O-272 Letrozole-induced endometrial preparation improved pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle
Authors: Kato K , Ezoe K , Fukuda J , Takeshima K , Shinohara K 
Published: June 2022

Study question

Does letrozole-induced endometrial preparation affect pregnancy outcomes, perinatal outcomes, and congenital anomalies after single vitrified-warmed blastocyst transfers (SVBTs) when compared with the natural cycle?

Summary answer

Letrozole-induced endometrial preparation improved live birth rate without any adverse effects on perinatal outcomes and congenital anomalies after SVBTs.

What is known already

Letrozole treatment is considered an effective option in endometrial preparation for frozen embryo transfers in patients with ovulation disorders or irregular menstruation; however, the effectiveness of letrozole-induced endometrial preparation is still unclear in ovulatory patients. Furthermore, there is no comparative study reporting on pregnancy complications and congenital anomalies after frozen embryo transfers comparing natural and letrozole-assisted cycles.

Study design, size, duration

This retrospective study, at a major academic fertility centre, analysed a total of 14,611 clinical records of women who underwent SVBTs comprising both natural and letrozole-assisted cycles between July 2015 and June 2020. The cycle characteristics, pregnancy outcomes (clinical pregnancy, ongoing pregnancy, and live birth), and the incidence of pregnancy complications and congenital anomalies were statistically compared between the natural and letrozole groups.

Participants/materials, setting, methods

The study reviewed ovulatory patients who underwent their first SVBT during the study period. Some patients took letrozole during the early proliferative phase to promote follicular development and maturation (letrozole group). Ovulation was triggered by GnRH agonist and SVBTs were performed on day five after ovulation. Propensity score matching was performed to reduce any bias from patient characteristics. Multivariate logistic analysis was performed to evaluate the effects of letrozole administration on pregnancy and perinatal outcomes.

Main results and the role of chance

After propensity score matching, the characteristics of patients and transferred blastocysts were comparable between groups. The serum progesterone level was also significantly increased in the letrozole group (P &lt; 0.0001). Although no difference was observed regarding implantation rate between groups, the rates of clinical pregnancy, ongoing pregnancy, and delivery in the letrozole group were all significantly higher than that in the natural group (P = 0.0273, P = 0.0162, P = 0.0479, respectively). The incidence of early pregnancy loss, miscarriage, and stillbirth were comparable between groups. Multivariate logistic regression analysis also demonstrated that the administration of letrozole during an SVBT cycle significantly improved the live birth rate (AOR, 1.160; P = 0.0355). The incidence of pregnancy complications was comparable between groups. The caesarean section rate was significantly lower in the letrozole group than that in the natural group (P = 0.0464). Gestational age, birth length, birth weight, and infant sex, as well as the incidence of pregnancy complications and birth defects, were statistically comparable between groups. Furthermore, multivariate logistic regression analysis showed that perinatal outcomes were not affected by letrozole-induced endometrial preparation, although the incidence of caesarean section was decreased in the letrozole group (AOR, 0.788; P = 0.0355).

Limitations, reasons for caution

Our findings are not compared with reported incidences of pregnancy complications and congenital anomalies in natural pregnancy. Furthermore, the study was retrospective in nature, and further multicentre studies are required to ascertain the generalisability of these findings for other clinics with different protocols and/or patient demographics.

Wider implications of the findings

Letrozole administration both extended the proliferative phase and increased luteal function, resulting in an improvement of live birth rates without any adverse effects. Therefore, letrozole-induced endometrial preparation might be a safe and more effective strategy for patients with shortened proliferative phase or insufficient luteal function.

Trial registration number

not applicable