Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

Association of Female Sexual Dysfunction and Fertility: a cross sectional study.

BACKGROUND: Sexual function plays an essential role in the bio-psychosocial wellbeing and quality of life of women and disturbances in sexual functioning often result in significant distress. Female sexual dysfunction (FSD) and subfertility are common problems affecting approximately 43 and 20% of women respectively. However, despite the high prevalence of both conditions, little has been studied on the effects of subfertility on sexual functioning especially in sub-Saharan Africa. We set out to compare the prevalence of female sexual dysfunction in patients on assessment for sub-fertility and those either seeking or already on fertility control services at a private tertiary teaching hospital in Kenya. METHODS: This was an analytical cross sectional study. Eligible women of reproductive age (18-49 years), attending the gynaecological clinics with complaints of subfertility and those seeking fertility control services were requested to fill a general demographic tool containing personal data and the Female Sexual Function Index (FSFI) questionnaire after informed consent. Prevalence of sexual dysfunction was calculated as a percentage of patients not achieving an overall FSFI score of 26.55. Univariate and multivariate analysis were done to compare clinical variables to delineate the potential association. RESULTS: The prevalence of female sexual dysfunction was 31.2% in the subfertile group and 22.6% in fertility control group. The difference was not statistically significant (p = 0.187). The mean domain and overall female sexual function scores were lower in the subfertile group than the fertility control group though this was not statistically significant. The most prevalent sexual domain dysfunctions in both the subfertility and fertility control groups were desire and arousal while the least in both groups was satisfaction dysfunction. Subfertility type was not associated with sexual dysfunction. Higher education attainment was protective of female sexual dysfunction in the subfertile group while use of hormonal contraception was associated with greater sexual impairment in the fertility control group. On logistic regression analysis, higher maternal age and alcohol use appeared to be protective against sexual dysfunction. CONCLUSION: The present study demonstrated no association between the fertility status and the prevalence female sexual dysfunction. Subfertility type was not associated with sexual dysfunction. Education level and hormonal contraception use were associated with female sexual dysfunction in the subfertile and fertility control groups respectively while alcohol use and higher maternal age appeared to be protective against sexual dysfunction.

Empowering HIV-infected women in low-resource settings: A pilot study evaluating a patient-centered HIV prevention strategy for reproduction in Kisumu, Kenya.

BACKGROUND: Female positive/male negative HIV-serodiscordant couples express a desire for children and may engage in condomless sex to become pregnant. Current guidelines recommend antiretroviral treatment in HIV-serodiscordant couples, yet HIV RNA viral suppression may not be routinely assessed or guaranteed and pre-exposure prophylaxis may not be readily available. Therefore, options for becoming pregnant while limiting HIV transmission should be offered and accessible to HIV-affected couples desiring children. METHODS: A prospective pilot study of female positive/male negative HIV-serodiscordant couples desiring children was conducted to evaluate the acceptability, feasibility, and effectiveness of timed vaginal insemination. Eligible women were 18-34 years with regular menses. Prior to timed vaginal insemination, couples were observed for two months, and tested and treated for sexually transmitted infections. Timed vaginal insemination was performed for up to six menstrual cycles. A fertility evaluation and HIV RNA viral load assessment was offered to couples who did not become pregnant. FINDINGS: Forty female positive/male negative HIV-serodiscordant couples were enrolled; 17 (42.5%) exited prior to timed vaginal insemination. Twenty-three couples (57.5%) were introduced to timed vaginal insemination; eight (34.8%) achieved pregnancy, and six live births resulted without a case of HIV transmission. Seven couples completed a fertility evaluation. Four women had no demonstrable tubal patency bilaterally; one male partner had decreased sperm motility. Five women had unilateral/bilateral tubal patency; and seven women had an HIV RNA viral load (≥ 400 copies/mL). CONCLUSION: Timed vaginal insemination is an acceptable, feasible, and effective method for attempting pregnancy. Given the desire for children and inadequate viral suppression, interventions to support safely becoming pregnant should be integrated into HIV prevention programs.

Factors associated with a positive depression screen after a miscarriage.

INTRODUCTION: Miscarriages are a common pregnancy complication and positive depression screen after a miscarriage has been shown to be high in our population. Various factors are associated with an increased risk of developing depression after a miscarriage. However, these factors vary across populations studied with no studies existing in our region. We set out to determine the factors associated with a positive depression screen among post-miscarriage women at the Aga Khan University hospital, Nairobi. METHODS: Patients were recruited at the 2 weeks clinic review after a miscarriage in the gynaecological clinics. They were screened using the Edinburgh postnatal depression scale for depression after a miscarriage. Analysis was done using Univariate and multivariate analysis to compare clinical variables between the screen - positive and screen - negative women in order to delineate the potential pattern of association between the two among the study subjects. RESULTS: Positive depression screen was detected in 34.1% of the patients recruited. Univariate analysis revealed that education level (p = 0.039) and mode of conception (p = 0.005) impacted on the outcome of the depression screen. In multivariate analysis, multiple factors impacted on the depression screen and these included: age (p = 0.009), education level (p = 0.001), gestation at miscarriage (p = 0.04), marital status (p = 0.043), prior miscarriage (p = 0.011) and mode of conception (p = 0.03). CONCLUSION: Factors that seem to impact on the positive depression screen include a younger age, low education level, an older gestational age at miscarriage, being single, an assisted mode of conception and prior miscarriage. These factors may be used to triage women after a miscarriage in order to pick up those who may screen positive for depression after a miscarriage.

Prevalence of positive depression screen among post miscarriage women- A cross sectional study.

BACKGROUND: Miscarriages are a common pregnancy complication affecting about 10-15% of pregnancies. Miscarriages may be associated with a myriad of psychiatric morbidity at various timelines after the event. Depression has been shown to affect about 10-20% of all women following a miscarriage. However, no data exists in the local setting informing on the prevalence of post-miscarriage depression. We set out to determine the prevalence of positive depression screen among women who have experienced a miscarriage at the Aga Khan University hospital, Nairobi. METHODS: The study was cross-sectional in design. Patients who had a miscarriage were recruited at the post-miscarriage clinic review at the gynecology clinics at Aga Khan University Hospital, Nairobi. The Edinburgh postpartum depression scale was used to screen for depression in the patients. Prevalence was calculated from the percentage of patients achieving the cut -off score of 13 over the total number of patients. RESULTS: A total of 182 patients were recruited for the study. The prevalence of positive depression screen was 34.1% since 62 of the 182 patients had a positive depression screen. Moreover, of the patients who had a positive depression screen, 21(33.1%) had thoughts of self-harm. CONCLUSION: A positive depression screen is present in 34.1% of women in our population two weeks after a miscarriage. Thoughts of self-harm are present in about a third of these women (33.1%) hence pointing out the importance of screening these women using the EPDS after a miscarriage.

Endometrial tuberculosis compounding polycystic ovary syndrome in a subfertile woman: a case report.

BACKGROUND: Asymptomatic female genital tuberculosis can impair tubal and endometrial function and later present as subfertility. A majority of the patients with genital tuberculosis in endemic regions present with subfertility and the delay in presentation, coupled with the potential the disease has in mimicking other gynecological conditions, renders it elusive. In addition to the challenge of diagnosing genital tuberculosis, fertility outcomes after treatment are not impressive. This is particularly so in the background of another confounding subfertility factor to which interventional efforts may initially be directed, at the expense of undiagnosed genital tuberculosis. We therefore present a case of subfertility due to endometrial tuberculosis, but confounded by other subfertility factors notably polycystic ovary syndrome. To the best of our knowledge this case report is the first of its kind in the literature. CASE PRESENTATION: This is a case report of a 42-year-old woman of African descent who presented to our fertility clinic with a 10-year history of primary subfertility and amenorrhea of 6 years duration. She was a nurse in a medical ward and had no prior history of tuberculosis. She had undergone a diagnostic laparoscopy 8 years prior which demonstrated dense pelvic adhesions and an impression of tubal factor subfertility was made. At presentation, her gonadal hormone profile and pelvic ultrasound were consistent with polycystic ovary syndrome. A negative response to a progesterone challenge test prompted a hysteroscopic evaluation which revealed endometrial atrophy. Endometrial biopsies confirmed histological features consistent with tuberculosis. Normal endometrial function was not restored despite adequate treatment and her options were limited to surrogacy or adoption. CONCLUSIONS: Genital tuberculosis is elusive in presentation and clinicians should consider it in patients with amenorrhea and/or tubal disease from tuberculosis-endemic regions. Due to the attendant high cost of fertility treatment and associated poor fertility outcomes, it is prudent to explore options to diagnose it early. A routine endometrial biopsy in a patient with subfertility in a tuberculosis-endemic area would be pragmatic. An alternative algorithm in management would be risk stratification prior to endometrial biopsy.

Assisted reproduction services provision in a developing country: time to act?

OBJECTIVE: To conduct a survey in a developing country to gauge the extent of subfertility and the current state of assisted reproductive technology (ART) service provision and explore factors limiting access to ART services. DESIGN: Cross-sectional online survey. SETTING: The study was co-ordinated at the Aga Khan University Hospital, Nairobi, Kenya. SUBJECT(S): One hundred eighty-eight obstetricians and gynecologists registered with the Kenya Obstetrics and Gynecology Society were invited to complete the survey. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): A total of 47 responses (25%) were received after completion of the survey. The overall rate of subfertility was 26.1% among the gynecology consultations, with 50% attributed to tubal factors and 15% due to male factors. Assisted reproductive service provision (IVF/intracytoplasmic sperm injection) was severely limited to only three units, despite the reported high rate of tubal disease. The high cost of treatment, patients' limited finances, and limited local services were almost universally cited as the main barriers to ART services in Kenya. CONCLUSION(S): The demand for ART in developing countries is not in doubt. Simplified, less costly, and more accessible ART approaches need to be considered in developing countries, even though the benefits and outcomes of such approaches may not be apparent immediately.

Multiple bowel perforations requiring extensive bowel resection and hysterectomy after microwave endometrial ablation.

Heavy menstrual bleeding, or menorrhagia, is a primary cause of morbidity in women. Herein, we present the case of a 41-year-old woman who underwent day-surgery endometrial microwave ablation because of dysfunctional uterine bleeding. She had undergone previous laparoscopic sterilization, and had no other risk factors except for a retroverted uterus. The procedure was performed without any documented difficulties. The patient was readmitted the following day with clinical signs of acute abdomen. Emergency laparotomy revealed a large perforation on the anterior uterine wall, full-thickness burns in the distal ileum, and multiple ischemic areas in the ileum, cecum, and ascending colon secondary to microwave burns. A right hemicolectomy was required, with extended ileal resection and subtotal hysterectomy with ovarian conservation. Although microwave endometrial therapy seems to offer many advantages, in particular in terms of efficiency and technique, complications occur, and extensive safety measures must be implemented to prevent adverse effects such as occurred in this patient.