The influence of the attending midwife on the occurrence of episiotomy: A retrospective cohort study.

BACKGROUND: Episiotomy at the time of vaginal birth can result in short- and long-term complications for women. Therefore, it is important to study factors that influence the occurrence of episiotomy. AIM: To examine to what extent the individual factors of clinical midwives in the same working conditions contribute to variations in episiotomy. METHODS: A retrospective cohort study was performed at a secondary care hospital in Amsterdam, the Netherlands, using data from women who were assisted by a clinical midwife during birth in 2016. The clinical midwives filled out a questionnaire to determine individual factors. The predictive value of the individual factors of the clinical midwives was examined in a multiple logistic regression model on episiotomy. RESULTS: A total of 1302 births attended by 27 midwives were included. The mean episiotomy rate was 12.7%, with a range from 3.2% to 30.8% among midwives (p = 0.001). When stratified for parity, within the primipara group there was a significant variation in episiotomy among midwives with a range from 7.9% to 47.8% (p = 0.006). No significant variation was found in the occurrence of third/fourth degree tears or intact perineum. There was a significant difference in episiotomy for maternal indication among midwives (p = 0.041). Predictors for an episiotomy were number of years since graduation and place of bachelor education of the clinical midwife. CONCLUSION: This study shows that individual factors of clinical midwives influence the rate of episiotomy. Predictors for an episiotomy were the number of years since graduation and place of bachelor education. This shows that continuous training of clinical midwives could contribute to reducing the number of unnecessary episiotomies. Since suspected fetal distress is the only evidence based indication to perform an episiotomy, there is room for improvement given the variation in the number of episiotomies performed for maternal indication.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

Delayed versus immediate oxytocin infusion after amniotomy for induction of labour: A randomised controlled pilot trial.

OBJECTIVE: To get a preliminary understanding of the amniotomy-to-delivery interval, patients' experiences and risks by awaiting spontaneous contractions after amniotomy and to explore the need and feasibility for a larger randomised controlled trial. METHODS: We performed a randomised controlled pilot trial in a peripheral teaching hospital in Amsterdam, The Netherlands. Women with term, singleton pregnancy in vertex position undergoing labour induction for one of the five following indications: prolonged pregnancy, mild hypertensive disorders, diabetes, expected macrosomia, maternal request, were randomised to amniotomy with 12-hours delayed oxytocin (DO), or amniotomy with immediate oxytocin (IO). RESULTS: A total of 64 women was included in the analysis. The median amniotomy-to-delivery interval for the DO-group was 15 h (IQR 8-21), and 6 h (IQR 5-11) for the IO-group (HR, 0.41; 95% CI, 0.24-0.70), with equal patient reported childbirth perception in the overall group (P=0.43). Parous women reported a significantly less positive perception of labour (P=0.02) and used pain relief more often (RR, 2.93; 95% CI, 1.05-8.19) in the DO-group. The proportion of women delivered within 24 h was not significantly different between groups (RR, 0.30; 95% CI, 0.05-1.83). Other delivery and neonatal outcomes did not differ significantly between groups, possibly due to being underpowered. CONCLUSION: Preliminary results show that amniotomy-to-delivery interval was prolonged with 9 h in the DO-group, with equal patient reported childbirth perception in the overall group. Parous women have a less positive perception of their delivery and used pain relief more often when oxytocin was delayed. Delaying oxytocin infusion after amniotomy should be further investigated in an adequately powered randomised trial.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.

The role of metformin in polycystic ovary syndrome: a systematic review.

This meta-analysis evaluated the effectiveness of metformin in subfertile women with polycystic ovary syndrome (PCOS). Only randomized trials investigating the effectiveness of metformin and PCOS definition consistent with the Rotterdam consensus criteria, were eligible. Primary outcome was live birth rate. A literature search identified 27 trials. In therapy naïve women, we found no evidence of a difference in live birth rate when comparing metformin with clomifene citrate (CC) [relative risks (RR) 0.73; 95% confidence interval (CI) 0.51-1.1] or comparing metformin plus CC with CC (RR 1.0; 95% CI 0.82-1.3). In CC-resistant women, metformin plus CC led to higher live birth rates than CC alone (RR 6.4; 95% CI 1.2-35); metformin also led to higher live birth rates than laparoscopic ovarian drilling (LOD) (RR 1.6; 95% CI 1.1-2.5). We found no evidence for a positive effect of metformin on live birth when added to LOD (RR 1.3; 95% CI 0.39-4.0) or FSH (RR 1.6; 95% CI 0.95-2.9), or when co-administered in IVF (RR 1.5; 95% CI 0.92-2.5). In IVF, metformin led to fewer cases of ovarian hyperstimulation syndrome (OHSS) (RR 0.33; 95% CI 0.13-0.80). This meta-analysis demonstrates that CC is still first choice therapy for women with therapy naïve PCOS. In CC-resistant women, the combination of CC plus metformin is the preferred treatment option before starting with LOD or FSH. At present, there is no evidence of an improvement in live birth when adding metformin to LOD or FSH. In IVF, metformin leads to a reduced risk of OHSS.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

OBJECTIVE: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. DESIGN: Randomised clinical trial. SETTING: Multicentre trial in 20 Dutch hospitals. PARTICIPANTS: 228 women with polycystic ovary syndrome. INTERVENTIONS: Clomifene citrate plus metformin or clomifene citrate plus placebo. MAIN OUTCOME MEASURE: The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. RESULTS: 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). CONCLUSION: Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55906981 [controlled-trials.com].