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

Risk of cancer in children and young adults conceived by assisted reproductive technology

STUDY QUESTION: Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER: Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY: Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION: A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS: All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers’ questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE: The median follow-up was 21 years (interquartile range (IQR): 17–25) and was shorter in ART-conceived children (20 years, IQR: 17–23) compared with naturally conceived children (24 years, IQR: 20–30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72–1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90–1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73–2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81–2.85; 1.80, 95% CI: 0.65–4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81–7.37) and melanoma (HR = 1.86, 95% CI: 0

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

The value of chromosomal analysis in oligozoospermic men

Abstract not availableÇarcia Stegen, Minouche M.E. van Rumste, Ben Willem J. Mol, and Carolien A.M. Kok

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

Measuring outcomes in fertility trials: can we rely on clinical pregnancy rates?

ObjectiveTo assess whether the estimates of treatment effect in randomized clinical trials (RCTs) in reproductive medicine differ when either clinical pregnancy or live birth is used as the outcome measure.DesignMetaanalysis.SettingWe analyzed RCTs in reproductive medicine found in systematic reviews published in the Cochrane Library that reported on both clinical pregnancy and live birth.Patient(s)Subfertile couples.Intervention(s)For each individual RCT, data on clinical pregnancy and live birth were extracted.Main outcome measure(s)We compared the outcome of each study by calculating a kappa-statistic (statistically significant treatment effective or not) and by comparing the odds ratio by calculating the ratio of the odds ratios (ROR).Result(s)We found 67 systematic reviews, of which 42 reported on pregnancy and live birth. These 42 reviews included 654 RCTs, of which 143 (22%) reported both on pregnancy and live birth. The pregnancy loss rates in the treatment and control groups were comparable. Of the 143 RCTs, the conclusion based on pregnancy rate and live birth rate was comparable (kappa value of 0.81; 95% confidence interval [CI], 0.68-0.94). The odds ratios estimating treatment effect from pregnancy and live birth were also comparable (ROR, 1.01, 95% CI 0.9 to 1.12).Conclusion(s)Only a minority of randomized clinical trials in reproductive medicine report on live birth. Conclusions on the effectiveness of a treatment based on either clinical pregnancy or live birth as endpoints are comparable.Jane F. Clarke, Minouche M. E. van Rumste, Cindy M. Farquhar, Neil P. Johnson, Ben W. J. Mol, and Peter Herbiso