Clinical trial NCT04039204
Conditions: Endometriosis Unexplained Infertility
Sponsor: Wake Forest University Health Sciences
Start date: 2022-01-15; Completion date: 2023-08-09
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Studies suggest that undiagnosed endometriosis results in poor reproductive outcomes in the setting of In Vitro Fertilization and Embryo Transfer (IVF-ET). Biomarkers that predict endometriosis including B-cell lymphoma (BCL6) and Sirtuin 1 (SIRT1) are associated with reduced pregnancy rates following IVF-ET. Treatment with gonadotropin releasing hormone (GnRHr) receptor agonists (leuprolide acetate depot) has been shown to improve pregnancy rates following embryo transfer (ET). In this randomized controlled trial, a new generation GnRHr antagonist, elagolix, will be compared to oral contraceptives (OCPs) for suppression of suspected endometriosis prior to ET. Both groups will receive two months of treatment prior to frozen embryo transfer of a single euploid embryo. Outcomes will include pregnancy rate, miscarriage rate and ongoing and live birth rate following treatment. Patients experiencing unanticipated problems or who experience adverse events such that they do not tolerate the treatment they are assigned, will be allowed to discontinue treatment and be provided the opportunity to use the other treatment if they so choose. The outcomes of such cycles would be collected separately and included as observational data only and not included in the randomized data analysis. Alternatively, they can simply drop out of the study and resume medical therapy as appropriate or pursue frozen embryo transfer as previously planned.

Detailed description:
Although meta-analyses have not demonstrated an effect of endometriosis on IVF outcomes, most women with endometriosis undergoing IVF have not been diagnosed or treated for their disease. Recent evidence suggests that biomarkers for endometriosis predict IVF failure and miscarriage. Further suppression of endometriosis prior to IVF has been shown to dramatically improve pregnancy rates in unexplained infertility with suspected endometriosis. Elagolix (Orilissa) is a new generation FDA approved orally active GnRHr antagonist that is rapidly reversible, for the treatment of endometriosis and pelvic pain. There have been no studies on the efficacy of elagolix for the treatment of endometriosis-associated infertility. Given the recent study in Fertility and Sterility demonstrating IVF outcome prediction using BCL6 as a biomarker for the presence of endometriosis and subsequent preliminary data showing benefit using surgery and GnRH agonist therapy, there is adequate rationale to examine the use of the orally active, non-peptide compound (elagolix) for estrogen suppression prior to frozen embryo transfer in women who test positive for BCL6 and an associated protein, SIRT1. In this multi-central randomized controlled trial (RCT), the EFFECT Trial, the investigators plan to recruit 100 subjects with prior unexplained IVF failure with positive endometrial BCL6/SIRT1 expression. To qualify all subjects will need to have a preimplantation genetic testing (PGT-A) tested euploid embryo and intentions to undergo frozen embryo transfer. Subjects will be randomized to receive elagolix (200 mg BID) or OCPs for 2 months prior to standardized FET. Primary study outcomes will be pregnancy outcome.

Arms: arm 1: Elagolix will be dosed at the higher dose used in pelvic pain trials, 200 mg twice a day for 2 months. arm 2: Elagolix will be compared to a less potent standard commonly used prior to IVF or embryo transfer, namely estrogen containing birth control pills.
Interventions: intervention 1: Elagolix intervention 2: Ortho Cyclen
Intervention descriptions: intervention 1: This orally active, reversible GnRH antagonist will be used to suppress endometriosis by lowering estrogen levels for 2 months prior to FET intervention 2: Oral contraceptive prescribed by physician.

Protocol documents:
Prot_SAP_001.pdf: 
Official Title:  Elagolix for Fertility Enhancement Clinical Trial (EFFECT) 
NCT04039204
IRB-Approved Date: 6/1/2023


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Study Title: Elagolix for Fertility Enhancement Clinical Trial (The EFFECT Trial) 
Principal Investigator: Bruce A Lessey MD, PhD (Wake Health) 
Co-Investigators: Steven L. Young MD, PhD (University of North Carolina, Chapel 
Hill) and Ruth Lathi, MD, Stanford University 
Sponsor or funding source: (e.g. NIH, NICHD) 
Background, Rationale and Context 
Endometriosis is defined as the presence of endometrial glands and stroma outside the 
endometrial cavity. It affects at least 176 million women worldwide and over 10 million in 
the U.S.A., result in in an annual U.S. cost of over $22 billion. The impact on IVF has 
not been well studied, since most women with the disease are not counted, and those 
included in meta-analyses have already been surgically treated.  Recent work from our 
laboratory has identified two endometrial proteins, BCL6 and SIRT1, that are associated 
with endometriosis and together cause progesterone resistance, the sine quo non of 
endometriosis (Evers-Hoeker et al 2017; Yoo et al, 2018). The over-expression of BCL6 
has been shown to be associated with IVF failure (Almquist 2018; Figure 1) and had a 
high sensitivity and specificity for detection of endometriosis (Ever-Hoeker et al, 2017).  
Recurrent IVF implantation failure has also been shown to be treatable with suppression 
of menses using leuprolide acetate, letrozole, or both together (Surrey et al., 2017; 
Miller et al., 2012; Steiner et al., 2019).  Furthermore, treatment of women with elevated 
BCL6 with surgery or medical suppression for 2 months prior to embryo transfer 
(Lupron) improves outcomes compared to controls (Likes et al, 
2019).  
Figure 1: BCL6 and IVF success. The darker staining for 
BCL6 
provides 
an 
indication 
for 
the 
presence 
of 
endometriosis. When women entering an IVF cycle were 
tested, those positive for BCL6 (> 1.4 HSCORE) had a 
significantly decreased pregnancy rate compared to women 
with low BCL6.(Almquist et al., 2018). 
Elagolix (Orilissa) is a new generation FDA approved orally active GnRH 
antagonist that is rapidly reversible, for the treatment of endometriosis and pelvic 
pain (Taylor et al., NEJM 2018). There have been no randomized controlled trials 
examining the efficacy of elagolix for the treatment of endometriosis-associated 
infertility. Given the recent study in Fertility and Sterility demonstrating that IVF 
outcome prediction using BCL6 and subsequent preliminary data showing benefit 
using surgery and GnRH agonist therapy (Likes et al., 2019), and data on 
recurrent implantation failure responding to GnRH agonist and aromatase 
inhibitors (Steiner et al., 2019), there is adequate rationale to examine the use of 
this orally active, non-peptide compound (elagolix) for menstrual suppression prior 
to frozen embryo transfer in women who test positive for SIRT1 and BCL6 and 
therefore has suspected endometriosis.  In addition, during the conduct of this 
RCT to study elagolix treatment to study pregnancy outcomes and miscarriage 


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(primary and secondary outcomes), we are collecting blood (estradiol and 
cytokine measurements) to study the effect of medical suppression on 
inflammatory biomarkers in blood as well.  
 
Objectives 
To perform a prospective, open label randomized controlled trial for women who 
failed IVF with euploid embryos who have suspected endometriosis based on 
elevated elevated SIRT1/BCL6, comparing 2 months of elagolix (200 mg BID) to 
oral contraceptives (orthocylen; OPCs).  
Primary clinical objective is to determine methods to improve clinical pregnancy 
rates in these subjects who later undergo frozen embryo transfer with euploid 
(genetically tested) embryos.  
 
Justification 
The study will examine whether elagolix is superior to OCPs for fertility 
enhancement prior to frozen embryo transfer in women with unexplained prior 
implantation failure with euploid embryos. We will only use 200 mg twice a day 
dosing of elagolix, since the once daily approved dose of 150 mg does not reliably 
prevent ovulation and menstruation (Taylor et al., 2017). In women with 
menstruation, breakthrough bleeding or ovulation, a lower dose will efficiently 
eliminate the inflammatory changes that we are hoping to suppress. Further, we 
the goal of our study is to mimic depot leuprolide acetate which is completely 
suppressive of menstruation; thus the 200 mg BID dose, which is FDA approved 
for treatment of moderate to severe pelvic pain, will be used. It is possible that 
elagolix treatment will not be superior to OCPs. There has not been a head to 
head comparison of either elagolix or leuprolide acetate for endometriosis related 
symptoms of pain or infertility, so this type of comparison is needed.  
 
Methods and Measures 
 
Patients with at least one unexplained IVF failure after transfer of a normal euploid 
embryo who previously test positive for BCL6 and SIRT1 will be eligible to 
participate. Each will undergo initial endometrial biopsy, blood draw in the mid-
secretory phase. Data will be evaluated separately to estimate the prevalence of 
positive BCL6 and/or SIRT1 in this group of women with failed euploid embryo 
transfer.  Results of the biopsy will be shared with the patient and the clinicians 
performing the FET cycle, indicating whether they will be eligible for enrollment in 
the study.  Inclusion criteria will include, therefore, over-expression of endometrial 
proteins SIRT1 and BCL6 and the availability of frozen euploid embryos for a 
future FET. Each subject who agrees to enroll will be randomized to one of two 
treatment arms (elagolix 200 mg BID or an oral birth control pill for two months).   
After completion of 2 months of treatment, blood collection will be performed on all 
subjects. The treatments will not be blinded to the patient and the researchers. All 
subjects at the conclusion of treatment will undergo immediate entry into a 


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standardized frozen embryo cycle (FET) cycle using a single euploid embryo. 
Eight days after embryo transfer, serum hCG levels will be obtained on day 8 after 
the FET. Outcomes will be recorded including estradiol, progesterone and hCG 
measurements and documentation of pregnancy outcomes based on ultrasound. 
The outcome variables will include 1) cancellation; 2) not pregnant; 3) biochemical 
pregnancy; 4) ongoing pregnancy (sac with cardiac activity) and 5) live birth rate.  
Miscarriage rate will be calculated based pregnancy loss/number of pregnancies 
(not counting biochemical pregnancy).   
FET cycles will begin without intervening menstruation. Subjects will begin estrace 
2 mg for 4 days, going to 4 mg for 4 days and then back to 2 mg for 4 days. 
Progesterone in oil IM injections will be started when the lining is > 6 mm and has 
a trilaminar appearance. Transfer will occur 126 hours after the start of 
progesterone, which is continued until 10 weeks gestation if pregnant. If the hCG 
test is negative, POI will be discontinued.  
If the FET is delayed for any reason, whatever treatment the subject is on 
(elagolix or OCPs) will be extended for up to 2 weeks to avoid interruption in 
treatment prior to embryo transfer.  
 
Design 
A prospective randomized open label controlled trial. Primary outcome will be live birth 
rate, with secondary outcomes including pregnancy rates, miscarriage rates, measures 
of inflammation, after treatment at the time of frozen embryo transfer. 
 
Programmed FET Cycle 
i. Patients will be advised to call within a week of stopping the last dose 
of treatment 
ii. On day 3 after stopping, patients should begin taking estradiol 2mg PO 
BID 
iii. First monitoring visit should be scheduled for cycle day 9-11 and 
should include E2, P4, LH, and pelvic ultrasound 
1. If endometrium is > 7mm and trilaminar, initiation of 
progesterone may be scheduled to facilitate FET on desired 
date 
2. If endometrium is < 7mm and/or not trilaminar, estradiol should 
be increased to 2mg PO TID and another monitoring visit should 
be scheduled in 4-5 days 
iv. Timing of progesterone start 
1. If endometrium is > 7mm and trilaminar, initiation of 
progesterone may be scheduled to facilitate desired FET date 
2. In all cases, progesterone should be initiated with the goal of 
126 hours of progesterone exposure prior to FET 
3. Progesterone to be utilized is progesterone in oil (PIO) 50mg IM 
daily 


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v. Consideration should be given to cycle cancellation in the following 
circumstances: 
1. Endometrium < 7mm after 2-3 weeks of exogenous estradiol 
2. Persistent non-trilaminar endometrium after 2-3 weeks of 
exogenous estradiol 
3. Presence of significant fluid in the endometrial cavity 
4. If follicular recruitment is noted, conversion to natural cycle FET 
may be considered 
 
Setting 
 
The EFFECT trial will be conducted at three academic teaching institutions with 
accredited Reproductive Endocrinology and Infertility (REI) programs involved in In Vitro 
Fertilization cycles.  Wake Forest will be the central IRB and provide data safety 
monitoring board (DSMB) capabilities for the study.  
 
Subjects selection criteria 
 
Only patients with previous IVF failure who are suspected or known to have 
endometriosis on the basis of elevated endometrial BCL6 and SIRT1 will be included in 
this study.  The selection criteria includes the use of these two biomarkers as which 
defines a specific study population of interest. This inclusion of biomarkers was part of 
an NIH proposal that was submitted to and funded by the NIH. SIRT1 is strongly 
induced by resveratrol which has been shown to reduce embryo implantation (Ochiai 
2019a) and endometrial decidualization (Ochiai  2019b), supporting the biology as 
outlined in this proposal. We hypothesize that suppression of endometriosis will have 
the effect of reducing cytokines associated with inflammation which is part of the 
endometriosis pathogenesis. Each participant will be required to have at least 1 euploid 
embryo (preimplantation genetic tested and normal) with intentions to transfer that 
embryo in a frozen embryo transfer (FET) cycle.  
 
• Inclusion Criteria 
1. Age – 18 to 42 
2.  Parity – G0 or greater 
3.  AMH ≥ 0.5 and ≤ 10 
4.  Planning to undergo FET and PGT-A within 1 year of enrollment 
5.  Must have blastocyst(s) by day 6 that were biopsied for PGT-A 
6.  Has a previous endometrial biopsy showing elevated BCL6 and SIRT1 
expression. 
7.  Endometrial thickness at time of transfer ≥ 6 and ≤ 14 
• Exclusion Criteria 
1. Uterine fibroids > 4 cm in size, if intramural  
2.  Polycystic ovary syndrome (PCOS) according with the Rotterdam criteria 
3.  Ovarian failure and subjects receiving donor oocytes/embryos 
4.  Failure to identify at least 1 euploid embryo for FET 


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5.  Anti-cardiolipid and/or lupus anti-coagulant abnormalities by history 
6.  Diabetes mellitus (Type I or Type II) 
7.  Untreated hypothyroidism 
8.  Hyperprolactinemia 
9.  BMI ≤ 17 and ≥ 40 
10.  Uncorrected uterine anomaly 
11.  Women with osteoporosis 
12.  Women with moderate or severe hepatic impairment defined by Child-Pugh 
Classes B (moderate) and C (severe) 
13.  Women using strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin) 
14. Women at high risk of thromboembolic disorders including those that smoke, 
have cardiac valvular disease, atrial fibrillation, hypertension not controlled by 
medication, and a history of severe migraines.  
15. Severe renal disease with GFR < 15 ml/min. 
 
Sample Size 
 
Based on previous studies (Likes et al., 2019) we calculated that 50 patients (25 per 
arm) are required to have a 90% chance of detecting, as significant at the 5% level, an 
increase in the primary outcome measure from 11% live birth in the OCP group to 50% 
in the elagolix group. We decided to include 50 subjects per treatment arm (elagolix 
200 mg BID vs OCPs) for 2 months, because unlike the Likes study, we are not using a 
no treatment control arm, and OCPs may have some benefit over no treatment. Having 
a non-randomized, no treatment control group to follow will allow us some flexibility, 
however, in comparing outcomes over time. 
 
Enrollment may vary between sites, but we hope to recruit approximately 1/2 of the 
subjects at our site with the remainder at each of the other 2 sites (UNC and Stanford).  
We will perform interim analyses after 25 subjects per arm for safety assessment. 
Based on the 12 months of treatment in the original study (Taylor et al., 2017), safety 
concerns are minimal. Nevertheless, we will halt the study using the following stopping 
rules:  
1) If after 25 subjects per arm, the OCP ongoing pregnancy rate is higher than the 
treatment arm with elagolix 
2) There is no difference between the no treatment controls and the elagolix treatment 
are at 25 patients per arm 
 
We will perform an interim analysis after 25 subjects per arm to recalculate sample size 
requirements based on the outcomes at that point (Kuman and Chakraborty 2016). 
 
The choice to use oral contraceptives as a comparator group was made based on 
surveys of potential subjects who voiced concerns about being assigned to a placebo 
(no treatment) arm. It was felt, and the NIH reviewers agreed, that having an active 
comparator group would be acceptable.  OCPs, while a first line treatment for 
endometriosis, may not be as suppressive of endometriosis as traditional GnRH agonist 
therapy, although no head to head comparison studies are available.  Finally, the 


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choice to not compare 2 doses of elagolix is based on published results from the 
Taylor study (Taylor et al., NEJM, 2017) showing a high proportion of subjects in the 
150 mg per day dosing group that ovulated and/or menstruated. Bleeding, ovulation or 
menstruation is a clearly defined problem that would increase inflammation instead of 
decreasing it, which is the goal of this study. 
 
Interventions and Interactions 
 
Visit 1: Screening and enrollment. Following initial screening of potential subjects 
with an IVF failure, a positive SIRT1 and BCL6 on endometrial biopsy and 
available euploid embryos for transfer, patients will meet with the research nurse 
who will review all inclusion and exclusion criteria and obtain informed consent 
from eligible patients.   
Visit 2  First day of menses. Patients will be instructed to call with the menses at 
which time an hCG measurement will be made to rule out pregnancy. Subjects 
will be prepared for their two treatment cycles. Patients will be randomized using 
computer generated assignments to receive either 200 mg of elagolix twice daily 
or daily OCPs (Ortho Cyclen). The medications will be formulated into 2 tablets 
per day to blind the subjects and researchers. The center will call and receive the 
treatment by means of an interactive voice-response system. The trials will be 
conducted in accordance with International Conference on Harmonisation 
guidelines and applicable regulations and ethical principles of the Declaration of 
Helsinki. All the women provided written informed consent for the study protocol. 
Women will be instructed to use two forms of non-hormonal contraception; 
monthly pregnancy tests were performed including an initial hCG test prior to 
beginning the medication. During the course of two months of treatment subjects 
will be encouraged to call in and speak to the research nurse or their clinician with 
any concerns or reports of side effects. Bone mineral or other safety parameters 
previously performed in the Elaris I-IV studies by Abbvie showed that we should 
not expect adverse events due to the brevity of the exposure. 
 
Visit 3: All subjects will be seen at 1 month time interval and adverse reactions to 
the medial treatments reviewed and recorded. The second month of medications 
will be dispersed at that time. Adverse events will be coded with the use of 
the Medical Dictionary for Regulatory Activities, versions 19.0. We will use 
Fisher’s exact test to compare the incidence of any adverse event in the elagolix 
group with the incidence in the OCP group. All reported P values will be 
considered two-sided, and confidence intervals for safety end points will be 
considered relevant at the 95% level. 
 
Visit 4:  After completion of 2 months of treatment with  elagolix or OCPs,  
subjects will return for collection of blood (serum and plasma) which will be 
collected, processed and stored at -80° C for later evaluation. Subjects will be 
prepared for the upcoming FET cycle. 
 


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Visit 5: Completion of the study. Patients will return periodically for standardized 
treatments as part of their FET cycle for endometrial preparation, ultrasound and 
embryo transfer as dictated by the clinicians in the practice. Outcomes will be 
recorded and extracted from their SART database for pregnancy included 
extended follow-up for live birth rate.  
 
Patients experiencing unanticipated problems with the protocol or who experience 
adverse events such that they do not tolerate the treatment they are assigned, will 
be allowed to discontinue treatment and be provided the opportunity to use the 
other treatment if they so choose. The outcomes of such cycles would be 
collected separately and included as observational data only and not included in 
the randomized data analysis. Alternatively, they can simply drop out of the study 
and resume medical therapy as appropriate or pursue frozen embryo transfer as 
previously planned. 
 
Outcome Variables 
The following outcome data will be collected on each subject: 
1) BCL6/SIRT1 HSCOREs 
2) hCG level (first) 
3) Progesterone levels at first hCG measurement (ng/dl) 
4) hCG level (second) 
5) Pregnancy outcome (not pregnant, pregnant biochemical, pregnant 
miscarriage, pregnant ectopic, pregnant ongoing, pregnant delivered, 
pregnant 2nd or 3rd trimester loss) 
6) Categorical outcome (pregnant/not pregnant; summary designation) 
7) Comments related to overall outcomes 
8) Number of sacs (0, 1, 2, 3) 
 
 
Independent Variables 
The following demographic data will be collected on each subject: 
1) Age (based on date of birth) 
2) Weight 
3) BMI 
4) Gravidy/Parity  
5) Randomization group (elaglox, OCPs, non-randomized control) 
6) Embryo grade 
7) Number of remaining euploid embryos 
8)  PGT-A results (narrative) 
9)  Endometrial thickness  
10) Peak estradiol levels (pg/dl) 
11) Comments regarding embryo transfer 
12) Embryo transfer physician (name) 
13) Number of embryos transferred (confirm that 1 was transferred) 
 


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Analytical Plan 
Statistical analysis: Statistical analyses will be performed using the Student’s t-
test for data from the two groups. All data will be presented as means ± SEM. p < 
0.05 was considered statistically significant.  Fisher's exact test, relative risk, and 
95% confidence interval (CI) will be used for comparisons of categorical data.  
 
Independent Variables. 
Measurement of hormones. Estrogen, progesterone and hCG assays will be run 
by the hospital’s clinical laboratories using a competitive antibody technology. 
Venous blood will be drawn into serum separator tubes and taken immediately to 
the clinical lab for processing (available 24 hours per day).  
 
Results will be analyzed initially using descriptive statistics.  Comparison between 
groups will be done using chi square tests for proportions, and t-tests for continuous 
variables.  Regression analysis will be performed to identify independent outcome 
predictors.  Other inferential statistical analysis will be conducted as appropriate. 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
Subjects who failed IVF or FET with a previous endometrial biopsy showing elevated 
endometrial BCL6 and SIRT1 will be identified as part of ongoing care.  We do not 
discriminate on the basis of race or economic status, although we do have age and BMI 
cut-off criteria defined in the protocol.  Subjects will be approached in the privacy of the 
clinic and all conversations will be confidential. 
 
• We plan to use a recruitment flyers in the clinic to help motivate and identify 
willing subjects. A copy of this poster is provided with the submission material 
for IRB review. 
• Privacy will be protected and no records kept until subjects/patients agree to 
participate in the study?   
• If an individual declines participation including randomization any and all 
documents will be destroyed.  
 
Informed Consent 
 
Signed informed consent will be obtained from each subject by her physician or a clinic 
research nurse. Consent will be obtained in the CFEM clinical space where patients 
receive their care from the REI unit.  Other centers will use clinical research staff to 
consent patients in private offices under similar conditions.  
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study 
outcomes, minimizing to the fullest extent possible the collection of any information that 
could directly identify subjects, and maintaining all study information in a secure 
manner.  To help ensure subject privacy and confidentiality, only a unique study 


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identifier will appear on the data collection form.  Any collected patient identifying 
information corresponding to the unique study identifier will be maintained on a linkage 
file, store separately from the data.  The linkage file will be kept secure, with access 
limited to designated study personnel.  Following data collection subject identifying 
information will be destroyed 3 years after completion of the study, consistent with data 
validation and study design, producing an anonymous analytical data set.  Data access 
will be limited to study staff.  Data and records will be kept locked and secured, with any 
computer data password protected.  No reference to any individual participant will 
appear in reports, presentations, or publications that may arise from the study. 
 
Data and Safety Monitoring 
The principal investigator and PIs at UNC and Stanford will be responsible for the 
monitoring of the data and safety of study participants.  The principal investigator will be 
assisted by other members of the study staff. A data safety monitoring board (DSMB) 
through WFBH will be established to oversee the entire project.  
 
Per FDA request, we will assess suicidal ideation as part of our safety evaluation. At 
each visit subjects will be asked whether they have had any thoughts of self-harm as 
part of their encounter or if there has been any change in thoughts that include suicide.  
This screening will be two part, since this drug has been well studied and suicide risk is 
considered very low (Taylor et al., 2017). If a subject reports having suicidal ideation, 
we will use the PHQ-9 survery, commonly used in primary care. This instrument has a 
sensitivity of 78% and specificity of 70% (Runeson et al, 2017) and refer the individual 
for psychiatric evaluation. Subjects will be withdrawn from the study based on the 
outcomes of these two steps if they appear to be affected by either treatment toward 
self harm. 
 
We will exclude subjects with moderate to severe hepatic or renal disease or 
osteoporosis. We have added to the consent information on avoidance of pregnancy.  
 
Any pregnancy resulting in live birth that arises while taking active drug (elagolix or 
OCPs) will be identified and followed up to 1 year for any problems that might arise as a 
result of exposure as an early fetus.  
 
Excessive or unexpected bleeding may be considered an adverse event since the 
purpose of this study is to achieve and maintain amenorrhea for subjects prior to their 
next frozen embryo transfer. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or 
protocol changes will be promptly reported by the principal investigator or designated 
member of the research team to the IRB and sponsor or appropriate government 
agency if appropriate. 
 
 
 


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References 
Almquist LD, Likes CE, Stone B, et al. Endometrial BCL6 testing for the prediction of in 
vitro fertilization outcomes: a cohort study. Fertility and sterility. 2017; 108: 1063-9. 
 
Evans-Hoeker E, Lessey BA, Jeong JW, et al. Endometrial BCL6 Overexpression in 
Eutopic Endometrium of Women With Endometriosis. Reprod Sci. 2016; 23: 1234-41. 
 
Kumar A, and Chakraborty BS. Interim analysis: A rational approach of decision making 
in clinical trials. J Advanced Pharmaceutical Tech and Res.2017; 7:118-122. 
 
Lessey BA, Lebovic DI, Taylor RN. Eutopic endometrium in women with 
endometriosis: ground zero for the study of implantation defects. Semin Reprod 
Med. 2013 Mar;31(2):109-24. 
 
Likes CE, Cooper LJ, Efird J, Forstein DA, Miller PB, Savaris R, Lessey BA. 
Medical or surgical treatment before embryo transfer improves outcomes in women 
with abnormal endometrial BCL6 expression. J Assist Reprod Genet. 2019 
Mar;36(3):483-490. 
 
Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA, Higdon HL 3rd, 
Kitawaki J, Lessey BA. Endometrial receptivity defects during IVF cycles with and 
without letrozole. Hum Reprod. 2012 Mar;27(3):881-8. 
 
 
Ochiai A, Kuroda K, Ikemoto Y, Ozaki R, Nakagawa K, Nojiri S, Takeda S, 
Sugiyama R. Influence of resveratrol supplementation on IVF-embryo transfer cycle 
outcomes. Reprod Biomed Online. 2019a Aug;39(2):205-210. 
 
Ochiai A, Kuroda K, Ozaki R, Ikemoto Y, Murakami K, Muter J, Matsumoto A, 
Itakura A, Brosens JJ, Takeda S. Resveratrol inhibits decidualization by 
accelerating downregulation of the CRABP2-RAR pathway in differentiating human 
endometrial stromal cells. Cell Death Dis. 2019b Mar 20;10(4):276. 
 
Runeson B, Odenberg J, Pettersson A, Edbom T, Adamsson I, Waem M. Instruments 
for the assessment of suicide risk: A systemic review evaluating the certainty of the 
evidence. PLOS One 2017; 12:e0180292.  
 
Steiner N, Shrem G, Tannus S, Dahan SY, Balayla J, Volodarsky-Perel A, Tan SL, 
Dahan MH. Effect of GnRH agonist and letrozole treatment in women with recurrent  
implantation failure. Fertil Steril. 2019 Jul;112(1):98-104. 
 
Surrey ES, Katz-Jaffe M, Kondapalli LV, Gustofson RL, Schoolcraft WB. GnRH 
agonist administration prior to embryo transfer in freeze-all cycles of patients  
with endometriosis or aberrant endometrial integrin expression. Reprod Biomed 
Online. 2017 Aug;35(2):145-151. 
 
Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, 


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Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, 
Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. 
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH 
Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. 
 
Yoo JY, Kim TH, Fazleabas AT, et al. KRAS Activation and over-expression of 
SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone 
Resistance. Scientific reports. 2017; 7: 6765. 
 

ICF_000.pdf: 
Official Title:  Elagolix for Fertility Enhancement Clinical Trial (EFFECT)  
NCT04039204
IRB-Approved Date: 4/6/2023


Page 1 of 13
Adult Consent Form
IRB Version 2_11/11/2020
Department/Section of Obstetrics and Gynecology
WAKE FOREST School of Medicine
Informed Consent 
ELAGOLIX FOR FERTILITY ENHANCEMENT TRIAL (EFFECT)
Informed Consent Form to Participate in Research
Bruce A. Lessey MD, PhD, Principal Investigator
SUMMARY
You are invited to participate in a research study. The purpose of this research is to study a drug 
called elagolix (ABT-620) for the treatment of infertility and IVF failure.  You are invited to be 
in this study because you are a woman age 18 to 42 who may have endometriosis and infertility 
who is planning to transfer a normal (euploid) embryo in the future. Your participation in this 
research will involve 4 to 5 visits and last about 3 to 4 months. 
Participation in this study will involve being randomized to receive either elagolix or a standard 
oral contraceptive (birth control pill) every day for 2 months.  All research studies involve some 
risks.  A risk to this study that you should be aware of is that you might experience side effects 
of the treatments, including headache, nausea or hot flashes.  There is the possibility that you 
may benefit from participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  There may be other choices available to you.  Some other choices may include 
under-going embryo transfer without prior treatment.  You will not lose any services, benefits, or 
rights you would normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is Bruce A Lessey MD, PhD. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his/her 
contact information is: Bruce A Lessey, MD, PhD,
 
 Ph 
. 
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at
 or the Research Subject 
Advocate at Wake Forest at 
.
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INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you have Infertility and tested positive for biomarkers of endometriosis and you 
are contemplating a future transfer of an embryo. Your participation is voluntary. Please take 
your time in making your decision as to whether or not you wish to participate. Ask your study 
doctor or the study staff to explain any words or information contained in this informed consent 
document that you do not understand. You may also discuss the study with your friends and 
family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to test whether a drug used to treat endometriosis associated 
pain can be helpful for enhancing fertility in the setting of In Vitro Fertilization and Embryo 
Transfer (IVF-ET). Elagolix is a drug that reduces estrogen and can improve symptoms of 
endometriosis. One of those symptoms is infertility and implantation failure.  Elagolix has been 
approved by the US Food and Drug Administration (FDA) for the treatment of pain and 
endometriosis, but it has not been approved for use for fertility enhancement. 
In this study elagolix will be compared to birth control pills (OCPs). In this study you will either 
receive the active study medication, elagolix or OCPs. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
100 people at 3 research sites will be needed to compete this study, including approximately 40 to 
50 number people at this research site. In order to identify the necessary number of subjects needed 
here, we may need to screen as many as 100 subjects, since some people will not qualify to be 
included in the study and others may decide not to be randomized. We expect that up to 50 subjects 
may be non-randomized controls. 
WHAT IS INVOLVED IN THE STUDY?
You are eligible for this study because you previous had an unsuccessful embryo transfer and 
you have tested positive for two biomarkers of endometriosis, BCL6 and SIRT1. Because you 
have normal (euploid) frozen embryos and are planning to undergo a frozen embryo transfer 
(FET) in the future, you are eligible to be part of this study. 
If you agree to participate, you will be randomized into one of the study groups described below. 
Randomization means that you are put into a group by chance. It is like flipping a coin. You will 
have an equal chance of being placed in either group. 
The treatment study will consist of 4 phases:
1) The consent process
2) Randomization to one of two treatment groups
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3) Treatment with elagolix or OCPs for 2 months
4) Frozen embryo transfer cycle
Your participation will last approximately 3 to 4 months and include 5 extra clinic visits. 
If you qualify to participate in this study, you will be randomly assigned by chance (like flipping 
a coin) to receive the study drug, elagolix or birth control pills. 
Procedures:
If you agree to be in the study, you will undergo some procedures and activities. These include 
performing a blood test for hCG (human menopausal gonadotropin) to rule out pregnancy and 
blood will be collected and stored for measurements related to inflammation (cytokines).  Other 
products in blood (white blood cells) will be collected for measurements on micro ribonucleic 
acids (miRNAs), as a blood test for endometriosis. If you receive elagolix, you will be asked to 
take 1 pill twice a day, either 1 hour before a meal or 2 hours after a meal.  If you are in the OCP 
group, you will be asked to take 1 pill a day 1 hour before a meal or 2 hours after a meal. The 
medications will be prescribed for 2 months, but you will come in after 1 month to evaluate you 
for any side-effects you might be experiencing.  We will ask you to keep a daily diary of any 
side-effects you might be experiencing. 
Blood drawing
You will have approximately 3 tablespoons of blood withdrawn from a vein at the beginning and 
end of the treatments. 
Visits:
Visit 1: Screening and enrollment. Following initial screening of potential subjects with an 
IVF failure and available euploid embryos for transfer, patients will meet with the research 
nurse who will review all inclusion and exclusion criteria and obtain informed consent from 
eligible patients.  Patients with positive BCL6 and SIRT1 on previous endometrial biopsy 
with failed IVF and available embryos intending FET will be consented. 
Visit 2  First day of your period (menses). Patients will be instructed to call with the menses 
at which time an hCG measurement and a blood draw will be performed. Subjects will be 
prepared for their two treatment cycles. Patients will be randomized using computer 
generated assignments to receive 200 mg of elagolix twice daily or daily OCPs 
(orthocyclin). 
Visit 3: All subjects will be seen at 1 month time interval and the daily diary reviewed and 
adverse reactions recorded. The second month of medications will be dispersed at that 
time. 
Visit 4:  After completion of 2 months of treatment with elagolix or OCPs,  subjects will 
return for collection of blood (serum and plasma which will be collected, processed and 
stored at -80° C for later evaluation. Subjects will be prepared for the upcoming FET 
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cycle.
Visit 5: Completion of the study. Patients will return periodically for standardized 
treatments as part of their FET cycle for endometrial preparation, ultrasound and embryo 
transfer as dictated by the clinicians in the practice. 
Visit 6: Subjects will return 8 to 9 days after embryo transfer for a pregnancy test. hCG 
levels and progesterone levels will be recorded.  Follow-up ultrasounds performed for 
pregnancy monitoring will be examines and pregnancy outcomes will be recorded and/or 
extracted from their SART database for pregnancy included extended follow-up for live 
birth rate, obtained from SART database. 
If you choose to be in the control group, you will have the standard embryo transfer protocol. 
We can send copies of your test results to your personal physician. Even if you do not wish to 
have any of your medical information sent to your physician, you can still participate in this 
research study.
Do you request that we send important medical findings from your study tests/exams to your 
personal physician? 
[   ] Yes
[   ] No
___________ Initials
STORAGE of Biological Specimens (insert the following section if you will 
STORE biological samples for use in future research)
If you agree to participate in this study, we will (draw 3 tablespoons of the blood) to use for future 
research. This sample will be kept and may be used in future research to learn more about other 
diseases.  Your sample will be obtained (at the CFEM clinic) at Wake Forest University Baptist 
Medical Center. The sample will be stored in the Research Laboratory at Watlington Hall and will 
be given only to researchers approved by (PI of study).  An Institutional Review Board (IRB) must 
also approve any future research study using your tissue sample. In order to participate in this 
study, you must be willing to provide this sample for future research. 
The research that may be performed with your blood/tissue sample is not designed to help you 
specifically. There is no personal benefit to you from taking part in this aspect of the research 
study. It might help people who have diseases at some point in the future, but it is not known if 
this will happen. The results of the research performed with your blood /tissue will not be given 
to you or your doctor. The results will not be put in your medical record. The research using your 
blood/tissue sample will not affect your care.
Your blood/tissue sample will be used only for research and will not be sold. The findings from 
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this research may result in the future development of products that are of commercial value. 
There are no plans to share any of the profits with you which may occur as a result of the 
research.
Your blood/tissue sample will be stored with a unique identifier and will not include any 
identifiable information about you such as your name, address, telephone number, social 
security number, medical record number or any of the identifiers outlined in the HIPAA 
Privacy Rule. The unique identifier will be a randomly assigned number and only the 
principal investigator will have access to the code that links the unique identifier to you. 
Your name, address, social security number, etc., will never be disclosed to future 
researchers and neither will the code that links your identifiers to the sample.
In the future, people who do research may need to know more about your health. While 
the study investigator may give reports about your health, he/she will NOT be given your 
name, address, phone number, or any other identifying information about who you are, 
unless you agree to be contacted in the future.
____YES you many contact for future research studies
____NO I do not want to be contacted regarding future research studies.
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for about 3 to 4 months. Because pregnancy is an outcome of this study, 
we will use information in the SART database to document the outcome of your pregnancy up 
until the time of delivery. 
You can stop participating at any time. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. 
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. Risks and side effects related to the procedures and drugs we are studying 
include:
Most commons side effects of elagolix:

Headache

Feeling sick to one’s stomach (nausea)

Hot flashes 
Less common side effects

Dizziness or light headed

Diarrhea

Changes in mood including depression

Acne
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
Migraine headaches

Vaginal bleeding

Tiredness or fatigue

Hair loss

Difficulty sleeping

Vomiting

Changes in sexual desire

Swelling or bloating

Ovarian cysts
Most common side effects of birth control pills (OCPs)

Nausea

Bloating

Vaginal bleeding or spotting

Migraine headaches

Changes in mood or sexual desire
Vaginal bleeding
Excessive vaginal bleeding has sometimes occurred with either of the proposed treatments. 
Bleeding that becomes excessive, unexpected or unrelenting while on therapy may lead to 
withdrawal from the study and the request to stop treatment with that medication.  Subjects that 
experience such events leading to withdrawal from the study, will be offered treatment with the 
alternative treatment arm for 2 more months and outcomes followed in an observational arm of 
the study.
Bone mineral density and risk of fracture
While long term use of elagolix at the higher dose was associated with some bone loss and 
potential risk of fracture, previous studies show that this risk is small for short term use as in this 
study. 
Effects on Lipids
Long term use of elagolix has been shown to adversely affect lipid profiles, but for short term 
use this is unlikely to occur. 
Allergic Reactions
There is always a possibility of an allergic reaction to any medication. Some cases of allergic 
reaction include rash, have been reported in women taking elagolix. Some people who 
experienced these reactions required treatment and, in some cases, stopped the study drug. 
Depression or suicidal thoughts
Although uncommon, some women on estrogen lowering drugs may have mood changes that 
could become serious over time. After starting the treatments, the study personnel will be asking 
you if you are experiencing any sad thoughts or thoughts related to self-harm. Questionnaires to 
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evaluate the severity of any mood changes could be administered and some subjects may need to 
be withdrawn from the study if those mood changes are interfering with your personal safety. As 
part of this study, you will be asked questions about your mood while on this medication. If we 
learn that you or someone else is in danger of harm, the study team is required to report that 
information to the proper authorities.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other risks that we cannot predict. You should 
tell the research staff about all the medications, vitamins and supplements you take and any 
medical conditions you have. This may help avoid side effects, interactions and other risks.
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
A Data Safety and Monitoring Committee, an independent group of experts, will be reviewing 
the data from this research throughout the study.
You may experience discomfort, bruising and/or bleeding where the needle is inserted. 
Occasionally some people become dizzy lightheaded or feel faint. Infection may occur on rare 
occasions.  Frequent donation of blood can result in low iron in your blood (iron deficient 
anemia).  
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of childbearing 
potential must use a reliable method of birth control while participating in this study. Reliable methods of 
birth control are: abstinence (not having sex), tubal ligation, or vasectomy of the partner (with confirmed 
negative sperm counts) in a monogamous relationship (same partner). An acceptable, although less 
reliable, method involves the careful use of condoms and spermicidal foam or gel and/or a diaphragm 
with spermicide with Plan B used for any noticed condom or diaphragm failures. We encourage you to 
discuss this issue further with your physicians if you have any questions.
Pregnant women are excluded from participation in this study. Because NO method of birth 
control is 100% reliable, a pregnancy test is required at least 10 days from your last normal 
menstrual period, if you are a sexually active woman of childbearing potential.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may be direct benefit to you.  We hope the 
information learned from this study will benefit other people in the future. The benefits of 
participating in this study may be: You may have an improved chance at getting pregnant by 
participating in this study. Because endometriosis suppression has been shown to improve 
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pregnancy rates in other studies, both treatment arms may offer benefit to you. Because 
individuals respond differently to therapy, no one can know in advance if it will be helpful in 
your particular case.
WHAT OTHER CHOICES ARE THERE?
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have these options:
You can also agree to be part of this study without undergoing randomization, but allowing the 
study team to follow your outcomes after FET without further treatment.  This is a valuable way 
to help advance our understanding of endometriosis and its effect on fertility. You can decline 
participation in the study and continue with your fertility treatments. 
WHAT ARE THE COSTS?
All study costs, including any study medications and procedures related directly to the study, will 
be paid for by the study. Costs for your regular medical care, which are not related to this study, 
will be your own responsibility.
WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
The purpose of this research study is to obtain data or information on the safety and effectiveness 
of elagolix; the results will be provided to the sponsor, the Food and Drug Administration and 
other federal and regulatory agencies as required.
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. The researchers with this Certificate may not disclose or use information, documents, or 
biospecimens that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other action, suit, or proceeding, or be used as evidence, for example, if there is a 
court subpoena, unless you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is not 
connected with the research except, if there is a federal, state, or local law that requires 
disclosure (such as to report child abuse or communicable diseases but not for federal, state, or 
local civil, criminal, administrative, legislative, or other proceedings, see below); if you have 
consented to the disclosure, including for your medical treatment; or if it is used for other 
scientific research, as allowed by federal regulations protecting research subjects. 
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The Certificate cannot be used to refuse a request for information from personnel of the United 
States federal or state government agency sponsoring the project that is needed for auditing or 
program evaluation by the NIH which is funding this project or for information that must be 
disclosed in order to meet the requirements of the federal Food and Drug Administration 
(FDA).  You should understand that a Certificate of Confidentiality does not prevent you from 
voluntarily releasing information about yourself or your involvement in this research. If you 
want your research information released to an insurer, medical care provider, or any other person 
not connected with the research, you must provide consent to allow the researchers to release it.
WILL YOU BE PAID FOR PARTICIPATING?
You will receive no payment or other compensation for taking part in this study.
The findings from this research may result in the future development of products that are of 
commercial value. There are no plans to provide you with financial compensation or for you to 
share in any profits if this should occur.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by the NIH. The sponsor is providing money or other support to 
Wake Forest University Health Sciences to help conduct this study. Elagolix, the drug under 
study, is manufactured by AbbVie. The Principal Investigator, Dr. Bruce Lessey, is a scientific 
advisor for AbbVie and has received compensation from AbbVie for consulting services related 
to the development of elagolix. Dr. Lessey also has a financial interest in the biomarkers being 
used in the research. This means that the results of this study could lead to personal profit for the 
investigator if the biomarkers are licensed for use related to this research.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A 
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management, at 
.
If you are injured, the insurer may require information such as your name, social security 
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number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Bruce A Lessey MD, PhD, at
.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information about your health or behaviors is considered 
Protected Health Information. The information we will collect for this research study includes:

Age

Weight and height

Pregnancy history

Infertility diagnosis

Prior medical records about infertility treatments

Hormone levels during FET

Details regarding embryos and transfer

Pregnancy outcomes
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), 
the Department of Health and Human Services (DHHS) and similar agencies in other countries.  
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
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information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
Any Protected Health Information collected from you in this study that is maintained in the 
research records and will be kept for at least six years after the study is finished. At that time any 
research information not already in your medical record will either be destroyed or it will be de-
identified. 
You can tell Dr. Bruce Lessey that you want to take away your permission to use and share your 
Protected Health Information at any time by sending a letter to this address:
Bruce A Lessey MD, PhD
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial.  Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record.  This part of the medical record will only be available to people 
who have authorized access to your medical record.  If you are not a patient at this Medical 
Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the results.  You can search this Web site at any time. 
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
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medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because you were not able or willing to undergo a frozen embryo 
transfer or if you were non-compliant in taking the study medications.  Information that 
identifies you may be removed from the data or specimens that are collected as part of this study 
and could be used for future research or shared with others without additional consent.  You will 
be given any new information we become aware of that would affect your willingness to 
continue to participate in the study. 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, Bruce A Lessey MD, PhD at 
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
 or the 
Research Subject Advocate at 
. You will be given a copy of this signed consent 
form. 
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
For this study, I agree to be randomized to the treatment arms Yes_____    No______  
______(Initial)
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Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent:___________________________ Date:_________ Time:________ am pm
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