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中华妇幼临床医学杂志(电子版) ›› 2023, Vol. 19 ›› Issue (06) : 629 -635. doi: 10.3877/cma.j.issn.1673-5250.2023.06.002

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促性腺激素释放激素拮抗剂对子宫内膜容受性影响的研究现状
王丽1, 王月莺2, 周芬3, 郭宇堃4, 魏丽娜2,†()   
  1. 1. 济宁医学院临床医学院，济宁　272000；济宁市妊娠障碍性疾病研究重点实验室，济宁　272000
    2. 济宁市妊娠障碍性疾病研究重点实验室，济宁　272000；济宁市第一人民医院生殖医学科，济宁　272000
    3. 济宁市第一人民医院生殖医学科，济宁　272000
    4. 川北医学院临床医学院，南充　637000
  • 收稿日期:2023-06-22 修回日期:2023-11-09 出版日期:2023-12-01
  • 通信作者: 魏丽娜

Current research status in effect of gonadotropin-releasing hormone antagonist on endometrial receptivity

Li Wang1, Yueying Wang2, Fen Zhou3, Yukun Guo4, Lina Wei2,†()   

  1. 1. School of Clinical Medicine of Jining Medical University, Jining 272000, Shandong Province, China; Key Laboratory of Pregnancy Disorders Research of Jining City, Jining 272000, Shandong Province, China
    2. Key Laboratory of Pregnancy Disorders Research of Jining City, Jining 272000, Shandong Province, China; Department of Reproductive Medicine of Jining No.1 People′s Hospital, Jining 272000, Shandong Province, China
    3. Department of Reproductive Medicine of Jining No.1 People′s Hospital, Jining 272000, Shandong Province, China
    4. School of Clinical Medicine of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
  • Received:2023-06-22 Revised:2023-11-09 Published:2023-12-01
  • Corresponding author: Lina Wei
  • Supported by:
    National Natural Science Foundation for Youth of China(82101756)
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王丽, 王月莺, 周芬, 郭宇堃, 魏丽娜. 促性腺激素释放激素拮抗剂对子宫内膜容受性影响的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(06): 629-635.

Li Wang, Yueying Wang, Fen Zhou, Yukun Guo, Lina Wei. Current research status in effect of gonadotropin-releasing hormone antagonist on endometrial receptivity[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(06): 629-635.

相较于辅助生殖技术(ART)领域采用的传统促性腺激素释放激素激动剂(GnRH-a)，近年新兴的促性腺激素释放激素拮抗剂(GnRH-A)具有以下更符合女性生理过程的优势。①缩短不孕患者ART治疗周期；②减少ART不孕患者外源性促性腺激素用量；③无GnRH-a降调节导致的低雌激素水平发生；④显著降低卵巢过度刺激综合征(OHSS)发生率；⑤显著降低周期取消率等。研究结果显示，对于采取GnRH-a或GnRH-A方案进行ART治疗的不孕患者，在新鲜胚胎(3 d胚)移植周期中，采取GnRH-A方案，较采取GnRH-a方案不孕患者的临床妊娠率低，并且差异有统计学意义(P<0.05)；但是在冷冻胚胎移植周期中，则采取上述2种方案者的临床妊娠率比较，差异无统计学意义(P>0.05)。这表明，新鲜胚胎移植周期采取GnRH-A方案治疗的不孕患者临床妊娠率较低，可能是GnRH-A方案对不孕患者的子宫内膜容受性产生不利影响，而并非影响卵子质量和胚胎发育的缘故，而对GnRH-A可能影响子宫内膜容受性的推测，迄今尚无定论。笔者拟就GnRH-A对体外受精-胚胎移植(IVF-ET)女性的子宫内膜容受性相关蛋白表达水平、相关分子表达水平、相关免疫细胞功能及数量影响与其对子宫内膜厚度及血流影响4个方面的最新研究进展进行阐述，旨在揭示GnRH-A方案导致不孕患者子宫内膜容受性不足的机制，从而发现治疗子宫内膜容受性不足的新靶点，提高采取GnRH-A方案患者的临床妊娠率，为优化GnRH-A治疗方案提供理论参考。

关键词: 体外受精, 胚胎移植, 子宫内膜, 促性腺素释放激素, 促性腺激素释放激素拮抗剂, 子宫内膜容受性, 胚胎植入, 不育, 女(雌)性

Compared with classical gonadotropin-releasing hormone agonist (GnRH-a) used in the field of assisted reproductive technology (ART), newly developed gonadotropin-releasing hormone antagonist (GnRH-A) in recent years has the following advantages of being more in line with physiological processes of women. ①Shorten the ART treatment cycle. ②Reduced the amount of ART exogenous gonadotropin. ③There is no occurrence of hypogyny symptoms due to the down-regulation of GnRH-a. ④Significantly reduce the incidence of ovarian hyperstimulation syndrome (OHSS). ⑤Significantly reduce cycle cancellation rate.Results of literature studies showed that the clinical pregnancy rate of infertile patients with treatment of GnRH-a and GnRH-A was lower if the GnRH-A protocol was adopted in fresh embryo (3 d embryo) transfer cycles than the GnRH-a protocol, and the difference was statistically significant (P<0.05); however, in the case of frozen embryo transfer, there was no statistically significant difference in pregnancy rate between two protocols (P>0.05). This suggested that the lower pregnancy rate of GnRH-A during the fresh embryo transfer cycle may be caused by the adverse effects of GnRH-A on endometrial receptivity of infertile patients, rather than the reason of ovum quality and embryo development. The speculation that GnRH-A may affect endometrial receptivity is inconclusive so far. The author intends to elaborate the latest research progress on endometrium receptivity related protein expression levels, related molecular expression levels, the effects of related immune cell function and quantity on endometrial thickness and blood flow in women undergoing in vitro fertilization and embryo transfer (IVF-ET) with GnRH-A protocol. The aim is to reveal the mechanism of endometrial receptivity deficiency in infertile patients caused by GnRH-A protocol, so as to find new targets for the treatment of endometrial receptivity deficiency, improve the clinical pregnancy success rate of patients taking GnRH-A protocol, and provide theoretical reference for optimizing the treatment of GnRH-A.

Key words: Fertilization in vitro, Embryo transfer, Endometrium, Gonadotropin-releasing hormone, Gonadotropin-releasing hormone antagonist, Endometrial receptivity, Embryo implantation, Infertility, Female
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