Endometrial preparation with vs without ovulation for frozen-embryo transfer: systematic review and meta-analysis of randomized controlled trials

Why clinicians should know about it

• Picked for Neonatology (top studies of the week, 30 August 2026): Systematic review of endometrial preparation for frozen‑embryo transfer
• Picked for Obstetrics and Gynecology (top studies of the week, 30 August 2026): Systematic review of endometrial preparation for frozen‑embryo transfer
• Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 30 August 2026): High-quality evidence in a top journal

Abstract

OBJECTIVE: To compare the effectiveness and safety of endometrial-preparation methods with ovulation (maintaining a corpus luteum) vs those without ovulation (artificial/programmed cycles) for frozen-embryo transfer. METHODS: We searched PubMed, Scopus, Web of Science and major clinical trial registries from inception to 22 February 2026 for randomized controlled trials (RCTs) comparing endometrial preparation with ovulation (natural, modified natural or stimulated cycles) against endometrial preparation without ovulation (artificial cycles) for frozen-embryo transfer. The primary outcomes were live-birth rate and presence of hypertensive disorders of pregnancy (HDP). Secondary outcomes included clinical-pregnancy rate, cycle cancelation rate, pregnancy loss and neonatal outcomes (preterm birth and birth weight). Risk of bias was assessed using the Cochrane Risk-of-Bias version 2 tool and trustworthiness was evaluated using the INveStigating ProblEmatic Clinical Trials in Systematic Reviews tool. Data were pooled using random-effects meta-analysis to estimate the risk ratio (RR) with 95% CI. A sensitivity analysis was performed excluding studies categorized as having a high risk of bias and those with serious concerns regarding trustworthiness. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We included 17 RCTs involving a total of 10 611 participants. We identified high-certainty evidence that endometrial preparation with ovulation significantly reduced the risk of pregnancy loss (RR, 0.75 (95% CI, 0.65-0.86)) and resulted in equivalent clinical-pregnancy rates (RR, 1.02 (95% CI, 0.98-1.06)) compared with endometrial preparation without ovulation. Moderate-certainty evidence showed comparable live-birth rates overall (RR, 1.07 (95% CI, 0.95-1.22)). However, exclusion of studies at high risk of bias and one outlier trial with a high difference in cycle-cancelation rate between groups revealed significantly higher live-birth rates for endometrial preparation with vs without ovulation (RR, 1.15 (95% CI, 1.01-1.31)). Moderate-certainty evidence also indicated a protective trend against HDP with ovulation (RR, 0.77 (95% CI, 0.55-1.07)), and no significant difference in the rate of macrosomia between groups (RR, 0.98 (95% CI, 0.73-1.30)). Evidence regarding other outcomes was of low or very low certainty. CONCLUSIONS: Endometrial preparation with ovulation offers an advantage over artificial cycles by significantly reducing the risk of pregnancy loss following frozen-embryo transfer. The available evidence also suggests that there are higher live-birth rates when cycle cancelation is minimized. Clinicians should prioritize endometrial preparation with ovulation, aiming for a low cycle-cancelation rate, in order to reduce the rate of pregnancy loss and maximize the rate of live birth in women undergoing frozen-embryo transfer. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.

Abstract as published, via PubMed.