Mode
Text Size
Log in / Sign up

Letrozole protocol associated with higher live birth and lower adverse outcomes versus estrogen-progesterone in ovulation disorder FET

Letrozole protocol associated with higher live birth and lower adverse outcomes versus estrogen-prog…
Photo by engin akyurt / Unsplash
Key Takeaway
Consider that Letrozole protocols may be associated with higher live birth rates and lower risks of miscarriage and adverse pregnancy outcomes in ovulation disorder FET patients.

This single-center retrospective cohort study evaluated 3,896 women (552 with ovulation disorders receiving letrozole, 3,344 receiving estrogen-progesterone) undergoing frozen-thawed embryo transfer. Participants were categorized into two groups: 552 women receiving ovulation induction with Letrozole (OI group) and 3,344 women receiving an artificial programmed protocol with estrogen and progesterone (EP group). Data were analyzed using propensity-score matching to adjust for baseline differences.

The primary analysis focused on live birth rates, while secondary outcomes included early spontaneous miscarriage, gestational diabetes mellitus in singleton births, and low birth weight in singleton births. The study found that the live birth rate was significantly higher in the OI group (38.1%) compared to the EP group (33.4%), with a p-value of 0.042.

Regarding adverse outcomes, the early spontaneous miscarriage rate was significantly lower in the OI group (13.1%) versus the EP group (18.9%), with an odds ratio of 1.450 (95% CI: 1.085-1.963) for the EP group. Similarly, gestational diabetes mellitus occurred less frequently in the OI group (7.9%) compared to the EP group (14.6%), and low birth weight was also lower in the OI group (7.9% vs. 14.1%).

The study did not report specific adverse events, discontinuations, or detailed tolerability data. Key limitations include the retrospective design and single-center setting, which may affect generalizability. While adjusted analyses suggest an association between the Letrozole protocol and improved outcomes, the observational nature of the study precludes definitive causal conclusions. Clinicians should interpret these results with caution regarding broader application.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
Several endometrial preparation protocols are available in frozen-thawed embryo (FET) transfer cycles. The aim of this study was to compare the clinical outcomes, obstetrical and neonatal complications between ovulation disorder patients undergoing FET with ovulation induction protocol and patients with artificial programmed protocol. A single-center retrospective cohort study using propensity-score matching (PSM) was conducted. Ovulation disorder women undergoing FET using ovulation induction medicine Letrozole (OI group), or estrogen/progesterone (EP) for endometrial preparation were included. Clinical outcomes, obstetrical and neonatal complications were compared before and after PSM. Multiple logistic regression models were performed to demonstrate the independent impact of endometrial protocols on pregnancy outcomes. A total of 552 women in OI group and 3344 women in EP group were included. As for pregnancy outcomes after PSM, patients in OI group were with significantly higher live birth rate (38.1% vs. 33.4%; P = 0.042), and lower early spontaneous miscarriage rate (13.1% vs. 18.9%; P = 0.032). In singleton birth, the prevalence of GDM (7.9% vs. 14.6%; P = 0.037), and LBW (7.9% vs. 14.1%; P = 0.042) was significantly lower in patients from OI group as compared with EP group. In patients after PSM, after adjusting for covariates, EP protocol was a risk factor of early spontaneous miscarriage rate (OR = 1.450, 95%CI: 1.085-1.963; P = 0.029), GDM (OR = 1.627, 95%CI: 1.288-2.601; P = 0.034), and LBW (OR = 1.852, 95%CI: 1.127-2.250; P = 0.041). As compared with EP protocol, using Letrozole to achieve endometrial preparation prior to FET may yield a decreased risk of early spontaneous miscarriage rate, GDM, and as well as LBW in ovulation disorder patients undergoing FET.
Free Newsletter

Clinical research that matters. Delivered to your inbox.

Join thousands of clinicians and researchers. No spam, unsubscribe anytime.