Global epidemiology of Neisseria gonorrhoeae in infertile populations: protocol for a systematic review.

INTRODUCTION: A key target of the WHO's 'Global Health Sector Strategy on sexually transmitted infections, 2016-2021' is achieving 90% reduction in Neisseria gonorrhoeae (gonorrhoea for short) incidence globally by 2030. Though untreated, gonorrhoea has been linked to infertility, the epidemiology of this infection in infertile populations remains poorly understood and somewhat a neglected area of reproductive health. Our proposed systematic review aims to fill this gap by characterising comprehensively gonorrhoea infection in infertile populations globally. METHODS AND ANALYSIS: All available studies of gonorrhoea infection in infertile populations, including infertility clinic attendees, will be systematically reviewed informed by Cochrane Collaboration guidelines. Findings will be reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources will be searched using broad index terms exploded to cover all subheadings and free text terms with no language or year restriction. Any epidemiological measure in infertile populations based on primary data will be eligible for inclusion. Measures based on different assay types will be extracted as separate studies for different analyses. Only one biospecimen type per assay type will be considered based on a predefined priority order. Samples including fewer than 10 participants or assessing infection in the upper genital tract will be excluded. Quality assessments will be conducted for all measures included in the review. Meta-analyses will be implemented using DerSimonian-Laird random effect models to estimate the mean prevalence of gonorrhoea in infertile populations globally, and stratified by WHO region, assay type, sex, infertility type, infertility diagnosis, among other factors. Detailed heterogeneity assessment will be performed, and potential sources of between-study heterogeneity will be explored using meta-regression. Review will be conducted from 26 March 2018 to 28 July 2019. ETHICS AND DISSEMINATION: An institutional review board clearance is not required as all data are publicly available. The findings will be disseminated through a peer-reviewed publication and international scientific meetings/workshops with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42018102934

Global epidemiology of Neisseria gonorrhoeae in infertile populations: systematic review, meta-analysis and metaregression.

OBJECTIVE: To provide an in-depth systematic assessment of the global epidemiology of gonorrhoea infection in infertile populations. METHODS: A systematic literature review was conducted up to 29 April 2019 on international databases and WHO regional databases, and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All prevalence measures of gonorrhoea infection among infertile populations, based on primary data, qualified for inclusion. Infertile populations were broadly defined to encompass women/men undergoing infertility evaluation or treatment (infertility clinic attendees and partners). Pooled mean prevalence by relevant strata was estimated using random-effects meta-analysis. Associations with prevalence and sources of heterogeneity were explored using metaregression. Risk of bias was assessed using four quality domains. FINDINGS: A total of 147 gonorrhoea prevalence studies were identified from 56 countries. The pooled mean prevalence of current gonorrhoea infection was estimated globally at 2.2% (95% CI 1.3% to 3.2%), with the highest prevalence in Africa at 5.0% (95% CI 1.9% to 9.3%). The mean prevalence was higher for populations with tubal factor infertility (3.6%, 95% CI 0.9%-7.7%) and mixed cause and unexplained infertility (3.6%, 95% CI 0.0% to 11.6%) compared with other diagnoses, such as ovarian and non-tubal infertility (0.1%, 95% CI 0.0% to 0.8%), and for secondary (2.5%, 95% CI 0.2% to 6.5%) compared with primary (0.5%, 95% CI 0.0% to 1.7%) infertility. Metaregression identified evidence of variations in prevalence by region and by infertility diagnosis, higher prevalence in women than men and a small-study effect. There was a trend of declining prevalence by about 3% per year over the last four decades (OR=0.97, 95% CI 0.95 to 0.99). CONCLUSIONS: Gonorrhoea prevalence in infertile populations is several folds higher than that in the general population, with even higher prevalence in women with tubal factor infertility and in individuals with secondary infertility. These findings support the potential role of gonorrhoea in infertility and suggest that some infertility is possibly preventable by controlling gonorrhoea transmission. PROSPERO REGISTRATION NUMBER: CRD42018102934

Commentary: Obesity and Weight Gain in Pregnancy and Postpartum: an Evidence Review of Lifestyle Interventions to Inform Maternal and Child Health Policies

We read with interest the recent review published in Frontiers in Endocrinology that was focused on obesity and weight gain in pregnancy and postpartum. The review of systematic reviews and meta-analyses, investigating the effects of lifestyle interventions on gestational weight gain (GWG) and postpartum weight retention (PPWR), provides evidence showing that lifestyle interventions can reduce excess weight gain and associated risk factors. We agree unconditionally that the burden of maternal and childhood obesity needs to be reduced urgently.Funding for this research has been provided from the Australian Government's Medical Research Future Fund (MRFF)

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

Abstract 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 INTEREST(S) 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

The cost effective IVF strategies in assisted reproduction technology programmes (art)

Thesis (PhD)--Stellenbosch University, 2016.CHAPTER I Understanding the physiology of oocyte(s) recruited, selected and retrieved in a cycle of assisted reproductive technology (ART) is fundamentally important towards the development of the embryo with great potential for conception and live birth. This is discussed in detail. More important is the interpretation and utilization of the scientific evidence in this chapter to explore less expensive methods of optimizing oocyte quality in mild ovarian stimulation in vitro fertilization (IVF). CHAPTER II Clomiphene citrate (CC) is an inexpensive and safe drug that can be used alone or in combination with gonadotropins in IVF. Clinical outcomes in different IVF treatments using CC were reviewed and discussed in detail. The major concern regarding CC in ART is the risk of premature luteinizing hormone (LH) surge with subsequent detrimental effect on the oocyte quality. This issue is discussed with outlined strategies (inexpensive) to minimize the risk. CHAPTER III The effective methods to prevent premature LH surge in ART include gonadotropin releasing hormone antagonists (GnRHa) and gonadotropin releasing hormone agonists (GnRH). But these methods are expensive and unaffordable in resourcelimited countries. We therefore performed a randomised controlled trial to evaluate a simple method of prolonged usage of CC as a strategy to prevent premature LH surge in ART treatment. The protocol is described in detail. The trial showed that prolonged usage of CC did not suppress premature LH surge in mild ovarian stimulation ART. But it motivated us to explore other inexpensive strategies for lowering the risk of premature LH surge such as pre-treatment with oral contraceptives, the use of tamoxifen and the use of progesterone during ovarian stimulation. CHAPTER IV Stellenbosch University https://scholar.sun.ac.za In our endeavour to explore strategies to make ART accessible, a public-private interaction (PPI) model is described in detail, highlighting different areas where the cost of IVF can be significantly reduced. They include infrastructure and equipment, personnel, ovarian stimulation protocol (detailed in Chapters II and III) and modification in the laboratory routine regarding oocyte retrieval. CHAPTER V This meta-analysis compared mild ovarian stimulation IVF with conventional treatment in order to counsel patients appropriately. The study showed significantly better outcomes in terms of live birth rates and ongoing pregnancy rates per started cycle, all in favour of conventional stimulation IVF, which therefore currently remains the preferred treatment of choice. CHAPTER VI Understanding the physiology of folliculogenesis has made it possible to integrate mild ovarian stimulation in our unit ART programme at a low cost. (Chapter I) Reassuring clinical outcomes of CC in ART also motivated the unit to maintain low cost of treatment with the use of safe and effective medication. (Chapter II) The finding that prolonged usage of CC does not reduce the risk of premature LH surge has also allowed the unit to maintain the old protocol of 5 days’ use, but motivated us to explore other inexpensive methods. (Chapter III) The PPI model certainly managed to make ART treatment accessible to subfertile couples that would have never had a chance to be proud parents. (Chapter IV) Because this model is feasible and can be implemented at a reasonably low cost, it presents a viable option to make ART accessible in resource-limited countries.HOOFSTUK I Dit is uiters belangrik om die fisiologie van oosiet(e) werwing, seleksie en onttrekking in ‘n geassisteerde reproduktiewe tegnologie (ART) siklus te verstaan om ‘n embrio met groot potensiaal vir konsepsie en lewendige geboorte te ontwikkel. Dit word in meer detail bespreek. Meer belangrik is die interpretasie en gebruik van wetenskaplike bewyse in hierdie hoofstuk om goedkoper metodes te ondersoek om oosiet kwaliteit met matige ovariële stimulasie in vitro bevrugting (IVB) te verhoog. HOOFSTUK II Klomifeen sitraat (CC) is ‘n goedkoop en veilige middel wat alleen of in kombinasie met gonadotropiene in IVB gebruik kan word. Kliniese uitkomste in verskillende IVB behandelings met CC is ondersoek en in detail bespreek. Die grootste bekommernis rakende CC in ART is die risiko van voortydige LH styging met daaropvolgende nadelige invloed op die oosiet kwaliteit. Dit word bespreek met ‘n verduideliking van strategieë (goedkoop) om die risiko te verminder. HOOFSTUK III Effektiewe metodes om voortydige LH styging in ART te voorkom sluit gonadotropien vrystellende hormoon antagoniste (GnRHa) en gonadotropien vrystellende hormoon agoniste (GnRH) in. Hierdie metodes is egter duur en onbekostigbaar in lande met beperkte hulpbronne. Ons het dus ‘n gerandomiseerde gekontroleerde studie uitgevoer om ‘n eenvoudige metode van verlengde gebruik van CC te ondersoek as ‘n strategie om voortydige LH oplewing in ART behandeling te voorkom. Die protokol is in detail bespreek. Die studie het bevind dat langdurige gebruik van CC nie voortydige LH styging met matige ovariële stimulasie ART onderdruk het nie. Dit het ons egter motiveer om na ander goedkoop maniere te kyk om die risiko van voortydige LH oplewing te verminder, soos vooraf behandeling met orale voorbehoedmiddels, die gebruik van tamoksifeen en die gebruik van progesteroon gedurende ovariële stimulasie. HOOFSTUK IV In ons poging om metodes te ondersoek om ART toeganklik te maak, word die publieke-privaat interaksie (PPI) model breedvoerig beskryf met die klem op verskillende areas waar die koste van IVF aansienlik verminder kan word. Dit sluit in infrastruktuur and toerusting, personeel, ovariële stimulasie protokol (verduidelik in Hoofstukke II en III) en aanpassing van laboratorium roetine betreffende die onttrekking van oosiete. HOOFSTUK V Hierdie meta-analiese het matige stimulasie IVF met gebruiklike behandeling vergelyk sodat pasiënte deeglik ingelig kon word. Die studie het merkbaar beter uitkomste in terme van lewendgebore syfers en voortgaande geboorte syfers per aanvang siklus, almal ten gunste van gebruiklike stimulasie, getoon wat tans die behandeling van keuse bly. HOOFSTUK VI Om die fisiologie van follikulogenese te verstaan het dit moontlik gemaak om matige ovariële stimulasie in ons eenheid se ART program te integreer teen ‘n lae koste.(Hoofstuk I) Gerusstellende kliniese uitkomste van CC in ART het ook die eenheid motiveer om ‘n laekoste behandeling te handhaaf met die gebruik van veilige en effektiewe medikasie. (Hoofstuk II) Die bevindinge dat langdurige gebruik van CC nie die risiko vir voortydige LH styging verminder nie het ons eenheid in staat gestel om ‘n ou protokol van 5 dae gebruik te handhaaf, maar ons gemotiveer om ander goedkoop metodes te ondersoek. (Hoofstuk III) Die PPI model het beslis ART behandeling toeganklik gemaak vir subfertiele egpare wat geen kans sou hê om trotse ouers te word nie. (Hoofstuk IV) Omdat hierdie model haalbaar is en dit uitgevoer kan word teen ‘n redelike lae koste, skep dit ‘n lewensvatbare opsie om ART toeganklik te maak in lande met beperkte hulpbronne.Doctora

Estimating the government public economic benefits attributed to investing in assisted reproductive technology: a South African case study: Fiscal analysis of IVF in South Africa

Limited resources and high treatment costs are arguments often used in many public health systems in low- and middle-income countries to justify providing limited treatments for people with infertility. In this analysis, we apply a government public economic perspective to evaluate public subsidy for in-vitro fertilization (IVF) in South Africa. A fiscal model was developed that considered lifetime direct and indirect taxes paid and government transfers received by a child conceived by IVF. The model was constructed from public data sources and was adjusted for mortality, age-specific educational costs, participation in the informal economy, proportions of persons receiving social grants, and health costs. Based on current proportions of individuals receiving social grants and average payments, including education and health costs, we estimate each citizen will receive ZAR513,165 (USD35,587) in transfers over their lifetime. Based on inflated age-specific earnings, we estimate lifetime direct and indirect taxes paid per citizen of ZAR452,869 (USD31,405) and ZAR494,521 (USD34,294), respectively, which also includes adjustments for the proportions of persons participating in the informal economy. The lifetime net tax after deducting transfers was estimated to be ZAR434,225 (USD31,112) per person. Based on the average IVF investment cost needed to achieve one live birth, the fiscal return on investment (ROI) for the South African Government is 5.64. Varying the discount rate from 4% to 7%, the ROI ranged from 9.54 to 1.53, respectively. Positive economic benefits can emanate from public financing of IVF. The fiscal analytic framework described here can be a useful approach for health services to evaluate future public economic benefits

Should home-based ovulation predictor kits be offered as an additional approach for fertility management for women and couples desiring pregnancy? a systematic review and meta-analysis

CITATION: Yeh, P. T., et al. 2019. Should home-based ovulation predictor kits be offered as an additional approach for fertility management for women and couples desiring pregnancy? a systematic review and meta-analysis. BMJ Global Health, 4(2):4:e001403, doi:10.1136/bmjgh-2019-001403.The original publication is available at https://gh.bmj.comENGLISH ABSTRACT: Introduction to inform the WHO Guideline on self-care interventions, we conducted a systematic review of the impact of ovulation predictor kits (OPKs) on time-topregnancy, pregnancy, live birth, stress/anxiety, social harms/adverse events and values/preferences. Methods Included studies had to compare women desiring pregnancy who managed their fertility with and without OPKs, measure an outcome of interest and be published in a peer-reviewed journal. We searched for studies on PubMed, CINAHL, LILACS and EMBASE through November 2018. We assessed risk of bias assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for observational studies, and conducted meta-analysis using random effects models to generate pooled estimates of relative risk (RR). Results Four studies (three RCTs and one observational study) including 1487 participants, all in high-income countries, were included. Quality of evidence was low. Two RCTs found no difference in time-to-pregnancy. All studies reported pregnancy rate, with mixed results: one RCT from the 1990s among couples with unexplained or male-factor infertility found no difference in clinical pregnancy rate (RR: 1.09, 95% CI 0.51 to 2.32); two more recent RCTs found higher self-reported pregnancy rates among OPK users (pooled RR: 1.40, 95% CI 1.08 to 1.80). A small observational study found higher rates of pregnancy with lab testing versus OPKs among women using donor insemination services. One RCT found no increase in stress/anxiety after two menstrual cycles using OPKs, besides a decline in positive affect. No studies measured live birth or social harms/adverse events. Six studies presented end-users’ values/preferences, with almost all women reporting feeling satisfied, comfortable and confident using OPKs. Conclusion A small evidence base, from high-income countries and with high risk of bias, suggests that homebased use of OPKs may improve fertility management when attempting to become pregnant with no meaningful increase in stress/anxiety and with high user acceptability.https://gh.bmj.com/content/4/2/e001403Publisher's versio

A new approach to tubal re-anastomosis in South Africa

The original publication is available at http://www.sajog.org.za/index.php/SAJOG/article/view/369Contraception by means of fallopian tube sterilisation is the most common method used worldwide, and it is estimated that on average 138 million women of reproductive age are sterilised globally each year. Several studies have indicated that the incidence of tubal re-anastomosis in previously sterilised women is 1 - 2%.Publishers' Versio