Ben W. Mol

Description:Objective: To develop a core outcome set for male infertility trials. Methods: A two-round Delphi survey and consensus development workshop were undertaken with healthcare professionals, researchers and clinicians globally. Methods: 334 participants from 39 countries participated in the Delphi Survey, while 44 participants from 21 countries participated in the consensus development workshop. NA MAIN OUTCOME MEASURES: The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set which focuses on female-factor outcomes. Results: The outcomes identified include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. Conclusions: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes, which are inconsistently reported at present. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set for male infertility trials. Background: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.

Description:Sildenafil citrate may increase uteroplacental blood flow. Its ability to reduce perinatal complications related to fetal hypoxia during labor is uncertain. To compare the effectiveness of intrapartum maternal oral sildenafil citrate vs placebo in improving perinatal outcomes potentially related to intrapartum hypoxia in term pregnancies. This pragmatic, multicenter, investigator-initiated, placebo-controlled randomized clinical trial including 3257 women was conducted in 13 Australian hospitals from September 6, 2021, to June 28, 2024. The last date of follow-up (28-day neonatal mortality) was July 26, 2024. Women aged 18 years or older with singleton or dichorionic twin pregnancies, planning vaginal birth at term by either spontaneous labor or induction of labor, were recruited. Women were assigned to 50 mg oral sildenafil citrate every 8 hours up to 150 mg or equivalent placebo. The primary composite outcome was intrapartum stillbirth, neonatal death, Apgar score less than 4 at 5 minutes (a score of <4 at 5 minutes is indicative of severe neonatal depression at birth, with scores ranging from 0 to 10), acidosis at birth (umbilical cord artery pH <7.0), hypoxic ischemic encephalopathy, neonatal seizures, neonatal respiratory support for greater than 4 hours, neonatal unit admission for greater than 48 hours, persistent pulmonary hypertension of the newborn, or meconium aspiration syndrome. Secondary outcomes were the individual components of the primary composite and emergency cesarean delivery or instrumental birth for intrapartum fetal distress. A total of 3257 women were randomized to sildenafil citrate (n = 1626 women and 1634 infants) or placebo (n = 1631 women and 1641 infants). Mean (SD) maternal age and gestation at randomization were similar in both groups (31.7 [5.1] vs 31.5 [5.0] years and 39.5 [1.2] vs 39.5 [1.1] weeks, respectively). A total of 868 participants (53.4%) vs 874 participants (53.6%) were of Australia/New Zealand ethnicity and 315 participants (19.4%) vs 311 participants (19.1%) were of European ethnicity. Most participants were nulliparous (944 of 1624 [58.1%; 2 missing values] vs 966 of 1630 [59.3%; 1 missing value]). Induction of labor occurred in 1353 of 1621 women (83.5%) in the sildenafil citrate group and 1348 of 1627 women (82.9%) in the placebo group. The primary outcome occurred in 83 of 1625 women (5.1%) in the sildenafil citrate group and 84 of 1625 (5.2%) in the placebo group (relative risk, 1.02; 95% CI, 0.75-1.37). Sildenafil citrate had no significant effect on emergency cesarean delivery or instrumental vaginal birth for fetal distress (relative risk, 1.12; 95% CI, 0.98-1.29) or on any of the individual components of the primary outcome. Subgroup analyses showed no evidence of heterogeneity of treatment effect. Sildenafil citrate did not result in a lower incidence of adverse perinatal outcomes potentially related to intrapartum hypoxia. anzctr.org.au Identifier: ACTRN12621000231842.

Description:Background: The optimal methods and settings for induction of labour (IOL) in terms of effectiveness, safety, and women's experience are still not elucidated. Objective: To compare the effectiveness and safety of outpatient versus inpatient cervical ripening settings for IOL. Methods: MEDLINE, Embase, Emcare, CINAHL Plus, Scopus, Cochrane Library, WHO ICTRP and clinicaltrials.gov from inception to July 2024. Methods: Randomised controlled trials, viable singleton gestation, no language restrictions, all the published and unpublished data. Methods: An individual participant data meta-analysis. Results: Eleven out of 18 (61.1%) eligible RCTs shared IPD, totalling 2593 pregnant individuals undergoing IOL (62.2% of all participants in the published RCTs). Among the shared RCTs, four used balloon catheters alone in both groups. Three RCTs compared outpatient balloon catheter with inpatient balloon catheter plus oxytocin. Another three RCTs compared outpatient balloon catheter to inpatient vaginal dinoprostone. One RCT used Dilapan-S in both groups. No trials evaluating outpatient use of vaginal prostaglandins were identified. Vaginal birth (11 RCTs, 2584 women, 67.8% vs. 70.2%, aOR 0.95, 95% CI 0.70; 1.30), composite perinatal outcome (9 RCTs, 2525 women, 11.1% vs. 11.7%, aOR 0.93, 95% CI 0.75; 1.16) and composite maternal (10 RCTs, 2480 women, 14.3% vs. 15.4%, aOR 0.89, 95% CI 0.65; 1.20) outcome did not differ between outpatient and inpatient groups. The outpatient group had a lower risk of acidosis, more epidural analgesia, and more oxytocin. There were no perinatal deaths in either group. Conclusions: Overall effectiveness, perinatal and maternal safety are comparable between outpatient setting cervical ripening with a mechanical method and inpatient with any method. Background: PROSPERO: CRD42022313183.

Description:Objective: We aim to assess which variables are associated with recruitment failure of obstetrical and gynaecological randomised controlled trials (RCTs), leading to an extension of the study period. Methods: Nationwide study. Methods: A cohort of RCTs supported by the trial centre of the Dutch Consortium of Obstetrics and Gynaecology. Methods: We included 83 RCTs that recruited patients between 1 March 2003 and 1 December 2023. Methods: Main outcome was recruitment target not achieved within 6 months after the preplanned recruitment period. Secondary outcomes were recruitment target not achieved within an extension period of at least 12 months and premature termination of the trial. In all RCTs, we collected information on variables with a potential effect on recruitment failure, recorded at five levels; patient, doctor, participating centre, study organisation and study design. Results: In total, 46 of 83 RCTs (55%) did not achieve their targeted recruitment within the preplanned study period with a maximal extension period of 6 months. The most relevant variables for recruitment failure in multivariable risk prediction modelling were presence of a no-treatment arm (where treatment is standard clinical practice), a compensation fee of less than €200 per included patient, funding of less than €350 000, while a preceding pilot study lowered this risk. Conclusions: We identified that the presence of a no-treatment arm, low funding and a low compensation fee per included patient were the most relevant risk factors for recruitment failure within the preplanned period, while a preceding pilot study lowered this risk. Awareness of these variables is important when designing future studies.

Description:This study aimed to investigate the associations between the post-wash total progressively motile sperm count (TPMSC) in the first intrauterine insemination (IUI) cycle and pregnancy outcomes of the second IUI cycle. Data were retrieved from the clinical database at the Reproductive Center of Peking University Third Hospital (Beijing, China) between January 2011 and December 2022. Couples were included in this retrospective cohort study if they had unexplained or mild male factor infertility and were treated with IUI for two consecutive cycles using the same protocol. A total of 8290 couples were included in the analysis. The mean ± standard deviation (s.d.) age of women was 32.0 ± 3.5 years. We categorized groups based on the post-wash TPMSC (×106) levels in the first IUI cycle: group 1 (0 < TPMSC < 1, n = 1290), group 2 (1 ≤ TPMSC < 2, n = 863), group 3 (2 ≤ TPMSC < 3, n = 800), group 4 (3 ≤ TPMSC < 4, n = 783), group 5 (4 ≤ TPMSC < 5, n = 1541), group 6 (5 ≤ TPMSC < 6, n = 522), group 7 (6 ≤ TPMSC < 7, n = 547), group 8 (7 ≤ TPMSC < 8, n = 175), group 9 (8 ≤ TPMSC < 9, n = 556), group 10 (9 ≤ TPMSC < 10, n = 192), and group 11 (TPMSC ≥ 10), n = 1021). The primary outcome was live birth rate of the second IUI cycle. Live birth rates were 7.9%, 5.8%, 7.6%, 7.4%, 7.3%, 8.4%, 7.5%, 7.4%, 8.8%, 8.9%, and 7.6% in each group, respectively. There were no statistically significant differences in clinical pregnancy rates or live birth rates between any groups and those with the post-wash TPMSC <1 × 106. In an IUI program for unexplained and mild male factor infertility, the post-wash TPMSC in the first IUI cycle was not significantly associated with the live birth rate in the second IUI cycle.