Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN):A randomised, two-by-two factorial trial

Background: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse. Methods: In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449. Findings: Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women allocated to gonadotrophins had more livebirths than those allocated to clomifene citrate (167 [52%] of 327 women vs 138 [41%] of 334 women, relative risk [RR] 1·24 [95% CI 1·05–1·46]; p=0·0124). Addition of intrauterine insemination did not increase livebirths compared with intercourse (161 [49%] vs 144 [43%], RR 1·14 [95% CI 0·97–1·35]; p=0·1152). Multiple pregnancy rates for the two comparisons were low and not different. There were three adverse events: one child with congenital abnormalities and one stillbirth in two women treated with clomifene citrate, and one immature delivery due to cervical insufficiency in a woman treated with gonadotrophins. Interpretation: In women with normogonadotropic anovulation and clomifene citrate failure, a switch of treatment to gonadotrophins increased the chance of livebirth over treatment with clomifene citrate; there was no evidence that addition of intrauterine insemination does so. Funding: The Netherlands Organization for Health Research and Development

Maternal characteristics associated with referral to obstetrician-led care in low-risk pregnant women in the Netherlands: A retrospective cohort study

Background In the Netherlands, maternity care is divided into midwife-led care (for low-risk women) and obstetrician-led care (for high-risk women). Referrals from midwife-led to obstetrician-led care have increased over the past decade. The majority of women are referred during their pregnancy or labour. Referrals are based on a continuous risk assessment of the health and characteristics of mother and child, yet referral for non-medical factors and characteristics remain unclear. This study investigated which maternal characteristics are associated with women’s referral from midwife-led to obstetrician-led care. Materials and methods A retrospective cohort study in one midwife-led care practice in the Netherlands included 1096 low-risk women during January 2015–17. The primary outcomes were referral from midwife-led to obstetrician-led care in (1) the antepartum period and (2) the intrapartum period. In total, 11 maternal characteristics were identified. Logistic regression models of referral in each period were fitted and stratified by parity. Results In the antepartum period, referral among nulliparous women was associated with an older maternal age (aOR, 1.07; 95%CI, 1.05–1.09), being underweight (0.45; 0.31–0.64), overweight (2.29; 1.91–2.74), or obese (2.65; 2.06–3.42), a preconception period >1 year (1.34; 1.07–1.66), medium education level (0.76; 0.58–1.00), deprivation (1.87; 1.54–2.26), and sexual abuse (1.44; 1.14–1.82). Among multiparous women, a referral was associated with being underweight (0.40; 0.26–0.60), obese (1.61; 1.30–1.98), a preconception period >1 year (1.71; 1.27–2.28), employment (1.38; 1.19–1.61), deprivation (1.23; 1.03–1.46), highest education level (0.63; 0.51–0.80), psychological problems (1.24; 1.06–1.44), and one or multiple consultations with an obstetrician (0.68; 0.58–0.80 and 0.64; 0.54–0.76, respectively). In the intrapartum period, referral among nulliparous women was associated with an older maternal age (1.02; 1.00–1.05), being underweight (1.67; 1.15–2.42), a preconception period >1 year (0.42; 0.31–0.57), medium or high level of education (2.09; 1.49–2.91 or 1.56; 1.10–2.22, respectively), sexual abuse (0.46; 0.33–0.63), and multiple consultations with an obstetrician (1.49; 1.15–1.94). Among multiparous women, referral was associated with an older maternal age (1.02; 1.00–1.04), being overweight (0.65; 0.51–0.83), a preconception period >1 year (0.33; 0.17–0.65), non-Dutch ethnicity (1.98; 1.61–2.45), smoking (0.75; 0.57–0.97), sexual abuse (1.49; 1.09–2.02), and one or multiple consultations with an obstetrician (1.34; 1.06–1.70 and 2.09; 1.63–2.69, respectively). Conclusions This exploratory study showed that several non-medical maternal characteristics of low-risk pregnant women are associated with referral from midwife-led to obstetrician-led care, and how these differ by parity and partum period

Maternal characteristics associated with referral to obstetrician-led care in low-risk pregnant women in the Netherlands: A retrospective cohort study.

BackgroundIn the Netherlands, maternity care is divided into midwife-led care (for low-risk women) and obstetrician-led care (for high-risk women). Referrals from midwife-led to obstetrician-led care have increased over the past decade. The majority of women are referred during their pregnancy or labour. Referrals are based on a continuous risk assessment of the health and characteristics of mother and child, yet referral for non-medical factors and characteristics remain unclear. This study investigated which maternal characteristics are associated with women's referral from midwife-led to obstetrician-led care.Materials and methodsA retrospective cohort study in one midwife-led care practice in the Netherlands included 1096 low-risk women during January 2015-17. The primary outcomes were referral from midwife-led to obstetrician-led care in (1) the antepartum period and (2) the intrapartum period. In total, 11 maternal characteristics were identified. Logistic regression models of referral in each period were fitted and stratified by parity.ResultsIn the antepartum period, referral among nulliparous women was associated with an older maternal age (aOR, 1.07; 95%CI, 1.05-1.09), being underweight (0.45; 0.31-0.64), overweight (2.29; 1.91-2.74), or obese (2.65; 2.06-3.42), a preconception period >1 year (1.34; 1.07-1.66), medium education level (0.76; 0.58-1.00), deprivation (1.87; 1.54-2.26), and sexual abuse (1.44; 1.14-1.82). Among multiparous women, a referral was associated with being underweight (0.40; 0.26-0.60), obese (1.61; 1.30-1.98), a preconception period >1 year (1.71; 1.27-2.28), employment (1.38; 1.19-1.61), deprivation (1.23; 1.03-1.46), highest education level (0.63; 0.51-0.80), psychological problems (1.24; 1.06-1.44), and one or multiple consultations with an obstetrician (0.68; 0.58-0.80 and 0.64; 0.54-0.76, respectively). In the intrapartum period, referral among nulliparous women was associated with an older maternal age (1.02; 1.00-1.05), being underweight (1.67; 1.15-2.42), a preconception period >1 year (0.42; 0.31-0.57), medium or high level of education (2.09; 1.49-2.91 or 1.56; 1.10-2.22, respectively), sexual abuse (0.46; 0.33-0.63), and multiple consultations with an obstetrician (1.49; 1.15-1.94). Among multiparous women, referral was associated with an older maternal age (1.02; 1.00-1.04), being overweight (0.65; 0.51-0.83), a preconception period >1 year (0.33; 0.17-0.65), non-Dutch ethnicity (1.98; 1.61-2.45), smoking (0.75; 0.57-0.97), sexual abuse (1.49; 1.09-2.02), and one or multiple consultations with an obstetrician (1.34; 1.06-1.70 and 2.09; 1.63-2.69, respectively).ConclusionsThis exploratory study showed that several non-medical maternal characteristics of low-risk pregnant women are associated with referral from midwife-led to obstetrician-led care, and how these differ by parity and partum period

Maternal characteristics associated with referral to obstetrician-led care in low-risk pregnant women in the Netherlands: A retrospective cohort study

Background In the Netherlands, maternity care is divided into midwife-led care (for low-risk women) and obstetrician-led care (for high-risk women). Referrals from midwife-led to obstetrician-led care have increased over the past decade. The majority of women are referred during their pregnancy or labour. Referrals are based on a continuous risk assessment of the health and characteristics of mother and child, yet referral for non-medical factors and characteristics remain unclear. This study investigated which maternal characteristics are associated with women’s referral from midwife-led to obstetrician-led care. Materials and methods A retrospective cohort study in one midwife-led care practice in the Netherlands included 1096 low-risk women during January 2015–17. The primary outcomes were referral from midwife-led to obstetrician-led care in (1) the antepartum period and (2) the intrapartum period. In total, 11 maternal characteristics were identified. Logistic regression models of referral in each period were fitted and stratified by parity. Results In the antepartum period, referral among nulliparous women was associated with an older maternal age (aOR, 1.07; 95%CI, 1.05–1.09), being underweight (0.45; 0.31–0.64), overweight (2.29; 1.91–2.74), or obese (2.65; 2.06–3.42), a preconception period >1 year (1.34; 1.07–1.66), medium education level (0.76; 0.58–1.00), deprivation (1.87; 1.54–2.26), and sexual abuse (1.44; 1.14–1.82). Among multiparous women, a referral was associated with being underweight (0.40; 0.26–0.60), obese (1.61; 1.30–1.98), a preconception period >1 year (1.71; 1.27–2.28), employment (1.38; 1.19–1.61), deprivation (1.23; 1.03–1.46), highest education level (0.63; 0.51–0.80), psychological problems (1.24; 1.06–1.44), and one or multiple consultations with an obstetrician (0.68; 0.58–0.80 and 0.64; 0.54–0.76, respectively). In the intrapartum period, referral among nulliparous women was associated with an older maternal age (1.02; 1.00–1.05), being underweight (1.67; 1.15–2.42), a preconception period >1 year (0.42; 0.31–0.57), medium or high level of education (2.09; 1.49–2.91 or 1.56; 1.10–2.22, respectively), sexual abuse (0.46; 0.33–0.63), and multiple consultations with an obstetrician (1.49; 1.15–1.94). Among multiparous women, referral was associated with an older maternal age (1.02; 1.00–1.04), being overweight (0.65; 0.51–0.83), a preconception period >1 year (0.33; 0.17–0.65), non-Dutch ethnicity (1.98; 1.61–2.45), smoking (0.75; 0.57–0.97), sexual abuse (1.49; 1.09–2.02), and one or multiple consultations with an obstetrician (1.34; 1.06–1.70 and 2.09; 1.63–2.69, respectively). Conclusions This exploratory study showed that several non-medical maternal characteristics of low-risk pregnant women are associated with referral from midwife-led to obstetrician-led care, and how these differ by parity and partum period

Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome

BACKGROUND: Ovulation induction with follicle stimulating hormone (FSH) is the second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate (CC). OBJECTIVES: To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with CC-resistant PCOS. SEARCH METHODS: We searched the Menstrual Disorders & Subfertility Group's Specialist Register of controlled trials, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to October 2014), EMBASE (1980 to October 2014), CINAHL (1982 to October 2014), National Research Register and web-based trials databases such as Current Controlled Trials. There was no language restriction. SELECTION CRITERIA: All randomised controlled trials reporting data on comparing clinical outcomes in women with PCOS who did not ovulate or conceive on CC, and undergoing ovulation induction with urinary FSH (uFSH: FSH-P or FSH-HP), HMG/HP-HMG or recombinant FSH. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that used co-treatment with CC, metformin, LH or letrozole. DATA COLLECTION AND ANALYSIS: Three review authors (NW, MN and MvW) independently selected studies for inclusion, assessed study quality and extracted study data. Primary outcomes were live birth rate per woman (effectiveness outcome) and incidence of ovarian hyperstimulation syndrome (OHSS) per woman (safety outcome). Secondary outcomes were clinical pregnancy, miscarriage, multiple pregnancy, total gonadotrophin dose and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the odds ratio (OR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. MAIN RESULTS: The review includes 14 trials with 1726 women. Ten trials compared rFSH versus urinary-derived gonadotrophins (three rFSH versus HMG and seven rFSH versus FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P.We found no evidence of a difference in live birth for rFSH versus urinary-derived gonadotrophins (OR 1.26, 95% CI 0.80 to 1.99, 5 trials, 505 women, I² = 0%, low-quality evidence) or clinical pregnancy rate (OR 1.08, 95% CI 0.83 to 1.39, 8 trials, 1330 women, I² = 0, low-quality evidence). This suggests that for the observed average live birth per woman with urinary-derived FSH of 16%, the chance of live birth following rFSH is between 13% and 26%.For the comparison HMG or HP-HMG versus FSH-P there was also no difference in the evidence on live birth rate (OR 1.36, 95% CI 0.58 to 3.18, 3 trials, 138 women, I² = 0%, low-quality evidence). This suggests that for a woman with a live birth rate of 18% with HMG or HP-HMG, the chance of live birth following uFSH is between 9% and 37%.Trial authors used various definitions for OHSS. Pooling the data, we found no evidence of a difference for rFSH versus urinary-derived gonadotrophins (OR 1.52, 95% CI 0.81 to 2.84, 10 trials, 1565 women, I(2) = 0%, very low-quality evidence) and for HMG or HP-HMG versus FSH-P (OR 9.95, 95% CI 0.47 to 210.19, 2 trials, 53 women, I² = 0%, very low-quality evidence). AUTHORS' CONCLUSIONS: In women with PCOS and CC resistance or CC failure, we found no evidence of a difference in live birth and OHSS rates between urinary-derived gonadotrophins and rFSH or HMG/HP-HMG. Evidence for all outcomes was of low or very low quality. We suggest weighing costs and convenience in the decision to use one or the other

Gonadotrophins for ovulation induction in women with polycystic ovary syndrome

BACKGROUND: Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate. OBJECTIVES: To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate. SEARCH METHODS: In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions. SELECTION CRITERIA: All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole. DATA COLLECTION AND ANALYSIS: Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. MAIN RESULTS: The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no difference in the incidence of multiple pregnancy between treatments (RR 0.89, 95% CI 0.33 to 2.44; one trial, N = 661; I² = 0%; moderate-quality evidence). Gonadotrophins resulted in more clinical pregnancies than continued clomiphene citrate (RR 1.31, 95% CI 1.13 to 1.52; one trial, N = 661; I² = 0%; moderate-quality evidence), and more miscarriages (RR 2.23, 95% CI 1.11 to 4.47; one trial, N = 661; I² = 0%; moderate-quality evidence). None of the women developed OHSS. AUTHORS' CONCLUSIONS: There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial

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Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome

Clomiphene citrate (CC) is generally considered first-line treatment in women with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction with follicle-stimulating hormone (FSH; gonadotrophins) is second-line treatment for women who do not ovulate or conceive while taking CC. Metformin may increase the effectiveness of ovulation induction with gonadotrophins and may promote safety by preventing multiple pregnancy. To determine the effectiveness and safety of metformin co-treatment during ovulation induction with gonadotrophins with respect to rates of live birth and multiple pregnancy in women with PCOS. We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and the Cumulative Index to Nursing and Allied Health Literature (CINAH) on 8 June 2016, and the reference lists of included and other relevant studies. We searched ongoing trials registries in the World Health Organization (WHO) portal and on clinicaltrials.gov on 4 September 2016. We included randomised controlled trials (RCTs) reporting data on comparison of clinical outcomes in women with PCOS undergoing ovulation induction with gonadotrophins plus metformin versus gonadotrophins alone or gonadotrophins plus placebo. We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth rate and multiple pregnancy rate. Secondary outcomes were ovulation rate, clinical pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, miscarriage rate, cycle cancellation rate and adverse effects. We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34; two RCTs, n = 180; I(2) = 0%; low-quality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46; four RCTs, n = 232; I(2) = 0%; low-quality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31; five RCTs, n = 264; I(2) = 0%; low-quality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; four RCTs, n = 232; I(2) = 0%; low-quality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09; two RCTs, n = 91; I(2) = 0%; very low-quality evidence). Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practic

Does the postcoital test predict pregnancy in WHO II anovulatory women? A prospective cohort study

Objective To assess the capacity of the postcoital test (PCT) to predict pregnancy in WHO II anovulatory women who are ovulatory on clomiphene citrate (CC). In these women, an abnormal PCT result could be associated with lower pregnancy chances, but this has never been proven or refuted. Study design Prospective cohort study was performed between December 2009 and September 2012 for all women who started ovulation induction with CC in one university clinic and two teaching hospitals in the Netherlands. A PCT was performed in one of the first three ovulatory cycles. Ovulation induction with CC was continued for at least six cycles. The PCT was judged to be positive if at least one progressive motile spermatozo was seen in one of five high power fields at 400× magnification. The primary outcome was time to ongoing pregnancy, within six ovulatory cycles. Results In 152 women the PCT was performed. 135 women had a reliable, well-timed PCT. The ongoing pregnancy rate was 44/107 (41%) for a positive and 10/28 (36%) for a negative PCT. The hazard rate for ongoing pregnancy was 1.3 (95% CI 0.64–2.5) for a positive versus a negative PCT. Thirty five of 77 (46%) women with clear mucus had an ongoing pregnancy versus 12 of 45 (27%) women in whom the mucus was not clear (HR 2.0; 95% CI 1.02–3.84, p = 0.04). Conclusion The present study suggests that the outcome of the postcoital test in women with WHO-II anovulation that undergo ovulation induction with CC does not have a large effect on ongoing pregnancy chances over time

Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage

BACKGROUND: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcut aneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in t he group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, −2.6 percentage points; 95% confidence interval [CI], −15.0 to 9.9; aspirin only vs. placebo, −6.2 percentage points; 95% CI, −18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, −10.8 to 15.0; aspirin alone vs. placebo −5.4 percentage points; 95% CI, −18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)Stef P. Kaandorp, Mariëtte Goddijn, Joris A.M. van der Post, Barbara A. Hutten, Harold R. Verhoeve, Karly Hamulyák, Ben Willem Mol, Nienke Folkeringa, Marleen Nahuis, Dimitri N.M. Papatsonis, Harry R. Büller, Fulco van der Veen and Saskia Middeldor