Although there were no statistical differences, the study groups were small and heterogenic, with a number of potential biases. We therefore recommend a standardized methodology of follow-up studies after ART, with well-defined groups of ICSI with ejaculated sperm, ICSI with epididymal sperm and ICSI with testicular sperm, and a control group of naturally conceived children.
Study question Does uninterrupted embryo culture with or without the application of a time-lapse monitoring (TLM) selection algorithm lead to higher (cumulative) ongoing pregnancy rates? Summary answer Uninterrupted embryo culture with or without a TLM selection algorithm and interrupted culture with morphological embryo selection all resulted in comparable (cumulative) ongoing pregnancy rates. What is known already The application of TLM for embryo development has been claimed to improve success rates of IVF and ICSI treatments. Systematic reviews, however, show that evidence supporting the routine clinical use of TLM in IVF laboratories is limited and well-designed RCTs are needed to assess its clinical value. The uninterrupted and stable culture conditions in a TLM incubator may cause an increase of the clinical success rate independent from a possible improvement mediated by TLM based embryo selection procedures. Therefore, three study groups were needed to distinguish these two mechanisms. Study design, size, duration In this multicenter, double-blind, superiority RCT, women were prospectively randomized in three groups between 2017-2020: 1) TLE (Time-Lapse Eeva): embryo selection based on the Eeva® Test (a day three TLM algorithm, used adjunctively with morphology) and uninterrupted culture. 2) TLR (Time-Lapse Routine): routine morphological embryo selection and uninterrupted culture. 3) CON (Control): routine morphological embryo selection and interrupted culture. Embryos were cultured in Geri+ incubators. Randomization was stratified for laboratory-site and ovum pickup number. Participants/materials, setting, methods Women scheduled for day three single embryo transfer (SET) during their first, second or third ovum pickup were included. Primary endpoints were: 1) cumulative ongoing pregnancy rate (cOPR) including fresh SET and associated cryo transfers within 12 months of all women; 2) ongoing pregnancy rate (OPR) after fresh SET in a good-prognosis population: women <41.0 years, ≥5 oocytes, ≥4 fertilized oocytes. Odds ratios (OR) with 95% CI were adjusted for laboratory-site and ovum pickup number. Main results and the role of chance A total of 1731 women were randomly assigned to TLE (577), TLR (579) or CON (575). The 12 month cOPR did not differ significantly between the groups (p = 0.85) with a cOPR of 50.8% (293/577) in TLE, 50.9% (295/579) in TLR and 49.4% (284/575) in CON (TLE vs TLR: OR 0.99, 95% CI 0.79 – 1.25; TLE vs CON: OR 1.06, 95% CI 0.84 – 1.33; CON vs TLR: OR 0.94, 95% CI 0.75 – 1.19). In the good-prognosis population, the OPR after fresh SET was 38.2% (125/327) in TLE, 36.5% (118/323) in TLR and 37.8% (123/325) in CON (p = 0.90). Consistent results were found for pregnancy and live birth rates after fresh embryo transfer and cumulatively within one year. A planned subgroup analysis of three female age groups revealed interaction between age group and treatment on cOPR (p = 0.02). In women of 39 years and older (n = 245), the cOPR was higher in TLE compared to TLR (40.0% vs 23.7%: OR 2.10, 95% CI 1.05-4.21) with no difference between TLE vs CON (40.0% vs 31.5%: OR 1.44, 95% CI 0.76-2.71). Limitations, reasons for caution This study investigated embryo culture in the Geri+ incubator and the Eeva® Test algorithm, which predicts blastocyst formation on day three and was used in combination with morphology for embryo selection, while more TLM systems and algorithms are currently available. Wider implications of the findings Neither embryo selection based on a TLM selection algorithm in combination with morphology (TLE) nor the uninterrupted culture conditions in the Geri+ incubator (TLR) improved (cumulative) ongoing pregnancy and live birth rates after IVF or ICSI. Widespread application for fertility treatments with the promise of improved outcomes should be questioned. Trial registration number NL5314
Background Insemination with donor sperm is an option for couples for whom in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) has been unsuccessful, couples with azoospermia and for single women or same sex couples. 1 Cervical insemination versus intra-uterine insemination of donor sperm for subfertility (Review)
STUDY QUESTION For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? SUMMARY ANSWER In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. WHAT IS KNOWN ALREADY Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain. STUDY DESIGN, SIZE, DURATION We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. PARTICIPANTS/MATERIALS, SETTING, METHODS We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. MAIN RESULTS AND THE ROLE OF CHANCE Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: −30% to −9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD −24%, 90% CI −36% to −13%) in line with inferiority of EM. LIMITATIONS, REASONS FOR CAUTION Our trial did not reach the planned sample size, therefore the results are limited by the number of participants. WIDER IMPLICATIONS OF THE FINDINGS This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. STUDY FUNDING/COMPETING INTEREST(S) The trial was supported by a grant of the SEENEZ healthcare initiative. The subsidizing parties were The Dutch Organisation for Health Research and Development (ZonMW 837004023, www.zonmw.nl) and the umbrella organization of 10 health insurers in The Netherlands. E.R.G. receives personal fees from Titus Health care outside the submitted work. M.G. declares unrestricted research and educational grants from Guerbet, Merck and Ferring not related to the presented work, paid to their institution VU medical centre. A.B.H. reports receiving travel and speakers fees from Nordic Pharma and Merck and he is member of the Nordic Pharma ANGEL group and of the Safety Monitoring Board of Womed. C.B.L. reports speakers fee from Inmed and Yingming, and his department receives research grants from Ferring, Merck and Guerbet paid to VU medical centre. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck. M.v.W. received a grant from the Netherlands Organisation for Health Research and Development ZonMW (80-8520098-91072). F.M. received two grants from the Netherlands Organisation for Health Research and Development ZonMW (NTR 5599 and NTR 6590). The other authors report no competing interest. TRIAL REGISTRATION NUMBER Dutch Trial register NL5455 (NTR5599) TRIAL REGISTRATION DATE 18 December 2015 DATE OF FIRST PATIENT’S ENROLMENT 26 January 2017
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.