The Interaction between Embryo Developmental Stage and Endometrial Preparation Protocol on Live Birth Outcomes in Frozen-Thawed Embryo Transfer: A Retrospective Cohort Study.

OBJECTIVES

The objectives were to evaluate the independent associations of embryo developmental stage and endometrial preparation protocol with live birth after frozen-thawed embryo transfer (FET) and secondarily to explore whether an interaction exists between these two factors.

DESIGN

A retrospective cohort study of 1,214 eligible first FET cycles (from an initial cohort of 1,634 cycles), stratified by embryo type (D3 high-quality cleavage-stage embryos vs. D5 non-top-quality blastocysts) and endometrial protocol (modified natural cycle [mNC] vs. artificial cycle [AC]).

PARTICIPANTS/MATERIALS, SETTING,

METHODS

All included patients were undergoing their first FET cycle. The primary exposure variables were embryo type and endometrial preparation protocol. The primary outcome was live birth per transfer cycle. A multivariable logistic regression model was employed to test for an interaction between embryo type and endometrial preparation protocol and to calculate adjusted odds ratios (aORs) after controlling for female age, anti-Müllerian hormone level, duration of infertility, and endometrial thickness. Exploratory subgroup analysis was performed based on age (<35 years vs. ≥35 years). Model performance was evaluated using the Hosmer-Lemeshow test and the area under the receiver operating characteristic curve.

RESULTS

No statistical evidence of an interaction was detected between embryo type and endometrial preparation protocol (adjusted p = 0.453). In the adjusted model, both factors were independent predictors of live birth rate. The live birth rate was significantly higher following the transfer of a D5 non-top-quality blastocyst compared to a D3 high-quality cleavage-stage embryo (aOR = 1.48, 95% CI: 1.14-1.93). The mNC protocol was associated with a significantly higher live birth rate than the AC protocol (aOR = 1.78, 95% CI: 1.28-2.49). In exploratory age-stratified analyses, the association between mNC and live birth reached statistical significance in patients aged <35 years (OR = 1.66, p < 0.001) but not in those aged ≥35 years (OR = 1.62, p = 0.194); however, the interaction term between age group and endometrial protocol was not significant (P for interaction = 0.312).

LIMITATIONS: The retrospective design may introduce selection bias and confounding, and findings from a single center may not be fully generalizable.

CONCLUSIONS

In this retrospective cohort, embryo developmental stage and endometrial preparation protocol were each associated with live birth outcomes, and no statistical evidence of an interaction was detected. These findings should be interpreted as associations rather than causal effects. Exploratory age-stratified findings are hypothesis-generating and require confirmation in prospective studies.