36 Or 38 hours from ovulation trigger to Oocyte Pick-Up and ICSI outcomes: interim analysis of a multicentre single-blinded randomized controlled trial

Abstract

Study question: Does the period from Ovulation Trigger to Oocyte Pick-Up affect oocyte maturation rate and Intracytoplasmic Sperm Injection Outcomes? Summary answer: 36 and 38-hour trigger to OPU intervals yielded similar oocyte maturation and fertilization rates and pregnancy outcomes. What is known already: The trigger to OPU interval is typically scheduled around 36 hours, yet follicular response and cumulus expansion vary among patients and stimulation protocols. Small studies and physiologic data suggest that a slightly longer interval may allow more oocytes to complete meiosis, potentially improving metaphase two (MII) oocyte yield without increasing risk of premature ovulation, but evidence is inconsistent. A pragmatic, multicentre randomized trial with standardized outcome definitions and blinding is needed to quantify any benefit and evaluate whether laboratory gains translate into pregnancy and live birth outcomes. Study design, size, duration: Multi-center, blinded, parallel-group randomized controlled trial. Women are randomized 1:1 on trigger day to OPU at 36 h or 38 h. Central web-based randomization with variable block sizes was stratified by center, female age, intended transfer day (day 3 or Day 5) and PGT-A status (yes/no). Total of 850 participants were required to detect a 10% absolute increase in MII/follicle with 80% power (two-sided α = 0.05). This interim analysis included 550 participants. Participants/materials, setting, methods: Women aged 18–42 years undergoing ART were enrolled at seven centers. Stimulation protocols and laboratory followed routine practice of each participationg center. All mature oocytes were fertilized by ICSI; embryo transfers (single or double, day 3 or 5, fresh or frozen) were done as per each clinic’s protocol. Primary outcomes: MII oocytes per ≥10 mm follicle aspirated. Secondary outcomes: oocyte maturation, fertilization (2PN/MII injected), clinical pregnancy, and ongoing pregnancy/live birth rates. Main results and the role of chance: Interim analysis blinded for treatment allocation included 550 (Group A n = 273, Group B n = 277) participants with similar baseline characteristics (median female age 30 years in both groups (p = 0.3); similar antral follicle counts (median 15 vs 14), similar distribution of stimulation protocols and trigger modes. Oocyte maturity and embryology outcomes were comparable: median MII oocytes 10 (IQR 7-16) vs 9 (6-16) (p = 0.20); maturation rate 78.9% (IQR (66.7-88.6) vs 77.8% (IQR 66.7, 87.3) (p = 0.80); fertilization rate 76.9%(IQR 62.5-88.2) vs 75.0% (IQR 60.0-88.2) (p = 0.30). Embryo transfer occurred in 464 cycles, distribution of day 3 (47 (20%) vs 45 (20%)), and day 5 transfers (172 (73%) vs 168 (73%)) were similar in both groups; p > 0.90) and there were 84% vs 80% single embryo transfers (p = 0.30). Ongoing pregnancy or live birth rate per initiated cycle was 30.4% (n = 83) vs 28.5% (n = 79). Limitations, reasons for caution: This interim analysis includes 65% of the planned sample, yet the differences seem very small and unlikely to change with further recruitment. Wider implications of the findings: If confirmed in the final analysis, extending trigger-OPU timing to 38 hours is unlikely to change oocyte maturation rate or ICSI outcomes. It seems OPU can be flexibly scheduled between 36 and 38 hours.