来曲唑微刺激卵巢：高龄女性获得整倍体囊胚的有效方案！

Study question

研究问题

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

对于高龄女性（AMA），与使用枸橼酸克罗米酚（CC）相比，使用芳香化酶抑制剂来曲唑（LTZ）的卵巢微刺激方案（MOS）是否能产生更多的优质囊胚？

Summary answer

总结答案

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)

对于高龄女性，使用来曲唑的卵巢微刺激方案是一个可以提供更多优质囊胚的方案。

What is known already

已知情况

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.

移植优质囊胚的年轻女性临床妊娠率可达40%或以上，而高龄女性（40岁）仅为35%。因此，对于高龄女性通常使用高剂量的促性腺激素。然而，有时候尽管患者和临床医生都竭尽全力，但收效不佳。许多高龄女性的卵巢储备较低，因此需要使用较低剂量的促性腺激素进行卵巢刺激。在MOS过程中使用克罗米芬或来曲唑可减少促性腺激素的用量，但不能确定在此过程中，使用克罗米芬还是来曲唑，哪个更优。

Study design, size, duration

研究设计，规模，持续时间

 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.

这项回顾性研究于2020年1月至2021年4月期间进行。共有288名女性接受卵巢微刺激。当然，153名使用克罗米芬（CC组），133名使用来曲唑（LTZ组）。比较了两组的ART结果。其中，年龄40岁的女性被分为两组CC-O40（n=61）和LTZ-O40（n=54）。比较两组ART的结局。

Participants/materials, setting, methods

参与者/材料，设置，方法

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.

所有女性在月经第3—9天连续7天每日顿服100mg克罗米芬或5mg来曲唑，同时在月经第3、5、7、9天予r-FSH 225 IU。在月经第10天后，当确认有3个或更多发育良好的卵泡（直径 20mm）时，予rec-hCG和GnRH-a鼻喷雾剂进行双扳机，35—36小时后进行取卵（OPU）。

Main results and the role of chance

主要结果和机会的作用

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<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<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<0.05), and the difference was significant even for AMA women (LTZO40; 40.5%, CC-O40; 16.7%, respectively, p< 0.05).

CC组中平均获卵数为7.5±5.3（平均数±标准差），显著高于LTZ组（6.3±4.7；P＜0.05）。CC组和LTZ组平均囊胚数和形态良好的囊胚数相似，分别为（2.8±3.0和1.8±2.4）和（2.4±2.7和1.4±2.0）（P=NS）。对于高龄女性，CC-O40组的平均囊胚数为1.7±1.8，与LTZ-O40组相似（1.7±1.8，P=NS）。LTZ-O40组囊胚形成率明显高于CC-O40组（58.5% vs 46.6%，P＜0.05）；但LTZ-O40组的优质囊胚形成率与CC-O40组相似（30.8% vs 23.3%，P=NS）。LTZ组的整倍体率显著高于CC组（53.4% vs 38.0%，P＜0.05）；即使在高龄女性中也有显著差异（LTZ-O40 vs CC-O40，40.5% vs 16.7%，P＜0.05）。

Limitations, reasons for caution

局限性，谨慎的理由

 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.

本研究是一项研究人群数量有限的对照试验。此外，所有病例均未进行滋养外胚层（TE）活检。需要进一步的研究来确定芳香化酶抑制剂对获得形态良好的囊胚或整倍体囊胚的影响。

Wider implications of the findings

研究结果更广泛的含义

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.

高龄女性采用LTZ+MOS囊胚形成率和整倍体率均显著高于CC+MOS。LTZ等芳香化酶抑制剂的特性促进了胚胎的发育。

参考文献：

T Horikawa, K Nakagawa, K Shiobara, K Kuroda, T Maruyama, S Takamizawa, R Sugiyama, 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, Human Reproduction, Volume 39, Issue Supplement_1, July 2024, deae108.183, https://doi.org/10.1093/humrep/deae108.183