卵泡期高孕激素状态下促排卵方案的应用进展

doi:10.12280/gjszjk.20230476

摘要/Abstract

摘要：

辅助生殖技术中，控制性促排卵过程中预防内源性黄体生成素（luteinizing hormone，LH）峰的过早出现至关重要。传统的控制性促排卵方案使用促性腺激素释放激素（gonadotropin-releasing hormone，GnRH）类似物（GnRH激动剂或拮抗剂）抑制内源性LH水平，存在成本高、使用不方便等缺点。卵泡期高孕激素状态下促排卵（progestin-primed ovarian stimulation，PPOS）方案利用外源性孕激素对垂体的负反馈作用抑制LH水平，已被证实在各种人群中均可获得较好的临床结局，其子代安全性也得到初步证实。综述PPOS方案的具体机制、不同外源性孕激素类药物的应用、不同人群的应用效果及子代安全性等。

关键词: 排卵诱导, 生殖技术, 辅助, 促黄体激素, 妊娠结局, 早发LH峰, 卵泡期高孕激素状态促排卵

Abstract:

In assisted reproductive technology, it is very important to prevent the premature endogenous luteinizing hormone (LH) peak in process of controlled ovarian stimulation. Traditional controlled ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) analogues (GnRH agonists or antagonists) to inhibit the level of endogenous LH have many disadvantages such as high cost and inconvenient use. Progestin-primed ovarian stimulation (PPOS) protocol has been proved to achieve good clinical outcomes in various populations by the negative feedback effect of exogenous progesterone on pituitary gland to inhibit LH level, and its offspring safety has also been preliminarily confirmed. In this paper, the mechanism of PPOS, application of different exogenous progesterone drugs, application effects of different populations and offspring safety of PPOS were reviewed.

Key words: Ovulation induction, Reproductive techniques, assisted, Luteinizing hormone, Pregnancy outcome, Premature LH surge, Progestin-primed ovarian stimulation

李彩华, 郭培培, 姜小花, 方有燕, 周平, 魏兆莲. 卵泡期高孕激素状态下促排卵方案的应用进展[J]. 国际生殖健康/计划生育杂志, 2024, 43(1): 68-73.

LI Cai-hua, GUO Pei-pei, JIANG Xiao-hua, FANG You-yan, ZHOU Ping, WEI Zhao-lian. Application Progress of Progestin-Primed Ovarian Stimulation[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(1): 68-73.

参考文献 37

[1]	Kuang Y, Chen Q, Fu Y, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization[J]. Fertil Steril, 2015, 104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. pmid: 25956370
[2]	Dierschke DJ, Yamaji T, Karsch FJ, et al. Blockade by progesterone of estrogen-induced LH and FSH release in the rhesus monkey[J]. Endocrinology, 1973, 92(5):1496-1501. doi: 10.1210/endo-92-5-1496. pmid: 4633016
[3]	Richter TA, Robinson JE, Lozano JM, et al. Progesterone can block the preovulatory gonadotropin-releasing hormone/luteinising hormone surge in the ewe by a direct inhibitory action on oestradiol-responsive cells within the hypothalamus[J]. J Neuroendocrinol, 2005, 17(3):161-169. doi: 10.1111/j.1365-2826.2005.01287.x.
[4]	Dong J, Wang Y, Chai WR, et al. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial[J]. BJOG, 2017, 124(7):1048-1055. doi: 10.1111/1471-0528.14622.
[5]	Guo YC, Chen PY, Li TT, et al. Different progestin-primed ovarian stimulation protocols in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection: an analysis of 1188 cycles[J]. Arch Gynecol Obstet, 2019, 299(4):1201-1212. doi: 10.1007/s00404-019-05065-4.
[6]	Yu S, Long H, Chang HY, et al. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles[J]. Hum Reprod, 2018, 33(2):229-237. doi: 10.1093/humrep/dex367.
[7]	Zhang J, Du M, Li Z, et al. Comparison of Dydrogesterone and Medroxyprogesterone in the Progestin-Primed Ovarian Stimulation Protocol for Patients With Poor Ovarian Response[J]. Front Endocrinol(Lausanne), 2021, 12:708704. doi: 10.3389/fendo.2021.708704.
[8]	杜明泽, 张俊韦, 于晓娜, 等. 卵巢低反应人群应用高孕酮状态下促排卵方案中地屈孕酮和醋酸甲羟孕酮的对比:一项倾向性评分匹配队列研究[J]. 中华生殖与避孕杂志, 2023, 43(7):670-675. doi: 10.3760/cma.j.cn101441-20220304-00096.
[9]	Zhu X, Ye H, Fu Y. Duphaston and human menopausal gonadotropin protocol in normally ovulatory women undergoing controlled ovarian hyperstimulation during in vitro fertilization/intracytoplasmic sperm injection treatments in combination with embryo cryopreservation[J]. Fertil Steril, 2017, 108(3):505-512.e2. doi: 10.1016/j.fertnstert.2017.06.017.
[10]	Guo H, Li J, Shen X, et al. Efficacy of Different Progestins in Women With Advanced Endometriosis Undergoing Controlled Ovarian Hyperstimulation for in vitro Fertilization-A Single-Center Non-inferiority Randomized Controlled Trial[J]. Front Endocrinol(Lausanne), 2020, 11:129. doi: 10.3389/fendo.2020.00129.
[11]	Xu S, Wang X, Zhang Y, et al. Comparison the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in patients with normal ovarian reserve function[J]. Gynecol Endocrinol, 2023, 39(1):2217263. doi: 10.1080/09513590.2023.2217263.
[12]	Xi Q, Tao Y, Qiu M, et al. Comparison Between PPOS and GnRHa-Long Protocol in Clinical Outcome with the First IVF/ICSI Cycle: A Randomized Clinical Trial[J]. Clin Epidemiol, 2020, 12:261-272. doi: 10.2147/CLEP.S226414. pmid: 32184672
[13]	张怡, 王婧, 尹太郎, 等. 高孕激素下促排卵方案在卵巢正常反应人群中的应用效果评价[J]. 生殖医学杂志, 2021, 30(11):1455-1459. doi: 10.3969/j.issn.1004-3845.2021.11.009.
[14]	Kalafat E, Turkgeldi E, Yıldız S, et al. Outcomes of a GnRH Agonist Trigger Following a GnRH Antagonist or Flexible Progestin-Primed Ovarian Stimulation Cycle[J]. Front Endocrinol(Lausanne), 2022, 13:837880. doi: 10.3389/fendo.2022.837880.
[15]	莫莉菁, 付伟平, 朱琴, 等. 高孕激素下促排卵方案在卵巢高反应人群中的应用效果观察[J]. 浙江医学, 2021, 43(8):845-848, 853. doi: 10.12056/j.issn.1006-2785.2021.43.8.2020-4055.
[16]	Zhu X, Ye H, Ye J, et al. Progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in women with polycystic ovarian syndrome undergoing in vitro fertilization treatments with frozen-thawed embryo transfer: a prospective randomized controlled trial[J]. Ann Transl Med, 2021, 9(5):387. doi: 10.21037/atm-20-1592.
[17]	Gurbuz AS, Gode F. Dydrogesterone-primed ovarian stimulation is an effective alternative to gonadotropin-releasing hormone antagonist protocol for freeze-all cycles in polycystic ovary syndrome[J]. J Obstet Gynaecol Res, 2020, 46(8):1403-1411. doi: 10.1111/jog.14267.
[18]	Huang TC, Huang MZ, Seow KM, et al. Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol[J]. Sci Rep, 2021, 11(1):22732. doi: 10.1038/s41598-021-02227-w.
[19]	Yang L, Liang F, Yuan Y, et al. Efficacy of progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review and meta-analysis[J]. Front Endocrinol(Lausanne), 2023, 14:1224858. doi: 10.3389/fendo.2023.1224858.
[20]	罗希, 赵淑云, 黄永俐, 等. 两种促排卵方案用于卵巢储备功能下降患者的自身对照研究[J]. 中国妇产科临床杂志, 2021, 22(6):575-578. doi: 10.13390/j.issn.1672-1861.2021.06.005.
[21]	Li Z, Jia R, Wang K, et al. Analysis of cumulative live birth rate and perinatal outcomes in young patients with low anti-müllerian hormone levels using two ovulation promotion protocols: A cohort study[J]. Front Endocrinol(Lausanne), 2022, 13:938500. doi: 10.3389/fendo.2022.938500.
[22]	黄丽萨, 张耀, 杨德辉, 等. 卵泡期高孕激素状态下促排卵方案与拮抗剂方案在预期卵巢低反应患者中的应用比较[J]. 四川医学, 2020, 41(9):938-941. doi: 10.16252/j.cnki.issn1004-0501-2020.09.010.
[23]	Pai AH, Sung YJ, Li CJ, et al. Progestin Primed Ovarian Stimulation (PPOS) protocol yields lower euploidy rate in older patients undergoing IVF[J]. Reprod Biol Endocrinol, 2023, 21(1):72. doi: 10.1186/s12958-023-01124-3.
[24]	Zhang S, Yin Y, Li Q, et al. Comparison of Cumulative Live Birth Rates Between GnRH-A and PPOS in Low-Prognosis Patients According to POSEIDON Criteria: A Cohort Study[J]. Front Endocrinol(Lausanne), 2021, 12:644456. doi: 10.3389/fendo.2021.644456.
[25]	Du M, Zhang J, Li Z, et al. Comparison of the Cumulative Live Birth Rates of Progestin-Primed Ovarian Stimulation and Flexible GnRH Antagonist Protocols in Patients With Low Prognosis[J]. Front Endocrinol(Lausanne), 2021, 12:705264. doi: 10.3389/fendo.2021.705264.
[26]	卜晓萌, 张巧利, 刘艳君, 等. 拮抗剂方案与早卵泡期高孕激素促排卵方案应用于POSEIDON 3型卵巢低反应患者的效果比较[J]. 中国优生与遗传杂志, 2021, 29(4):458-461. doi: 10.13404/j.cnki.cjbhh.20210812.005.
[27]	Tu X, You B, Jing M, et al. Progestin-Primed Ovarian Stimulation Versus Mild Stimulation Protocol in Advanced Age Women With Diminished Ovarian Reserve Undergoing Their First In Vitro Fertilization Cycle: A Retrospective Cohort Study[J]. Front Endocrinol(Lausanne), 2021, 12:801026. doi: 10.3389/fendo.2021.801026.
[28]	Zhao S, Wang C. Efficacy of progestin-primed ovarian stimulation (PPOS) versus minimal stimulation in women of advanced maternal age with poor ovarian response under the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) criteria[J]. Ann Palliat Med, 2023, 12(1):133-140. doi: 10.21037/apm-22-1448. pmid: 36747387
[29]	Lin G, Zhong X, Li S, et al. The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis[J]. Front Endocrinol(Lausanne), 2023, 14:1232935. doi: 10.3389/fendo.2023.1232935.
[30]	江美燕, 杨慧春, 陈楠, 等. 首次长方案IVF/ICSI-ET失败再次不同促排卵治疗方案临床效果比较[J]. 浙江医学, 2022, 44(2):158-162,168. doi: 10.12056/j.issn.1006-2785.2022.44.2.2021-2988.
[31]	高红, 林莉, 颜晓红, 等. 高孕激素状态下促排卵方案在反复常规超促排卵失败的体外受精/卵胞质内单精子注射-胚胎移植患者中的应用[J]. 中华生殖与避孕杂志, 2020, 40(2):94-100. doi: 10.3760/cma.j.issn.2096-2916.2020.0036.
[32]	Mu Z, Sa Y, Sun Z, et al. Ovulation induction with high progesterone levels may be more suitable for elderly patients with low ovarian response[J]. J Gynecol Obstet Hum Reprod, 2021, 50(2):101661. doi: 10.1016/j.jogoh.2019.101661.
[33]	邱佩嫦, 陈彩蓉, 况玉兰, 等. 年轻卵巢低反应患者体外受精-胚胎移植重复周期促排卵方案探讨[J]. 岭南急诊医学杂志, 2021, 26(3):254-256,265. doi: 10.3969/j.issn.1671-301X.2021.03.011.
[34]	Wang L, Wang J, Zhang Y, et al. Analysis of euploidy rates in preimplantation genetic testing for aneuploidy cycles with progestin-primed versus GnRH agonist/antagonist protocol[J]. Eur J Med Res, 2023, 28(1):28. doi: 10.1186/s40001-023-01000-1. pmid: 36642707
[35]	Giles J, Cruz M, Cobo A, et al. Medroxyprogesterone acetate: an alternative to GnRH-antagonist in oocyte vitrification for social fertility preservation and preimplantation genetic testing for aneuploidy[J]. Reprod Biomed Online, 2023, 47(2):103222. doi: 10.1016/j.rbmo.2023.04.013.
[36]	Zolfaroli I, Ferriol GA, Mora JH, et al. Impact of progestin ovarian stimulation on newborn outcomes: a meta-analysis[J]. J Assist Reprod Genet, 2020, 37(5):1203-1212. doi: 10.1007/s10815-020-01755-0.
[37]	Li D, Hu Z, Chen Q, et al. Neonatal outcomes and congenital malformations in children born after progestin-primed ovarian stimulation protocol[J]. Front Endocrinol(Lausanne), 2022, 13:965863. doi: 10.3389/fendo.2022.965863.