Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study) : a randomized controlled trial

Funding The study received a grant from The Netherlands Organisation for Health Research and Development (ZonMw; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis and interpretation of data or writing of the manuscript.Peer reviewedPublisher PD

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometnal scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between - 0.7% and 9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/11 I for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

How are neonatal and maternal outcomes reported in randomised controlled trials (RCTs) in reproductive medicine?

STUDY QUESTION: How do randomised controlled trials (RCTs) in reproductive medicine report maternal and neonatal outcomes, specifically singleton live birth? SUMMARY ANSWER: Despite the widespread appeal to use singleton live birth as the outcome measure in subfertility trials, 80% of RCTs fail to do so, and fail to report on neonatal and maternal outcomes. WHAT IS KNOWN ALREADY: The aim of reproductive medicine is to assist subfertile couples in their wish to have children. A decade ago it was proposed to use singleton live birth as the outcome measure. We assessed whether clinical research has followed this recommendation, and how neonatal/maternal outcomes are reported. STUDY DESIGN, SIZE, DURATION: A review of the published literature from 1 January 1966 to 31 December 2012 was performed using the Cochrane database. We compared the time periods before and after 2004; the year after ESHRE recommended the use of singleton live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched the Cochrane database for RCTs in reproductive medicine, and recorded the number of studies that used singleton live birth as the outcome measure. We also recorded the reporting neonatal and maternal outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 910 RCTs that reported on fertility treatments, of which 182 RCTs (20%) reported on singleton live birth [before 2004 96/518 (19%); after 2003 86/392 RCTs (22%)]. Singleton live birth was the primary outcome in 68 RCTs (7.4%). Only 44 RCTs (4.8%) reported on neonatal outcome, while 52 RCTs (5.7%) reported on maternal outcome. LIMITATIONS, REASONS FOR CAUTION: We only included Cochrane reviews, thus report here only on the higher quality studies. The actual reporting on maternal and neonatal outcome may even be lower when studies of lower quality are included. WIDER IMPLICATIONS OF THE FINDINGS: Although a decade ago singleton live birth was recommended as the outcome measure of reproductive medicine research, this has not been followed; currently most clinical research in reproductive medicine does not report beyond the occurrence of pregnancy. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for the study. The authors have no conflicts of interest to declare.M. Braakhekke, E.I. Kamphuis, M.M. van Rumste, F. Mol, F. van der Veen and B.W. Mo

The value of chromosomal analysis in oligozoospermic men

Objective: To determine the prevalence of chromosomal abnormalities in relation to sperm concentration in subfertile oligozoospermic men. Design: Retrospective cohort study. Setting: Two teaching hospitals. Patient(s): We retrospectively studied all men who received chromosomal analysis prior to intracytoplasmic sperm injection (ICSI) treatment from 2000 to 2010 in two teaching hospitals. Intervention(s): None. Main Outcome Measure(s): The results of chromosomal analysis and semen analysis were recorded. The frequency of abnormal karyotypes was analyzed in relation to the sperm concentration, categorized as extreme oligozoospermia (>0 to 1 to 5 to 20 million/mL). Result(s): Among 582 male ICSI candidates, the rates of abnormal karyotypes were 1.2% (2/162), 2.2% (5/227), and 1.5% (2/130) for men with extreme, severe, and moderate oligozoospermia, respectively. No abnormalities were present in normospermic men. Conclusion(s): The risk of conceiving a viable child with unbalanced structural chromosomal abnormalities in men with oligozoospermia may not justify karyotyping. (Fertil Steril (R) 2012;98:1438-42. (C) 2012 by American Society for Reproductive Medicine.

The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis

BACKGROUND: The influence of multifollicular growth on pregnancy rates in subfertile couples undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH) remained unclear. METHODS: Relevant papers were identified by searching MEDLINE, EMBASE and the Cochrane Library. A meta-analysis was performed and Mantel-Haenszel pooled odd ratios (ORs) and risk differences with 99% confidence intervals (CIs) were calculated to express the relation between the number of follicles and pregnancy rates. RESULTS: We included 14 studies reporting on 11 599 cycles. The absolute pregnancy rate was 8.4% for monofollicular and 15% for multifollicular growth. The pooled OR for pregnancy after two follicles as compared with monofollicular growth was 1.6 (99% CI 1.3-2.0), whereas for three and four follicles, this was 2.0 and 2.0, respectively. Compared with monofollicular growth, pregnancy rates increased by 5, 8 and 8% when stimulating two, three and four follicles. The pooled OR for multiple pregnancies after two follicles was 1.7 (99% CI 0.8-3.6), whereas for three and four follicles this was 2.8 and 2.3, respectively. The risk of multiple pregnancies after two, three and four follicles increased by 6, 14 and 10%. The absolute rate of multiple pregnancies was 0.3% after monofollicular and 2.8% after multifollicular growth. CONCLUSIONS: Multifollicular growth is associated with increased pregnancy rates in IUI with COH. Since in cycles with three or four follicles the multiple pregnancy rate increased without substantial gain in overall pregnancy rate, IUI with COH should not aim for more than two follicles. One stimulated follicle should be the goal if safety is the primary concern, whereas two follicles may be accepted after careful patient counsellin

Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial

Contains fulltext : 232470.pdf (Publisher’s version ) (Open Access)BACKGROUND: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. METHODS: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 μg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 6-8 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. FINDINGS: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79•1%) of 172 participants reached complete evacuation compared to 101 (58•7%) of 172 participants in the placebo group (p<0•0001, RR 1•35, 95% CI 1•16-1•56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0•0005) (Table 3). INTERPRETATION: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL. FUNDING: Healthcare Insurers Innovation Foundation, Radboud University Medical Centre, Canisius Wilhelmina Hospital

Bipolar Radiofrequency Endometrial Ablation Compared With Hydrothermablation for Dysfunctional Uterine Bleeding A Randomized Controlled Trial

OBJECTIVE: To compare the effectiveness of two second-generation ablation techniques, bipolar radiofrequency impedance-controlled endometrial ablation and hydrothermablation, in the treatment of menorrhagia. METHODS: This study was a double-blind, randomized controlled trial, which took place in a large teaching hospital in The Netherlands with 500 beds. Women with menorrhagia were randomly allocated to bipolar radiofrequency ablation (bipolar group) and hydrothermablation (hydrotherm group). At follow-up, both women and observers remained unaware of the type of treatment that had been performed. The primary outcome was amenorrhea. Secondary outcome measures were patient satisfaction and reintervention. RESULTS: We included 160 women in the study, of which 82 were allocated to the bipolar group and 78 to the hydrotherm group. No complications occurred in either of the treatment groups. After 12 months, 87% (65 of 75) of the patients in the bipolar group were completely satisfied with the result of the treatment compared with 68% (48 of 71) in the hydrotherm group (relative risk 1.3, 95% confidence interval [CI] 1.03-1.6). The amenorrhea rates were 47% (35 of 75) in the bipolar group and 24% (17 of 71) in the hydrotherm group (relative risk 2.0, 95% CI 1.2-3.1). The relative risks for a reintervention in the bipolar group compared with the hydrotherm group was 0.29 (95% CI 0.12-0.67), whereas for hysterectomy, this was 0.49 (95% CI 0.15-1.5). CONCLUSION: In the treatment of menorrhagia, bipolar radiofrequency endometrial ablation system is superior to hydrothermablation. (Obstet Gynecol 2010;116:819-26