Patient perspectives and preferences on cerclage and preterm birth: a focus group study.

AIM: This qualitative focus group study aims to asses cerclage-related symptoms, the impact of a cerclage on daily functioning and patient perspectives of their healthcare experience. This study extends beyond the current focus on surgical and obstetric outcomes of a cerclage, thereby contributing to a more comprehensive understanding of the challenges faced by individuals in the context of extreme preterm birth and fetal loss and the impact of a cerclage on multiple facets in life. METHODS: Participants were recruited from the Amsterdam University Medical Center, Amsterdam, the Netherlands or via the website of a Dutch patient organization for (extreme) preterm birth. Eligible participants were ≥ 18 years old with a previous vaginal and/or abdominal cerclage with a subsequent delivery at ≥ 34 weeks of gestation with neonatal survival. Two focus group discussions (FGD) were performed. A predefined format was used, which was identical for both the vaginal and abdominal cerclage group. The International Classification of Functioning, Disability and Health (ICF-DH) was used to provide structure. Outcomes were a broad range of participants reported perspectives on physical, emotional, and social-related quality of life. RESULTS: In the Vaginal Cerclage Group (VCG) and Abdominal Cerclage Group (ACG), respectively, 11 and 8 participants were included. Fear for a subsequent pregnancy loss was the most limiting factor to perform daily activities during pregnancy in all participants with a cerclage. Fear to conceive again because of prior second-trimester fetal loss was experienced by 27% in the VCG and 13% in the ACG. The majority of participants experienced a reduction in anxiety after placement of their cerclage (VCG = 64%, ACG = 75%). Decreased mobility/bedrest (VCG = 100%, ACG = 75%) and blood loss (VCG = 55%, ACG = 13%) were frequently mentioned complaints during pregnancy with cerclage. Other aspects mentioned in both groups were social isolation, the lack of societal participation, and the perceived need to quit work and sports. All participants in the abdominal cerclage group reported a lack of comprehensible and unambiguous information about obstetric management and expectations during pregnancy in secondary care hospitals. Clear communication between secondary and tertiary care hospitals about obstetric management following an abdominal cerclage, for example, about the need for cervical length measurements by ultrasound, the need for bedrest or advice concerning sexual activity was missing (63%). Psychologic support was desired in half of all participants, but was not offered to them. CONCLUSIONS: The fear of a subsequent pregnancy loss was reported as the most limiting factor in daily life by all participants. Cerclage placement resulted in the reduction of anxiety. Participants mentioned a significant impact of bedrest and activity restriction during pregnancy with cerclage on social participation and daily activities. Unfortunately, no high level evidence is available on this matter. Patients might even benefit from appropriate levels of physical activity throughout their pregnancy to promote their overall well-being. More evidence is needed to determine the optimal level of physical activity. There is a need for clear and unambiguous patient information about obstetric management.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

STUDY QUESTION: Does lifestyle intervention consisting of an energy-restricted diet, enhancement of physical activity and motivational counseling prior to IVF improve embryo utilization rate (EUR) and cumulative live birth rate (CLBR) in women with obesity? SUMMARY ANSWER: A 6-month lifestyle intervention preceding IVF improved neither EUR nor CLBR in women with obesity in the first IVF treatment cycle where at least one oocyte was retrieved. WHAT IS KNOWN ALREADY: A randomized controlled trial (RCT) evaluating the efficacy of a low caloric liquid formula diet (LCD) preceding IVF in women with obesity was unable to demonstrate an effect of LCD on embryo quality and live birth rate: in this study, only one fresh embryo transfer (ET) or, in case of freeze-all strategy, the first transfer with frozen-thawed embryos was reported. We hypothesized that any effect on embryo quality of a lifestyle intervention in women with obesity undergoing IVF treatment is better revealed by EUR and CLBR after transfer of all fresh and frozen-thawed embryos. STUDY DESIGN SIZE DURATION: This is a nested cohort study within an RCT, the LIFEstyle study. The original study examined whether a 6-month lifestyle intervention prior to infertility treatment in women with obesity improved live birth rate, compared to prompt infertility treatment within 24 months after randomization. In the original study between 2009 and 2012, 577 (three women withdrew informed consent) women with obesity and infertility were assigned to a lifestyle intervention followed by infertility treatment (n = 289) or to prompt infertility treatment (n = 285). PARTICIPANTS/MATERIALS SETTING METHODS: Only participants from the LIFEstyle study who received IVF treatment were eligible for the current analysis. In total, 137 participants (n = 58 in the intervention group and n = 79 in the control group) started the first cycle. In 25 participants, the first cycle was cancelled prior to oocyte retrieval mostly due to poor response. Sixteen participants started a second or third consecutive cycle. The first cycle with successful oocyte retrieval was used for this analysis, resulting in analysis of 51 participants in the intervention group and 72 participants in the control group. Considering differences in embryo scoring methods and ET day strategy between IVF centers, we used EUR as a proxy for embryo quality. EUR was defined as the proportion of inseminated/injected oocytes per cycle that was transferred or cryopreserved as an embryo. Analysis was performed per cycle and per oocyte/embryo. CLBR was defined as the percentage of participants with at least one live birth from the first fresh and subsequent frozen-thawed ET(s). In addition, we calculated the Z-score for singleton neonatal birthweight and compared these outcomes between the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: The overall mean age was 31.6 years and the mean BMI was 35.4 ± 3.2 kg/m2 in the intervention group, and 34.9 ± 2.9 kg/m2 in the control group. The weight change at 6 months was in favor of the intervention group (mean difference in kg vs the control group: -3.14, 95% CI: -5.73 to -0.56). The median (Q25; Q75) number of oocytes retrieved was 4.00 (2.00; 8.00) in the intervention group versus 6.00 (4.00; 9.75) in the control group, and was not significantly different, as was the number of oocytes inseminated/injected (4.00 [2.00; 8.00] vs 6.00 [3.00; 8.75]), normal fertilized embryos (2.00 [0.50; 5.00] vs 3.00 [1.00; 5.00]) and the number of cryopreserved embryos (2.00 [1.25; 4.75] vs 2.00 [1.00; 4.00]). The median (Q25; Q75) EUR was 33.3% (12.5%; 60.0%) in the intervention group and 33.3% (16.7%; 50.0%) in the control group in the per cycle analysis (adjusted B: 2.7%, 95% CI: -8.6% to 14.0%). In the per oocyte/embryo analysis, in total, 280 oocytes were injected or inseminated in the intervention group, 113 were utilized (transferred or cryopreserved, EUR = 40.4%); in the control group, EUR was 30.8% (142/461). The lifestyle intervention did not significantly improve EUR (adjusted odds ratio [OR]: 1.36, 95% CI: 0.94-1.98) in the per oocyte/embryo analysis, taking into account the interdependency of the oocytes per participant. CLBR was not significantly different between the intervention group and the control group after adjusting for type of infertility (male factor and unexplained) and smoking (27.5% vs 22.2%, adjusted OR: 1.03, 95% CI: 0.43-2.47). Singleton neonatal birthweight and Z-score were not significantly different between the two groups. LIMITATIONS REASONS FOR CAUTION: This study is a nested cohort study within an RCT, and no power calculation was performed. The randomization was not stratified for indicated treatment, and although we corrected our analyses for baseline differences, there may be residual confounding. The limited absolute weight loss and the short duration of the lifestyle intervention might be insufficient to affect EUR and CLBR. WIDER IMPLICATIONS OF THE FINDINGS: Our data do not support the hypothesis of a beneficial short-term effect of lifestyle intervention on EUR and CLBR after IVF in women with obesity, although more studies are needed as there may be a potential clinically relevant effect on EUR. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). A.H. has received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.J.M. reports consultancy for Guerbet, has been a member of the ObsEva advisory board and holds Stock options for ObsEva. B.W.J.M. has received research funding from Guerbet, Ferring and Merck. F.J.M.B. reports personal fees from membership of the external advisory board for Merck Serono and a research support grant from Merck Serono, outside the submitted work. TRIAL REGISTRATION NUMBER: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530). https://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1530.

Quadruple torsion of the fallopian tube in an 18-year-old virgin: a rare twist.

In this report, we describe an 18-year-old nulliparous virgo, with no medical history, who presented herself at the emergency department with symptoms of lower abdominal pain and nausea with vomiting. On examination, an echogenic unilocular cyst with possible relation to the right ovary was found. The working diagnosis was an ovarian torsion. She underwent a diagnostic laparoscopy which revealed a quadruple torsion of the fallopian tube with hydrosalpinx. Detorsion of the tube was performed, and the tube was drained using diathermic incision. After the surgery, the patient recovered rapidly. Ultrasonic evaluation 38 days later showed an echogenic area measuring 2×3 cm suspected for persistent hydrosalpinx. Because of the asymptomatic postoperative period, the patient was treated conservatively, and no further treatment was performed.

Influence of endometrial thickness on pregnancy rates in modified natural cycle frozen-thawed embryo transfer.

INTRODUCTION: Pregnancy after frozen-thawed embryo transfer (FET) is a multifactorial process. Although embryo quality is a key factor in determining pregnancy, other factors, including maternal determinants, are also considered to be predictive. Even though an association between endometrial thickness measured by transvaginal ultrasound and pregnancy rates has been reported in patients undergoing various assisted reproductive technology treatments, whether endometrial thickness predicts achieving pregnancy after natural cycle FET (NC-FET) remains unclear. MATERIAL AND METHODS: In this cohort study, 463 patients allocated to the modified NC-FET (mNC-FET) arm of a previously published randomized controlled trial were included. Monitoring in mNC-FET cycles consisted of regular ultrasound scans, measuring both dominant follicle and endometrial thickness. When the dominant follicle reached a size of 16-20 mm, an injection of human chorionic gonadotrophin was administered and embryo thawing and transfer planned. No minimal endometrial thickness was defined below which transfer was to be deferred. The primary endpoint was ongoing pregnancy rate. RESULTS: Overall, the ongoing pregnancy rate per started FET cycle was 12.5%. Multivariate regression analyses showed that embryo quality was the only significant predictor for ongoing pregnancy. Mean endometrial thickness did not differ between patients achieving ongoing pregnancy and those who did not (9.0 vs. 8.8 mm, p = 0.4). Comparable results were obtained with regard to clinical pregnancy, live birth and miscarriage rates. The area under the receiver operator curve was 0.5, indicating little discriminatory value of endometrial thickness. CONCLUSIONS: Given that endometrial thickness was not found to be predictive of pregnancy after mNC-FET, cancellation based on endometrial thickness alone may not be justified.

Association between periconceptional weight loss and maternal and neonatal outcomes in obese infertile women.

BACKGROUND: Obesity in women of reproductive age has deleterious effects on reproductive and offspring health. In this study, we aimed to evaluate the association between the magnitude of periconceptional body-mass index (BMI) change and maternal and neonatal outcomes in obese infertile women who participated in the LIFEstyle study. The LIFEstyle study was a randomized controlled trial, evaluating if a six-month lifestyle intervention program prior to infertility treatment in obese infertile women improved birth rates, compared to prompt infertility treatment. METHODS AND FINDINGS: This is an exploratory post hoc analysis of the LIFEstyle study. We recorded periconceptional BMI change in women with an ongoing pregnancy, pooling data of all women, regardless of randomization arm. Periconceptional BMI change was calculated using weight at randomization and the periconceptional weight (measured in kilograms 12 weeks before or after conception and expressed as BMI change in units BMI (kg/m2)). Subsequently, women were categorized into quartiles according to the magnitude of their periconceptional change in BMI. The odds of maternal and neonatal outcomes were calculated using logistic regression analysis, comparing women in each of the first three weight change quartiles separately, and combined, to women in the fourth quartile. The fourth quartile was chosen as reference group, since these women had the least weight loss. We adjusted for periconceptional BMI, nulliparity and smoking status. In addition, we performed a subgroup analysis for singleton pregnancies. In the LIFEstyle study, 321 obese infertile women achieved an ongoing pregnancy which was conceived within 24 months after randomization. Periconceptional BMI change was available in 244 of these women (76%). Median BMI at randomization was 35.9 kg/m2. Women in the first quartile (Q1) had a periconceptional BMI change of <-2.1 kg/m2, women in the second quartile (Q2) -2.1 to -0.9 kg/m2, women in the third quartile (Q3) -0.9 to 0.1 kg/m2 and women in the fourth quartile (Q4) gained ≥0.1 kg/m2. There were no significant differences between women in the quartiles regarding rates of excessive gestational weight gain (in term pregnancies), gestational diabetes, preterm birth, induction of labor, spontaneous vaginal birth and Caesarean section. Compared to women in Q4, the adjusted odds ratios, aOR, and 95% confidence interval for a hypertensive complication were; 0.55 (0.22-1.42) for women in Q1, 0.30 (0.12-0.78) for women in Q2, 0.39 (0.16-0.96) for women in Q3 and 0.39 (0.19-0.82) for women in Q1 to Q3 combined. In the subgroup analysis, investigating singleton pregnancies only, the statistically significant decreased rate of a hypertensive complication remained in women in Q2 (aOR 0.27, 95% CI 0.10-0.72) and Q3 (aOR 0.39, 95%CI 0.16-0.98) and when comparing women in Q1 to Q3 together to women in Q4 (aOR 0.38, 95%CI 0.18-0.80). Furthermore, there was a significantly decreased aOR (95%CI) of preterm birth in women in Q2 (0.24, 0.06-0.98) and when combining women in Q1 to Q3 (0.37, 0.14-0.97) compared to women in Q4. CONCLUSIONS: These results suggest that a periconceptional decrease in BMI in obese infertile women could lead to a decrease of the rates of hypertensive pregnancy complications and preterm birth. The results are limited by the exploratory nature of the analyses and further evidence is necessary to provide more definitive conclusions.

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.

Longer time interval between semen processing and intrauterine insemination does not affect pregnancy outcome.

OBJECTIVE: To study whether the pregnancy outcome of intrauterine insemination (IUI) is affected by a longer time interval between semen processing and insemination. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENT(S): Couples with subfertility and an indication for IUI over a 10-year period. INTERVENTION (S): Insemination performed the day after but within 24 hours of semen collection and processing (delayed insemination) compared with insemination performed immediately after sperm collection and processing (immediate insemination). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate, defined as a pregnancy confirmed by ultrasound at 10 to 12 weeks of gestation. RESULT(S): In total, 1,136 cycles were analyzed. In 77 of 547 couples (14%) an ongoing pregnancy occurred after delayed insemination, and in 77 of 589 couples (13%) an ongoing pregnancy occurred after immediate insemination. Both groups had similar baseline characteristics. After adjustment for confounders, there was no difference in the ongoing pregnancy rate between delayed as compared with immediate insemination (odds ratio 0.89; 95% confidence interval, 0.63-1.25). CONCLUSION(S): There is no negative effect on pregnancy rate when IUI of processed sperm is delayed until the next day. This approach allows additional flexibility for couples when the male partner is not available on the day of ovulation, and it allows for a spread of workload in the laboratory.

Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial.

BACKGROUND: Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths. METHODS: We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852. FINDINGS: Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93-1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy. INTERPRETATION: Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. FUNDING: The Dutch Organisation for Health Research and Development (ZonMW).

Randomized Trial of a Lifestyle Program in Obese Infertile Women.

BACKGROUND: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.).

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

BACKGROUND AND OBJECTIVES: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. CONCLUSIONS: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. LIMITATIONS: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. FUTURE WORK: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

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.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

BACKGROUND: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTS: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

The inSIGHT study: costs and effects of routine hysteroscopy prior to a first IVF treatment cycle. A randomised controlled trial.

BACKGROUND: In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11-45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle. METHODS/DESIGN: Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study. DISCUSSION: The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment. TRIAL REGISTRATION: NCT01242852.

The LIFESTYLE study: costs and effects of a structured lifestyle program in overweight and obese subfertile women to reduce the need for fertility treatment and improve reproductive outcome. A randomised controlled trial.

BACKGROUND: In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome. METHODS/DESIGN: Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m2. Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders.In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient's weight. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs.Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group. DISCUSSION: The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1530.

[Problems in early pregnancy require special care: 'early pregnancy units']. / Problemen vroeg in de zwangerschap vereisen speciale zorg: 'Jonge zwangerschapsunits'.

Problems in the first trimester of pregnancy frequently occur. Examples are miscarriage, ectopic pregnancy and recurrent miscarriage. In Dutch hospitals there is a growing interest in the setting up of 'early pregnancy units' (EPUs). The aim of these EPUs is to improve the quality of care for women with early pregnancy problems by centralising the care and knowledge available. This centralisation could prevent over- and underdiagnosis and over- and undertreatment. Moreover, EPUs could improve the logistics of clinical research. The potential effectiveness of these units in the Netherlands still needs to be investigated.

Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.

OBJECTIVE: To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. DESIGN: Randomised controlled trial. SETTING: Secondary and tertiary hospitals in the Netherlands. PARTICIPANTS: 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. INTERVENTION: Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. MAIN OUTCOME MEASURE: Ongoing pregnancy within 12 months. RESULTS: . The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). CONCLUSION: The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy.