The Role of Hydrosalpinx in Recurrent Miscarriage
Conditions: Abortion, Spontaneous, Miscarriage, Recurrent, Hydrosalpinx
Sponsor: University of Birmingham

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IRAS ID: 232650, UoB Research Governance Reference Number: RG_17-150 
Protocol v1.1, 28-Dec -2017 
 
 
 
The role of hydrosalpinx in recurrent 
miscarriage 
PROTOCOL 
Version 1.1 
28th December 2017 
 
Chief Investigator 
Professor Arri Coomarasamy   
Tel: 0121 627 2775 
Email:  a.coomarasamy@bham.ac.uk 
Key contacts: 
 The CI is responsible for the medical oversight of the study. 
 
 Professor Arri Coomarasamy is the Director of the Tommy's National 
Centre for Miscarriage Research 
 
 Dr. Adam Devall is the Trial Manager for Tommy’s National Centre for 
Miscarriage Research: 0797 182 3452; a.j.devall@bham.ac.uk 
 
 Dr. Sean Jennings is the Research Governance and Ethics Manager for 
the University of Birmingham (Sponsor): 0121 414 3794; 
researchgovernance@contacts.bham.ac.uk 

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Table of Contents 
The role of hydrosalpinx in recurrent miscarriage study design group .................................................. 3 
Principal Investigator & Chief Investigator ......................................................................................... 3 
Study Design and Management .......................................................................................................... 3 
Co-Investigators .................................................................................................................................. 3 
Background ............................................................................................................................................. 4 
Epidemiology of miscarriage ............................................................................................................... 4 
Tubal disease and its effect on reproductive outcomes ..................................................................... 4 
Detection of tubal disease .................................................................................................................. 5 
Rationale for this study ....................................................................................................................... 5 
Objectives ............................................................................................................................................... 6 
Study Design ........................................................................................................................................... 6 
Population to be studied......................................................................................................................... 6 
Inclusion criteria .................................................................................................................................. 6 
Exclusion criteria ................................................................................................................................. 6 
Identifying Participants ....................................................................................................................... 6 
Data to be collected and tests to be performed ..................................................................................... 6 
Outcomes to be measured ..................................................................................................................... 7 
Method of collection of data and outcomes .......................................................................................... 7 
Consent to participation and feedback of results ................................................................................... 8 
Dissemination of study results ................................................................................................................ 8 
Withdrawal process ................................................................................................................................ 8 
Patient Journey ....................................................................................................................................... 8 
Accrual and Analysis ............................................................................................................................... 9 
Sample Size ......................................................................................................................................... 9 
Statistical Analysis ............................................................................................................................... 9 
Data management and archiving ............................................................................................................ 9 
Safety reporting (Adverse Events and Serious Adverse Events) ........................................................... 10 
Serious breaches ................................................................................................................................... 10 
Insurance and indemnity ...................................................................................................................... 10 
End of study definition .......................................................................................................................... 10 
Study Oversight and Quality Assurance processes ............................................................................... 10 
Funding and Sponsorship ...................................................................................................................... 10 
Study Flow Chart ................................................................................................................................... 12 
List of References .................................................................................................................................. 13 

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IRAS ID: 232650, UoB Research Governance Reference Number: RG_17-150 
Protocol v1.1, 28-Dec -2017 
 
The role of hydrosalpinx in recurrent miscarriage study 
design group 
 
Principal Investigator & Chief Investigator 
Professor Arri Coomarasamy 
Professor of Gynaecology, University of Birmingham 
Birmingham Women’s Hospital 
Telephone: 0121 627 2775 
a.coomarasamy@bham.ac.uk 
 
Study Design and Management 
Dr Jayasish Ghosh 
Clinical Research Fellow and Registrar in Obstetrics and Gynaecology  
Birmingham Women’s Hospital 
Telephone: 0121 623 6837 
jayasish.ghosh@nhs.net 
 
Co-Investigators 
Dr Ioannis D Gallos 
Honorary Clinical Lecturer and Sub-speciality Trainee in Reproductive Medicine and Surgery 
Birmingham Women’s Hospital 
Telephone: 0121 623 6837 
I.D.Gallos@bham.ac.uk 
 
Dr Justin J Chu 
Academic Clinical Lecturer and Registrar in Obstetrics and Gynaecology 
Birmingham Women’s Hospital 
Telephone: 0121 623 6837 
justinchu@doctors.org.uk 
 
 
 
 
 
 

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Background 
Epidemiology of miscarriage 
Miscarriage, also known as spontaneous pregnancy loss before the fetus reaches viability, is a 
common early pregnancy complication. One in five pregnancies miscarries, which equates to over 
250,000 miscarriages a year and 38,349 hospital admissions in the UK between April 1st 2015 and 
March 31st 2016.1, 7 Miscarriage can be devastating to women and couples trying to conceive. It is a 
significant source of physical and psychological morbidity for many women and couples, the effects of 
which can endure for many months.8 Yet for all the physical and mental sequelae and the economic 
costs, we have made little progress in treating this distressing condition.  
 
Most miscarriages happen in the first 12 weeks of pregnancy because of sporadic chromosomal 
abnormalities.9 However, for women with recurrent miscarriages, there may be genetic factors such 
as parental chromosomal abnormalities, embryonic chromosomal abnormalities, as well as structural 
anatomical abnormalities such as congenital uterine malformations causing miscarriage.10-17 Other risk 
factors include endocrine disease such as diabetes, systemic and genital infections and thrombophilia 
such as Anti-Phospholipid Syndrome.18, 19 The full list is recorded in appendix A for reference. However, 
despite very thorough investigation (full list of recommended investigations is outlined in Appendix 
B), a significant proportion of women with recurrent miscarriage will be labelled as unexplained and 
be left with no definitive answers, treatments or sometimes sadly, hope.20 
 
Tubal disease and its effect on reproductive outcomes 
C. trachomatis is the most common sexually transmitted infection in the UK.2 C. trachomatis often has 
no symptoms, but can have serious health consequences, including fallopian tube damage. Untreated 
C. trachomatis infection in pregnancy may increase the risk of miscarriage, preterm birth, low birth 
weight and stillbirth.4-6  
 
A severe form of tubal damage is when the tube is blocked and filled with fluid, a condition called 
hydrosalpinx.  They are classically caused by ascending infections from the lower genital tract such as 
chlamydia, which cause pelvic inflammatory disease, causing the tubes to appear swollen and 
enlarged.21 Hydrosalpinx is associated with a dramatic reduction in the chances of a live birth with 
assisted reproductive techniques.22 This is explained by reduced implantation chances and increased 
pregnancy losses in the presence of a hydrosalpinx.22 It is therefore strongly recommended that 
hydrosalpinges are removed or treated by tubal surgery prior to IVF.23  
 
It has been suggested that hydrosalpinx may have a causative role in recurrent miscarriage. The 
biological rationale for this increase in pregnancy losses is not yet well understood. It has been 
postulated that the hydrosalpinx fluid may be embryotoxic as it can include micro-organisms, 
endotoxins, cytokines and free radicals causing oxidative stress.24, 25 This fluid may therefore alter the 
endometrial receptivity causing a disturbed cytokine cascade, which impedes implantation.26 
Additionally, as the fallopian tube is occluded distally, the hydrosalpinx fluid may drain into the 
endometrial cavity having a flushing effect on the developing embryo hindering implantation.27 
 

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Detection of tubal disease  
Investigation of suspected tubal disease is currently recommended for women with subfertility by 
laparoscopy or hysterosalpingography (HSG).23 Women who are not known to have comorbidities 
(such as pelvic inflammatory disease, previous ectopic pregnancy or endometriosis) should be offered 
HSG to screen for tubal occlusion because this is a reliable test for ruling out tubal occlusion, and it is 
less invasive and makes more efficient use of resources than laparoscopy.23 A HSG involves the 
passage of a radio-opaque contrast media through the female cervix whilst simultaneously taking 
serial radiographs to examine the patency and free spill of the media into the abdominal cavity. It 
requires radiographers, specialist radiographic equipment and exposure to radiation. Furthermore, a 
HSG is performed in a radiology department and requires a radiologist to interpret them.  
 
Where appropriate expertise is available, screening for tubal occlusion using hysterosalpingo-
contrast-ultrasonography (HyCoSy) can be considered because it is an effective alternative to HSG for 
women who are not known to have comorbidities.23 A HyCoSy is an outpatient procedure which only 
requires a special contrast media and an USS machine which is usually present in most gynaecological 
out-patient departments. It is performed at the same time as a pelvic ultrasound, which is 
recommended for both women with subfertility or recurrent miscarriages.20, 23 The contrast media is 
injected through the cervix and its flow into the uterus and out through the fallopian tubes is tracked 
in real time using the ultrasound machine to detect tubal patency and pathology. A HyCoSy is a 
standard investigation for fertility problems. 
 
Laparoscopy is an invasive operative investigation where by a fibre optic camera inserted through the 
umbilicus is used to directly visualise the passage of dye through the fallopian tubes thereby 
confirming their patency and function. Women who are thought to have comorbidities should be 
offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed and treated at 
the same time. Laparoscopy costs the NHS significantly more than HSG or HyCoSy and carries more 
risk. Costs associated with laparoscopy are in the form of theatre use and staffing, equipment used, 
recovery facilities and a ward bed.  
 
In addition to the tubal investigations mentioned above, it is also necessary to identify whether 
women undergoing these investigations have concurrent genital tract infection before undertaking 
tubal assessment.   Tests to diagnose genital C. trachomatis infections have evolved rapidly and nucleic 
acid amplification tests (NAAT), such as polymerase chain reaction (PCR) are now widely available. 
NAAT has been estimated to have a sensitivity of over 90% and a specificity of 99%, regardless of 
sampling from a cervical swab or by urine specimen.28 A screen for C. trachomatis infection is 
recommended before women undergo any form of uterine instrumentation. 
 
Rationale for this study 
Miscarriage affects one in five pregnancies and little progress has been made in understanding and 
treating this distressing condition.1 C. trachomatis is the most common sexually transmitted infection 
in the UK.2 C. trachomatis infection can have serious health consequences, including fallopian tube 
damage. Untreated C. trachomatis infection and tubal damage have been associated with miscarriage 
and adverse pregnancy outcomes such as preterm birth, low birth weight and stillbirth.4-6 A cohort 
study is needed to establish the prevalence of tubal disease in women with recurrent miscarriages.  
HyCoSy will be performed to identify tubal disease and establish the magnitude of the problem in the 

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recurrent miscarriage population. The prognosis of tubal disease on miscarriage and other obstetric 
outcomes, and the role of medical interventions such as tubal surgery (to treat hydrosalpinx) on 
reducing miscarriage and adverse obstetric outcomes will also be studied.  
Objectives 
1. Establish the prevalence of hydrosalpinx in the recurrent miscarriage population. 
2. Establish the prognosis of women diagnosed with recurrent miscarriage with concurrent hydrosalpinx. 
3. Explore the role of tubal surgery for improving reproductive outcomes in women with recurrent 
miscarriage population and hydrosalpinx. 
Study Design 
This is a prospective observational cohort study. 
Population to be studied 
Potential participants will be approached at the Tommy’s recurrent miscarriage clinic held at the 
Birmingham Women’s Hospital.  
Inclusion criteria 
 
Age 18-45 
 
Women diagnosed with recurrent miscarriage i.e. 2 or more miscarriages 
 
Ability to give informed consent 
Such a wide inclusion criteria will enable a true assessment of the prevalence of hydrosalpinges in the 
recurrent miscarriage population. 
Exclusion criteria 
 
Allergy to contrast media used for Hysterosalpingo-contrast-sonogram 
 
Allergy to sonographic gel used for ultrasound scanning 
 
Anatomical anomaly meaning transvaginal ultrasound scan not possible 
 
Stenosed/occluded cervix meaning contrast media unable to be introduced via cervix 
 
Inability to give informed consent 
 
Pregnant at the time of recruitment 
 
Declined recruitment 
 
Identifying Participants 
Patients will have been given the patient information leaflet prior to their appointment, when they 
are sent their appointment details letter. 
All women presenting to the clinic will be screened for the eligibility criteria by the routine healthcare 
provider. They will then be approached by Dr Jayasish Ghosh or one of the members of the research 
team and offered recruitment into the study.  
Data to be collected and tests to be performed 
 
Genital infection screen – This is required as per national guidance prior to any uterine 
instrumentation to reduce the risk of subsequent pelvic inflammatory disease during 

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Hysterosalpingo-contrast-sonography. The self-taken vulvovaginal swab and one high vaginal 
swab will then be sent to the microbiology laboratory of the Birmingham Women’s Pathology 
department and will undergo testing for active infection causing bacteria for example C. 
Trachomatis, N. Gonorrhoea, C. Albicans or bacterial vaginosis. These tests will be in the form 
of microscopy, culture and sensitivities, polymerase chain reaction and Nugent’s scoring. The 
storage and testing these swabs will be managed in line the Human Tissue Act, 2004.  
 
To establish the first objective of prevalence, recruited patients will be screened with a 
Hysterosalpingo-contrast-sonogram (HyCoSy) for the presence or absence of hydrosalpinges. 
Outcomes to be measured 
 
To establish the second objective of prognosis of women with recurrent miscarriage and 
concurrent hydrosalpinges, pregnancy outcome data will be collected from both groups of 
patients (patients who screen positive and those who screen negative for hydrosalpinges). 
Specifically this will include: 
1. Biochemical pregnancy – a positive pregnancy test either on urine or serum pregnancy 
testing before ultrasound evidence of a gestational sac 
2. Clinical pregnancy – a pregnancy confirmed by evidence of a fetal heartbeat on 
ultrasound scan or using ultrasound parameters (ultrasound visualization of a 
gestational sac, embryonic pole with heartbeat). 
3. Pregnancy loss and at what gestation the pregnancy was lost – if unfortunately the 
patient suffered from a further miscarriage or still birth, the gestation in weeks of the 
loss will be noted 
4. Ectopic pregnancy – if a clinical pregnancy is seen on ultrasound scan but its location 
of implantation has taken place outside the uterine cavity, this is known as an ectopic 
pregnancy. Ectopic pregnancies are usually inside the fallopian tube although rarely 
they can be abdominal, ovarian or cervical.  
5. Live births – if fortunately a patient has a live birth this will be noted.  
 
To explore the role of tubal surgery, the same pregnancy outcomes listed above will be 
collected for the group of patients that were treated by their usual healthcare provider with 
surgery for their hydrosalpinges. 
 
Method of collection of data and outcomes 
 
The genital infection screen will be performed by taking a self-taken vulvovaginal swab and a 
high vaginal swab after written informed consent has been gained. The high vaginal swab will 
be taken by Dr Jayasish Ghosh, a General Medical Council and Royal College of Obstetricians 
and Gynaecologists registered registrar who is fully competent in such a procedure. 
 
The presence or absence of hydrosalpinges will be noted at HyCoSy which will be performed 
after recruitment and written informed consent has been gained. A urine pregnancy test will 
also be performed prior to the HyCoSy to ensure the patient is not unknowingly already 
pregnant which would exclude them from the study. The HyCoSy and pregnancy test will be 
performed by Dr Jayasish Ghosh, a General Medical Council and Royal College of Obstetricians 
and Gynaecologists registered registrar who is fully competent in such a procedure. 
 
The pregnancy outcome data listed above will be collected via a telephone consultation or 
email correspondence, conducted at 6 months and 12 months either post HyCoSy or post 

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treatment. Should the patient not recall all of the information needed, she will be consented 
to examine her hospital patient records. Should the patient have had treatment at a different 
hospital trust, she would also have been consented to collect the specific information needed 
directly from that particular hospital’s patient records.  
Consent to participation and feedback of results 
 
The conduct of this study will be in accordance with the principles of Good Clinical Practice. 
All potential participants will be offered a patient information leaflet as well as a copy of the 
consent form. Participants will be made aware that they can withdraw from the trial at any 
stage and have their information destroyed. 
 
Patients will be informed of the results of their genital infection screen and appropriate 
treatment will be provided as necessary as per Birmingham Women’s Hospital antimicrobial 
prescribing guidelines.  
 
Patients will also be informed if their pregnancy test performed prior to HyCoSy is positive as 
they will no longer be able to take part in the study. 
 
HyCoSy findings will also be shared with the participants at the time of the scan. Any HyCoSy 
findings that may require urgent gynaecological attention will be referred to the on call 
gynaecology team at the Birmingham Women’s Hospital with the patient’s consent. Any other 
ultrasound findings that require non urgent follow up, will be shared with the GP or routine 
healthcare provider, with the patient’s consent. 
Dissemination of study results  
The results of the study in terms of the prevalence of hydrosalpinges in the recurrent miscarriage 
population and the prognosis of women with recurrent miscarriage and concurrent hydrosalpinx will 
be disseminated to all participants via an email newsletter at the conclusion of the study. The results 
of comparing outcomes between patients who were treated for their hydrosalpinges versus those 
who were not, will be also be disseminated to all study participants and those who were not treated 
will be offered discussion about treatment after the conclusion of the study if treatment shows 
significant benefit. 
Withdrawal process 
Participants will be informed that they are able to withdraw from the study at any point without giving 
a reason and without any impact on their care, however, information gathered up until that point may 
be still used in the study. 
Patient Journey 
The patient will be sent the patient information leaflet at the same time as they receive the 
appointment letter thus ensuring sufficient time to read the written information related to the study 
before consent is taken. Written informed consent will be taken by good clinical practice trained 
research midwives or Dr Jayasish Ghosh, a General Medical Council and Royal College of Obstetricians 
and Gynaecologists registered registrar who is fully competent at taking consent and is also good 
clinical practice trained.  
If a patient consents to participation, they will have the swabs performed as detailed in the method 
of collection of data and outcomes section above. If the swabs show an infection this will be treated 

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as per the Birmingham Women’s Hospital microbiology prescribing guidelines. At a subsequent 
appointment they will have a HyCoSy to detect the hydrosalpinges instead of their usual transvaginal 
pelvic ultrasound scan. A HyCoSy, as detailed in the background section above, incorporates a 
transvaginal ultrasound scan but is more detailed due to the use of contrast media to detect tubal and 
uterine pathology which may not be visible on normal transvaginal ultrasound. The result of which 
will be fed back to the patient and their usual clinician. They will then discuss with this clinician any 
treatment that maybe required.  
If a hydrosalpinx is detected they will discuss with their usual clinician whether tubal surgery and what 
type would be appropriate. Surgery would then be carried out in the usual manner by the usual 
clinician. All patients would now be in one of three groups, those with no hydrosalpinx, those with a 
hydrosalpinx who did not have surgical treatment and those with a hydrosalpinx who did have surgical 
treatment of their hydrosalpinx. All three cohorts will then be followed up for 12 months as detailed 
in the method of collection of data and outcome section above. A pictorial representation of the 
patient journey is shown below in the study flow chart section.  
Accrual and Analysis 
Sample Size 
We will attempt to recruit approximately 203 patients. For a prevalence survey in a condition where 
the prevalence is unknown, but it is not expected to be higher than 25% for obtaining a 95% level of 
confidence and precision at 0.05 we have estimated that 184 patients are required. To account for up 
to a 10% level of attrition, 203 patients should be recruited.   
Statistical Analysis 
For the prevalence survey of hydrosalpinx in the recurrent miscarriage population data will be 
presented using descriptive statistics.  We will examine the prevalence data within subgroups created 
from clinical characteristics for example age, body mass index, previous sexually transmitted 
infections to identify high risk groups for hydrosalpinx. 
For the comparison of the cohorts we will report numbers of individuals at each stage of study e.g. 
numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, 
completing follow-up, and analysed. The reasons for non-participation at each stage will be described. 
We will also describe the characteristics of study participants (e.g. demographic, clinical) and potential 
confounders (e.g. age, body mass index.) We will indicate the number of participants with missing 
data for each variable of interest and compute data for missing covariates using maximum likelihood 
estimation. We will summarise follow-up time (e.g. average and total amount) and report numbers of 
outcome events over time for each cohort. We will report unadjusted relative risk estimates and, if 
applicable, confounder-adjusted estimates and their precision (e.g. at the 95% confidence interval). 
We will endeavour to translate estimates of relative risk into absolute risk for a meaningful time 
period. Subgroup analyses will be also performed according to the risk stratification described above.   
Data management and archiving 
The swab results and ultrasound records will be kept in locked surroundings at all times at the 
Birmingham Women’s Hospital NHS Foundation Trust.  A separate log will be kept which connects the 
patient identifiable data with the study allocation number and this will be destroyed at the end of the 
study period. Information will be collected on secured computers and all research team members will 
have had prior training in Good Clinical Practice. 

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All data originating from this research will be kept in secured, locked surroundings in the Academic 
Department of Birmingham Women’s Hospital.  Electronic data will be held on the University of 
Birmingham Network and it will be accessed through University of Birmingham computers. All results, 
records and data will be managed in line with the Data Protection Act, 1998 and the Human Tissue 
Act, 2004.  
Safety reporting (Adverse Events and Serious Adverse 
Events) 
Adverse events (AE) are defined as any untoward medical occurrence in a study participant, which 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavourable and unintended sign (including abnormal laboratory finding), symptom, or disease. 
Occurrence of AEs will be recorded and reported to chief investigator. Any SAE will also be recorded 
in the study notes.  
When an AE has occurred which is suspected to be a potential SAE, the Chief Investigator will assess 
the causality and severity of the AE. If the AE is confirmed as being a SAE, the CI will follow the 
University of Birmingham Standard Operating Procedures for SAE reporting, including reporting to the 
Sponsor. Follow-up of the event will continue until the event is considered resolved by all parties 
involved or a final outcome has been reached. 
Serious breaches 
In the unlikely event that a Serious Breach occurs, standard University of Birmingham procedures and 
SOPs for Serious Breach reporting will be followed. 
Insurance and indemnity 
The University of Birmingham purchases Clinical Trials Cover, which provides automatic cover for all 
Clinical Trials including those where the University accepts responsibility as sponsor, for any harm that 
comes about due to the University’s, or its staff’s negligence in relation to the design or management 
of the trial. In some cases, cover can also be provided in the case of non-negligent harm to participants. 
End of study definition 
Within 90 days of the final endpoint assessment of the final participant the main REC will be notified 
of the study’s end and a summary of the clinical study report will be provided within 12 months of the 
end of the study. The study is expected to last three years. 
Study Oversight and Quality Assurance processes 
The Chief Investigator will oversee the quality of the study, and the study team will allow 
representatives of the Sponsor to monitor the study, including access to source documents as 
requested. 
Funding and Sponsorship  
Study funding is provided by Tommy’s a UK charity that funds research into miscarriage, stillbirth and 
premature birth. Tommy's National Centre for Miscarriage Research is directed from The University 

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of Birmingham by Professor Arri Coomarasamy but jointly hosted by three other UK universities, 
namely Imperial College London and The University of Warwick and is based at four NHS hospitals in 
Birmingham, Coventry and London. The partner institutions work closely with the University of 
Birmingham to ensure synergy and added value, whilst a vibrant programme of joint research 
meetings enables junior and senior colleagues to share disciplinary expertise and research news. The 
centre is seeking to understand why miscarriage happens, if it is likely to happen again, how to prevent 
it, and how to provide appropriate aftercare. 
The University of Birmingham will be sponsoring this study (sponsorship reference number RG_ 17-
150). The University of Birmingham is characterised by a tradition of innovation. Research at the 
University has broken new ground, pushed forward the boundaries of knowledge and made an impact 
on people’s lives. The University was ranked 15th in the UK and 82nd in the world in the QS World 
University Rankings for 2016-17.  

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Study Flow Chart 
Consented to recruitment 
 
Perform genital infection screening 
Routine healthcare provider screens 
patients at recurrent miscarriage clinic 
for eligibility criteria and consents 
patient for discussion with member of 
the research team. 
Research team member formally 
consents patient with consent form for 
recruitment into study and takes genital 
infection screen 
Follow up at 6 and 12 months via 
telephone/ face to face/ email 
consultation and examination of 
patient records 
Follow up at 6 and 12 months via 
telephone/ face to face/ email 
consultation and examination of 
patient records 
Follow up at 6 and 12 months via 
telephone/ face to face/ email 
consultation and examination of 
patient records 

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List of References 
1. Miscarriage Association. Background information, Miscarriage. Available from: 
https://www.miscarriageassociation.org.uk/media-queries/background-information/ 
[Accessed July 13th 2017] 
2. Public Health England. Sexually Transmitted Infections and Chlamydia Screening in England, 
2016. 2017. Available from: 
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/617020/H
ealth_Protection_Report_STIs_NCSP_2017.pdf [Accessed: July 13th 2017] 
3. Mamoun Kassabji, Jerry A. Sims, Lisa Butler, Suheil J. Muasher Reduced pregnancy outcome 
in patients with unilateral or bilateral hydrosalpinx after in vitro fertilization. European 
Journal of Obstetrics & Gynecology and Reproductive Biology. 1994; 56(2): 129-132. 
Available from: http://www.sciencedirect.com/science/article/pii/0028224394902690 
[Accessed July 13th 2017] 
4. Giakoumelou S, Wheelhouse N, Cuschieri K, Entrican G, Howie SE, Horne AW. The role of 
infection in miscarriage. Hum Reprod Update. 2016; 22(1): 116-33. 
doi:10.1093/humupd/dmv041. 
5. Gravett MG, Nelson HP, DeRouen T, Critchlow C, Eschenbach DA, Holmes KK. Independent 
Associations of Bacterial Vaginosis and Chlamydia trachomatis Infection With Adverse 
Pregnancy Outcome. JAMA.1986; 256(14):1899-1903. 
doi:10.1001/jama.1986.03380140069024 
6. Martin DH, Koutsky L, Eschenbach DA, Daling JR, Alexander ER, Benedetti JK, Holmes KK. 
Prematurity and Perinatal Mortality in Pregnancies Complicated by Maternal Chlamydia 
trachomatis Infections. JAMA.1982; 247(11):1585-1588. 
doi:10.1001/jama.1982.03320360035027 
7. NHS Digital. Hospital Maternity Activity 2015-2016. 2016. Available from: 
http://content.digital.nhs.uk/searchcatalogue?productid=23494&q=%22nhs+maternity+stati
stics%22&topics=0%2fHospital+care&sort=Relevance&size=10&page=1#top [Accessed July 
13th 2017] 
8. Ingrid H. Lok, Richard Neugebauer, Psychological morbidity following miscarriage. Best 
Practice & Research Clinical Obstetrics & Gynaecology. 2007; 21(2): 229-247. 
doi:10.1016/j.bpobgyn.2006.11.007 
9. M. Goddijn, N.J. Leschot. Genetic aspects of miscarriage. Best Practice & Research Clinical 
Obstetrics & Gynaecology. 2000; 14(5): 855-865. Available from: 
http://dx.doi.org/10.1053/beog.2000.0124. [Accessed July 13th 2017] 
10. de Braekeleer M, Dao TN. Cytogenetic studies in couples experiencing repeated pregnancy 
losses. Hum Reprod.  1990; 5(5): 519–28. 
11. Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of 
recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod. 1994; 
9(7) :1328–32.  
12. Mary D. Stephenson, Sony Sierra. Reproductive outcomes in recurrent pregnancy loss 
associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod. 
2006; 21(4): 1076-1082. doi: 10.1093/humrep/dei417 

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13. Franssen MTM, Korevaar JC, van der Veen F, Leschot NJ, Bossuyt PMM, Goddijn M. 
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