Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342)

Abstract 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, 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 17/111 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. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports ‘other’ from Ferring BV, personal fees from Up to date Hyperthecosis, ‘other’ from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE 31 July 2015. DATE OF FIRST PATIENT’S ENROLMENT 26 January 2016.

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Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial

Human Reproduction Open ◽

10.1093/hropen/hoz030 ◽

2019 ◽

Vol 2019 (4) ◽

Cited By ~ 1

Author(s):

L Kluge ◽

C Bergh ◽

S Einarsson ◽

A Pinborg ◽

A-L Mikkelsen Englund ◽

...

Keyword(s):

Live Birth ◽

Weight Reduction ◽

Birth Rate ◽

Controlled Trial ◽

Live Birth Rate ◽

Obese Women ◽

Live Births ◽

Randomized Controlled ◽

Cumulative Live Birth

Abstract STUDY QUESTION Did weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2 years? SUMMARY ANSWER Weight loss prior to IVF did not increase CLBR. WHAT IS KNOWN ALREADY Few studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity. STUDY DESIGN, SIZE, DURATION A 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Nine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38 years of age having a BMI ≥30 and < 35 kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12 weeks and 3–5 weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE 42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P = 0.56; odds ratio (OR) 1.16, 95% CI: 0.74–1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2 years. The mean weight gain over the 2 years was 8.6 kg, while women in the IVF-only group had a mean weight loss of 1.2 kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and − 0.055 (1.271) (mean, SD) in the IVF-only group (P = 0.25; mean difference between groups, 0.327; 95% CI: −0.272 to 0.932). LIMITATIONS, REASON FOR CAUTION All data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR. WIDER IMPLICATIONS OF THE FINDINGS The follow-up indicates that for women with a BMI ≥30 and < 35 kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2 years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred. STUDY FUNDING/COMPETING INTEREST(S) The 2-year follow-up was financed by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-70940 and ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose. TRIAL REGISTRATION NUMBER ClinicalTrials.gov number, NCT01566929.

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Fresh versus frozen single embryo transfer in Chinese women of advanced age undergoing IVF/ICSI: a study protocol for a randomized controlled trial

10.21203/rs.3.rs-18972/v1 ◽

2020 ◽

Author(s):

Miaoxin Chen ◽

Yuanyuan Wu ◽

Xin Huang ◽

Wenqiang Liu ◽

Wentao Li ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Controlled Trial ◽

Live Birth Rate ◽

Advanced Age ◽

Cumulative Live Birth Rate ◽

Fresh Embryo Transfer ◽

Randomized Controlled

Abstract Background: Elective frozen cleavage embryo transfer resulted in significantly higher live birth rate in patients with polycystic ovary syndrome but not in ovulatory women compared with fresh embryo transfer. Further, elective single frozen blastocyst transfer had significantly higher live birth rate in ovulatory women compared with single fresh blastocyst transfer. However, it is unknown whether single frozen cleavage embryo transfer results in higher cumulative live birth rate in women of advanced age undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The aim of this study is to compare the effectiveness of frozen cleavage embryo transfer with fresh cleavage embryo transfer in Chinese women of advanced age. Methods: This study is a double-blind randomized controlled clinical trial (1:1 treatment ratio of frozen embryo transfer vs. fresh embryo transfer). A total of 840 women of advanced age with normal ovarian reserve undergoing the first cycle of IVF or ICSI will be enrolled and randomized into two parallel groups. Participants in group A will undergo frozen single cleavage embryo transfer, and participants in group B will undergo fresh single cleavage embryo transfer. The primary outcome is the cumulative live birth rate of the trial IVF/ICSI cycle within 12 months after randomization. This study is powered to detect an absolute difference of 8% (23% vs 15%) at the significance level of 0.05 and 80% statistical power based on a two-sided test. Discussion: The results of this study will provide evidence for the efficacy and safety of frozen cleavage embryo transfer compared with fresh cleavage embryo transfer in women of advanced age undergoing IVF/ICSI. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029330. Registered on 25 Jan 2020. Keywords: Frozen embryo transfer, advanced age, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), live birth, randomized controlled trial.

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