Impact of endometrial thickness on reproductive outcome in fresh and frozen–thawed embryo transfer: systematic review and meta‐analysis

Abstract

Objective: To evaluate the impact of endometrial thickness on the reproductive outcomes of embryo transfer (ET) treatments using both cut-off-based meta-analysis and meta-analysis of proportions.

Methods: This was a systematic review and meta-analysis of comparative studies (randomized controlled trials, cohort studies, case-control studies) and descriptive studies (cross-sectional studies, case series) published in English, French, German, Italian or Spanish and analyzing the impact of endometrial thickness on the rates of embryo implantation, clinical pregnancy, live birth, miscarriage and/or ectopic pregnancy in fresh and/or frozen-thawed ET cycles. Live-birth rate was defined as the primary outcome. The literature search was conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science and ÍnDICEs-CSIC, from inception of each database until 1 September 2024. The risk of bias was assessed using the Newcastle-Ottawa scale for analytical studies and the Joanna Briggs Institute tool for descriptive studies. Pooled effects were estimated as odds ratios (OR) or risk differences obtained from a random-effects model, with 95% CIs. Linear meta-regression was used to assess the relationship between risk difference and endometrial thickness cut-off. Meta-analysis of proportions was performed as a secondary analysis, comparing outcome rates between 2-mm intervals of endometrial thickness and a reference category (≥ 6 to < 8 mm).

Results: A total of 67 studies were included, of which 22 were cohort studies and 45 were descriptive. In fresh ET cycles, the live-birth rate was higher in patients with a thicker endometrium across cut-offs from ≥ 5 mm (OR, 5.66 (95% CI, 1.10-28.98)) to ≥ 15 mm (OR, 1.49 (95% CI, 1.26-1.77)). Effect size decreased linearly as the cut-off increased (P < 0.0001; R2 = 61.5%). Meta-analysis of proportions found significant differences in live-birth rate when the reference category (≥ 6 to < 8 mm) (0.26 (95% CI, 0.22-0.30); I2 = 94.3%) was compared to the groups with endometrial thickness of ≥ 4 to < 6 mm (0.17 (95% CI, 0.14-0.20); I2 = 0%), ≥ 10 to < 12 mm (0.35 (95% CI, 0.28-0.42); I2 = 99.2%), ≥ 12 to < 14 mm (0.43 (95% CI, 0.33-0.53); I2 = 99.5%) and ≥ 14 to < 16 mm (0.39 (95% CI, 0.27-0.51); I2 = 99.2%). In frozen-thawed ET cycles, thicker endometrium was associated with a higher live-birth rate for cut-offs between ≥ 5 mm (OR, 2.65 (95% CI, 1.23-5.72); I2 = 0%) and ≥ 8 mm (OR, 1.17 (95% CI, 1.10-1.24); I2 = 13%). A linear relationship between endometrial thickness and effect size was observed for this analysis (P < 0.0001; R2 = 73.8%). In fresh ET cycles, endometrial thickness was correlated positively with the rates of clinical pregnancy and embryo implantation, inversely with miscarriage rate and showed no correlation with ectopic pregnancy. In frozen-thawed ET cycles, thicker endometrium was correlated positively with the rate of clinical pregnancy and inversely with that of miscarriage. Evidence quality was rated as very low in 70% of assessments because of bias and inconsistency.

Conclusions: Endometrial thickness is associated with reproductive outcomes, but demonstrates a gradient of effectiveness as a prognostic indicator, rather than offering a critical threshold below which ET should be avoided. ET scheduling should consider endometrial thickness alongside other prognostic factors. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.