Study question

Does endometrial thickness show a non-linear association with fetal heartbeat, and does its clinical interpretation depend on embryo quality components?\

Summary answer

Endometrial thickness showed a non-linear association with fetal heartbeat; overall embryo quality predicted outcomes in optimal thickness, whereas trophectoderm quality dominated under thin endometrial conditions.

What is known already

Endometrial thickness is widely studied as a prognostic marker of pregnancy outcomes in fresh IVF cycles, with many studies reporting non-linear associations. However, reported cut-offs and plateau ranges vary substantially, and interpretation of extreme thickness values remains inconsistent.

Embryo quality, assessed by Gardner grading, is a major determinant of IVF success. In clinical practice, however, endometrial thickness and embryo quality are often considered independently, despite implantation being the result of their interaction. Large multicenter data integrating endometrial thickness with specific embryo quality components remain limited.

Study design, size, duration

This retrospective multicenter cohort study analyzed 7,759 fresh IVF cycles conducted between January 2018 and November 2024 across five IVF clinics. All included cycles had documented endometrial thickness measured on the day of embryo transfer.

Participants/materials, setting, methods

Fresh embryo transfer cycles from five IVF clinics were analyzed. Endometrial thickness was measured using ultrasound on the day of embryo transfer. Non-linear associations with fetal heartbeat were assessed using restricted cubic spline models. Thickness ranges were further evaluated using categorical logistic regression. Center-specific estimates were pooled using random-effects meta-analysis. Sub-analyses were conducted in day-5 fresh embryo transfers with embryo grading assigned by senior embryologists.

Main results and the role of chance

Restricted cubic spline analysis demonstrated a clear non-linear association between endometrial thickness and fetal heartbeat. Fetal heartbeat probability increased from approximately 7 mm, rose steeply from 8 mm, peaked near 10 mm, and plateaued thereafter. Based on this pattern, the 8–12 mm range was defined as the optimal reference.

Cycles with endometrial thickness <8 mm had significantly lower odds of fetal heartbeat compared with the reference (odds ratio 0.84, 95% confidence interval 0.72–0.98, p = 0.024), whereas thickness >12 mm showed no significant difference. Random-effects meta-analysis confirmed consistent effect direction across centers.

In sub-analyses incorporating embryo grading, embryo stage, inner cell mass (ICM), and trophectoderm (TE) grade were all significant predictors of fetal heartbeat within the optimal 8-12 mm range, reflecting the clinical relevance of the conventional Gardner grading framework under receptive endometrial conditions.

In contrast, under thin endometrial conditions (<8 mm), TE grade was the only embryo component that consistently predicted fetal heartbeat, with stronger effect sizes than those observed in the optimal range. This pattern suggests that when endometrial receptivity is compromised, functional competence of the trophectoderm may play a bigger role in successful implantation.

Limitations, reasons for caution

This retrospective study may be influenced by unmeasured clinical and laboratory confounders. Extremely thin endometrial thickness categories included relatively few cycles. Embryo grading analyses were limited by missing data, resulting in reduced sample size and limited statistical power for subgroup analyses.

Wider implications of the findings

While overall embryo quality is informative under optimal endometrial conditions, trophectoderm quality may warrant prioritization in patients with thin endometrium, supporting adaptive, environment-specific embryo selection strategies rather than universal thresholds.