既往诊断卵巢低反应患者的卵泡激活：一项随机对照试验。

Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial.

机构信息

Instituto Valenciano de Infertilidad-Reproductive Medicine Associates (IVIRMA) London, London, United Kingdom; Instituto Valenciano de Infertilidad (IVI) Foundation- Instituto de Investigaciones Sanitarias La Fe, Valencia, Spain; Elizabeth Garrett Anderson Institute for Women's Health (EGA IfWH), University College London (UCL), London, United Kingdom.

Instituto Valenciano de Infertilidad (IVI) Foundation- Instituto de Investigaciones Sanitarias La Fe, Valencia, Spain.

出版信息

Fertil Steril. 2022 Apr;117(4):747-755. doi: 10.1016/j.fertnstert.2021.12.034.

DOI:10.1016/j.fertnstert.2021.12.034

PMID:35367015

Abstract

OBJECTIVE

To investigate whether ovarian fragmentation for follicular activation (OFFA) improves ovarian reserve markers and in vitro fertilization (IVF) outcomes in women with poor ovarian response (POR).

DESIGN

Randomized, controlled trial, with parallel assignment.

SETTING

University hospital.

PATIENT(S): Thirty-four women with POR according to the European Society of Human Reproduction and Embryology criteria.

INTERVENTION(S): Women with POR were randomly allocated to receive ovarian fragmentation in 1 ovary or to no intervention (control group). Ovarian reserve markers were followed at 2-week intervals for 6 months. In vitro fertilization cycles were initiated when the antral follicle count (AFC) doubled or at the end of follow-up.

MAIN OUTCOME MEASURE(S): The primary outcome was the number of metaphase II (MII) oocytes obtained. Antral follicle count, antimüllerian hormone level, and reproductive outcomes were recorded as secondary outcomes. Exploratory outcomes included surgical results and analysis of protein and gene expression.

RESULT(S): Ovarian fragmentation for follicular activation resulted in an increase in AFC in the intervention ovary compared with the control ovary and an increase in total AFC in the OFFA group compared with controls. Serum antimüllerian hormone and follicle-stimulating-hormone levels did not improve in the OFFA group throughout the follow-up period. Fifteen patients from each arm underwent IVF. In the control group, 33 MII oocytes were retrieved and 18 embryo transfers were performed, with a 20% pregnancy rate and an 18.7% live birth rate per cycle. In the OFFA group, 23 MII oocytes were retrieved and 11 embryo transfers were performed, with a 13.3% pregnancy rate and a 6.7% live birth rate per cycle. Reproductive outcomes did not significantly differ between the groups. Hippo pathway inhibition was confirmed by an 18.8% reduction in the phospho-YAP/YAP (Yes-associated protein 1) ratio and BIRC and CCN overexpression after fragmentation.

CONCLUSION(S): Ovarian fragmentation for follicular activation in women with POR resulted in an increase in AFC but did not modify IVF outcomes when compared with controls.

CLINICAL TRIAL REGISTRATION NUMBER

NCT02354963.

摘要

目的

研究卵泡激活卵巢碎裂术（OFFA）是否能改善卵巢储备标志物和体外受精（IVF）结局在卵巢反应不良（POR）的女性中。

设计

随机、对照试验，平行分配。

地点

大学医院。

患者

根据欧洲人类生殖与胚胎学会标准，POR 的 34 名女性。

干预

POR 女性随机分配接受单侧卵巢碎裂术或不干预（对照组）。卵巢储备标志物在 6 个月内每 2 周随访一次。当窦卵泡计数（AFC）翻倍或随访结束时开始进行 IVF 周期。

主要观察指标

主要结局是获得的中期 II（MII）卵母细胞数量。记录窦卵泡计数、抗苗勒管激素水平和生殖结局作为次要结局。探索性结局包括手术结果和蛋白质及基因表达分析。

结果

与对照组相比，卵巢滤泡激活的卵巢碎裂术导致干预侧的 AFC 增加，与对照组相比，OFFA 组的总 AFC 增加。在整个随访期间，OFFA 组的血清抗苗勒管激素和卵泡刺激素水平没有改善。每组各有 15 名患者接受了 IVF。在对照组中，共获得 33 个 MII 卵母细胞，进行了 18 次胚胎移植，每个周期的妊娠率为 20%，活产率为 18.7%。在 OFFA 组，共获得 23 个 MII 卵母细胞，进行了 11 次胚胎移植，每个周期的妊娠率为 13.3%，活产率为 6.7%。两组的生殖结局无显著差异。磷酸化 YAP/YAP（Yes-associated protein 1）比率和 BIRC、CCN 过表达证实了 Hippo 通路的抑制，其降幅分别为 18.8%。