formal review for the updated fifth edition of the MEC. A summary of the changes between the fourth and fifth editions of this document is available in Part II, section 2.6, pp. 93-96.  Recommendations for use of hormonal contraception for women at high risk of HIV infection, women living with HIV, and women living with HIV using antiretroviral therapy (ART)
12a. Women at high risk of HIV infection
Women at high risk of acquiring HIV can use the following hormonal contraceptive methods without restriction: COCs, combined injectable contraceptives (CICs), combined contraceptive patches and rings, POPs, POIs (DMPA and NET-EN), and LNG and ETG implants (MEC Category 1).
Women at high risk of acquiring HIV can generally use LNG-IUDs (MEC Category 2).
Range: Moderate to very low 12b. Women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2)
Women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2) can use the following hormonal contraceptive methods without restriction: COCs, CICs, combined contraceptive patches and rings, POPs, POIs (DMPA and NET-EN), and LNG and ETG implants (MEC Category 1).
Women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2) can generally use the LNG-IUD (MEC Category 2).
Range: Moderate to very low 12c. Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4)
Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) can use the following hormonal contraceptive methods without restriction: COCs, CICs, combined contraceptive patches and rings, POPs, POIs (DMPA and NET-EN), and LNG and ETG implants (MEC Category 1).
Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) generally should not initiate use of the LNG-IUD (MEC Category 3) until their illness has improved to asymptomatic or mild HIV clinical disease (WHO stage 1 or 2).
Women who already have an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).
a GRADE assessment includes the quality categories of very low, low, moderate and high. When a range is presented, the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. See the specific GRADE 12d. Women living with HIV using antiretroviral therapy (ART)
Range: Low to very Low Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)
Women taking any NRTI can use all hormonal contraceptive methods without restriction: COCs, CICs, combined contraceptive patches and rings, POPs, POIs (DMPA and NET-EN), and LNG and ETG implants (MEC Category 1).
Women taking any NRTI can generally use the LNG-IUD (MEC Category 2), provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any NRTI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease.
Women taking any NRTI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).
Non-nucleoside/ nucleotide reverse transcriptase inhibitors (NNRTIs) containing efavirenz or nevirapinecontaining ART Women using NNRTIs containing either efavirenz or nevirapine can generally use COCs, CICs, combined contraceptive patches and rings, POPs, NET-EN, and LNG and ETG implants (MEC Category 2).
Women using efavirenz or nevirapine can use DMPA without restriction (MEC Category 1).
Women taking any NNRTI can generally use the LNG-IUD (MEC Category 2), provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any NNRTI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease.
Women taking any NNRTI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).

# NNRTIs containing etravirine and rilpivirine
Women using the newer NNRTIs containing etravirine and rilpivirine can use all hormonal contraceptive methods without restriction (MEC Category 1).
ART: antiretroviral therapy; ARV: antiretroviral (medication); CHC: combined hormonal contraceptive; CIC: combined injectable contraceptive; COC: combined oral contraceptive; Cu-IUD: copper-bearing IUD; DMPA: depot medroxyprogesterone acetate; ETG: etonogestrel; GRADE: Grading Recommendations, Assessment, Development and Evaluation; GRC: Guidelines Review Committee; IM: intramuscular; IUD: intrauterine device; LNG: levonorgestrel; NET-EN: norethisterone enanthate; POC: progesterone-only contraceptive; NRTI: nucleoside/nucleotide reverse transcriptase inhibitor; NNRTI: non-nucleoside/nucleotide reverse transcriptase inhibitor; POI: progresterone-only injectable; POP: progesterone-only pill; SC: subcutaneous; SVT: superficial venous thrombosis; VTE: venous thromboembolism.
a GRADE assessment includes the quality categories of very low, low, moderate and high. When a range is presented, the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. See the specific GRADE 12d. Women living with HIV using antiretroviral therapy (ART) (continued)
Range: Low to very Low Protease inhibitors (e.g. ritonavir and ARVs boosted with ritonavir)
Women using protease inhibitors (e.g. ritonavir and ARVs boosted with ritonavir) can generally use COCs, CICs, combined contraceptive patches and rings, POPs, NET-EN, and LNG and ETG implants (MEC Category 2).
Women using protease inhibitors (e.g. ritonavir and ARVs boosted with ritonavir) can use DMPA without restriction (MEC Category 1).
Women taking any PI can generally use the LNG-IUD (MEC Category 2), provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any PI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease.
Women taking any PI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).

# Raltegravir (integrase inhibitor)
Women using the integrase inhibitor raltegravir can use all hormonal contraceptive methods without restriction (MEC Category 1).
Women taking an RI can generally use the LNG-IUD (MEC Category 2), provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking an RI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease.
Women taking an RI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).
ART: antiretroviral therapy; ARV: antiretroviral (medication); CHC: combined hormonal contraceptive; CIC: combined injectable contraceptive; COC: combined oral contraceptive; Cu-IUD: copper-bearing IUD; DMPA: depot medroxyprogesterone acetate; ETG: etonogestrel; GRADE: Grading Recommendations, Assessment, Development and Evaluation; GRC: Guidelines Review Committee; IM: intramuscular; IUD: intrauterine device; LNG: levonorgestrel; NET-EN: norethisterone enanthate; NNRTI: non-nucleoside/nucleotide reverse transcriptase inhibitor; NRTI: nucleoside/nucleotide reverse transcriptase inhibitor; POC: progesterone-only contraceptive; POI: progresterone-only injectable; POP: progesterone-only pill; SC: subcutaneous; SVT: superficial venous thrombosis; VTE: venous thromboembolism.
a GRADE assessment includes the quality categories of very low, low, moderate and high. When a range is presented, the range reflects the Part I Development of the Medical eligibility criteria for contraceptive use, fifth edition
- 1 Background

# Overview and scope of the guidelines
Over the past 40 years, there have been significant advances in the development of new contraceptive technologies, including changes in formulations and dosing, schedules for administration and novel delivery systems. However, current policies and health-care practices in some countries are based on scientific studies of contraceptive products that are no longer in wide use, on long-standing theoretical concerns that have never been substantiated or on the personal preference or bias of service providers. These outdated policies or practices often result in limitations to both the quality of, and the access to, family planning services for clients.
The goal of this document is to improve access to, and quality of, family planning services by providing policymakers, decision-makers and the scientific community with recommendations that can be used for developing or revising national guidelines on medical eligibility criteria used in the provision of all hormonal contraceptives, intrauterine devices, barrier methods, fertility awareness-based methods, coitus interruptus, lactational amenorrhoea method, male and female sterilization, and emergency contraception. These evidencebased recommendations do not indicate a "best" method that should be used given a particular medical context; rather, review of the recommendations allows for consideration of multiple methods that could be used safely by people with certain health conditions (e.g. hypertension) or characteristics (e.g. age).
Because country situations and programme environments vary so greatly, it is inappropriate to set firm international guidelines on criteria for contraceptive use. However, it is expected that national programmes will use these recommendations for updating or developing their own contraceptive eligibility guidelines according to national health policies, needs, priorities and resources, while reflecting upon local values and preferences.
There are a total of four WHO guidance documents (cornerstones) pertaining to contraception; two that focus on evidence-based recommendations (primarily targeted towards policy-makers and programme managers) and two that focus on application of the recommendations (primarily targeted towards health-care providers). All four cornerstones are best interpreted and used in a broader context of reproductive and sexual health care. These four documents, listed below, are updated periodically to reflect changes in the medical and scientific knowledge.
Evidence-based recommendations for provision of contraception:
- Medical eligibility criteria for contraceptive use (MEC)provides guidance regarding "who" can use contraceptive methods safely; and 2. Selected practice recommendations for contraceptive use (SPR) -provides guidance regarding "how" to use contraceptive methods safely and effectively.
Practical tools for front-line providers of contraceptive counselling and services:
- Decision-making tool for family planning clients and providers -counselling tool that supports both provider and client in the process of choosing a contraceptive method; and 4. Family planning: a global handbook for providers -offers evidence-based information on service delivery, method by method.
Figure 1. The four cornerstones of family planning guidance

# Medical eligibility criteria for contraceptive use

# Selected practice recommendations for contraceptive use
These are evidence-based guidance and consensus-driven guidelines. They provide recommendations made by expert working groups based on an appraisal of relevant evidence. They are reviewed and updated in a timely manner.
Process for assuring that the guidelines remain current:
- Identify new, relevant evidence as soon as it becomes available through an ongoing comprehensive bibliographic search.
- Critically appraise the new evidence.
- Evaluate the new evidence in light of prior evidence.
- Determine whether the newly synthesized evidence is sufficient to warrant an update of existing recommendations.
- Provide electronic updates on WHO's reproductive health web site (www.who.int/reproductivehealth) as appropriate and determine the need to convene an expert working group to reassess guidelines formally.

# Development of earlier editions of the Medical eligibility criteria for contraceptive use
This document builds on a process initiated in 1994 to develop the first edition. The initial process involved comparing the eligibility criteria used by different agencies for various contraceptives, preparing summaries of published medical and epidemiological literature relevant to medical eligibility criteria, and preparing a draft classification for review by a larger group of experts and agencies. Two expert Working Group meetings were organized by WHO, in March 1994 and May 1995, to review the background classifications and to formulate recommendations; publication of the document followed in 1996.
Since the publication of the first edition of the MEC, the guideline has been revised and updated three times. With each revision, a Working Group of multidisciplinary experts was assembled to review newly published evidence pertaining to the topics addressed in the guideline. Moreover, with each revision, the Working Group used the opportunity to consider inclusion of new medical conditions and new contraceptive methods, as appropriate.
The second edition of the MEC was based on the recommendations of an expert Working Group meeting held at WHO on 8-10 March 2000, which brought together 32 participants from 17 countries, including representatives of many agencies and organizations. The Working Group reviewed new evidence since the last meetings in 1994 and 1995, primarily obtained from systematic reviews of the most recent literature.
The third edition of the MEC, was based on the recommendations of an expert Working Group meeting held at WHO on 21-24 October 2003, which gathered 36 participants from 18 countries, including representatives of many agencies and organizations. Systematic reviews of the evidence were prepared on topics with newly published evidence since the meeting in 2000; they were presented to the Working Group and provided the basis for their decision-making. A Guideline Steering Group (GSG), comprising seven external members, was established for this edition. The GSG was formed to advise WHO on behalf of the larger expert Working Group on matters related to emerging published evidence on topics covered by the guideline during interim periods between expert Working Group meetings.
The fourth edition of the MEC was based on the recommendations of an expert Working Group meeting held at WHO on 1-4 April 2008, which brought together 43 participants from 23 countries, including nine agency representatives. Eighty-six new recommendations were developed and 165 recommendations were revised for the fourth edition. All members of the expert Working Group were asked to declare any conflict of interest and three of the experts declared conflicts of interest relevant to the subject matter of the meeting. These conflicts of interest were determined not to be sufficient to preclude the experts from participating in the deliberations and development of recommendations and thus they were not asked to withdraw from this process.
The Guidelines Review Committee (GRC) was established by the Director-General of WHO in 2007 to ensure that WHO guidelines are of a high methodological quality and are developed through a transparent, evidence-based decisionmaking process. The fourth edition of the MEC was reviewed by the newly established GRC and was approved on 16 September 2009.
To assure that the guidelines remain current between guideline meetings, new evidence is identified through an ongoing comprehensive bibiliographic search (the Continuous Identification of Research Evidence, or CIRE system) 1. This evidence is synthesized and reviewed. In circumstances where new evidence warrants further evaluation, the GSG is tasked with evaluating such evidence and issuing interim guidance if necessary. Since the release of the fourth edition of the MEC, interim guidance has been issued twice. At the request of the GSG, WHO first convened a technical consultation on 26 January 2010 via teleconference to review new evidence regarding the risk of venous thromboembolism (VTE) in postpartum women. The teleconference brought together members of the GSG and three experts on VTE during the postpartum period. All participants in the consultation were asked to declare any conflict of interest; two participants declared a conflict of interest relevant to the subject matter, but they were not asked to withdraw from the process of recommendation formulation because the WHO Secretariat and GSG did not find these conflicts of interest sufficient to preclude them from participating in the deliberations and development of recommendations. The GRC approved the updated recommendations on 21 April 2010.
Following new findings of epidemiological studies regarding the use of hormonal contraception and HIV acquisition, progression and transmission, a second technical consultation was convened by WHO during 31 January -1 February 2012. The meeting involved 75 individuals representing a wide range of stakeholders. Through a consensus-driven process, the group considered whether recommendations in the MEC pertaining to hormonal contraceptive use among women at high risk of HIV or women living with HIV should be changed in light of the accumulating evidence. All participants in the consultation were asked to declare any conflict of interest; 13 participants declared an academic conflict of interest relevant to the subject matter of the meeting. These conflicts of interest were determined not to be sufficient to preclude them from participating in the deliberations and development of recommendations and so they were not asked to withdraw from this process. The GRC approved the technical statement presenting the conclusions and updated recommendations of the meeting on 15 February 2012.

# Development of the Medical eligibility for criteria for contraceptive use, fifth edition
In preparation for the fifth edition of the document, both approval for the planning and ultimately the final document were obtained from the GRC. Several key aspects of the updating process were adjusted to be in closer alignment with requirements set forth in the WHO handbook for guideline development, authored by the GRC Secretariat. 2 Specifically, these alterations included:
- creation of groups with varying roles to undertake the revision;
- convening an additional consultation to define the scope of the revision, giving priority to controversial topics and those for which new evidence had emerged, including topics addressed in interim guidance, clarifying recommendations with a Category 2/3 classification, and drafting questions relating to population, intervention, comparator and outcome (PICO questions) to guide the preparation of systematic reviews; and
- applying the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach to evidence review and recommendation formulation. 3 The groups responsible for the development of the fifth edition of the MEC included: a WHO Secretariat; an Evidence Secretariat including a GRADE methodologist; a Guideline Steering Group (GSG); and a Guideline Development Group (GDG), which was formerly called the expert Working Group for the earlier MEC editions. The GSG, which has served as an external advisory group to WHO on family planning guidelines since 2003, was part of the larger GDG, to be compliant with WHO requirements for guideline development and to gain input from a larger advisory group. For a summary of the members of the WHO Secretariat, the Evidence Secretariat and the GDG, see the Acknowledgements at the beginning of this document.

# Prioritization of topics for the revision process
On 14-15 May 2013, the first GDG meeting convened in Ferney Voltaire, France, to initiate the revision process for the development of the fifth edition of the MEC. Prior to the meeting, the CIRE system 1 was used to identify recommendations from the fourth edition of the MEC for which new evidence was available.
To further inform decision-making with respect to clinical questions and priorities, the WHO Secretariat reached out to a broad group of stakeholders with expertise in family planning and familiarity with the guideline, including individuals from a number of implementing agencies, professional societies, and WHO regional and country offices, as well as the Ministry of Health in each of the Member States. They were asked to voluntarily complete an electronic 24-question anonymous survey available in English, French and Spanish, and to forward the link for the survey to others in their professional communities familiar with family planning and the MEC during the period 2 March -2 May 2013. The respondents were asked to rank the importance of various outcomes pertaining to topics that had been identified as priority questions for the current revision, as well as to suggest other outcomes and clinical questions of importance, and to give input regarding the format of the guidance. More than 250 individuals submitted completed surveys; these results were presented to the GDG during the meeting to inform the prioritization process.
At the meeting, the WHO Secretariat presented brief summaries of new evidence to the GDG to determine whether the existing recommendation remained consistent or had become inconsistent with the updated body of evidence. Recommendations considered to be possibly inconsistent with the updated body of evidence were selected for presentation and discussion at a larger meeting convened in March 2014. Recommendations considered to be consistent with the updated body of evidence, and recommendations for which no new evidence had been identified through CIRE were determined by the GDG to need no further review during the revision process.
Also at this first GDG meeting, the members were asked to consider whether WHO should include several new conditions, contraceptive methods and/or formulations of methods, based upon their global relevance and availability in multiple countries. Participants were also asked to review the two interim guidance documents released since the fourth edition. Further, during this meeting the GDG was asked to address current recommendations which were classified as category "2/3" in the fourth edition, as earlier reviews by the GRC noted that these recommendations may be confusing to users of the document.
Thus, topics were prioritized for review and consideration by the GDG at the second meeting in March 2014 based on meeting one or more of the following criteria: topics identified as controversial or of particular importance to the field; topics with new evidence, for which the existing recommendation was potentially inconsistent with the updated body of evidence; topics with interim guidance issued by WHO since the MEC fourth edition; newly introduced contraceptive methods; or recommendations from the MEC fourth edition that were determined to lack clarity by the GRC. All existing recommendations that did not fall into one of these categories were reaffirmed by the GRC and thus were not reviewed. Prioritized topics reviewed by the Guideline Development Group (GDG) using the GRADE process in 2014:
- Topics identified as important to the field and/or topics with new, potentially inconsistent evidence identified (6 topics):
- progesterone-only contraceptive (POC) use among breastfeeding women
- combined hormonal contraceptive (CHC) use among breastfeeding women
- CHC use among women with superficial venous disorders
- CHC use by age group
- hormonal contraceptive use among women using antiretroviral therapy
- emergency contraceptive pill (ECP) use among women with obesity (new condition added to ECP recommendations).
- Interim guidance issued by WHO since the MEC fourth edition (2 topics):
- CHC use during the postpartum period (guidance updated in 2010)
- hormonal contraceptive use among women at high risk of HIV acquisition and women living with HIV (guidance reaffirmed in 2012).
- New contraceptive methods added to the MEC for the fifth edition (4 methods):
- subcutaneously-administered depot medroxyprogesterone acetate (DMPA) 104 mg
- 2-rod levonorgestrel (LNG)-containing implant with 75 mg LNG/rod, approved for 4 years of use, i.e. Sino-implant (II)
- progesterone-releasing vaginal ring (PVR)
- ulipristal acetate (UPA) for emergency contraception. 4. Recommendations reviewed by the GDG for clarity, as required by the Guidelines Review Committee (GRC) (2 topics):
- intrauterine device (IUD) use among women with increased risk of sexually transmitted infections (STIs) (no new evidence identified since 2008 systematic review)
- CHC use among women with known dyslipidaemias.
All other existing recommendations from the MEC fourth edition (approximately 2000 recommendations): a
- reaffirmed by the GDG in March 2014.
CIRE: Continuous Identification of Research Evidence; GRADE: Grading Recommendations, Assessment, Development and Evaluation.
a Evidence continuously monitored using CIRE system. Topics not prioritized for 2014 update.
For the topics outlined in Table 1.1, the GDG developed questions using the PICO format (i.e. questions with specified populations, interventions, comparators and outcomes) to serve as the framework for the systematic reviews and GRADE evidence tables. In order to inform the MEC recommendations, PICO questions generally guide the systematic review to focus on studies of populations with the condition or characteristic of interest using a specific contraceptive method compared with the same population not using the method, reporting on critical safety outcomes. PICO questions were also crafted to also identify relevant indirect evidence that may have included comparator populations without the condition or characteristic of interest using the same method, or reporting on surrogate outcomes. These systematic reviews, therefore, assessed the safety risks of using a given method among women with a particular medical condition or characteristic. The remainder of the existing recommendations were determined to be consistent with the body of published evidence and did not need to be formally reviewed for this revision.

# Evidence identification and synthesis
For each of the priority topics listed in Table 1.1, systematic reviews were conducted in accordance with PRISMA guidelines to answer PICO-formatted questions regarding safety outcomes. 4 The systematic reviews may be accessed in Annex 2. In general, the PubMed and Cochrane databases were searched for studies published in any language in a peer-reviewed journal up to 15 January 2014, to inform the systematic reviews. Reference lists and direct contact with experts in the field were also used to identify other studies, including those in press; neither grey literature nor conference abstracts were included in these reviews. Due to heterogeneity of study designs, contraceptive formulations and outcome measures, meta-analyses were generally not performed. The quality of evidence presented in individual studies within a systematic review was assessed by review authors using the United States Preventive Services Task Force system. 5 GRADE evidence profiles were then prepared by a GRADE methodologist to assess the quality of the summarized evidence and include the range of the estimates of effect for each clinical outcome assessed. GRADE evidence profiles were prepared for each PICO question for which evidence was found and clinical outcomes were reported. The systematic reviews that resulted from this process were peer-reviewed by selected members of the GDG, and final drafts were made electronically available to all GDG members prior to the consultations. Printed copies of GRADE evidence profiles for each topic were also given to each GDG member during the March 2014 GDG meeting. The written and orally presented systematic reviews and GRADE evidence profiles served as the basis for the GDG's deliberations. The WHO Secretariat and the GDG reviewed all declarations of interest and, with the exception of two members (Dr Glasier and Dr Sitruk-Ware), found no conflicts of interest sufficient to preclude anyone from participating in the deliberations or development of recommendations. In the case of the two exceptions, the WHO Secretariat and the GDG agreed that their disclosed academic conflicts of interest were sufficient to preclude them from participating in the deliberations and development of recommendations relevant to ulipristal acetate (Dr Glasier) and the progesterone-releasing vaginal ring (Dr Sitruk-Ware). For details of the declared academic interests see Annex 1.
The GDG considered the overall quality of the safety evidence, paying particular attention to the strength and consistency of the data, according to the GRADE approach to evidence review. In most cases, the quality of evidence pertaining to each recommendation was low or very low and only addressed potential harms related to contraceptive use. To arrive at a category designation, within the range 1-4, the GDG considered these potential harms, the GRADE evidence profiles, the benefits of preventing unintended pregnancy, as well as the other GRADE constructs of values and preferences.
The GDG endorsed an approach to patient preferences and values that prioritized the availability of a wide range of contraceptive options, as women vary in their preferences regarding contraceptive selection and in the value they place on different beneficial and harmful outcomes. 6 7 In addition, the availability of a range of contraceptive options is critical because a woman's contraceptive choices are made at a particular time and in a particular societal and cultural context, and these choices are complex, multifactorial and subject to change. 8 9 Decision-making for contraceptive methods usually requires making trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.
Owing to the focus of this guidance on the safety of specific contraceptive methods for women with medical conditions or personal characteristics, opportunity costs were not formally assessed during the formulation of these recommendations since costs may vary widely throughout different regions. 10 Since publication of the first edition of the MEC in 1996, the 1-4 scale has been used to categorize medical eligibility for contraceptive use. These categories are well known by healthcare providers, professional organizations, training institutions and ministries of health as the basis for determining contraceptive eligibility for women with medical conditions or characteristics. As a result, to avoid confusion and retain consistency, it was determined that recommendations would not be defined as "strong" or "weak" according to GRADE methodology and would instead retain the 1-4 scale reflecting eligibility for contraceptive use.
Through consensus, the GDG arrived at new and revised recommendations, as well as upholding the majority of the existing recommendations using the categories 1-4. For the topics they reviewed in 2014 (see Box 1.1), the GDG considered the potential benefits and risks of contraceptive method use with respect to each of the medical conditions or personal characteristics assessed.
Owing to the public health importance of recommendations on hormonal contraceptive use for women at risk of HIV and women living with HIV, and based on encouragement from the GDG, WHO issued its contraceptive eligibility guidance for women living with HIV or at high risk of acquiring the infection in advance of the entire guideline revision.

# Reviewed recommendations
The Guideline Development Group (GDG) determined priority topics to be addressed as part of the revision process for the fifth edition (see Table 1.1).
- In 2014, the GDG focused specifically on the evidence pertaining to fracture risk among women of all ages, and the evidence for combined hormonal contraceptives (CHCs) and potential for decreased bone mineral density (BMD) among adolescents. BMD is a surrogate marker for fracture risk that may not be valid for premenopausal women, and therefore may not accurately predict current or future (postmenopausal) fracture risk (1)(2)(3). The risk of cardiovascular disease increases with age and may also increase with CHC use. In the absence of other adverse clinical conditions, CHC can be used until menopause.
- Due to heterogeneity of study designs, contraceptive formulations and outcome measures a meta-analysis was not performed.
- CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms, male or female, is recommended.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Evidence is inconsistent on the question of whether CHC use affects fracture risk (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), although three recent studies show no effect (4,5,15). CHC use may decrease BMD in adolescents, especially in those choosing very-low-dose formulations (< 30 g ethinylestradiol-containing combined oral contraceptives) (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). CHC use has little to no effect on BMD in premenopausal women (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), and may preserve bone mass in those who are perimenopausal (45)(46)(47)(48)(49)(50)(51)(52)(53)(54).

# Quality of the evidence
- Breastfeeding women < 6 weeks postpartum should not use combined hormonal contraceptives (combined oral contraceptives, combined contraceptive patch, combined contraceptive vaginal ring, combined injectable contraceptives) (MEC Category 4).
- Breastfeeding women  6 weeks to < 6 months postpartum (primarily breastfeeding) generally should not use CHCs (MEC Category 3).
- Breastfeeding women  6 months postpartum can generally use CHCs (MEC Category 2).
- Due to heterogeneity of study designs, contraceptive formulations and outcome measures, a meta-analysis was not performed.
- Combined hormonal contraceptives (CHCs) do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to combined oral contraceptives (COCs) during lactation. No consistent effects on infant growth or illness have been reported (1)(2)(3)(4)(5)(6). Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast-milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk of either serious or subtle long-term effects exists.

# Recommendations for combined hormonal contraceptives among postpartum women
- The Guideline Development Group (GDG) considered the balance of benefits and harms for CHC use among postpartum women, at different time points postpartum, and with and without other risk factors for VTE, including the risk of VTE in the postpartum period, the risks associated with rapid repeat pregnancy, the benefits of preventing rapid repeat pregnancy, and the availability of other contraceptive methods that are safe for use by postpartum women. The GDG also considered that risk of pregnancy during the first 21 days postpartum is very low, but increases after that time in non-breastfeeding women; ovulation before first menses is common (1).
- Due to heterogeneity of study designs, contraceptive formulations and outcome measures, a meta-analysis was not performed.
- CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with non-users at all time points postpartum. Rates were significantly different only after 13 weeks postpartum, but the numbers needed to harm were lowest in the first 6 weeks postpartum (2). VTE risk is elevated during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, declining to near baseline levels by 42 days postpartum (3)(4)(5)(6)(7).

# Quality of the evidence (intervention versus comparator; outcome)

# Recommendations for combined hormonal contraceptives among women with superficial venous disorders
The disease nomenclature has been updated to reflect current recognized standard terminology and more accurately describe the condition and sub-conditions. The overall name of the condition has been changed to "superficial venous disorders". The subcondition "superficial thrombophlebitis" has been changed to "superficial venous thrombosis" (SVT).
- Due to heterogeneity of study designs, contraceptive formulations and outcome measures, a meta-analysis was not performed.
- CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
One study suggested that among women with varicose veins, the rate of VTE and SVT was higher in oral contraceptive users compared with non-users; however, statistical significance was not reported and the number of events was small (1). One study demonstrated that among women with SVT, the risk of VTE was higher in oral contraceptive users compared with non-users (2).

# Quality of the evidence
- The Guideline Development Group (GDG) determined that the existing condition name, "known hyperlipidaemias", should be changed to "known dyslipidaemias" to better describe the spectrum of clinically important lipid abnormalities. They also specified that the condition should include only women "without other known cardiovascular risk factors" for better clarity.
- The GDG noted that the baseline absolute risk for cardiovascular disease among women of reproductive age is very low. Using available cardiovascular risk prediction models, even among healthy perimenopausal women with high total cholesterol and normal HDL, 10-year risks for cardiovascular disease remain low. The most recent guidelines from the Fifth Joint Task Force of the European Society of Cardiology, published in 2012, predict that a healthy woman aged 45-49 years with total cholesterol levels greater than 280 mg/dL has < 1% 10-year risk for fatal myocardial infarction (MI) or stroke; similarly, recent guidelines released by the American College of Cardiology and the American Heart Association predict a 1.9% 10-year risk for a non-fatal or fatal first MI or stroke. Further, it was concluded that even if combined oral contraceptive (COC) use increases risk for MI or stroke among women of reproductive age with known dyslipidaemias and no other risk factors for cardiovascular disease, the absolute risk for these serious adverse events remains low.
- Use of combined hormonal contraception (CHC) among women with severe genetic lipid disorders may warrant further clinical consideration given that these women are at much higher lifetime risk for cardiovascular disease.
- The GDG determined that risk for arterial thrombotic events was the main safety concern for women with known dyslipidaemias without other cardiovascular risk factors. Independent of COC use, there does not appear to be a clear association between dyslipidaemia and risk for VTE among women of reproductive age, and indirect evidence from one study identified in our systematic review noted only a slight increased risk for VTE among COC users with the condition compared to users without the condition. No comparative data were available to assess the risk of pancreatitis among women with known dyslipidaemias, and while it is well established that elevated triglyceride levels are associated with acute pancreatitis, severe hypertriglyceridemia is a very rare condition with a risk for pancreatitis associated with triglyceride levels  1000 mg/dL estimated at approximately 5%.
- Due to heterogeneity of study designs, contraceptive formulations and outcome measures, a meta-analysis was not performed.
- CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence

# Puerperal sepsis
- Breastfeeding (and non-breastfeeding) women with puerperal sepsis should not have an LNG-IUD inserted (MEC Category 4).
- Animal data suggest an effect of progesterone on the developing brain; whether similar effects occur following progestogen exposure in humans is unclear (1)(2)(3). Available data from clinical and observational trials do not suggest an increased risk for either breastfeeding performance or infant health outcomes with use of progestogen-only injectables compared to outcomes in studies using other progestogen-only methods (4)(5)(6)(7)(8). However, the Guideline Development Group felt that, as infants in the first 6 weeks of life may be exposed to higher hormone levels with use of progestogen-only injectables, as compared to the exposure using other methods of progestogen-only contraceptives (POCs), the theoretical risks of progestogen-only injectables may outweigh the benefits, particularly in settings with access to a wide variety of contraceptive methods.
- Due to heterogeneity of study designs, contraceptive methods/formulations and outcome measures, a metaanalysis was not performed.
- POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Forty-seven articles reporting on 45 different studies were identified in the systematic review that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Direct evidence demonstrates no effect of POCs on breastfeeding performance and generally demonstrates no harmful effects on infant growth, health or development (6,7,28,42). However, these studies have been inadequately designed to determine whether a risk of longterm effects exists.
One randomized trial found that immediate insertion of the LNG-IUD was associated with decreased breastfeeding duration compared with delayed insertion (5). Two other randomized controlled trials assessing early versus delayed initiation of POCs failed to show a difference in breastfeeding outcomes (4,16). In other studies, initiation of LNG-IUD after 4 weeks postpartum demonstrated no detrimental effect on breastfeeding outcomes (11,13,45).
Quality of the evidence < 6 weeks postpartum:
- Young women (menarche to < 18 years) can generally use DMPA (MEC Category 2).
- Women between the ages of 18 and 45 years can use DMPA without restriction (MEC Category 1)
- Women > 45 years old can generally use DMPA (MEC Category 2).
- Women with endometriosis can use DMPA without restriction (MEC Category 1).
- Women living with HIV who have asymptomatic or mild clinical disease (WHO stage 1 or 2) can use DMPA without restriction (MEC Category 1).
- Women living with HIV who have severe or advanced HIV clinical disease (WHO stage 3 or 4) can use DMPA without restriction (MEC Category 1).
- Women with a body mass index (BMI)  30 kg/m 2 can use DMPA without restriction (MEC Category 1).
- Young women (menarche to < 18 years) with a BMI  30 kg/m 2 can generally use DMPA (MEC Category 2).
- There is evidence for differential weight gain among normal-weight and obese adolescents who use DMPA, but not those using norethisterone enanthate (NET-EN). However, NET-EN is MEC Category 2 due to evidence regarding potential effects of NET-EN on bone mineral density among adolescents.
- The Guideline Development Group determined that no change to the existing recommendations for DMPA was warranted with inclusion of DMPA-SC as a new method.
- The body of evidence evaluating use of DMPA-SC and DMPA-IM among healthy women of reproductive age suggests a similar safety profile. Due to heterogeneity of study designs and outcome measures, a meta-analysis was not performed.
- DMPA-SC does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/ HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
A randomized trial evaluating changes in bone mineral density (BMD) among adult DMPA-SC and IM users demonstrated no differences at two years of follow-up (1). Limited evidence from three Phase 3 contraceptive trials reported no consistent differences in weight change or bleeding patterns according to age; adolescents aged < 18 years were not included in any studies (1)(2)(3). Two prospective, non-comparative studies demonstrated that women with endometriosis treated with DMPA-SC for six months experienced minimal weight gain and decreases in BMD; serious adverse events were rare and DMPA-SC improved pain symptoms associated with the condition (4,5). A randomized cross-over study reported that women living with HIV tolerated injection of DMPA-SC and that experiences of serious adverse events were rare and occurred at similar rates as in users of DMPA-IM (6). Evidence from three Phase 3 contraceptive trials and four reports from a small prospective cohort study reported similar contraceptive efficacy, weight change, bleeding patterns and other adverse effects, including variations in a number of biomarkers, among obese and non-obese DMPA-SC users (1,3,(7)(8)(9)(10)(11)(12).
DMPA-IM and DMPA-SC appear to be therapeutically equivalent; the two formulations demonstrate similar pharmacokinetics, effects on serum estradiol levels and high contraceptive efficacy (1). In addition, similar effects on weight change, bleeding patterns and experience of other adverse effects have been reported among healthy reproductive age users (1,3,13).

# Quality of the evidence
- Although there was no direct evidence regarding Sinoimplant (II) among women with medical conditions, studies were identified that looked at safety of the implant among healthy women compared to those who do not use the SI (II). In addition, the safety data from studies of other levonorgestrel (LNG) implants among women with medical conditions is used due to the similarity of SI (II) and other LNG implants in hormone formulation, quality profile and daily release rates. Given this, the panel decided to make the same recommendations for SI (II) as the other LNG implants. Due to heterogeneity of study designs and outcome measures, a meta-analysis was not performed.
- The Sino-implant (II) does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
No studies were identified that provided direct evidence on the use of the Sino-implant (II) among women with medical conditions in the MEC that included a comparison group.
When looking at the studies on healthy women, evidence from four studies comparing SI (II) users with users of other LNG-containing implants demonstrates that SI (II) has a similar safety profile with no significant differences in serious adverse events such as ectopic pregnancy or discontinuation due to medical problems (1-3).
When investigating serious adverse events in healthy women using SI (II), three articles were identified (1)(2)(3). These three articles reported on four randomized controlled trials (RCTs) and found no difference between users of SI (II) and users of SI (I) or Norplant with respect to incidence of serious adverse events. Similar effects on selected markers of disease in healthy women were seen for healthy women using SI (II) compared to women using SI (I) or Norplant. These markers of disease were liver function (3), weight (1,(4)(5)(6), blood pressure (1,6), bone mineral density (7), ovarian cysts and benign myomas (6). Two studies provided limited evidence regarding menorrhagia (1,8). The studies suggest that SI (II) is not harmful and may be beneficial for women with menorrhagia. One RCT found an increased pregnancy rate among women weighing 70 kg or over using SI (II) (9), while another RCT failed to find this association and also reported no association between duration of use, weight and pregnancy (3).

# Quality of the evidence
Women with medical conditions or other specific characteristics:
- For pregnant women, emergency contraceptive pill (ECP) use is not applicable. Although this method is not indicated for a woman with a known or suspected pregnancy, there is no known harm to the woman, the course of her pregnancy, or the fetus if ECPs are accidentally used.
- Women who are breastfeeding can use COCs or LNG regimens for ECPs without restriction (MEC Category 1). Women who are breastfeeding can generally use UPA (MEC Category 2). Breastfeeding is not recommended for one week after taking UPA since it is excreted in breastmilk. Breast-milk should be expressed and discarded during that time (1).
- Women who have experienced past ectopic pregnancies can use COCs, LNG or UPA for ECPs without restriction (MEC Category 1).
- Women with history of severe cardiovascular disease, including ischaemic heart disease, cerebrovascular attack, or other thromboembolic conditions, can generally use COCs, LNG or UPA for ECPs (MEC Category 2).
- Women with migraines can generally use COCs, LNG or UPA for ECPs (MEC Category 2).
- Women with severe liver disease, including jaundice, can generally use COCs, LNG or UPA for ECPs (MEC Category 2).
- Women using CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, fosphenytoine, nevirapine, oxcarbazepine, primidone, rifabutin, St John's wort/Hypericum perforatum) can use COCs, LNG or UPA for ECPs without restriction (MEC Category 1). Strong CYP3A4 inducers may reduce the effectiveness of ECPs.
- There are no restrictions on repeated ECP use for COCs, LNG or UPA (MEC Category 1). Recurrent ECP use is an indication that the woman requires further counselling on other contraceptive options. Frequently repeated ECP use may be harmful for women with conditions classified as Category 2, 3 or 4 for use of combined hormonal contraceptives (CHCs) or progestogen-only contraceptives (POCs).
- There are no restrictions for use of COCs, LNG or UPA for ECPs in cases of rape (MEC Category 1).
- Women who are obese can use COCs, LNG or UPA for ECPs without restriction (MEC Category 1). ECPs may be less effective among women with BMI  30 kg/m 2 than among women with BMI < 25 kg/m 2. Despite this, there are no safety concerns.
- Ulipristal acetate (UPA) was added as a new method to the MEC.
- The duration of use of ECPs is less than the duration of regular use of COCs or POPs and thus would be expected to have less clinical impact for women with history of severe cardiovascular complications, migraine or severe liver disease (including jaundice). There are no restrictions for the use of ECPs in cases of rape.
- The Guideline Development Group (GDG) decided to remove the condition "angina pectoris" from the MEC recommendations for ECPs. This condition does not appear elsewhere in the MEC and there was no evidence suggesting safety concerns for ECP use among women with angina pectoris.
- The GDG decided to change the term "history of severe cardiovascular complications" to "history of severe cardiovascular disease" to be more consistent with terminology used elsewhere in the MEC.
- According to labelling information, rifampicin markedly decreases UPA levels by 90% or more, which may decrease its efficacy (1). Theoretical concerns, therefore, extend to use of other CYP3A4 inducers as well as LNG and COCs, which have similar metabolic pathways to UPA.
- Due to heterogeneity of study designs and outcome measures, a meta-analysis was not performed.
- ECPs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Four direct studies examined LNG-ECP use among pregnant or breastfeeding women (2)(3)(4)(5). No studies were identified that examined UPA-or COC-ECP use among women with medical conditions or characteristics. One cohort study and one randomized controlled trial analysed outcomes among breastfeeding women (3)(4), and two cohort studies analysed outcomes among breastfeeding women (2,5). Poor pregnancy outcomes appear rare among pregnant women who used ECPs during conception cycle or early in pregnancy. Breastfeeding outcomes do not seem to differ between women exposed to LNG and those unexposed. One pharmacokinetic study demonstrates that LNG does pass to breast-milk but is found in minimal quantities (6).
A small pharmacokinetic study found that concomitant efavirenz use decreased LNG levels in women taking LNG-ECP (0.75 mg) by 56% compared with LNG-ECP alone (7).
There is limited evidence from one study that suggests obese women with BMI  30 kg/m 2 experience an increased risk of pregnancy after use of LNG compared with women with BMI < 25 kg/m 2 (8). Evidence from two studies suggests that obese women may also experience an increased risk of pregnancy after use of UPA compared with non-obese women, though this increase was not significant in one of the studies (8,9).

# Quality of the evidence
Women with certain characteristics or medical conditions: (intervention versus comparator; outcome)
- The Guideline Review Committee advised that this recommendation be revised to clarify the Category 2/3 recommendation in the MEC fourth edition. However, as no new evidence was identified to update this recommendation, there was no evidence to take through the GRADE process. This was addressed by the Guideline Development Group (GDG), who decided that the best course of action was to revise the clarification. The GDG highlighted the universal recommendation for dual protection with condoms, especially for women at increased risk of STIs.
- IUDs do not protect against STIs, including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Using an algorithm to classify STI risk status among IUD users, one study reported that 11% of women at high risk of STI experienced IUD-related complications compared with 5% of those not classified as high risk (1). In another small study, the incidence of PID after IUD insertion was low (2.2%) in a cohort of women considered to be at high risk based on high background rates of STIs in the general population (2).

# Quality of the evidence
For STI and IUD: No new evidence 11. Recommendations for use of progesterone-releasing vaginal ring
- If the progesterone-releasing vaginal ring (PVR) is accidentally used during pregnancy, there is no known harm to the woman, the course of her pregnancy, or the fetus.
- Due to heterogeneity of study designs and outcome measures, a meta-analysis was not performed.
- The PVR does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/ HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women is critical for upholding their reproductive rights. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decisionmaking for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence
Seven prospective cohort studies examined the effect of using the progesterone-releasing vaginal ring (PVR) on maternal health, breastfeeding performance, infant health and infant growth, compared with other hormonal and non-hormonal contraceptive methods, during the first year postpartum or longer (1)(2)(3)(4)(5)(6)(7).
Of the six studies that evaluated various measures of breastfeeding performance, neither duration of lactation (1,4,7), the proportion of women fully breastfeeding (2), the number of breastfeeding episodes (2,5), nor the timing of supplementary food introduction (6) significantly differed among PVR users compared with users of non-hormonal or progestogen-only contraceptives (POCs) during 12 months of observation.
No statistically significant differences in infant weight gain were observed among PVR users compared with women using non-hormonal or POCs (3,4,6) and similar patterns of infant weight gain were observed in another study that compared PVR and IUD users (5). One study reported no significant difference in infant health (5). 12a. Recommendations among women at high risk of HIV infection:

# Quality of the evidence
- Women at high risk of acquiring HIV can use the following hormonal contraceptive methods without restriction: combined oral contraceptive pills (COCs), combined injectable contraceptives (CICs), contraceptive patches and rings, progestogen-only pills (POPs), progestogen-only injectables (DMPA and NET-EN), and levonorgestrel (LNG) and etonogestrel (ETG) implants (MEC Category 1).
- Women at high risk of HIV who are using progestogenonly injectables (POIs) should be informed that available studies on the association between POI contraception and HIV acquisition have important methodological limitations hindering interpretation. Some studies suggest that women using POI contraception may be at increased risk of HIV acquisition; other studies have not found this association.
The public health impact of any such association would depend upon the local context, including rates of injectable contraceptive use, maternal mortality and HIV prevalence. This must be considered when adapting guidelines to local contexts. WHO expert groups continue to actively monitor any emerging evidence. At the meeting in 2014, as at the 2012 technical consultation, it was agreed that the epidemiological data did not warrant a change to the MEC. Given the importance of this issue, women at high risk of HIV infection should be informed that POIs may or may not increase their risk of HIV acquisition. Women and couples at high risk of HIV acquisition considering POIs should also be informed about and have access to HIV preventive measures, including male and female condoms.
- Women at high risk of acquiring HIV can generally use LNG-releasing IUDs (LNG-IUDs) (MEC Category 2).
- It is critically important that women and couples at risk of HIV infection be informed about and have access to male and female condoms, and other measures to prevent and reduce their risk of HIV infection and sexually transmitted infections (STIs), regardless of which form of contraception they choose.
- Hormonal contraceptives, including COCs, CICs, POPs, POIs, progestogen-only implants, and LNG-IUDs do not protect against STIs/HIV.

# Summary of the evidence (Question 1: HIV acquisition)
Twenty-two prospective observational studies have assessed the risk of HIV acquisition among women using a method of hormonal contraception versus the risk of HIV acquisition in women using a non-hormonal contraceptive method (i.e. condoms, Cu-IUD, withdrawal) or no contraceptive method (2-27).

# Combined hormonal contraceptives
Eight studies assessed the use of COCs and were considered to be "informative but with important limitations" (28). Seven of these studies found no statistically significant association between use of COCs and HIV acquisition (3,(5)(6)(7)(8)(9)(10)(11), although one study among sex workers in Kenya did (12).

# Progestogen-only contraceptives
Five studies assessed the use of NET-EN injectables and were considered to be "informative but with important limitations" (28). Four of them reported no statistically significant association with HIV acquisition (3,8,9,13), while one did (11).
Nine studies assessed DMPA, or, if a DMPA-specific result was unavailable, assessed non-specified injectables; these studies were considered to be "informative but with important limitations" (28). The results were mixed: three of the studies showed a significant increase in risk (5,11,12), one showed a significant increase in risk using one statistical model but this association was not statistically significant using another statistical model (6,7), and five showed no significant increase in risk (3,(8)(9)(10)13).
Two studies assessed implants, one of which was classified as "unlikely to inform the primary question" (4,28). Neither of these studies reported a statistically significant increased risk of HIV acquisition, but confidence intervals were wide (4,21).

# Quality of the evidence (Question 1: HIV acquisition)
For progestogen-only injectables (DMPA and NET-EN) and COCs: - Because there may be interactions between certain methods of hormonal contraception and certain antiretroviral medications (ARVs), refer to the recommendations on ART medication interactions (see p. 72).
- Hormonal contraceptives do not protect against sexually transmitted infections (STIs), including HIV. Consistent and correct use of condoms, male or female, is critical for prevention of HIV transmission to non-infected sexual partners, and for protection against other STIs. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women living with HIV who wish to prevent pregnancy is critical for upholding their reproductive rights and continues to be an important strategy for reducing vertical HIV transmission. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decision-making for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.
Summary of the evidence (Question 2: disease progression; Question 3: female-to-male transmission)
Two systematic reviews investigating Questions 2 and 3 informed the contraceptive eligibility recommendations for women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2).

# Combined hormonal contraceptives (CHCs)
Out of eight available studies, seven suggested no association between use of COCs and progression of HIV, as measured by CD4 count < 200 cells/mm 3 initiation of ART, or mortality (29)(30)(31)(32)(33)(34)(35). One randomized controlled trial found an increased risk of a composite outcome of declining CD4 count or death among COC users when compared with users of copper-bearing IUDs (Cu-IUDs) (36,37).
Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on femaleto-male HIV transmission by measuring seroconversions in male partners of women known to be using hormonal contraceptives. One of these studies reported an elevated, but not statistically significant, point estimate for COCs (5).
The other study also did not find a statistically significant association for COCs (4).
Studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have had mixed results. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).

# Progestogen-only contraceptives (POCs)
Out of six available studies, five suggested no association between use of progestogen-only injectable (POI) contraceptives and progression of HIV, as measured by CD4 count < 200 cells/mm 3 initiation of ART, or mortality (31)(32)(33)(34)(35). One randomized trial found an increased risk of a composite outcome of declining CD4 count or death among oral contraceptive (OC) users (COCs and POPs) when compared with users of Cu-IUDs; this study, however, had significant loss to follow-up and method-switching among groups, limiting its interpretation (36,37). One study found no difference in ART initiation or CD4 count between users and non-users of the LNG-IUD (54).
Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on femaleto-male HIV transmission by measuring seroconversions in male partners of women known to be using hormonal contraceptives. One study reported a statistically significant association between POI contraception and female-to-male transmission of HIV (5), while another study did not find a statistically significant association between use of DMPA and female-to-male HIV transmission (4). The findings of studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have been mixed. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). - Because there may be interactions between certain methods of hormonal contraception and certain antiretroviral medications (ARVs), refer to the recommendations on ART medication interactions (see p. 72).

# Quality of the evidence
- Hormonal contraceptives do not protect against sexually transmitted infections (STIs), including HIV. Consistent and correct use of condoms, male or female, is critical for prevention of HIV transmission to non-infected sexual partners, and for protection against other STIs. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women living with HIV who wish to prevent pregnancy is critical for upholding their reproductive rights and continues to be an important strategy for reducing vertical HIV transmission. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decision-making for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.

# Summary of the evidence (Question 2: disease progression; Question 3: female-to-male transmission)
Two systematic reviews investigating Questions 2 and 3 informed the contraceptive eligibility recommendations for women living with severe or advanced HIV clinical disease (WHO stage 3 or 4).
All of the identified studies excluded women with severe or advanced HIV clinical disease (WHO stage 3 or 4) from enrolment, although some participants experienced progression to severe or advanced disease during the trials.

# Combined hormonal contraceptives (CHCs)
Out of eight available studies, seven suggest no association between use of COCs and progression of HIV, as measured by CD4 count < 200 cells/mm 3 initiation of ART, or mortality (29)(30)(31)(32)(33)(34)(35). One randomized trial found an increased risk of a composite outcome of declining CD4 count or death among COC users when compared with users of copper-bearing IUDs (Cu-IUDs) (36,37).
Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on femaleto-male HIV transmission by measuring seroconversions in male partners of women known to be using hormonal contraceptives. One of these studies reported an elevated, but not statistically significant, point estimate for oral contraceptives (OCs) (5). The other study also did not find a statistically significant association for OCs (4).
Studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have had mixed results. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).

# Progestogen-only contraceptives (POCs), including LNG-IUD
Out of six available studies, five suggested no association between use of progestogen-only injectable contraceptives and progression of HIV, as measured by CD4 count < 200 cells/mm 3 initiation of ART, or mortality (31)(32)(33)(34)(35). One randomized trial found an increased risk of a composite outcome of declining CD4 count or death among OC (COC and POP) users when compared with Cu-IUD users; this study, however, had significant loss to follow-up and methodswitching among groups, limiting its interpretation (36,37).
One study found no difference in ART initiation or CD4 count between users and non-users of the LNG-IUD (54).
Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on femaleto-male HIV transmission by measuring seroconversions in male partners of women with known hormonal contraceptive use status. One of these studies reported a statistically significant association between injectable contraception and female-to-male transmission of HIV (5), while the other study did not find a statistically significant association between use of DMPA and female-to-male HIV transmission (4).
The findings of studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have been mixed. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). 12d. Recommendations among women living with HIV using antiretroviral therapy (ART)

# Quality of the evidence
- Women taking any nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) can use all hormonal contraceptive methods without restriction: combined oral contraceptive pills (COCs), contraceptive patches and rings, combined injectable contraceptives (CICs), progestogenonly pills (POPs), progestogen-only injectables (DMPA and NET-EN), and levonorgestrel (LNG) and etonogestrel (ETG) implants (MEC Category 1).
- Women using ART containing either efavirenz or nevirapine can generally use COCs, patches, rings, CICs, POPs, NET-EN and implants (MEC Category 2). However, women using efavirenz or nevirapine can use DMPA without restriction (MEC Category 1).
- Women using the newer non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), etravirine and rilpivirine, can use all hormonal contraceptive methods without restriction (MEC Category 1).
- Women using protease inhibitors (e.g. ritonavir and ARVs boosted with ritonavir) can generally use COCs, contraceptive patches and rings, CICs, POPs, NET-EN, and LNG and ETG implants (MEC Category 2), and can use DMPA without restriction (MEC Category 1).
- Women using the integrase inhibitor raltegravir can use all hormonal contraceptive methods without restriction (MEC Category 1).
- Hormonal contraceptives do not protect against sexually transmitted infections (STIs), including HIV. Consistent and correct use of condoms, male or female, is critical for prevention of HIV transmission to non-infected sexual partners, and for protection against other STIs. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
- Voluntary use of contraception by women living with HIV who wish to prevent pregnancy is critical for upholding their reproductive rights and continues to be an important strategy for reducing vertical HIV transmission. All women have the right to evidence-based, comprehensive contraceptive information, education and counselling to ensure informed choice. Women's contraceptive choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decision-making for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions and interpretations.
- Women living with HIV and using ARVs should discuss the potential impact of certain ARVs on contraceptive efficacy with their health-care provider.

# Summary of the evidence (Question 4: hormonal contraception-ART interactions)
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
NRTIs do not appear to have significant risk of interactions with hormonal contraceptive methods (55,56).

# Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Three clinical studies, including one large study, found use of nevirapine-containing ART did not increase ovulation or pregnancy rates in women using COCs (57)(58)(59)(60). For efavirenzcontaining ART, a pharmacokinetic study showed consistent significant decreases in contraceptive hormone levels in women using COCs, and a small clinical study showed higher ovulation rates in women taking efavirenz-containing ART and COCs (57,61,62). Etravirine and rilpivirine do not interact with COCs (63,64). One retrospective chart review of women using efavirenz-containing ART showed increased contraceptive failure rates for women using LNG implants (65). Based primarily on pharmacokinetic data, the effectiveness of DMPA is likely not affected by NNRTIs, and vice versa (66,67).

# Protease inhibitors (PIs)
Pharmacokinetic data suggest decreases in COC progestin levels with ritonavir and ritonavir-boosted PIs. In women using the patch, co-administration resulted in higher progestin levels (68). One study found higher progestin levels with concurrent PI use in users of POPs (69). Based primarily on pharmacokinetic data, the effectiveness of DMPA is likely not affected by PIs, and vice versa (66,67).

# Integrase inhibitors
The integrase inhibitor raltegravir does not appear to interact with COCs (55,56,70,71). Restricted to studies classified as "considered informative with important limitations"; while all of these studies had important limitations or risk of bias, no study had all three major flaws -i.e.: (i) no adjustment for any measure of condom use; (ii) unclear measurement of exposure to hormonal contraception; (iii) inter-survey interval (time between study visits) < 6 months -and therefore were given an overall quality rating of "low" rather than "very low". An explanation of the quality assessment for each study included in this table is described in the systematic review by Polis et al., 2014

# Quality of the evidence

# Part II Using the recommendations 2.1 Background
The Medical eligibility criteria for contraceptive use (MEC) provides guidance regarding which clients can use contraceptive methods safely. The goal of the document is to improve access to, and quality of, family planning services by providing policy-makers, decision-makers and the scientific community with recommendations that can be used for developing or revising national guidelines on the medical eligibility criteria for the use of specific contraceptive methods. Methods covered by this guidance include all hormonal contraceptives, intrauterine devices, barrier methods, fertility awareness-based methods, coitus interruptus, lactational amenorrhoea method, male and female sterilization, and emergency contraception. These evidencebased recommendations do not indicate a "best" method that should be used in a particular medical context; rather, review of the recommendations allows for consideration of multiple methods that could be used safely by people with certain health conditions (e.g. hypertension) or relevant characteristics (e.g. age).

# Reproductive and sexual health care as a human right
The Programme of Action of the International Conference on Population and Development (ICPD) defines reproductive health as: "a state of complete physical, mental and social wellbeing, and not merely the absence of disease or infirmity, in all matters relating to the reproductive system and to its functions and processes" 1. The Programme of Action also states that the purpose of sexual health "is the enhancement of life and personal relations, and not merely counselling and care related to reproduction and sexually transmitted diseases". Recognizing the importance of agreements made at the ICPD and other international conferences and summits, the Beijing Declaration and Platform for Action defines reproductive rights in the following way: Reproductive rights embrace certain human rights that are already recognized in national laws, international human rights documents and other relevant consensus documents. These rights rest on the recognition of the basic right of all couples and individuals to decide freely and responsibly the number and spacing and timing of their children and to have the information and means to do so, and the right to attain the highest standard of sexual and reproductive health. 2 Among the Millennium Development Goals (MDGs) agreed by states in 2001, target 5b calls for universal access to reproductive health by 2015. Reproductive and sexual health care, including family planning services and information, is recognized not only as a key intervention for improving the health of men, women and children but also as a human right. International and regional human rights treaties, national constitutions and laws provide guarantees specifically relating to access to contraceptive information and services. These include the guarantee that states should ensure timely and affordable access to good quality sexual and reproductive health information and services, including contraception, which should be delivered in a way that ensures fully informed decision-making, respects dignity, autonomy, privacy and confidentiality, and is sensitive to individuals' needs and perspectives in a client-provider partnership. 3 A rights-based approach to the provision of contraceptives assumes a holistic view of clients, which includes taking into account clients' sexual and reproductive health care needs and considering all appropriate eligibility criteria when helping clients choose and use a family planning method safely.
Evidence shows that the respect, protection and fulfilment of human rights contribute to positive health outcomes. The provision of contraceptive information and services that respect individual privacy, confidentiality and informed choice, along with a wide range of safe contraceptive methods, increase people's satisfaction and continued use of contraception. 4 5 6 7 Delivery of care in accordance with the client's human and reproductive rights is fundamental to quality of care. The development of international norms for medical eligibility criteria and practice recommendations for contraceptive use is only one aspect of improving the quality of reproductive health care. Many family planning programmes have included screening, treatment and follow-up procedures that reflect high standards of public health and clinical practice, but these should not be seen as eligibility requirements for specific contraceptive methods. These procedures include the screening and treatment of cervical cancer, anaemia and sexually transmitted infections (STIs), and the promotion of breastfeeding and cessation of smoking. Such procedures should be strongly encouraged if the human and material resources are available to carry them out, but they should not be seen as prerequisites for the acceptance and use of family planning methods since they are not necessary to establish eligibility for the use or continuation of a particular method.

# Contraceptive choice
While this document primarily addresses medical eligibility criteria for contraceptive use, considerations of social, behavioural and other non-medical criteria -particularly client preference -must also be taken into account. To provide contraceptive choices to clients in a way that respects and fulfils their human rights necessitates enabling clients to make informed choices for themselves. Women's choices, however, are often taken away from them or limited by direct or indirect social, economic and cultural factors. From a woman's point of view, her choices are made at a particular time, in a particular societal and cultural context; choices are complex, multifactorial and subject to change. Decision-making regarding contraceptive methods usually requires the need to make trade-offs among the advantages and disadvantages of different methods, and these vary according to individual circumstances, perceptions and interpretations. Factors to consider when choosing a particular contraceptive method include the characteristics of the potential user, the baseline risk of disease, the adverse effects profile of different products, cost, availability and patient preferences.
This document does not provide recommendations about which specific product or brand to use after selecting a particular type of contraceptive method. Instead, it provides guidance for whether women with specific medical conditions or medically relevant physiological or personal characteristics are eligible to use various contraceptive methods. Decisions about what methods to use should also take into account clinical judgment and user preferences.
Issues of service quality and access that affect method use and choice
The following service-delivery criteria are universally relevant to the initiation and follow-up of all contraceptive method use:
- Clients should be given adequate information to help them make an informed, voluntary choice of a contraceptive method. This information should at least include:
-the relative effectiveness of the method;
-correct usage of the method;
-how it works;
-health risks and benefits of the method;
-signs and symptoms that would necessitate a return to the clinic;
-information on return to fertility after discontinuing method use; and -information on STI protection.
Information should be presented using language and formats that can be easily understood and accessed by the client.
- In order to offer methods that require surgical approaches, insertion, fitting and/or removal by a trained health-care provider (i.e. sterilization, implants, IUDs, diaphragms, cervical caps), appropriately trained personnel in adequately equipped and accessible facilities must be available, and appropriate infection-prevention procedures must be followed.
- Adequate and appropriate equipment and supplies need to be maintained and held in stock (e.g. contraceptive commodities, and supplies for infection-prevention procedures).
- Service providers should be provided with guidelines, client cards or other screening tools.

# Effectiveness of method
Contraceptive choice is in part dependent on the effectiveness of the contraceptive method in preventing unplanned pregnancy, which, in turn, is dependent for some methods not only on the protection afforded by the method itself, but also on how consistently and correctly it is used. Table 2.1 compares the percentage of women experiencing an unintended pregnancy during the first year of contraceptive method use when the method is used perfectly (consistently and correctly) and when it is used typically (assuming occasional non-use and/or incorrect use). Consistent and correct usage can both vary greatly with client characteristics such as age, income, desire to prevent or delay pregnancy, and culture. Methods that depend on consistent and correct usage by clients (e.g condoms and pills) have a wide range of effectiveness.
Most men and women tend to be more effective users as they become more experienced with a method. However, programmatic aspects also have a profound effect on how effectively (consistently and correctly) the method will be used.

# Conditions that expose a woman to increased risk as a result of unintended pregnancy
Women with conditions that may make unintended pregnancy an unacceptable health risk should be advised that, because of their relatively higher typical-use failure rates, sole use of barrier methods for contraception and behaviour-based methods of contraception may not be the most appropriate choice for them. These conditions are noted in Box 2.1. - HIV (WHO stages 1-4) b
- Ischaemic heart disease
- Malignant gestational trophoblastic disease
- Malignant liver tumours (hepatoma) and hepatocellular carcinoma of the liver (HCA)
- Schistosomiasis with fibrosis of the liver
- Severe (decompensated) cirrhosis
- Sickle cell disease
- STI b
- Systemic lupus erythematosus (SLE)
- Thrombogenic mutations
- Tuberculosis a Throughout this document, blood pressure measurements are given in mm Hg. To convert to kPa, multiply by 0.1333 (e.g. 120/80 mm Hg = 16.0/10.7 kPa).
b Dual protection is strongly recommended for protection against HIV/AIDS and other STIs when a risk of STI/HIV transmission exists. This can be achieved through the simultaneous use of condoms with other methods, or the consistent and correct use of condoms alone. Emergency contraceptives: Emergency contraceptive pills or insertion of a copper-bearing intrauterine device after unprotected intercourse substantially reduces the risk of pregnancy. 9
Lactational amenorrhea method: LAM is a highly effective, temporary method of contraception.  1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. Estimates of the probability of pregnancy during the first year of typical use for spermicides and the diaphragm are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; estimates for fertility-awareness-based methods, withdrawal, the male condom, the pill and Depo-Provera are taken from the 1995 and 2002 National Survey of Family Growth corrected for underreporting of abortion. See the text for the derivation of estimates for the other methods (Trussell, 2011).
2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. See the text for the derivation of the estimate for each method (Trussell, 2011).
3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.
The percentages becoming pregnant in columns 2 and 3 are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether.
5 Foams, creams, gels, vaginal suppositories and vaginal film.
6 The Ovulation Method and TwoDay Method are based on evaluation of cervical mucus. The Standard Days Method avoids intercourse on cycle days 8-19. The sympto-thermal method is a double-check method based on evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to determine the last fertile day.
7 Without spermicides.
8 With spermicidal cream or jelly.
9 Plan B One-Step, ella and Next Choice One Dose are the only dedicated products specifically marketed for emergency contraception in the United States at the time of writing. The label for Plan B One-Step (one dose is one white pill) says to take the pill within 72 hours after unprotected intercourse. Research has shown that all of the brands listed here are effective when used within 120 hours after unprotected sex. The label for Next Choice One Dose (one dose is one peach pill) says to take one pill within 72 hours after unprotected intercourse. The United States Food and Drug Administration has in addition declared the following 19 brands of oral contraceptives to be safe and effective for emergency contraception: Ogestrel (one dose is two white pills), Nordette (one dose is four light-orange pills), Cryselle, Levora, Low-Ogestrel, Lo/Ovral, or Quasence (one dose is four white pills), Jolessa, Portia, Seasonale or Trivora (one dose is four pink pills), Seasonique (one dose is four light-blue-green pills), Enpresse (one dose is four orange pills), Lessina (one dose is five pink pills), Aviane or LoSeasonique (one dose is five orange pills), Lutera or Sronyx (one dose is five white pills), and Lybrel (one dose is six yellow pills).

# Return to fertility
Among contraceptive methods, only male and female sterilization are regarded as irreversible (or permanent).
All other methods are reversible, usually with prompt return to fertility upon method discontinuation, with the exception of depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). The median delay in return to fertility with these methods is 10 and 6 months, respectively, from the date of the last injection, regardless of the duration of their use. Male and female sterilization should be regarded as permanent methods (no possibility of future childbearing), and all individuals and couples considering these methods should be counselled accordingly. No other methods result in permanent infertility.

# STIs and contraception: dual protection
In addition to the imperative of international norms for contraceptive provision to assure quality of care in services, the social, cultural and behavioural context of each client must also be considered. In this regard, the problems of exposure to STIs, including HIV, deserve special consideration because of the equal importance of preventing pregnancy and preventing transmission of infections among sexually active clients of reproductive age. When a risk of HIV and other STI transmission exists, 8 it is important that health-care providers offer information on safer sexual practices to prevent transmission and strongly recommend dual protection to all persons at significant risk, either through the simultaneous use of condoms with other methods or through the consistent and correct use of condoms alone for prevention of both pregnancy and STIs, including HIV. Women and men seeking contraceptive advice must always be reminded of the importance of condom use for preventing the transmission of STI/HIV and such use should be encouraged and facilitated where appropriate. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# How to use this document
The present document is intended for use by policy-makers, family planning programme managers and the scientific community. It aims to provide guidance to national family planning and reproductive health programmes in the preparation of guidelines for delivery of contraceptive services. It is not meant to serve as the actual guidelines but rather as a reference.
The guidance in this document is intended for interpretation at country and programme levels in a manner that reflects the diversity of situations and settings in which contraceptives are provided. While it is unlikely that the classification of categories in this document would change during this process, it is very likely that the application of these categories at country level will vary. In particular, the level of clinical knowledge and experience of various types of providers and the resources available at the service-delivery point will have to be taken into consideration.
Recommendations are presented in tables according to the contraceptive methods included in the guidance with each condition. Each condition was defined as representing either a known pre-existing medical/pathological condition (e.g. diabetes, hypertension) or a medically relevant individual characteristic (e.g. age, history of pregnancy).
It is expected that national and institutional health-care and service-delivery environments will decide the most suitable means for screening for conditions according to their public health importance. Client history will often be the most appropriate approach. A family planning provider may want to consult an expert in the underlying condition.

# Initiation and continuation
The medical eligibility criteria for the initiation and continuation of all contraceptive methods are used in the evaluation of eligibility. The assessment of continuation criteria is clinically relevant whenever a woman develops the condition while she is using the method. Where medical eligibility for initiation and continuation of a contraceptive method differ, these differences are noted in the columns of the tables for each contraceptive method (I = initiation; C = continuation). Where I and C are not denoted, the category is the same for initiation and continuation of use.
As shown in Table 2.2 in a simplified template of the tables for each contraceptive (provided in section 2.7), the first column indicates the conditions (each in a separate row). Several conditions are subdivided to differentiate between varying degrees of the condition. The second column classifies the condition for initiation and/or continuation into one of the four MEC categories, as described in section 2.3. The third column provides space for any necessary clarifications or presentation of evidence regarding the classification

# Using the categories in practice
Categories 1 and 4 are self-explanatory. Classification of a method/condition as Category 2 indicates the method can generally be used, but careful follow-up may be required. However, provision of a method to a woman with a condition classified as Category 3 requires careful clinical judgement and access to clinical services; for such a woman, the severity of the condition and the availability, practicality and acceptability of alternative methods should be taken into account. For a method/condition classified as Category 3, use of that method is not usually recommended unless other more appropriate methods are not available or acceptable. Careful follow-up will be required.
Where resources for clinical judgment are limited, such as in community-based services, the four-category classification framework can be simplified into two categories. With this simplification, a classification of Category 1 or 2 indicate that a woman can use a method, and a classification of Category 3 or 4 indicate that a woman is not medically eligible to use the method (see Table 2.3).

# Medical eligibility criteria (MEC) categories for contraceptive use Category 1
A condition for which there is no restriction for the use of the contraceptive method

# Category 2
A condition where the advantages of using the method generally outweigh the theoretical or proven risks

# Category 3
A condition where the theoretical or proven risks usually outweigh the advantages of using the method

# Category 4
A condition which represents an unacceptable health risk if the contraceptive method is used

# Programmatic implications
The following issues need to be addressed when applying the medical eligibility criteria in this document to programmes:
- informed choice
- elements of quality of care
- essential screening procedures for administering the methods

# - provider training and skills
- referral and follow-up for contraceptive use as appropriate.
Service-delivery practices that are essential for the safe use of the particular contraceptive method should be distinguished from practices that may be appropriate for good health care but are not related to use of the method. The promotion of good health-care practices unrelated to safe contraception should be considered neither as a prerequisite nor as an obstacle to the provision of a contraceptive method, but as complementary to it.
As a next step, the recommendations on medical eligibility criteria need to be considered in light of the country context, so as to be applicable to providers at all levels of the servicedelivery system. It is expected that national and institutional health-care and service-delivery environments will decide the most suitable means for screening for conditions according to their public health importance. Client history will often be the most appropriate approach. A family planning provider may want to consult an expert in the underlying condition. Countries will need to determine how far and by what means it may be possible to extend their services to the more peripheral levels of the health system. This may involve upgrading both staff and facilities where feasible and affordable, or it may require or a modest addition of equipment and supplies, and redeployment of space. It will also be necessary to address misperceptions sometimes held by providers and users about the risks and side-effects of particular methods, and to look closely at the needs and perspectives of women and men in the context of informed choice.
Adaptation is not always an easy task and is best done by those well acquainted with prevailing health conditions, behaviours and cultures. These improvements must be made within the context of users' informed choices and medical safety.
- 5 Clients with special needs

# People with disabilities
According to United Nations Convention on the Rights of Persons with Disabilities (CRPD), people with disabilities must have access, on an equal basis with others, to all forms of sexual and reproductive health care (Article 25) as part of the general right to marry, found a family and retain their fertility (Article 23) 9. Health-care professionals often fail to offer sexual and reproductive health services to people with disabilities, based on the common misconception that they are not sexually active. 10 Provision of contraceptive services to people with disabilities may, however, require decisions regarding appropriate contraception considering the preferences of the individual, the nature of the disability and the specifics of different contraceptive methods.
For example, some barrier methods may be difficult to use for those with limited manual dexterity; COCs may not be an appropriate method for women with impaired circulation or immobile extremities, even in the absence of known thrombogenic mutations, because of concerns about an increased risk of DVT; and other methods will be preferable for individuals with intellectual or mental health disabilities who have difficulty remembering to take daily medications. For women who have difficulty with menstrual hygiene, the impact of the contraceptive method on menstrual cycles should also be considered.
In all instances, medical decisions must be based upon informed choice, based on adequate sexual and reproductive health education. When the nature of the disability makes it more challenging to discern the will and preferences of the individual, contraceptives should only be provided in a manner consistent with Article 12 of the CRPD. Specifically, in such cases a process of supported decision-making should be instituted in which individuals who are trusted by the individual with disabilities, personal ombudsman and other support persons jointly participate with the individual in reaching a decision that is, to the greatest extent possible, consistent with the will and preference of that individual. Given the history of involuntary sterilization of persons with disabilities, often as a technique for menstrual management in institutions, 11 it is especially important to ensure that decisions about sterilization are only made with the full, uncoerced and informed consent of the individual, either alone or with support.
Adolescents in many countries lack adequate access to contraceptive information and services that are necessary to protect their sexual and reproductive health. There is an urgent need to implement programmes that both meet the contraceptive needs of adolescents and remove barriers to services. In general, adolescents are eligible to use all the same methods of contraception as adults, and must have access to a variety of contraceptive choices. Age alone does not constitute a medical reason for denying any method to adolescents. While some concerns have been expressed about the use of certain contraceptive methods by adolescents (e.g. the use of progestogen-only injectables by those below 18 years), these concerns must be balanced against the advantages of preventing unintended pregnancy. It is clear that many of the same eligibility criteria that apply to older clients also apply to young people. However, some conditions (e.g. cardiovascular disorders) that may limit the use of some methods in older women do not generally affect young people, since these conditions are rare in this age group.
Political and cultural factors may affect adolescents' ability to access contraceptive information and services. For example, where contraceptive services are available, adolescents (in particular unmarried ones) may not be able to obtain them because of restrictive laws and policies. Even if adolescents are able to obtain contraceptive services, they may not do so because of fear that their confidentiality will not be respected, or that health workers may be judgmental. All adolescents, regardless of marital status, have a right to privacy and confidentiality in health matters, including reproductive health care. Appropriate sexual and reproductive health services, including contraception, should be available and accessible to all adolescents without necessarily requiring parental or guardian authorization by law, policy or practice.
Social and behavioural issues should be key considerations in the choice of contraceptive methods by adolescents. For example, in some settings, adolescents are also at increased risk for STIs, including HIV. While adolescents may choose to use any one of the contraceptive methods available in their communities, in some cases, using methods that do not require a daily regimen may be more convenient. Adolescents,
married or unmarried, have also been shown to be less tolerant of side-effects and therefore have high discontinuation rates. Method choice may also be influenced by factors such as sporadic patterns of intercourse and the need to conceal sexual activity and contraceptive use. For instance, sexually active adolescents who are unmarried have very different needs from those who are married and want to postpone, space or limit pregnancy. Expanding the number of method choices offered can lead to improved satisfaction, increased acceptance and increased prevalence of contraceptive use.
Proper education and counselling -both before and at the time of method selection -can help adolescents address their particular needs and make informed and voluntary decisions. Every effort should be made to prevent the costs of services and/or methods from limiting the options available.

# Summary of changes within the MEC fifth edition
The following tables highlight changes within the fifth edition of the MEC, compared with the fourth edition (see Tables 2.4-2.6). These changes include: changes to MEC categories between the earlier editions and the fifth edition; recommendations for new conditions issued in the fifth edition; changes to the labelling of certain conditions (in order to be consistent with current clinical practice); and details for the new contraceptive methods included in this fifth edition.    (20). The absolute differences, however, are very small.
Limited data do not suggest that the small absolute risk for arterial events associated with COC use varies according to the type of progestogen (5,6,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).
Recommendations in this guidance are the same for all COC formulations, irrespective of their progestogen content.

# COMBINED INJECTABLE CONTRACEPTIVES (CICs)
Two CIC formulations, are considered here:
- Cyclofem = medroxyprogesterone acetate 25 mg plus estradiol cypionate 5 mg 2. Mesigyna = norethisterone enanthate 50 mg plus estradiol valerate 5 mg
CICs contain the naturally occurring estrogen, estradiol plus a progestogen (35)(36)(37)(38)(39). Estradiol is less potent, has a shorter duration of effect and is more rapidly metabolized than the synthetic estrogens used in other contraceptive formulations such as COCs, the combined contraceptive patch (P) and the combined contraceptive vaginal ring (CVR). These differences imply that the type and magnitude of estrogen-related sideeffects associated with CICs may be different from those experienced by COC/P/CVR users. In fact, short-term studies of CICs have shown little effect on blood pressure, haemostasis and coagulation, lipid metabolism and liver function in comparison with COCs (40)(41)(42). As CICs are administered by injection, the first-pass metabolism by the liver is avoided, thereby minimizing estradiol's effect on the liver.
However, CICs are a relatively new contraceptive method, and there are few epidemiological data on their long-term effects.
There is also the concern that, while the effect of the hormonal exposure associated with use of COCs and progestogen-only pills (POPs) can be reduced immediately by discontinuing their use, this is not the case with injectables, for which the effect continues for some time after the last injection.
Pending further evidence, the Guideline Development Group (GDG) concluded that the evidence available for COCs applies to CICs in many but not all instances. Therefore, the GDG assigned categories for CICs somewhere between the categories for COCs and POPs. However, for severe pathologies (e.g. ischaemic heart disease), the classification of conditions was the same as for COCs. The assigned categories should, therefore, be considered a preliminary, best judgement, which will be re-evaluated as new data become available.

# COMBINED CONTRACEPTIVE PATCH (P) AND COMBINED CONTRACEPTIVE VAGINAL RING (CVR)
The combined contraceptive patch (P) and combined vaginal ring (CVR) are relatively new contraceptive methods. Limited information is available on the safety of these methods among women with specific medical conditions. Moreover, epidemiological data on the long-term effects of P and CVR use were not available for the GDG to review. Most of the available studies received support from the manufacturers of these methods.
According to available evidence, the P provides a comparable safety and pharmacokinetic profile to COCs with similar hormone formulations (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Reports of transient, short-term breast discomfort and skin-site reactions were greater among P users; however, less than 25% of users experienced these events (45,49,50,(56)(57)(58)61). Limited evidence suggests the effectiveness of the P may decline for women weighing 90 kg or more (58,60).
According to available evidence, the CVR provides a comparable safety and pharmacokinetic profile and has similar effects on ovarian function to COCs with similar hormone formulations in healthy women (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75). Evidence from use in obese women (BMI  30 kg/m 2 found that weight gain for women in this category was not different between CVR users and COC users (76). Limited evidence from use in women post medical and surgical abortion found no serious adverse events and no infection related to use during three cycles of follow-up post-abortion (77), and limited evidence on women with lowgrade squamous intraepithelial lesions found that use of the vaginal ring did not worsen the condition (64).
Pending further evidence, the GDG concluded that the evidence available for COCs applies to the combined contraceptive P and CVR, and therefore the P and CVR should have the same categories as COCs. The assigned categories should, therefore, be considered a preliminary, best judgement, which will be re-evaluated as new data become available.

# COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV.  (103,104,(110)(111)(112)(113)(114)(115)(116)(117). BMD is a surrogate marker for fracture risk that may not be valid for premenopausal women, and which, therefore, may not accurately predict current or future (postmenopausal) fracture risk (118)(119)(120).

# COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. POST-ABORTION Clarification: COCs, P, CVR or CICs may be started immediately post-abortion.
Evidence: Women who started taking COCs immediately after first-trimester medical or surgical abortion did not experience more sideeffects or adverse vaginal bleeding outcomes or clinically significant changes in coagulation parameters compared with women who used a placebo, an IUD, a non-hormonal contraceptive method, or delayed COC initiation (134)(135)(136)(137)(138)(139)(140)(141).
Limited evidence on women using the CVR immediately after first-trimester medical or surgical abortion indicated no serious adverse events and no infection related to CVR use during 3 cycles of follow-up post-abortion (77).  (146,147,(151)(152)(153)(154)(155)(156). Limited evidence suggests obese women are no more likely to gain weight after 3 cycles of using CVR or COCs than overweight or normal-weight women. A similar weight gain during 3 months was noted in both the COC group and the CVR group across all BMI categories (76). Overall, evidence suggests that contraceptive effectiveness is maintained among obese CHC users (157)(158)(159)(160)(161)(162)(163)(164)(165)(166)(167)(168)(169)(170)(171)(172); however, among women with very high BMI using COC, evidence is inconsistent (161,167,171). No association was found between pregnancy risk and BMI among P users (161,167,171). The effectiveness of the patch decreased among women who weighed > 90 kg in 1 study (172). Clarification: It is desirable to have blood pressure measurements taken before initiation of COC, P, CVR or CIC use. However, in some settings, blood pressure measurements are unavailable. In many of these settings, pregnancy-related morbidity and mortality risks are high, and COCs, P, CVR or CICs may be among the few methods widely available. In such settings, women should not be denied use of COCs, P, CVR or CICs simply because their blood pressure cannot be measured.
a) First trimester 1 1 1 1 b) Second trimester 1 1 1 1 c)

# COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Evidence: Among women with thrombogenic mutations, COC users had a 2-to 20-fold higher risk of thrombosis than non-users (3,155,.

# COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Evidence: Among women with migraine, women who also had aura had a higher risk of stroke than those without aura (240)(241)(242). Women with a history of migraine who use COCs are about 2-4 times as likely to have an ischaemic stroke as non-users with a history of migraine (142,154,181,182,(240)(241)(242)(243)(244)(245)(246).

# BENIGN OVARIAN TUMOURS (INCLUDING CYSTS
) 1 1 1 1 SEVERE DYSMENORRHOEA 1 1 1 1
Evidence: There was no increased risk of side-effects with COC use among women with dysmenorrhoea compared with women not using COCs. Some COC users had a reduction in pain and bleeding (259,260).

# GESTATIONAL TROPHOBLASTIC DISEASE
Evidence: Following molar pregnancy evacuation, the balance of evidence found COC use did not increase the risk of post-molar trophoblastic disease, and some COC users experienced a more rapid regression in human chorionic gonadotropin (hCG) levels, compared with nonusers (261)(262)(263)(264)(265)(266)(267)(268). Limited evidence suggests that use of COCs during chemotherapeutic treatment does not significantly affect the regression or treatment of post-molar trophoblastic disease compared with women who used a non-hormonal contraceptive method or depot medroxyprogesterone acetate (DMPA) during chemotherapeutic treatment (269).
a) Decreasing or undetectable -hCG levels
1 1 1 1 b) Persistently elevated -hCG levels or malignant disease 1 1 1 1 CERVICAL ECTROPION 1 1 1 1 CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) 2 2 2 2
Evidence: Among women with persistent human papillomavirus (HPV) infection, long-term COC use ( 5 years) may increase the risk of carcinoma in situ and invasive carcinoma (64,270). Limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition (64).

# CHCs COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. ii) past and no evidence of current disease for 5 years CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV.  (380)(381)(382)(383)(384)(385)(386). One randomized controlled trial found an increased risk of a composite outcome of declining CD4 count or death among COC users when compared with users of copper-bearing IUDs (387,388). Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on female-to-male HIV transmission by measuring seroconversions in male partners of women known to be using hormonal contraceptives. One of these studies reported an elevated, but not statistically significant, point estimate for COCs (378). The other study also did not find a statistically significant association for COCs (389). Studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have had mixed results. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (381,(390)(391)(392)(393)(394)(395)(396)(397)(398)(399)(400)(401)(402)(403)(404).
3 3 3 3 ENDOMETRIAL CANCER 1 1 1 1 OVARIAN CANCER 1 1 1 1 UTERINE FIBROIDS a)
Severe or advanced HIV clinical disease (WHO stage 3 or 4)
THYROID DISORDERS a) Simple goitre 1 1 1 1 b) Hyperthyroid 1 1 1 1 c) Hypothyroid 1 1 1 1 GASTROINTESTINAL CONDITIONS GALL BLADDER DISEASE a) Symptomatic i) treated by cholecystectomy 2 2 2 2
ii) medically treated b) Carrier 1 1 1 1 1 1 1 1 Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk of hepatocellular carcinoma (431,432). For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction (408,433,434). Evidence is limited for COC use during active hepatitis (435,436).  (440,441).
c) Chronic 1 1 1 1 1 1 1 1 CIRRHOSIS a) Mild (compensated) 1 1 1 1 b)

# Abacavir (ABC)

# COMBINED HORMONAL CONTRACEPTIVES (CHCs)
CHCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Clarification: Antiretroviral drugs have the potential to either decrease or increase the levels of steroid hormones in women using hormonal contraceptives. Pharmacokinetic data suggest potential drug interactions between some antiretroviral drugs (particularly some NNRTIs and ritonavir-boosted PIs) and some hormonal contraceptives. These interactions may reduce the effectiveness of the hormonal contraceptive.
Evidence: Three clinical studies, including 1 large study, found use of nevirapine-containing ART did not increase ovulation or pregnancy rates in women taking COCs (442)(443)(444)(445). For efavirenzcontaining ART, a pharmacokinetic study showed consistent significant decreases in contraceptive hormone levels in women taking COCs, and a small clinical study showed higher ovulation rates in women taking efavirenz-containing ART and COCs (445)(446)(447). Etravirine and rilpivirine do not interact with COCs (448,449). Clarification: Although the interaction of rifampicin or rifabutin therapy with COCs, P, CVR or CICs is not harmful to women, it is likely to reduce the effectiveness of COCs, P, CVR or CICs. Use of other contraceptives should be encouraged for women who are long-term users of either of these drugs. When a COC is chosen, a preparation containing a minimum of 30 g EE should be used.
Efavirenz (EFV) 2 2 2 2 Etravirine (ETR) 1 1 1 1 Nevirapine (NVP) 2 2 2 2 Rilpivirine (RPV) 1 1 1 1 c)
Evidence: The balance of the evidence suggests that rifampicin reduces the effectiveness of COCs (520)(521)(522)(523)(524)(525)(526)(527)(528)(529)(530)(531)(532)(533)(534)(535). Data on rifabutin are limited, but effects on metabolism of COCs are less than with rifampicin, and small studies have not shown evidence of ovulation (363,522,535).

# RECOMMENDATIONS REVIEWED FOR FIFTH EDITION
These recommendations were reviewed according to WHO requirements for guideline development, as part of the preparation of the Medical eligibility criteria for contraceptive use, fifth edition. The Population, Intervention, Comparator, Outcome (PICO) questions developed by the Guideline Development Group (GDG) and the databases searched to retrieve the evidence, which guided the preparation of systematic reviews, are described in greater detail in Part I of this document. Additionally, GRADE evidence profiles, the overall GRADE assessment of the quality of the evidence, summaries of the evidence supporting the recommendation(s), and other supplementary remarks from the GDG regarding the recommendations, are available in Part I.

# ADDITONAL COMMENTS AGE
Age  40 years: The risk of cardiovascular disease increases with age and may also increase with combined hormonal contraceptive (CHC) use. In the absence of other adverse clinical conditions, CHCs can be used until menopause.

# PAST ECTOPIC PREGNANCY
The risk of future ectopic pregnancy is increased in these women. CHCs provide protection against pregnancy in general, including ectopic gestation.

# DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM
Family history of DVT/PE (first-degree relatives): Some conditions which increase the risk of DVT/PE are heritable.

# VALVULAR HEART DISEASE
Among women with valvular heart disease, CHC use may further increase the risk of arterial thrombosis; women with complicated valvular heart disease are at greatest risk.
Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia. 2004;24(Suppl 1):1-150. 12 12 Available at: 

# VAGINAL BLEEDING PATTERNS
Irregular menstrual bleeding patterns are common among healthy women.

# UNEXPLAINED VAGINAL BLEEDING
There are no conditions that cause vaginal bleeding that will be worsened in the short term by use of CHCs.

# CERVICAL ECTROPION
Cervical ectropion is not a risk factor for cervical cancer, and there is no need for restriction of CHC use.

# CERVICAL CANCER (AWAITING TREATMENT)
There is some theoretical concern that CHC use may affect prognosis of the existing disease. While awaiting treatment, women may use CHCs. In general, treatment of this condition renders a woman sterile.

# BREAST DISEASE
Breast cancer: Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with CHC use.

# ENDOMETRIAL CANCER
COC use reduces the risk of developing endometrial cancer.
Awaiting treatment: Women may use COCs, CICs, P or CVR. In general, treatment of this condition renders a woman sterile.

# OVARIAN CANCER
COC use reduces the risk of developing ovarian cancer.
Awaiting treatment: Women may use COCs, CICs, P or CVR. In general, treatment of this condition renders a woman sterile.

# UTERINE FIBROIDS
COCs do not appear to cause growth of uterine fibroids, and CICs, P and CVR are not expected to either.

# CHCs PELVIC INFLAMMATORY DISEASE (PID)
COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. Whether CICs, P or CVR reduce the risk of PID among women with STIs is unknown but they do not protect against HIV or lower genital tract STIs.

# GALL BLADDER DISEASE
COCs, CICs, P or CVR may cause a small increased risk of gall bladder disease.
There is also concern that COCs, CICs, P or CVR may worsen existing gall bladder disease.
Unlike COCs, CICs have been shown to have minimal effect on liver function in healthy women, and have no first-pass effect on the liver.

# HISTORY OF CHOLESTASIS
Pregnancy-related: History of pregnancy-related cholestasis may predict an increased risk of developing COC-related cholestasis.
Past-COC-related: History of COC-related cholestasis predicts an increased risk with subsequent COC use.

# LIVER TUMOURS
There is no evidence regarding hormonal contraceptive use among women with hepatocellular adenoma.
COC use in healthy women is associated with development and growth of hepatocellular adenoma.
There is anecdotal evidence from countries where thalassaemia is prevalent that COC use does not worsen the condition.

# IRON-DEFICIENCY ANAEMIA
CHC use may decrease menstrual blood loss.

# Progestogen-only contraceptives (POCs)

# PROGESTOGEN-ONLY PILLS (POPs)
POPs contain only a progestogen and no estrogen.

# PROGESTOGEN-ONLY INJECTABLES (POIs)
These injectables include depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN).
There are three formulations considered here:
- DMPA-IM = 150 mg of DMPA given intramuscularly 2. DMPA-SC = 104 mg of DMPA given subcutaneously

# NET-EN = 200 mg of NET-EN given intramuscularly
Identified evidence for the conditions of age, obesity, endometriosis and HIV among DMPA-SC users appear consistent with existing recommendations for DMPA-IM (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Further, DMPA-SC and DMPA-IM appear to be therapeutically equivalent, with similar safety profiles when used by healthy women (3,5,11). Pending further evidence, the Guideline Development Group (GDG) concluded that the evidence available for DMPA-IM applies to DMPA-SC and, therefore, DMPA-SC should have the same categories as DMPA-IM; the assigned recommendations should be considered a preliminary best judgement, which will be re-evaluated as new data become available.

# PROGESTOGEN-ONLY IMPLANTS
Progestogen-only implants are a type of long-acting, reversible contraception. The various types of implants that are considered here are the following: No studies were identified that provided direct evidence on the use of the Sino-implant (II) among women with medical conditions in the MEC and included a comparison group. Evidence from three studies of healthy women demonstrate that Sino-implant (II) has a similar safety and pharmacokinetic profile to that of other LNG implants, with no significant differences in serious adverse events, such as ectopic pregnancy or discontinuation due to medical problems (13)(14)(15). Therefore, safety data from studies of other LNG implants among women with medical conditions were used due to the similarity of Sino-implant (II) and other LNG implants in hormone formulation, quality profile and daily release rates. The GDG assigned the same recommendations for Sinoimplant (II) as for the other LNG implants.

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. shows a weak association with fracture, although 1 large study suggests that women who choose DMPA may be at higher risk for fracture even prior to initiation of the method (16). It is unclear whether adult women with long durations of DMPA use can regain BMD to baseline levels before entering menopause and whether adolescents can reach peak bone mass after discontinuation of DMPA. The relationship between these changes in BMD during the reproductive years and future fracture risk is unknown. Studies generally find no effect of POCs other than DMPA on BMD (5,12,.

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. BREASTFEEDING  Clarification: There is theoretical concern about the potential exposure of the neonate to DMPA/NET-EN during the first 6 weeks postpartum. In many settings, however, pregnancy-related morbidity and mortality risks are high, and access to services is limited. In such settings, DMPA/NET-EN may be among the few methods widely available and accessible to breastfeeding women immediately postpartum.
Evidence: Direct evidence demonstrates no harmful effect of POCs on breastfeeding performance  and generally demonstrates no harmful effects on infant growth, health or development (74,76,89,99); however, these studies have been inadequately designed to determine whether a risk of long-term effects exists. Animal data suggest an effect of progesterone on the developing brain; whether similar effects occur following progestogen exposure in humans is unclear (110)(111)(112). POST-ABORTION Clarification: POCs may be started immediately postabortion.
Evidence: Limited evidence suggests that there are no adverse side-effects when an LNG implant or NET-EN are initiated after first-trimester abortion (113)(114)(115)(116). POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. OBESITY Clarification: There is evidence for differential weight gain among normal-weight and obese adolescents who use DMPA, but not among those using NET-EN. However, NET-EN is Category 2 due to evidence regarding potential effects of NET-EN on BMD among adolescents (see row: Age).
Evidence: Among adult women, there is generally no association between baseline weight and weight gain among DMPA users compared with non-users.
Evidence is mixed for adolescent DMPA users, with some studies observing greater weight gain among obese compared with normal-weight users, but other studies showing no association. Methodological differences across studies may account for the differences in findings. Data on other POC methods and other adverse outcomes are limited (10,(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133). Clarification: When multiple major risk factors exist, the risk of cardiovascular disease may increase substantially. Some POCs may increase the risk of thrombosis, although this increase is substantially less than with combined oral contraceptives (COCs). The effects of DMPA and NET-EN may persist for some time after discontinuation.

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. Evidence: There is no direct evidence on the use of POCs among women with DVT/PE on anticoagulant therapy. Although evidence on the risk of venous thrombosis with the use of POCs is inconsistent in otherwise healthy women, any small increased risk is substantially less than that with COCs (134)(135)(136).
Limited evidence indicates that intramuscular injections of DMPA in women on chronic anticoagulation therapy does not pose a significant risk of haematoma at the injection site or increase the risk of heavy or irregular vaginal bleeding (137,138). Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# DEPRESSIVE DISORDERS
DEPRESSIVE DISORDERS 1 1 1 Clarification:
The classification is based on data for women with selected depressive disorders. No data on bipolar disorder or postpartum depression were available. There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives.
Evidence: POC use did not increase depressive symptoms in women with depression compared with baseline (160)(161)(162)(163).

# REPRODUCTIVE TRACT INFECTIONS AND DISORDERS
VAGINAL BLEEDING PATTERNS a) Irregular pattern without heavy bleeding

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. UNEXPLAINED VAGINAL BLEEDING (suspicious for serious condition)
Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. Before evaluation 2 3 3
ENDOMETRIOSIS 1 1 1 BENIGN OVARIAN TUMOURS (including cysts) 1 1 1 SEVERE DYSMENORRHOEA 1 1 1 GESTATIONAL TROPHOBLASTIC DISEASE a) Decreasing or undetectable -hCG levels 1 1 1 b) Persistently elevated -hCG levels or malignant disease 1 1 1 CERVICAL ECTROPION 1 1 1 CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) 1 2 2
Evidence: Among women with persistent human papillomavirus (HPV) infection, long-term DMPA use ( 5 years) may increase the risk of carcinoma in situ and invasive carcinoma (164).
CERVICAL CANCER (awaiting treatment) POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  Evidence: Evidence suggests that there may be an increased risk of chlamydial cervicitis among DMPA users at high risk of STIs. For other STIs, there is either evidence of no association between DMPA use and STI acquisition or too limited evidence to draw any conclusions. There is no evidence for other POCs (165)(166)(167)(168)(169)(170)(171)(172).
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (186)(187)(188)(189)(190). One randomized trial found an increased risk of a composite outcome of declining CD4 count or death among oral contraceptive users (COCs and POPs) when compared with users of copper-bearing IUDs; this study, however, had significant loss to follow-up and method switching among groups, limiting its interpretation (188,191). One study found no difference in ART initiation or CD4 count between users and non-users of the LNG-IUD (192). Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on female-to-male HIV transmission by measuring seroconversions in male partners of women living with HIV and known to be using hormonal contraceptives. One study reported a statistically significant association between use of POIs and female-to-male transmission of HIV (180), while another study did not find a statistically significant association between use of DMPA and female-to-male HIV transmission (184). The findings of studies indirectly assessing the effects of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have been mixed. Most of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (189,(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207).
SEVERE OR ADVANCED HIV CLINICAL DISEASE (WHO STAGE 3 OR 4) 1 1 1

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (209,210). There is only limited and inconsistent evidence regarding the development of non-insulin-dependent diabetes among users of POCs with a history of gestational diabetes (211)(212)(213)(214).
b) Non-vascular disease Evidence: Among women with insulin-or non-insulindependent diabetes, limited evidence on the use of progestogen-only methods (POPs, DMPA injectable, LNG implant) suggests that these methods have little effect on short-term or long-term diabetes control (e.g. HbA1c levels), haemostatic markers or lipid profile (215)(216)(217)(218).

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
THYROID DISORDERS a) Simple goitre 1 1 1 b) Hyperthyroid 1 1 1 c) Hypothyroid 1 1 1 GASTROINTESTINAL CONDITIONS GALL BLADDER DISEASE a) Symptomatic i) treated by cholecystectomy 2 2 2 ii) medically treated 2 2 2 iii) current 2 2 2 b) Asymptomatic 2 2 2 HISTORY OF CHOLESTASIS a) Pregnancy-related 1 1 1 b) Past-COC related 2 2 2 VIRAL HEPATITIS a) Acute or flare 1 1 1 b) Carrier 1 1 1 c) Chronic 1 1 1 CIRRHOSIS a) Mild (compensated) 1 1 1 b) Severe (decompensated) 3 3 3 LIVER TUMOURS a) Benign i) focal nodular hyperplasia 2 2 2
Evidence: There is limited, direct evidence that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (219)(220)(221).
ii) hepatocellular adenoma 3
3 3 b) Malignant (hepatoma) 3 3 3
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (230,231).
Abacavir (ABC) 1 1 1 Tenofovir (TDF) 1 1 1 Zidovudine (AZT) 1 1 1 Lamivudine (3TC) 1 1 1 Didanosine (DDI) 1 1 1 Emtricitabine (FTC) 1 1 1 Stavudine (D4T) 1 1 1 b) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Clarification: Antiretroviral drugs have the potential to either decrease or increase the levels of steroid hormones in women using hormonal contraceptives. Pharmacokinetic data suggest potential drug interactions between some antiretroviral drugs (particularly some NNRTIs and ritonavir-boosted PIs) and some hormonal contraceptives. These interactions may reduce the effectiveness of the hormonal contraceptive.
Evidence: One retrospective chart review of women using efavirenz-containing ART showed increased contraceptive failure rates for women using LNG implants (232). Based primarily on pharmacokinetic data, the effectiveness of DMPA is likely not affected by NNRTIs, and vice versa (233,234).
Efavirenz (EFV) 2 DMPA=1 NET-EN=2 2 Etravirine (ETR) 1 1 1 Nevirapine (NVP) 2 DMPA=1 NET-EN=2 2 Rilpivirine (RPV) 1 1 1
Medical eligibility criteria for contraceptive use -Part II -PROGESTOGEN-ONLY CONTRACEPTIVES | 171

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. c) Protease inhibitors (PIs) Clarification: Antiretroviral drugs have the potential to either decrease or increase the levels of steroid hormones in women using hormonal contraceptives. Pharmacokinetic data suggest potential drug interactions between some antiretroviral drugs (particularly some NNRTIs and ritonavir-boosted PIs) and some hormonal contraceptives. These interactions may reduce the effectiveness of the hormonal contraceptive.
Evidence: One study found higher progestogen levels with concurrent PI use in users of POPs (238). Based primarily on pharmacokinetic data, the effectiveness of DMPA is likely not affected by PIs, and vice versa (233,234).
Ritonavir-boosted atazanavir (ATV/r) 2 DMPA=1 NET-EN=2 2 Ritonavir-boosted lopinavir (LPV/r) 2 DMPA=1 NET-EN=2 2 Ritonavir-boosted darunavir (DRV/r) 2 DMPA=1 NET-EN=2 2 Ritonavir (RTV) 2 DMPA=1 NET-EN=22
NET-EN=2 2 Clarification: Although the interaction of certain anticonvulsants with POPs, NET-EN and LNG/ETG implants is not harmful to women, it is likely to reduce the effectiveness of POPs, NET-EN and LNG/ETG implants. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is Category 1 because its effectiveness is not decreased by the use of certain anticonvulsants.
Evidence: Use of certain anticonvulsants may decrease the effectiveness of POCs (241)(242)(243).
b) Lamotrigine 1 1 1 Evidence: No drug interactions have been reported among women with epilepsy taking lamotrigine and using POCs (244).

# PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)
POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
ANTIMICROBIAL THERAPY a) Broad-spectrum antibiotics 1 1 1 b) Antifungals 1 1 1 c) Antiparasitics 1 1 1 d) Rifampicin or rifabutin therapy 3 DMPA=1 NET-EN=2 2
Clarification: Although the interaction of rifampicin or rifabutin with POPs, NET-EN and LNG/ETG implants is not harmful to women, it is likely to reduce the effectiveness of POPs, NET-EN and LNG/ETG implants. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is Category 1 because its effectiveness is not decreased by the use of rifampicin or rifabutin.

# RECOMMENDATIONS REVIEWED FOR FIFTH EDITION
These recommendations were reviewed according to WHO requirements for guideline development, as part of the preparation of the Medical eligibility criteria for contraceptive use, fifth edition. The Population, Intervention, Comparator, Outcome (PICO) questions developed by the Guideline Development Group (GDG) and the databases searched to retrieve the evidence, which guided the preparation of systematic reviews, are described in greater detail in Part I of this document. Additionally, GRADE evidence profiles, the overall GRADE assessment of the quality of the evidence, summaries of the evidence supporting the recommendation(s), and other supplementary remarks from the GDG regarding the recommendations, are available in Part I.

# ADDITIONAL COMMENTS PAST ECTOPIC PREGNANCY
POPs have a higher absolute rate of ectopic pregnancy compared with other POCs, but still less than using no method. The 75 g desogestrel-containing pill inhibits ovulation in most cycles, which suggests a low risk of ectopic pregnancy.
Vascular disease: There is concern regarding hypo-estrogenic effects and reduced high-density lipoprotein (HDL) levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation.

# DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM
Women on anticoagulation therapy who have a history of haemorrhagic ovarian cysts may benefit from DMPA use.

# CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE
There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation.
There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation.

# SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Severe thrombocytopenia increases the risk of bleeding. POCs may be useful in the treatment of menorrhagia in women with severe thrombocytopenia. However, given the increased or erratic bleeding that may be seen on initiation of DMPA and its irreversibility for 11-13 weeks after administration, initiation of this method in women with severe thrombocytopenia should be done with caution.
Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia. 2004;24(Suppl 1):1-150. 13 There is concern that severe headaches may increase with use of NET-EN, DMPA and implants. The effects of NET-EN and DMPA may persist for some time after discontinuation.

# VAGINAL BLEEDING PATTERNS
Irregular menstrual bleeding patterns are common among healthy women. POC use frequently induces an irregular bleeding pattern. Implant use may induce irregular bleeding patterns, especially during the first 3-6 months, but these patterns may persist longer. ETG users are more likely than LNG users to develop amenorrhoea.

# UNEXPLAINED VAGINAL BLEEDING
POCs may cause irregular bleeding patterns, which may mask symptoms of underlying pathology. The effects of DMPA and NET-EN may persist for some time after discontinuation.

# CERVICAL CANCER (AWAITING TREATMENT)
There is some theoretical concern that POC use may affect prognosis of the existing disease. While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile.

# BREAST DISEASE
Breast cancer: Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with POC use.

# ENDOMETRIAL CANCER
While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile.

# OVARIAN CANCER
While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile.

# UTERINE FIBROIDS
POCs do not appear to cause growth of uterine fibroids.

# PELVIC INFLAMMATORY DISEASE (PID)
Whether POCs, like COCs, reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STIs.
Nephropathy/retinopathy/neuropathy, other vascular disease, or diabetes of > 20 years' duration: There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. The effects of DMPA and NET-EN may persist for some time after discontinuation. Some POCs may increase the risk of thrombosis, although this increase is substantially less than with COCs.

# HISTORY OF CHOLESTASIS
Theoretically, a history of COC-related cholestasis may predict subsequent cholestasis with POC use. However, this has not been documented.

# LIVER TUMOURS
There is no evidence regarding hormonal contraceptive use among women with hepatocellular adenoma.
Given that COC use in healthy women is associated with development and growth of hepatocellular adenoma, it is not known whether other hormonal contraceptives have similar effects.

# IRON-DEFICIENCY ANAEMIA
Changes in the menstrual pattern associated with POC use have little effect on haemoglobin levels.

# Emergency contraceptive pills (ECPs) EMERGENCY CONTRACEPTIVE PILLS (ECPs)
ECPs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# RECOMMENDATIONS REVIEWED FOR FIFTH EDITION
These recommendations were reviewed according to WHO requirements for guideline development, as part of the preparation of the Medical eligibility criteria for contraceptive use, fifth edition. The population, intervention, comparator, outcome (PICO) questions developed by the Guideline Development Group (GDG) and the databases searched to retrieve the evidence, which guided the preparation of systematic reviews, are described in greater detail in Part I of this document. Additionally, GRADE evidence profiles, the overall GRADE assessment of the quality of the evidence, summaries of the evidence supporting the recommendation(s), and other supplementary remarks from the GDG regarding the recommendations, are available in Part I.

# ADDITIONAL COMMENTS
History of severe cardiovascular disease, migraine, and severe liver disease (including jaundice)
The duration of use of ECPs is less than that of regular use of COCs or POPs and thus would be expected to have a lower risk for adverse health outcomes.
There are no restrictions for the use of ECPs in cases of rape.

# Intrauterine devices (IUDs) INTRAUTERINE DEVICES (IUDs)
IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). One randomized controlled trial found that immediate insertion of the LNG-IUD was associated with decreased breastfeeding duration compared with delayed insertion (30). Two other randomized controlled trials assessing early vs delayed initiation of progestogen-only contraceptives failed to show a difference in breastfeeding outcomes (31,32). In other studies, initiation of LNG-IUD at 4 weeks postpartum or later demonstrated no detrimental effect on breastfeeding outcomes (33)(34)(35). POST-ABORTION a) First trimester 1 1 Clarification: IUDs can be inserted immediately after first-trimester, spontaneous or induced abortion.
Evidence: There was no difference in risk of complications for immediate vs delayed insertion of an IUD after abortion. Expulsion was greater when an IUD was inserted following a secondtrimester abortion vs a first-trimester abortion. There were no differences in safety or expulsions for post-abortion insertion of an LNG-IUD compared with a Cu-IUD (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). In women with very severe thrombocytopenia who are at risk for spontaneous bleeding, consultation with a specialist and certain pretreatments may be warranted.
Evidence: The LNG-IUD may be a useful treatment for menorrhagia in women with severe thrombocytopenia (54).

# INTRAUTERINE DEVICES (IUDs)
IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. Evidence: Evidence from studies examining the treatment effects of the LNG-IUD among women with heavy or prolonged bleeding reported no increase in adverse effects and found the LNG-IUD to be beneficial in the treatment of menorrhagia (74)(75)(76)(77)(78)(79)(80)(81).

# INTRAUTERINE DEVICES (IUDs)
IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# GESTATIONAL C TROPHOBLASTIC DISEASE
Evidence: Limited evidence suggests that women using an IUD following uterine evacuation for a molar pregnancy are not at increased risk of developing post-molar trophoblastic disease when compared to women using other methods of contraception (87)(88)(89)(90). IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. UTERINE FIBROIDS Evidence: Among women with fibroids, there were no adverse health events with LNG-IUD use, and there was a decrease in symptoms and size of fibroids for some women (91)(92)(93)(94)(95)(96)(97). Evidence: Among IUD users treated for PID, there was no difference in clinical course if the IUD was removed or left in place (98)(99)(100).

# INTRAUTERINE DEVICES (IUDs)
IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. Evidence: Using an algorithm to classify STI risk status among IUD users, 1 study reported that 11% of high-STI-risk women experienced IUDrelated complications compared with 5% of those not classified as high risk (104). In another small study, the incidence of PID after IUD insertion was low (2.2%) in a cohort of women considered to be high-risk based on high background rates of STIs in the general population (109).

# IUDs INTRAUTERINE DEVICES (IUDs)
IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (130,131). IUDs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# RECOMMENDATIONS REVIEWED FOR FIFTH EDITION
These recommendations were reviewed according to WHO requirements for guideline development, as part of the preparation of the Medical eligibility criteria for contraceptive use, fifth edition. The population, intervention, comparator, outcome (PICO) questions developed by the Guideline Development Group (GDG) and the databases searched to retrieve the evidence, which guided the preparation of systematic reviews, are described in greater detail in Part I of this document. Additionally, GRADE evidence profiles, the overall GRADE assessment of the quality of the evidence, summaries of the evidence supporting the recommendation(s), and other supplementary remarks from the GDG regarding the recommendations, are available in Part I.

# ADDITIONAL COMMENTS

# Puerperal sepsis
Insertion of an iud may substantially worsen the condition.
Immediate post-septic abortion: insertion of an iud may substantially worsen the condition.

# Past ectopic pregnancy
The absolute risk of ectopic pregnancy is extremely low due to the high effectiveness of iuds. However, when a woman becomes pregnant during iud use, the relative likelihood of ectopic pregnancy is greatly increased.
There is theoretical concern about the effect of levonorgestrel (LNG) on lipids. There is no restriction for copper-bearing IUDs (Cu-IUDs).

# Deep vein thrombosis/pulmonary embolism
The LNG-IUD may be a useful treatment for menorrhagia in women on chronic anticoagulation therapy.

# Current and history of ischaemic heart disease
There is theoretical concern about the effect of LNG on lipids. There is no restriction for Cu-IUDs.
There is theoretical concern about the effect of LNG on lipids. There is no restriction for Cu-IUDs.
Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: headache classification subcommittee of the international headache society. The international classification of headache dis-orders, 2nd edition. Cephalalgia. 2004;24(Suppl 1):1-150. 14 Severe dysmenorrhoea
Dysmenorrhoea may intensify with Cu-IUD use. LNG-IUD use has been associated with reduction of dysmenorrhoea.

# Cervial intraepithelial neoplasia (CIN)
There is some theoretical concern that LNG-IUDs may hasten the progression of CIN.

# Cervical cancer (awaiting treatment)
There is concern about the increased risk of infection and bleeding at insertion. The IUD will likely need to be removed at the time of treatment but, until then, the woman is at risk of pregnancy.

# Breast disease
Breast cancer: breast cancer is a hormonally sensitive tumour. Concerns about progression of the disease may be less with lng-iuds than with combined oral contraceptives (cocs) or higher-dose progestogen-only contraceptives (POCs).

# Endometrial cancer
There is concern about the increased risk of infection, perforation and bleeding at insertion. The iud will likely need to be removed at the time of treatment but, until then, the woman is at risk of pregnancy.

# Ovarian cancer
The IUD will likely need to be removed at the time of treatment but, until then, the woman is at risk of pregnancy.

# Uterine fibroids
Without distortion of the uterine cavity: Women with heavy or prolonged bleeding should be assigned the category for that condition.
With distortion of the uterine cavity: Pre-existing uterine fibroids that distort the uterine cavity may be incompatible with insertion and proper placement of the IUD.

# Anatomical abnormalities
Distorted uterine cavity: In the presence of an anatomic abnormality that distorts the uterine cavity, proper IUD placement may not be possible.

# Pelvic inflammatory disease (PID)
IUDs do not protect against STI/HIV/PID. In women at low risk of STIs, IUD insertion poses little risk of PID. Current risk of STIs and desire for future pregnancy are relevant considerations.
Pelvic: Insertion of an IUD may substantially worsen the condition.

# History of cholestasis
There is concern that a history of cholestasis related to combined hormonal contraceptives (CHCs) may predict subsequent cholestasis with LNG use. Whether there is any risk with use of an LNG-IUD is unclear.

# Liver tumours
There is no evidence regarding hormonal contraceptive use among women with hepatocellular adenoma. Given that COC use in healthy women is associated with development and growth of hepatocellular adenoma, it is not known whether other hormonal contraceptives have similar effects.

# Thalassaemia, sickle cell disease, iron-deficiency anaemia
There is concern about a risk of increased blood loss with Cu-IUDs.
Medical eligibility criteria for contraceptive use -Part II -COPPER-BEARING IUD FOR EMERGENCY CONTRACEPTION | 211

# Copper-bearing IUD for emergency contraception (E-IUD)
Use of a copper-bearing IUD (Cu-IUD) for emergency contraception (E-IUD) is highly effective for preventing pregnancy. For this purpose, a Cu-IUD can be inserted within five days of unprotected intercourse. However, when the time of ovulation can be estimated, the Cu-IUD can be inserted beyond five days after intercourse, if necessary, as long as the insertion does not occur more than five days after ovulation.
The eligibility criteria for general Cu-IUD insertion also apply for the insertion of E-IUDs (see section 2.7.4 on IUDs, pp..

# COPPER IUD FOR EMERGENCY CONTRACEPTION (E-IUD)
IUDs for emergency contraception do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV.
IUDs do not protect against STI/HIV or pelvic inflammatory disease (PID). Among women with chlamydial infection or gonorrhoea, the potential increased risk of PID with IUD insertion should be avoided. The concern is less for other STIs.

# Barrier methods (BARR) BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# CONDITION  additional comments after this table
CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY
NA NA NA NA = not applicable Clarification: None of these methods are relevant for contraception during known pregnancy. However, for women who continue to be at risk of STI/HIV during pregnancy, the correct and consistent use of condoms is recommended.

# BARR BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# BARR BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# SUPERFICIAL VENOUS DISORDERS

# BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# NEUROLOGIC CONDITIONS

# BARR BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# GESTATIONAL TROPHOBLASTIC DISEASE

# BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates. Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# GASTROINTESTINAL CONDITIONS
GALL BLADDER DISEASE a) Symptomatic i) treated by cholecystectomy 1 1 1 ii) medically treated 1 1 1 iii) current 1 1 1 b) Asymptomatic 1 1 1 HISTORY OF CHOLESTASIS a) Pregnancy-related 1 1 1 b) Past-COC-related 1 1 1 VIRAL HEPATITIS a) Acute or flare 1 1 1 b) Carrier 1 1 1 c) Chronic 1 1 1 CIRRHOSIS a) Mild (compensated) 1 1 1 b) Severe (decompensated) 1 1 1 LIVER TUMOURS a) Benign i) focal nodular hyperplasia 1 1 1 ii) hepatocellular adenoma 1 1 1 b) Malignant (hepatoma) 1 1 1 ANAEMIAS THALASSAEMIA 1 1 1 SICKLE CELL DISEASE 1 1 1 IRON-DEFICIENCY ANAEMIA 1 1 1 BARR BARRIER METHODS (BARR)
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.
If there is a risk of sexually transmitted infections (STIs), including HIV, then the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# CONDITION  additional comments after this table
CATEGORY I = initiation, C = continuation CLARIFICATIONS/EVIDENCE Condom Spermicide Diaphragm Condoms = male latex condoms, male polyurethane condoms, female condoms Diaphragm = diaphragm (with spermicide), cervical cap Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of their relatively higher typical-use failure rates.

# BARR ADDITIONAL COMMENTS Obesity
Severe obesity may make diaphragm and cap placement difficult.

# Valvular heart disease
Risk of urinary tract infection with the diaphragm may increase in a client with subacute bacterial endocarditis.

# Cervical cancer (awaiting treatment)
Repeated and high-dose use of nonoxynol-9 can cause vaginal and cervical irritation or abrasions.

# High risk of HIV
Category 4 for diaphragm use is assigned due to concerns about the spermicide, not the diaphragm.
Asymptomatic or mild HIV clinical disease (WHO stage 1 or 2)
Use of spermicides and/or diaphragms (with spermicide) can disrupt the cervical mucosa, which may lead to increased viral shedding and HIV transmission to uninfected sexual partners.
Severe or advanced hiv clinical disease (WHO stage 3 or 4)
Use of spermicides and/or diaphragms (with spermicide) can disrupt the cervical mucosa, which may lead to increased viral shedding and HIV transmission to uninfected sexual partners.

# History of toxic shock syndrome
Toxic shock syndrome has been reported in association with diaphragm use.

# Urinary tract infection
There is a potential increased risk of urinary tract infection with diaphragms and spermicides.

# Fertility awareness-based (FAB) methods
Fertility awareness-based (FAB) methods of family planning involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature (i.e. symptoms-based methods) or by monitoring cycle days (calendar-based methods).

# Symptom-based methods
Symptoms-based methods include the cervical mucus method (also called the ovulation method) and the TwoDay Method, which are both based on the evaluation of cervical mucus, and the sympto-thermal method, which is a double-check method based on evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to determine the last fertile day. There are no medical conditions that become worse because of use of FAB methods. In general, these methods can be provided without concern for health effects to people who choose them; therefore, the 1-4 recommendation categories do not apply to these methods. However, there are a number of conditions that make their use more complex. The existence of these conditions suggests that (i) use of FAB methods should be delayed until the condition is corrected or resolved, or (ii) use of FAB methods will require special counselling for the client, and a more highly trained provider is generally necessary to ensure correct use. The need for caution or delay in the use of these FAB methods is noted in the categories assigned in the table, per condition.

# Calendar-based methods

# FERTILITY AWARENESS-BASED (FAB) METHODS
Fertility awareness-based (FAB) methods do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  A = accept: There is no medical reason to deny the particular FAB method to a woman in this circumstance. C = caution: The method is normally provided in a routine setting, but with extra preparation and precautions. For FAB methods, this usually means that special counselling may be needed to ensure correct use of the method by a woman in this circumstance. D = delay: Use of this method should be delayed until the condition is evaluated or corrected. Alternative temporary methods of contraception should be offered.

# ADDITIONAL COMMENTS Breastfeeding
Fertility awareness-based (FAB) methods during breastfeeding may be less effective than when not breastfeeding. The lactational amenorrhoea method (LAM) does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. Women with conditions that make pregnancy an unacceptable risk should be advised that the LAM may not be appropriate for them because of its relatively higher typical-use failure rates.
The Bellagio Consensus provided the scientific basis for defining the conditions under which breastfeeding can be used safely and effectively for birth-spacing purposes, and programmatic guidelines were developed for the use of the LAM in family planning. These guidelines include the following three criteria, all of which must be met to ensure adequate protection from an unplanned pregnancy:
- amenorrhoea 2. fully or nearly fully breastfeeding 3. less than six months postpartum.
The main indications for breastfeeding remain the need to provide an ideal food for the infant and to protect it against disease. There are no medical conditions in which the use of the LAM is restricted and there is no documented evidence of its negative impact on maternal health. However, certain conditions or obstacles which affect breastfeeding may also affect the duration of amenorrhoea, making this a less useful choice for family planning purposes. These include:
Breastfeeding should be promoted, protected and supported in all populations, for all women who are HIV-negative or of unknown HIV status. A woman living with HIV, however, can transmit the virus to her child through breastfeeding. Yet breastfeeding, and especially early and exclusive breastfeeding, is one of the most critical factors for improving child survival. Breastfeeding also confers many other benefits in addition to reducing the risk of death.
There is now strong evidence that giving antiretroviral medications (ARVs) to either the HIV-positive mother or the HIV-exposed infant or both can significantly reduce the risk of transmitting HIV through breastfeeding. 15 This transforms the landscape in which decisions should be made by national health authorities and individual mothers. In the presence of If the infant is HIV-negative or of unknown HIV status:
A mother known to be living with HIV should only give commercial infant formula milk as a replacement feed to this infant when all of the following specific conditions are met:
- safe water and sanitation are assured at the household level and in the community, and 2. the mother or other caregiver can reliably provide sufficient infant formula milk to support normal growth and development of the infant, and 3. the mother or caregiver can prepare it cleanly and frequently enough so that it is safe and carries a low risk of diarrhoea and malnutrition, and 4. the mother or caregiver can, in the first six months, exclusively give infant formula milk, and 5. the family is supportive of this practice, and 6. the mother or caregiver can access health care that offers comprehensive child health services.
If the infant is known to be HIV-positive:
The mother is strongly encouraged to exclusively breastfeed for the first six months of the infant's life and to continue breastfeeding as per the recommendations for the general population, that is up to two years or beyond.
Women who are living with HIV should receive skilled counselling to help them. They should also have access to follow-up care and support, including family planning and nutritional support.

# Medication used during breastfeeding
In order to protect infant health, breastfeeding is not recommended for women using such drugs as: antimetabolites, bromocriptine, certain anticoagulants, corticosteroids (high doses), ciclosporin, ergotamine, lithium, mood-altering drugs, radioactive drugs and reserpine.

# Conditions affecting the newborn
Congenital deformities of the mouth, jaw or palate; newborns who are small-for-date or premature and needing intensive neonatal care; and certain metabolic disorders of the infant can all make breastfeeding difficult. Coitus interruptus (CI) does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/ HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms. Women with conditions that make pregnancy an unacceptable risk should be advised that CI may not be appropriate for them because of its relatively higher typical-use failure rates.
Coitus interruptus (CI), also known as withdrawal, is a traditional family planning method in which the man completely removes his penis from the vagina, and away from the external genitalia of the female partner, before he ejaculates. CI prevents sperm from entering the woman's vagina, thereby preventing contact between spermatozoa and the ovum.
This method may be appropriate for couples:
- who are highly motivated and able to use this method effectively;
- with religious or philosophical reasons for not using other methods of contraception;
- who need contraception immediately and have entered into a sexual act without alternative methods available;
- who need a temporary method while awaiting the start of another method;
- who have intercourse infrequently.
Some benefits of CI are that the method, if used correctly, does not affect breastfeeding and is always available for primary use or use as a back-up method. In addition, CI involves no economic cost or use of chemicals. There are no health risks associated directly with CI.
Men and women who are at high risk of STI/HIV infection should use a condom with each act of intercourse.
CI is unforgiving of incorrect use, and its effectiveness depends on the willingness and ability of the couple to use withdrawal with every act of intercourse.

# Surgical sterilization procedures (STER)
Given that sterilization is a surgical procedure that is intended to be permanent, special care must be taken to assure that every client makes a voluntary, informed choice of the method. Particular attention must be given in the case of young people, nulliparous women, men who have not yet been fathers and clients with mental health problems, including depressive conditions. All clients should be carefully counselled about the intended permanence of sterilization and the availability of alternative, long-term, highly effective methods. This is of extra concern for young people. The national laws and existing norms for the delivery of sterilization procedures must be considered in the decision process.
Transcervical methods of female sterilization are not addressed in these recommendations.
There is no medical condition that would absolutely restrict a person's eligibility for sterilization, although some conditions and circumstances will require that certain precautions are taken, including those where the recommendation is assigned as Category C (caution), D (delay) or S (special). For some of these conditions and circumstances, the theoretical or proven risks may outweigh the advantages of undergoing sterilization, particularly female sterilization. Where the risks of sterilization outweigh the benefits, long-term, highly effective contraceptive methods are a preferable alternative. Decisions in this regard will have to be made on an individual basis, considering the risks and benefits of sterilization versus the risks of pregnancy, and the availability and acceptability of highly effective, alternative methods.
Sterilization procedures should only be performed by welltrained providers in appropriate clinical settings using proper equipment and supplies. Appropriate service-delivery guidelines, including infection-prevention protocols, should be followed to maximize client safety.

# FEMALE SURGICAL STERILIZATION
Sterilization does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  Clarification: Elevated blood pressure should be controlled before surgery. There are increased anaesthesia-related risks and an increased risk of cardiac arrhythmia with uncontrolled hypertension. Careful monitoring of blood pressure intraoperatively is particularly necessary in this situation.  The woman is at high risk for complications associated with anaesthesia and surgery. If the woman has atrial fibrillation that has not been successfully managed or current subacute bacterial endocarditis, the procedure should be delayed.

# FEMALE SURGICAL STERILIZATION
Sterilization does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.

# FEMALE SURGICAL STERILIZATION
Sterilization does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.
additional comments after this table

# FEMALE SURGICAL STERILIZATION
Sterilization does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  (20,22,(43)(44)(45). S = special: The procedure should be undertaken in a setting with an experienced surgeon and staff, equipment needed to provide general anaesthesia, and other back-up medical support. For these conditions, the capacity to decide on the most appropriate procedure and anaesthesia regimen is also needed. Alternative temporary methods of contraception should be provided if referral is required or there is otherwise any delay.

# MALE SURGICAL STERILIZATION
Sterilization does not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national programmes as male condoms.  S = special: The procedure should be undertaken in a setting with an experienced surgeon and staff, equipment needed to provide general anaesthesia, and other back-up medical support. For these conditions, the capacity to decide on the most appropriate procedure and anaesthesia regimen is also needed. Alternative temporary methods of contraception should be provided if referral is required or there is otherwise any delay.

# ADDITIONAL COMMENTS FOR FEMALE STERILIZATION Parity
Nulliparous women: Like all women, they should be counselled about the permanency of sterilization and the availability of alternative, long-term, highly effective methods.
Postpartum < 7 days postpartum: Sterilization can be safely performed immediately postpartum.

# to < 42 days:
There is an increased risk of complications when the uterus has not fully involuted.
Pre-eclampsia/eclampsia: There are increased anaesthesia-related risks.
Prolonged rupture of membranes, 24 hours or more: There is an increased risk of postoperative infection.
Puerperal sepsis, intrapartum or puerperal fever: There is an increased risk of postoperative infection.
Severe antepartum or postpartum haemorrhage: The woman may be anaemic and unable to tolerate further blood loss.
Severe trauma to the genital tract (cervical or vaginal tear at the time of delivery): There may have been significant blood loss and anaemia.
Uterine rupture or perforation: There may have been significant blood loss or damage to abdominal contents.
Post-abortal sepsis or fever: There is an increased risk of postoperative infection.
Severe post-abortal haemorrhage: The woman may be anaemic and unable to tolerate further blood loss.
Severe trauma to the genital tract (cervical or vaginal tear at the time of abortion): The woman may be anaemic and unable to tolerate further blood loss. The procedure may be more painful.
Uterine perforation: There may have been significant blood loss or damage to abdominal contents.
Acute haematometra: The woman may be anaemic and unable to tolerate further blood loss.

# OTHER CONSIDERATIONS Multiple risk factors for arterial cardiovascular disease
Concurrent presence of multiple risk factors: There may be a high risk of complications associated with anaesthesia and surgery.

# Current and history of ischaemic heart disease
There is a high risk of complications associated with anaesthesia and surgery.
Cervical cancer (awaiting treatment), endometrial cancer, ovarian cancer
In general, the treatment renders a woman sterile.

# Uterine fibroids
Depending on the size and location of the fibroids, it might be difficult to localize the tubes and mobilize the uterus.

# Pelvic inflammatory disease (pid)
PID can lead to an increased risk of post-sterilization infection or adhesions.
There is an increased risk of postoperative infection.
There is a risk of hypoglycaemia or ketoacidosis when the procedure is performed, particularly if blood sugar is not well controlled before the procedure.

# Thyroid disorders
There is a higher risk of complications associated with anaesthesia and surgery.

# Viral hepatitis
There is a high risk for complications associated with anaesthesia and surgery.

# Sickle cell disease
There is an increased risk of pulmonary, cardiac or neurologic complications and possible increased risk of wound infection.
Medical eligibility criteria for contraceptive use -Part II -MALE STERILIZATION | 245

# Coagulation disorders
There is a higher risk of haematologic complications of surgery.

# Systemic infection or gastroenteritis
There are increased risks of postoperative infection, complications from dehydration, and anaesthesia-related complications.

# Fixed uterus due to previous surgery or infection
Decreased mobility of the uterus, fallopian tubes and bowel may make laparoscopy and minilaparotomy difficult and increase the risk of complications.

# Diaphragmatic hernia
For laparoscopy, a woman may experience acute cardiorespiratory complications induced by pneumoperitoneum or the Trendelenburg position.

# Kidney disease
Blood clotting may be impaired. There may be an increased risk of infection and hypovolemic shock. Condition may cause baseline anaemia, electrolyte disturbances, and abnormalities in drug metabolism and excretion.

# Severe nutritional deficiencies
There may be an increased risk of wound infection and impaired healing.

# Sterilization concurrent with caesarean section
There is no increased risk of complications in a surgically stable client.

# ADDITIONAL COMMENTS FOR MALE STERILIZATION Diabetes
Individuals with diabetes are more likely to get postoperative wound infections. If signs of infection appear, treatment with antibiotics needs to be given.

# Local infection
There is an increased risk of postoperative infection.

# Coagulation disorders
Bleeding disorders lead to an increased risk of postoperative haematoma formation, which, in turn, leads to an increased risk of infection.

# Systemic infection or gastroenteritis
There is an increased risk of postoperative infection.

# Large varicocele
The vas may be difficult or impossible to locate; a single procedure to repair varicocele and perform a vasectomy decreases the risk of complications.

# Large hydrocele
The vas may be difficult or impossible to locate; a single procedure to repair hydrocele and perform a vasectomy decreases the risk of complications.

# Filariasis; elephantiasis
If elephantiasis involves the scrotum, it may be impossible to palpate the spermatic cord and testis.

# Intrascrotal mass
This may indicate underlying disease.

# Inguinal hernia
Vasectomy can be performed concurrent with hernia repair.

# Sickle cell disease
There is an increased risk of pulmonary, cardiac or neurologic complications and possible increased risk of wound infection.
SUMMARY    Chelsea Polis collaborated on a trial investigating the acceptability of a subcutaneous injectable contraceptive; data collection for this study ceased in 2013. Pfizer, Inc. donated the injectable units, which were not yet commercially available, to her research unit for the conduct of the trial, but did not provide any monetary support.
Regine Sitruk-Ware received 1500 twice in a four-year period from Bayer to provide lectures on the future targets for a non-hormonal contraceptive in the female reproductive tract, and 4500 in 2014 from MSD to advise the company on the development of a progestin, nomegestrol acetate. As a result of her research related to the development of the progesteronereleasing vaginal ring, Dr Sitruk-Ware did not participate in the deliberations that lead to the inclusion of this method in the guideline nor the formulation of recommendations for use of this contraceptive method.
Lisa Soule is employed by the United States Food and Drug Administration (FDA), which is a regulatory body for hormonal contraceptives in the USA. In her role at the meeting, she represented the interests of the FDA, which serves the public health and not any commercial interests.
Carolyn Westhoff receives an honorarium from Agile Therapeutics to serve on its Scientific Advisory Board (approximately US$ 2500 per quarter). She receives honoraria as a member of the Data Safety and Monitoring Boards of both MSD and Bayer HealthCare to monitor contraceptive safety studies conducted by these companies (about US$ 3500 per year and 2700 per year, respectively). Westhoff's research unit receives funding to conduct studies on intrauterine devices (Bayer Healthcare and Medicine 360), a trial of the efficacy of self-administration of an injectable method of contraception (Pfizer, Inc.) and a trial on the safety and effectiveness of oral contraceptive pills (MSD).
Julie Williams is employed by the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MRHA). She was the lead rapporteur for the European Medicines Agency (EMA) Article 31 referral for combined hormonal contraceptives (CHCs), which considered risk of venous thromboembolism across the different products and how this influenced the balance of benefits and risks of these products. The review was considered by the EMA's Pharmacovigilence Risk Assessment Committee (PRAC) and the output of this review included the agreed PRAC recommendation and the Committee on Medicinal Products for Human Use (CHMP) Opinion. Both the PRAC recommendation and the CHMP Opinion have been made publically available on the EMA website and have resulted in changes to the product information for CHCs included in this Article 31 referral.