Objective: We aim to assess which variables are associated with recruitment failure of RCTs, leading to an extension of the study period.. Design: Nationwide cohort study. Setting: A cohort of RCTs supported by the trial centre of the Dutch Consortium of Obstetrics and Gynaecology. Population: We included 83 RCTs that recruited patients between March 1 st 2003 and December 1 st 2023. Main outcome measures: Primary outcome was recruitment target not achieved within six months after the pre-planned recruitment period. Secondary outcomes were recruitment target not achieved within an extension period of at least twelve months and premature termination of the trial. Results: In total, 46 of 83 RCTs (55%) did not achieve their targeted recruitment within the pre-planned study period with a maximal extension period of 6 months. The most relevant indicators for recruitment failure in multivariable risk prediction modelling were presence of a no-treatment arm, a compensation fee of less than 200 euros per included patient, funding of less than 350.000 euros, 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 pre-planned period, while a preceding pilot study lowered this risk. Awareness of these indicators is important when designing future studies.

Objective: To compare the effectiveness of cervical pessary and vaginal progesterone in improving long-term developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length (CL). Design: Randomized controlled trial (RCT). Setting: My Duc hospital, Ho Chi Minh City, VietNam. Population: Children born to women in an RCT comparing cervical pessary and progesterone (NCT02623881). Methods: At or after 2 years of age, their parents completed a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and Red flag questionnaire. Main Outcome Measures: Mean ASQ-3 scores, red flag signs, and the composite outcome of perinatal death or survival with any abnormal ASQ-3 score. Results: In original RCT, we randomized 300 women to pessary (n=150) or progesterone (n=150). After counting the number of perinatal death and lost to follow-up, in pessary group, 116 (82.8%) parents of 229 children returned the questionnaire versus 118 (82.5%) parents of 232 children in progesterone group. Mean ASQ-3 scores of the five skills, as well as red flag signs, did not differ significantly between the two groups. However, the percentage of children having died or having abnormal ASQ-3 scores in fine motor was significantly lower in the progesterone group (1.7% vs 6.1%, P=0.01). In an exploratory analysis, there were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3. Conclusions: Cervical pessary and progesterone have a comparable effect on developmental outcomes in ≥24 months of children born to women with twin pregnancies and short CL.

A document by Shi Ting Pang. Click on the document to view its contents.

Objective: To evaluate if elective single-blastocyst transfer (eSBT) could be adopted in women aged 36 or older? Design: Retrospective cohort study. Setting: Reproductive medicine center at a tertiary hospital. Population: Women aged ≥36 years received IVF ovarian stimulation cycles and had ≥ two blastocysts. Out of 429 women, 240 underwent eSBT and 189 double-blastocyst transfer (DBT) in the first transfer cycle. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers. Methods: Analysis was stratified for patients in age groups 36-37, 38-39 and ≥40, taking into account the quality of the blastocyst transferred, as graded by morphological examination. Main outcomes measures: Cumulative livebirth rate (cLBR) from all transfers (fresh and frozen) accruing from a single oocyte retrieval. Results: The cLBR was 74.2% (178/240) versus 63.0% (119/189) after eSBT versus DBT, respectively (aOR: 1.09 (0.68, 1.75)). Time to live birth did not vary significantly between the two groups (HR: 0.85 (0.68,1.08)). The total number of children born was 194 after eSBT (162 singletons and 16 pairs of twins) versus 154 (84 singletons and 35 twins) pairs of after DBT. The odds ratios for preterm birth (<37 weeks’ gestation) (0.37 (0.21-0.64)), and low birthweight (<2.5 kg) (0.31 (0.16, 0.60)) were all lower in eSBT group than in DBT group. Conclusions: In women aged ≥36 years old with at least two blastocysts, cLBR following single- versus double- blastocyst transfer was comparable while the odds of multiple livebirths and adverse perinatal outcomes were reduced.

Objective: To undertake a cost minimisation study of ST analysis (STan) plus cardiotocograpy (CTG) compared to CTG alone. Design: Cost-minimisation analysis alongside a randomised controlled trial [(1)](#ref-0001). Setting: A tertiary level maternity centre in Adelaide, South Australia. Population: Women in labour ≥36 weeks gestation, with a clinical indication for continuous electronic fetal monitoring. Methods: We utlilised a health service perspective covering randomisation to final maternal and neonatal discharge, including readmissions. Primary analysis was intention to treat, with secondary per protocol analysis. Post hoc analyses were conducted by sub-groups and after exclusion of outliers. Main outcome measure: Average cost per mother/baby dyad. Results: Costs were calculated for 957/968 patients (98.9%) using hospital financial data. There was no statistically significant evidence of difference between the two study arms but lower costs observed in the STan arm. Average cost per mother/baby dyad was AUD12,768 for Stan+CTG, compared with AUD15,027 for CTG alone. Lower costs were mainly due to lower neonatal costs, particularly for critical care. Maternal labour cost was nearly identical in the two arms. The difference was still shown, although with reduced magnitude, when outliers were removed and increased with a per protocol analysis. Conclusion: While not statistically significant, reduced costs were observed in the CTG+STan arm (average reduction per mother / baby dyad = AUD2,259).

Novel Gonadotrophin Releasing Hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix, and linzagolix have assessed treatment efficacy for fibroid related heavy menstrual blood loss in comparison to placebo. Marketing authorization has already been granted by several agencies including those in Europe, the United Kingdom, and the United States. Prior to marketing authorization, the European Medicines Agency recommends that Phase III registration trails should assess treatment efficacy in a representative study population, assess relevant outcomes with a comparison to gold-standard alternative treatment options and that long-term safety data will adequately be collected. In this review, we demonstrate limitations in the trial data generated to date, namely a lack of generalizability due to the restricted population studied, the absence of any comparison to alternative treatment methods, and findings limited to specific subgroups of patients because of the type of outcomes assessed. Symptoms related to uterine fibroids adversely affect many women’s quality of life and effective medical treatments are lacking. However, despite the urgent need for effective treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness, and cost-effectiveness in a representative population compared with alternative treatment methods before introduction into mainstream clinical practice.

Background: Multiple gestation has a higher incidence of preterm birth(PTB), especially in the presence of a short cervix. Objectives: To perform a systematic review and network meta-analysis(NMA) evaluating the effect of progesterone, cerclage, cervical pessary and their combination as treatments for preventing PTB<34 weeks. Search strategy: PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, BVS, Scopus, and grey literature were explored. Selection criteria: We included randomized controlled trials that compared an intervention with a control group or another intervention to prevent PTB in women with a twin pregnancy and a short cervix<40mm. Data collection and Analysis:Studies were checked for trustworthiness. We presented summary relative effect sizes(Odds Ratios) for each possible pair of interventions and we used the surface under the cumulative ranking curves(SUCRA) to rank all interventions. Main Results: A total of 20 studies participated in NMA. We found no evidence that the combined treatment of pessary and vaginal progesterone reduced the risk of spontaneous PTB <34 weeks when compared to no intervention(OR 0.68; 95%CI 0.16 to 2.9). Also, pessary(OR 0.78; 95%CI 0.49 to 1.3), vaginal progesterone(OR 0.79; CI95% 0.45 to 1.4) and injectable 17-OH progesterone alone(OR 0.85; CI95% 0.26 to 2.8) did not show a statistically significant reduction in spontaneous PTB. For overall PTB<34 weeks, findings were similar. Conclusions: We found no evidence that progesterone, cervical pessary, cerclage or their combination reduce PTB<34 weeks. There is an urgent need for randomized trials assessing these treatments in women with a multiple pregnancy and a short cervix.

Letter to Editor

Objective: To compare postoperative reproductive outcomes between salpingectomy and neosalpingostomy for bilateral severe hydrosalpinges. Design: Single center, prospective cohort study. Setting: A hospital affiliated to a medical college in China. Population: Women aged 20 to 45 years old, diagnosed with bilateral hydrosalpinges and scheduled for surgery were initial eligibility criteria. Women with previous tubal surgery or tubal pregnancy, no fertility intention, or no confirmation of severe bilateral hydrosalpinges during surgery were excluded. Methods: Bilateral salpingectomy or neosalpingostomy was performed based on a shared decision approach. Main outcome measures: The primary outcome was the cumulative livebirth rate. Secondary outcomes included time to first live birth, biochemical pregnancy, clinical miscarriage, ectopic pregnancy, mode of conception, and gestational age at delivery. Results: A total of 113 women were involved in the analysis. When the result of In Vitro Fertilization (IVF) in the neosalpingostomy group was incorporated, salpingectomy resulted in a higher cumulative livebirth rate (85.3% vs 76.0%, hazard ratio of the whole survival curve = 2.18, 95% CI 1.37 - 3.45), a lower risk of ectopic pregnancy (1.8% vs 20.7%, risk ratio = 0.07, 95% CI 0.01 - 0.57), and a shorter time to live birth than neosalpingostomy. 16/58 (27.6%) women in the neosalpingostomy group had a live birth via natural conception, compared to 0/55 (0.0%) in the salpingectomy group. Conclusions：Salpingectomy for bilateral severe hydrosalpinges resulted in a higher cumulative livebirth rate and a lower risk of ectopic pregnancy. However, neosalpingostomy can offer certain option for women to conceive naturally without IVF treatment.

Objective: To identify the association between cervical length (CL) and gestational age at birth. Design: Prospective cohort study. Setting: Seventeen Brazilian reference hospitals. Population: A cohort of 3139 asymptomatic singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial). Methods: Transvaginal ultrasound (TVU) to measure CL was performed from 18 to 22+6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks’ gestation. Main Outcome Measures: Area under receive operating characteristic curve (AUC), sensitivity, specificity, Kaplan-Meier curves for preterm birth (PTB), number needed to screen (NNS). Results: CL ≤25mm was associated with extremely severe, severe, moderate and late PTB, whereas a CL 25–30mm was directly associated with late sPTB. The AUC to predict sPTB<28 weeks was 0.82 and for sPTB<34 weeks was 0.67. Almost half of the sPTB occurred in nulliparous women and CL ≤30mm was associated with sPTB <37 weeks (OR = 7.84; 95%CI = 5.5–11.1). The NNS to detect one sPTB <34 weeks in women with CL ≤25mm is 121 and 248 screening tests are necessary to prevent one sPTB <34 weeks using vaginal progesterone prophylaxis. Conclusions: CL measured by TVU is associated with sPTB <34 weeks. Women with CL ≤30mm are at increased risk for late sPTB. Funding: Bill & Melinda Gates Foundation [OPP1107597], the Brazilian Ministry of Health, and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. Keywords: cervical length; number needed to screen; preterm birth; short cervix.

Objective: We developed a research usefulness tool collating published criteria and examined if randomised controlled trials (RCTs) addressing preterm birth were useful. Search Strategy: Cochrane library. Selection Criteria: Published RCTs within 56 preterm birth Cochrane reviews. Data Collection and Analysis: A usefulness tool was developed with eight criteria combining 13 items identified through literature searches and consensus. RCTs were evaluated for compliance with each item by multiple assessors (reviewer agreement 95-98%). Proportions with 95% confidence interval (CI) were calculated and compared for change over time using ≧ 2010 as a cut-off, with relative risks (RR). Main Results: Among 350 selected RCTs, only 38 (11%, 95% CI 8-15%) met half of the usefulness criteria. Compared to trials before 2010, recent trials used composite or surrogate (less informative) outcomes more often (13% vs 25%, RR 1.87, 95% CI 1.19-2.93). Only 17 trials reflected real life (pragmatism) in design (5%, 95% CI 3-8%), with no improvements over time. No trials reported involvement of mothers to reflect patients’ top priorities in question definition or outcomes selection. Recent trials were more transparent with prospective registration (0.5% vs 28%, RR 58, 95% CI 8-420%), availability of protocol (0.5% vs 15%, RR 32, 95% CI 4-237%) and data sharing statements (2% vs 8%, RR 3, 95% CI 1-10%). Conclusion: Clinical trials in preterm birth lacked many usefulness features, with one tenth of trials meeting half of the items evaluated. Use of informative outcomes, patient centeredness, pragmatism and transparency should be key targets for future research planning.

Background: Postpartum Haemorrhage (PPH) remains a leading cause of maternal mortality and morbidity worldwide, and the rate is increasing. Using a reliable predictive model could identify those at risk, support management and treatment, and improve maternal outcomes. Objectives: To systematically identify and appraise existing prognostic models for PPH and ascertain suitability for clinical use. Search strategy: MEDLINE, CINAHL, Embase, and the Cochrane Library were searched using combinations of terms and synonyms including ‘postpartum haemorrhage’, ‘prognostic model’, and ‘risk factors’ that were developed from a scoping review. Selection Criteria: Observational or experimental studies describing a prognostic model for risk of PPH, published in English. Data Collection and Analysis: The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist informed data extraction and Prediction Model Risk of Bias Assessment Tool guided analysis. Main Results: 16 studies met the inclusion criteria after screening 1612 records. All studies were hospital settings from 8 different countries. Models were developed for women who experienced vaginal birth (n=7), caesarean birth(n=2), any type of birth(n=2), hypertensive disorders(n=1) and those with placental abnormalities(n=4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation. Conclusions: No existing prognostic models for PPH are ready for clinical application. Future research is needed to externally validate existing models and potentially develop a new model that is reliable and applicable to clinical practice. Funding: This study received no funding. Keywords: Postpartum haemorrhage, prognostic model, prediction tool.