Study protocol for two randomised controlled trials evaluating the effects of Cerclage in the reduction of extreme preterm birth and perinatal mortality in twin pregnancies with a short cervix or dilatation: the TWIN Cerclage studies.

INTRODUCTION: Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage. METHODS AND ANALYSIS: We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05968794.

Prognosis-based management of unexplained infertility-why not?

Up to a half of couples seeking medical assistance for infertility are diagnosed with unexplained infertility, characterized by normal ovulation, tubal patency, and semen analysis results. This condition presents a challenge in determining the optimal treatment approach. Available treatments include IUI and IVF, but guidelines vary on when to offer each. Prognosis-based management is identified as a research priority, and various prediction models have been developed to guide treatment decisions. Prognostic factors include female age, duration of subfertility, and sperm parameters, among others. Prognosis-based strategies can enhance cost-effectiveness, safety, and patient outcomes, offering less invasive options to those with good prognoses and more aggressive interventions to those with poor prognoses. However, there is a gap between research evidence and its clinical application. In this article, we discuss the application of prognosis-based management in the context of unexplained infertility, highlighting its potential to improve clinical decision-making and patient outcomes.

Concerns about data integrity across 263 papers by one author.

OBJECTIVE: Comprehensive investigation of published work by authors suspected of academic misconduct can reveal further concerns. We aimed to test for data integrity concerns in papers published by an author with eight retracted articles. STUDY DESIGN: We investigated the integrity of all papers reporting on prospective clinical studies by this author. We assessed the feasibility of study methods, baseline characteristics, and outcomes. We plotted the author's clinical research activity over time. We conducted pairwise comparisons of text, tables, and figures to identify duplicate publications, and checked for consistency between conference abstracts, interim analyses, trial registrations, and final papers. Where indicated, we recalculated p-values from the reported summary statistics. RESULTS: We identified 263 papers claiming to have enrolled 74,667 participants between January 2009 and July 2022, 190 (72%) of which reported on studies that recruited from the Assiut Women's Health Hospital in Assiut, Egypt. The number of active studies per month was greatest between 2016 and 2019, with 88 ongoing studies in May 2017. We found evidence of data integrity concerns in 130 (49%) papers, 43 (33%) of which contained concerns sufficient to suggest that they could not be based on data reliably collected from human participants. CONCLUSION: Our investigation finds evidence of widespread integrity concerns in the collected work of one author. We recommend that the involved journals collaborate in a formal investigation.

Does growth hormone supplementation of in vitro fertilization/intracytoplasmic sperm injection improve cumulative live birth rates in women with poor embryonic development in the previous cycle?

BACKGROUND: Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. METHODS: This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. RESULTS: After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1-1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2-3.3). CONCLUSIONS: Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

A historical narrative review through the field of tocolysis in threatened preterm birth.

Preterm birth presents a significant challenge in clinical obstetrics, requiring effective strategies to reduce associated mortality and morbidity risks. Tocolytic drugs, aimed at inhibiting uterine contractions, are a key aspect of addressing this challenge. Despite extensive research over many years, determining the most effective tocolytic agents remains a complex task, prompting better understanding of the underlying mechanisms of spontaneous preterm birth and recording meaningful outcome measures. This paper provides a comprehensive review of various obsolete and current tocolytic drug regimens that were instituted over the past century, examining both historical contexts and contemporary challenges in their development and adoption. The examination of historical debates and advancements highlights the complexity of introducing new therapies. While the search for effective tocolytics continues, questions arise regarding their actual benefits in obstetric care and the necessity for ongoing exploration. The presence of methodological limitations in current research emphasizes the importance of well-designed randomized controlled trials with robust endpoints and extended follow-up periods.In response to these complexities, the consideration of shifting towards prevention strategies aimed at addressing the root causes of preterm labor becomes more and more evident. This potential shift may offer a more effective approach than relying solely on tocolytics to delay labor initiation.Ultimately, effectively managing threatened preterm birth necessitates ongoing investigation, innovation, and a willingness to reassess strategies in pursuit of optimal outcomes for mothers, neonates, and long-term child health.

Data integrity of 14 randomised controlled trials.

BACKGROUND: A review of the literature on iron treatments for iron-deficient anaemia in pregnancy indicated duplication of baseline and outcome tables in two separate randomised controlled trials (RCTs) that share only a single author. AIM: To assess the integrity of randomised clinical trials from Dr A.M. Darwish, Assiut University, Egypt. DESIGN: Assessment of Research Integrity. METHODS: We tabulated the characteristics of studies, compared baseline and outcome tables between articles and looked for implausible findings. We used the distribution of baseline p-values to assess whether the summary statistics of baseline characteristics were consistent with properly conducted randomisation. RESULTS: We identified 14 RCTs (1,405 participants) published between October 2004 and September 2019. Two pairs of studies showed considerable similarities in baseline characteristics, while another pair of studies was plagiarized. The analysis of baseline p-values indicated a low probability that all the studies featured randomised treatment allocation. CONCLUSION: Our analysis of the RCTs of Dr Darwish suggests possible integrity problems. We recommend a critical investigation of the studies that have not been retracted. Until that has been completed, these studies should not be used to inform clinical practice.

A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Can serum progesterone concentration direct a fresh or freeze-all transfer strategy in the first in vitro fertilisation cycle?

PURPOSE: To examine the interaction between serum progesterone concentration on the trigger day and choice of freeze-all and fresh transfer strategies on live birth in an unselected population as well as in patients over 35 years old. METHODS: We performed a retrospective cohort study of 26,661 patients commencing their first IVF cycle in a large fertility centre between 2015 and 2019, including 4687 patients over 35 years old. We performed a multivariable fractional polynomial interaction analysis within a logistic regression model to investigate the interaction between serum progesterone concentration and the choice of freeze-all or fresh transfer strategy following the first transfer. RESULTS: 15,539 patients underwent a fresh embryo transfer and 11,122 underwent a freeze-all strategy in their first IVF cycle. The freeze-all group had a higher live birth rate compared to the fresh group (43.9% vs 40.3%). After adjusting for confounding factors, there was a positive interaction between serum progesterone concentrations and the choice of a freeze-all versus fresh embryo transfer on live birth (p for interaction 0.0001), with a larger magnitude of effect when progesterone concentration was higher. Such an interaction was also observed in patients over 35 years old (p for interaction 0.01), but the treatment effect curve over progesterone concentrations was almost flat. CONCLUSIONS: In an unselected population, frozen transfer is associated with greater chances of live birth, especially in patients with higher serum progesterone concentration. In patients over 35 years old, the benefit of a freeze-all policy appears small across all serum progesterone concentrations.

VaNoLaH trial: a study protocol-a multinational randomised controlled trial including two identical substudies comparing vaginal versus vNOTES (vaginal natural orifice transluminal surgery) hysterectomy or laparoscopic versus vNOTES hysterectomy.

INTRODUCTION: Hysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with abdominal hysterectomy. Hysterectomy by vaginal natural orifice transluminal endoscopic surgery (vNOTES) is the latest innovation. It combines the vaginal approach and endoscopy via the vagina. Large pragmatic randomised controlled trials (RCTs) are lacking comparing outcomes after vNOTES, vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH). METHODS: Multicentre pragmatic RCT aiming to recruit 1000 women aged 18-75 years undergoing hysterectomy for benign disease. The RCT includes two identical substudies (groups A and B). If VH is considered safe and feasible, the patient will be randomised within group A (VH vs vNOTES). If VH is not considered safe or feasible, patients will be randomised within group B (LH vs vNOTES). ANALYSIS: Primary outcome is the proportion of women leaving the hospital within 12 hours after surgery. Secondary outcomes are hospitalisation time, conversion rates, duration of the surgical procedure, intraoperative complications, postoperative complications and readmission. ETHICS AND DISSEMINATION: The Ethical Board Committee at Imelda Hospital, Bonheiden, Belgium, has approved the research protocol 230704 (principal investigator). Before including patients, all centres will require local or national ethical approval. The results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05971875.

"Hypertension in Pregnancy Intervention Trial At Term" and "Disproportionate Intrauterine Growth Intervention Trial At Term" Studies.

In 2003, in the context of a national research funding program in which obstetric research was prioritized, several perinatal centers took the initiative to jointly submit a number of applications to the subsidy programs of Effectiveness Research and Prevention of ZonMw. This has led to the funding of the Obstetric Consortium with several projects, including the "Hypertension in Pregnancy Intervention Trial At Term" and the "Disproportionate Intrauterine Growth Intervention Trial At Term" studies. The studies showed that induction of labor for hypertension and growth restriction at term was the appropriate management. Subsequent implementation improved maternal and perinatal outcomes.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. OBJECTIVES: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. SEARCH STRATEGY: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. DATA COLLECTION AND ANALYSIS: An individual participant data meta-analysis was carried out. MAIN RESULTS: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

The use of intrapartum ultrasound in operative vaginal birth: a retrospective cohort study.

BACKGROUND: Poor outcomes from operative vaginal birth have been associated with failure to recognize malposition, breakdown in interdisciplinary communication, and deviation from accepted guidelines. We recently implemented a safety bundle including routine intrapartum ultrasound and a structured time-out and procedural checklist aiming to reduce maternal and perinatal morbidity from operative vaginal birth. OBJECTIVE: This study aimed to compare births where intrapartum ultrasound was used and those where it was not used during a safety bundle implementation period at Monash Health. STUDY DESIGN: We performed a retrospective cohort study at Monash Health during the transitional phase of implementing an operative vaginal birth safety bundle. We studied all women with operative vaginal birth and fully dilated cesarean delivery with a singleton cephalic term fetus. We compared births for which intrapartum ultrasound was used and those for which it was not. The primary outcome was neonates delivered in an unexpected position. Neonatal and maternal morbidity were also assessed, including a neonatal composite of Apgar score <7 at 5 minutes, cord lactate >8 mmol/L, need for resuscitation, significant birth trauma, or neonatal intensive care unit admission. To control for confounding by indication, we estimated propensity scores for the probability of using intrapartum ultrasound for each case based on maternal and labor characteristics, and adjusted the effect estimates for the propensity scores using multivariable logistic regression models. RESULTS: From August 2022 to July 2023, there were 1205 operative vaginal births or fully dilated cesarean deliveries at Monash Health, including 743 (61.7%) forceps, 346 (28.7%) vacuum, and 116 (9.6%) fully dilated cesarean deliveries. Over this time, we observed increased uptake of intrapartum ultrasound from 26% in August 2022 to 60% (P<.001) in July 2023, of the time-out from 21% to 58% (P<.001), and the checklist from 33% to 80% (P<.001) of operative second-stage births. Among the births where intrapartum ultrasound was used (n=509), compared with those where it was not (n=696), there were significantly more forceps births (67% vs 58%; adjusted odds ratio, 1.35; 95% confidence interval, 1.05-1.74; P=.021) and a reduction in vacuum births (24% vs 32%; adjusted odds ratio, 0.77; 95% confidence interval, 0.58-1.01; P=.059). There were no significant differences in fully dilated cesarean delivery or maternal morbidity. Intrapartum ultrasound use was associated with significantly fewer infants being delivered in an unexpected position (0.2% vs 2.2%; adjusted odds ratio, 0.08; 95% confidence interval, 0.00-0.44; P=.019) and a significant reduction in composite neonatal morbidity (22% vs 25%; adjusted odds ratio, 0.73; 95% confidence interval, 0.54-0.97; P=.031). CONCLUSION: During the implementation of a safety bundle, the use of ultrasound before operative vaginal birth was associated with fewer infants delivered in an unexpected position and reduced neonatal morbidity.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

Evaluating prognosis in unexplained infertility.

IMPORTANCE: The diagnosis of unexplained infertility presents a dilemma as it signifies both uncertainty about the cause of infertility and the potential for natural conception. Immediate treatment of all would result in overtreatment. Prediction models estimating the likelihood of natural conception and subsequent live birth can guide treatment decisions. OBJECTIVE: To evaluate if in couples with unexplained infertility, prediction models are effective in guiding treatment decisions. EVIDENCE REVIEW: This review examines 25 studies that assess prediction models for natural conception in couples with unexplained infertility in terms of derivation, validation, and impact analysis. FINDINGS: The largest prediction models have been integrated in the synthesis models of Hunault, which includes female age and infertility duration, having been pregnant before and motile sperm percentage. Despite its limited discriminative capacity, this model demonstrates excellent calibration. Importantly, the impact of the Hunault model has been evaluated in randomized clinical trials, and shows that in couples with unexplained infertility and 12-month natural conception chances exceeding 30%, immediate treatment with intrauterine insemination (IUI) and controlled ovarian hyperstimulation is not better than expectant management for 6 months. Below the threshold of 30%, treatment with IUI is superior over expectant management, but immediate in vitro fertilization was not better than IUI. CONCLUSION: In couples with unexplained infertility and a good prognosis for natural conception, treatment can be delayed, whereas in couples with a poor prognosis, immediate treatment (with IUI-controlled ovarian hyperstimulation) is warranted. RELEVANCE: These data indicate that in couples with unexplained infertility, integration of prediction models into clinical decision making can optimize treatment selection and maximize fertility outcomes while limiting unnecessary treatment.

Prevalence of female genital mutilation and associated factors among women and girls in Africa: a systematic review and meta-analysis.

BACKGROUND: Female genital mutilation (FGM) has zero health benefits. It can lead to short- and long-term risks and complications, including physical, sexual, and mental health and well-being of girls and women. It is a worldwide public health issue with more than 80% prevalence in Africa. It is a global imperative to strengthen work for the elimination, and the United Nations Sustainable Development Goal (SDG) strives to eliminate FGM and monitor the progress made. However, one of a challenge in tracking progress is establishing baseline prevalence data within regions and countries. Therefore, this review aimed to pool the prevalence of FGM in Africa and identify the promoting factors among women and girls. METHODS: This review was conducted according to the PRISMA checklist guideline. Both published and unpublished studies conducted from 2012 onwards were eligible. Studies written in non-English languages were excluded. To retrieve relevant studies; PubMed/Medline, Google Scholar, Science Direct, African Journals Online databases, and African Index Medicus (AIM) were searched using a combination of searching terms. The Newcastle-Ottawa Assessment Scale (NOS) tool was used to assess the quality of each included study. The Cochran's Q chi-square and I2 statistical tests were used to evaluate the heterogeneity of the included studies. The Funnel plot and Egger's regression test (p value < 0.05) were used to evaluate meh publication bias. We used STATA for analysis and the overall and subgroup pooled effect size was estimated using the random effect model with DerSimonian and Laired pooled effect method. The overall prevalence of FGM and the adjusted odds ratio (AOR) with 95%CI (confidence interval) for contributing factors were calculated and presented using a forest plot. RESULT: This study included 155 primary studies conducted on the prevalence and/or factors associated with FGM in Africa. The pooled prevalence of FGM was 56.4% (95%CI 49.7-63.6). The primary factors promoting the practice of FGM were family history of circumcision (AOR = 13.71, 95%CI 9.11-20.62), being a Muslim religion follower (AOR = 3.51, 95%CI 2.61-4.71), poor wealth index (AOR = 1.38, 95%CI1.27-1.51), higher age (AOR = 2.95, 95%CI 2.49-3.38), not attending formal education (AOR = 3.28, 95%CI 2.62-4.12), and rural residency (AOR = 2.27, 95%CI 1.84-2.80). CONCLUSION: The prevalence of FGM in Africa was found to be high. This study also observed a variation in FGM prevalence across regions and countries and a slight temporal decline over the study period. As the global community enters the final decade dedicated to eliminating FGM, there remains much to be done to achieve the elimination goal.

Attitudes, knowledge and practice regarding the anti-müllerian hormone test among general practitioners and reproductive specialists: A cross-sectional study.

OBJECTIVE: To describe clinicians' attitudes, knowledge and practice relating to the anti-müllerian hormone (AMH) test. DESIGN: Cross-sectional nationwide survey. SETTING: Australia. POPULATION OR SAMPLE: A total of 362 general practitioners (GPs), gynaecologists and reproductive specialists. METHODS: Clinicians were recruited through relevant professional organisations, with data collected from May 2021 to April 2022. MAIN OUTCOME MEASURES: Clinicians' attitudes, knowledge and practice relating to the AMH test, measured using multiple choice, Likert scales and open-ended items. RESULTS: Fifteen percent of GPs (n = 27) and 40% of gynaecologists and other specialists (n = 73) order at least one AMH test per month. Specialists reported raising the idea of testing most of the time, whereas GPs reported that patient request was more common. Half of clinicians lacked confidence interpreting (n = 182, 51%) and explaining (n = 173, 48%) an AMH result to their patients. Five percent (n = 19) believed the test was moderately/very useful in predicting natural conception/birth and 22% (n = 82) believed the same for predicting premature menopause, despite evidence that the test cannot reliably predict either. Forty percent (n = 144) had previously ordered the test to help with reproductive planning and 21% (n = 75) to provide reassurance about fertility. CONCLUSIONS: Clinicians reported use of AMH testing in clinical circumstances not supported by the evidence. With the proliferation of direct-to-consumer testing, efforts to support clinicians in the judicious use of testing and effectively navigating patient requests are needed.

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Intrapartum use of sildenafil citrate to prevent fetal compromise and emergency operative birth in term pregnancies in the United Kingdom and Australia: A preliminary cost-effectiveness analysis.

OBJECTIVE: To compare cost-effectiveness of oral sildenafil citrate, administered after onset of labor, with standard care to health system funders in the UK and Australia. METHODS: We conducted a modeled cost-effectiveness analysis, measuring costs and quality adjusted life years (QALYs), using a decision-analytic model covering onset of labor to 1 month post-birth. The relative risk of emergency cesarean section and operative vaginal birth was taken from a Phase 2 placebo controlled double blinded randomized control trial. RESULTS: Both options of care resulted in the same QALYs gained over the model time period (0.08). Sildenafil citrate was cost-saving compared with standard care, saving £92 per birth in the UK (AU$303 per birth in Australia). Sensitivity analyses did not identify any areas of uncertainty that stopped sildenafil citrate being cost saving compared with standard care. Threshold analysis revealed that sildenafil citrate would be cost saving up to a per birth drug or administration cost of £152.32 in the UK (AU$333.61 in Australia). CONCLUSION: Oral sildenafil citrate may be cost saving compared with standard care; however, the effects on neonatal outcomes still need to be demonstrated in large randomized trials.