# Reproductive and obstetric outcomes following frozen embryo transfer: letrozole combined with human menopausal gonadotropin versus hormone replacement cycle

## TL;DR

This study compares two protocols for frozen embryo transfer and finds similar live birth rates but differences in cesarean section and diabetes risks.

## Contribution

The study provides new evidence on the comparative effectiveness of ovulation induction versus hormone replacement protocols in frozen embryo transfers.

## Key findings

- No significant difference in live birth rates between the two protocols.
- OI protocol was linked to lower cesarean section and gestational diabetes risks.
- Subgroup analyses showed potential benefits of OI for women with ovulation disorders and older patients.

## Abstract

This study aimed to compare reproductive and obstetric outcomes between frozen embryo transfer (FET) cycles using letrozole combined with human menopausal gonadotropin (HMG) for ovulation induction (OI) and hormone replacement therapy (HRT) for endometrial preparation.

A retrospective cohort study was conducted on 1,880 FET cycles from 2016 to 2024. Cycles were stratified into the OI group (n = 902) and HRT group (n = 978) based on the endometrial preparation protocol. The primary outcome was live birth rate (LBR). Secondary outcomes included clinical pregnancy rate (CPR) and obstetric complications. Exploratory subgroup analyses were performed based on ovulatory status (normal ovulation vs. ovulation disorders) and age (<35 years vs. ≥35 years).

After adjustment for confounders, no statistically significant difference was observed in the primary outcome of LBR between the OI and HRT groups (OR = 1.145, 95% CI: 0.932–1.407; P = 0.198). Similarly, there was no significant difference in the secondary outcome of CPR (OR = 1.149, 95% CI: 0.944–1.398; P = 0.167). Analysis of other secondary outcomes revealed that the OI protocol was associated with a lower risk of cesarean section (OR = 0.619, 95% CI: 0.432–0.887; P = 0.009) and gestational diabetes mellitus (GDM) (OR = 0.339, 95% CI: 0.117–0.981; P = 0.046). Exploratory subgroup analyses suggested potential variations: In women with ovulation disorders, OI was associated with a higher CPR (OR = 1.624, 95% CI: 1.081–2.440; P = 0.020) and a lower preterm birth rate (OR = 0.682, 95% CI: 0.408–0.562; P = 0.023). In women ≥35 years, OI was associated with a markedly lower risk of GDM (OR = 0.038, 95% CI: 0.002–0.707; P = 0.028) and a non-significant trend toward higher LBR (OR = 1.521, 95% CI: 0.967–2.393; P = 0.07). In women <35 years, the OI cycle was associated with a lower cesarean section rate (OR = 641, 95% CI: 0.426–0.996; P = 0.034).

Adjusted analysis revealed comparable LBR between the OI and HRT protocols. The OI protocol was associated with a lower risk of cesarean section and GDM in the overall population, with exploratory subgroup analyses suggesting potential differential effects in specific patient groups. These findings warrant prospective validation.