P-586 Mild ovarian stimulation using the aromatase inhibitor letrozole (LTZ) is an effective stimulation protocol to obtain euploid blastocysts for women of an advanced maternal age
Authors: Horikawa T , Nakagawa K , Shiobara K , Kuroda K , Maruyama T , Takamizawa S , Sugiyama R 
Published: July 2024

Abstract

Study question
Does MOS with LTZ produce higher numbers of good-quality blastocysts compared with the use of clomiphene citrate (CC) for women of an advanced maternal age?

Summary answer
MOS using LTZ is a good ovarian stimulation protocol for a higher number of good-quality blastocysts for women of an advanced maternal age (AMA)

What is known already
The clinical pregnancy rate with a good blastocyst should be 40% or more among younger women, but about 35% for AMA women (≥40 years). Therefore, high-dose gonadotropins are usually used for AMA women. However, the best efforts for both patients and clinicians are sometimes in vain. Many AMA women show a lower ovarian reserve where ovarian stimulation with a lessened dose of gonadotropins is preferred. Taking CC or LTZ with MOS can reduce the amount of gonadotropins used, but it remains uncertain whether it is better to administer LTZ or CC together for MOS.

Study design, size, duration
This retrospective study was conducted between January 2020 and April 2021. A total of 288 women received MOS. Of course, 153 used CC (CC group) and 133 used LTZ (LTZ group). The ART outcomes were compared between these two groups. Among them, the women who were ≥40 years old were divided into two groups: CC-O40 (n = 61) and LTZ-O40 (n = 54). The ART outcomes were compared between the two groups.

Participants/materials, setting, methods
All women took either 100 mg of CC or 5 mg of LTZ daily for 7 days between menstrual cycle 3 (MC3) and MC9, and 225 IU of recombinant-FSH were administered on MC3, MC5, MC7 and MC9. On MC 10, when 3 or more well-developed follicles (≥ 20 mm in diameter) were confirmed, a dual-maturation trigger was performed using rec-hCG and GnRH agonist nasal spray, and then oocyte-pick up (OPU) was performed 35-36 hours afterward.

Main results and the role of chance
The number of retrieved oocytes in the CC group averaged 7.5 ± 5.3 (mean ± S.D.), which was significantly higher than that in the LTZ group (6.3 ± 4.7; p &lt; 0.05). The average number of blastocysts and morphologically good blastocysts was comparable in the CC and LTZ groups (CC group; 2.8 ± 3.0 and 1.8 ± 2.4; LTZ group; 2.4 ± 2.7 and 1.4 ± 2.0, respectively, [P=NS]). For AMA women, the average number of blastocysts in the CC-O40 group was 1.7 ± 1.8, which was similar to that in the LTZ-O40 group (1.7 ± 1.8, P=NS). The blastocyst formation rate in the LTZ-O40 group was 58.5%, which was significantly higher than that in the CC-O40 group (46.6%; P &lt; 0.05), but the rate for good blastocysts in the LTZ-O40 group (30.8%) was comparable to that in the CC-O40 group (23.3%, P=NS). The euploid rates in the LTZ group was 53.4%, which was significantly higher than that in the CC group (38.0%; P &lt; 0.05), and the difference was significant even for AMA women (LTZ-O40; 40.5%, CC-O40; 16.7%, respectively, p &lt; 0.05).

Limitations, reasons for caution
The study was a controlled trial with a limited number in the study population. Additionally, all cases had not received a trophectoderm (TE) biopsy. Further study is needed to determine the effect that an aromatase inhibitor exerts on obtaining either morphologically good blastocysts or euploid blastocysts.

Wider implications of the findings
AMA women showed blastocyst formation rates from LTZ with MOS significantly higher than that of the CC group, and euploid rates in the LTZ group were also significantly higher. The characteristics of an LTZ such as aromatase inhibitor enhanced the development of embryos.

Trial registration number
not applicable