激动剂长方案与拮抗剂方案对胚胎整倍体率的影响

doi:10.6040/j.issn.1671-7554.0.2022.1013

摘要/Abstract

摘要： 目的探讨促性腺激素释放激素类似物(GnRH-a)的选择对胚胎植入前非整倍体遗传学检测(PGT-A)周期胚胎整倍体率以及临床妊娠率的影响。方法选取2017年1月—2020年10月于山东大学生殖医学研究中心进行PGT-A周期的卵巢储备良好的年轻女性为研究对象(共359个周期、1 475个囊胚),根据促排卵方案分为拮抗剂组(n=157)、激动剂组(n=202)。应用单因素分析比较两组的基线参数、促排卵及取卵周期参数,并将差异有统计学意义的参数纳入Logistic回归模型进行多因素分析。其中主要观察指标为胚胎整倍体率,次要指标为临床妊娠率。结果单因素分析结果显示,激动剂组与拮抗剂组比较,优质囊胚率(41.4% vs 42.9%, P=0.335)、囊胚整倍体率(56.1% vs 52.6%, P=0.171)、冻融胚胎移植(CET)临床妊娠率(69.2% vs 63.2%, P=0.289)差异均无统计学意义。平衡女方年龄、BMI、MⅡ卵子数、多囊卵巢综合征(PCOS)诊断、促性腺激素(Gn)用量、人体毛绒膜促性腺激素(HCG)用量等参数后,选择GnRH激动剂或拮抗剂进行垂体抑制与胚胎整倍体率及临床妊娠率差异均无统计学意义(P>0.05)。对卵巢储备好的年轻患者而言,其获卵数与胚胎整倍体率差异有统计学意义(P=0.04,OR=1.02,95%CI:1.00~1.04)。结论 GnRH激动剂长方案和拮抗剂方案的选择不会影响胚胎整倍体率及临床妊娠率。因此在全胚冷冻周期中,对卵巢储备功能正常及卵巢高反应的年轻女性进行卵巢刺激可灵活选用拮抗剂方案和激动剂长方案。

关键词: 胚胎整倍体率, 卵巢刺激方案, 胚胎植入前非整倍体遗传学检测, 促性腺激素释放激素类似物, 冻融胚胎移植

Abstract: Objective To investigate the use of gonadotropin-releasing hormone(GnRH)analog on embryonic euploidy rate as well as clinical pregnancy rate(CPR)in preimplantation genetic testing for aneuploidy(PGT-A)cycles. Methods From Jan. 2017 to Oct. 2020, young women with good ovarian reserve who underwent PGT-A cycles were selected, including 359 cycles and 1,475 blastocysts. The subjects were divided into the antagonist group(n=157)and agonist group(n=202). The baseline parameters, ovulation induction and ovulation cycle parameters of the two groups were determined with univariate analysis, and parameters with statistically significant differences were included in multivariate Logistic regression analysis. The primary parameter was the euploidy rate, and secondary parameter was CPR. Results No statistically significant differences were found in the good-quality blastocysts rate from meiosis Ⅱ(MⅡ)oocytes(41.4% vs 42.9%, P=0.335), embryonic euploidy rate(56.1% vs 52.6%, P=0.171), and CPR(69.2% vs 63.2%, P=0.289)of cryo-thawed embryo transfer(CET). After female age, body mass index(BMI), number of MⅡ oocytes, polycystic ovarian syndrome(PCOS)diagnosis, dosages of gonadotropins(Gn)and human chorionic gonadotropin(HCG)were adjusted, the selection of GnRH analog to achieve pituitary suppression did not affect the embryonic euploidy rate or CPR(P>0.05). For young patients with good ovarian reserve, there was a low statistically significant association between the number of oocytes retrieved and embryonic euploidy rate(P=0.04, OR=1.02, 95%CI: 1.00-1.04). Conclusion Stimulation with long GnRH agonist protocol and GnRH antagonist protocol results in a fairly similar embryonic euploidy rate and clinical pregnancy rate for young patients with ideal ovarian reserve. The findings support the flexible use of GnRH analogs to optimize treatment for this group of patients.

Key words: Embryonic euploidy rate, Ovarian stimulation protocol, Preimplantation genetic testing, Gonadotropin-releasing hormone analog, Cryo-thawed embryo transfer

中图分类号:

R715.5

于文澔,张倩,孙梅,李鸿昌,朱月婷,姜文杰,颜军昊. 激动剂长方案与拮抗剂方案对胚胎整倍体率的影响[J]. 山东大学学报 (医学版), 2023, 61(1): 45-50.

YU Wenhao, ZHANG Qian, SUN Mei, LI Hongchang, ZHU Yueting, JIANG Wenjie, YAN Junhao. Comparison of the euploidy rate of PGT-A tested embryos between long GnRH agonist and GnRH antagonist protocols[J]. Journal of Shandong University (Health Sciences), 2023, 61(1): 45-50.

参考文献

[1] Källén B, Finnström O, Lindam A, et al. Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years[J]. Hum Reprod, 2010, 25(4):1026-1034.
[2] Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies[J]. Am J Obstet Gynecol, 2017, 217(3): 270-281.
[3] 胡琳莉, 黄国宁, 孙海翔, 等. 促排卵药物使用规范(2016)[J]. 生殖医学杂志, 2017, 26(4): 302-307. HU Linli, HUANG Guoning, SUN Haixiang, et al. CSRM guideline for the use of ovulation induction drug(2016)[J]. Journal of Reproductive Medicine, 2017, 26(4): 302-307.
[4] Filicori M, Cognigni GE, Arnone R, et al. Role of different GnRH agonist regimens in pituitary suppression and the outcome of controlled ovarian hyperstimulation [J]. Hum Reprod, 1996, 11(Suppl 3): 123-132.
[5] Wei D, Liu JY, Sun Y, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial[J]. Lancet, 2019, 393(10178): 1310-1318.
[6] Shi Y, Sun Y, Hao C, et al. Transfer of fresh versus frozen embryos in ovulatory women [J]. N Engl J Med, 2018, 378(2): 126-136.
[7] Mizrachi Y, Horowitz E, Farhi J, et al. Ovarian stimulation for freeze-all IVF cycles: a systematic review [J]. Hum Reprod Update, 2020, 26(1): 118-135.
[8] Capalbo A, Rienzi L, Cimadomo D, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts [J]. Hum Reprod, 2014, 29(6): 1173-1181.
[9] Mumusoglu S, Yarali I, Bozdag G, et al. Time-lapse morphokinetic assessment has low to moderate ability to predict euploidy when patient- and ovarian stimulation-related factors are taken into account with the use of clustered data analysis[J]. Fertil Steril, 2017, 107(2): 413-421.
[10] Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy(PGT-A): a committee opinion[J]. Fertil Steril, 2018,109(3): 429-436.
[11] Dahdouh EM, Balayla J, Garcia-Velasco JA, et al. PGT-A for recurrent pregnancy loss: evidence is growing but the issue is not resolved[J]. Hum Reprod, 2021, 36(10): 2805-2806.
[12] Poseidon Group(Patient-Oriented Strategies Encompassing Individualized Oocyte Number), Alviggi C, Andersen CY, et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept[J]. Fertil Steril, 2016, 105(6): 1452-1453.
[13] Ovarian Stimulation TEGGO, Bosch E, Broer S, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI[J]. Hum Reprod Open, 2020,2020(2): hoaa009. doi: 10.1093/hropen/hoaa009. eCollection 2020.
[14] Al-Inany HG, Youssef MA, Ayeleke RO, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology[J]. Cochrane Database Syst Rev, 2016, 4(4): CD001750. doi: 10.1002/14651858.CD001750.
[15] Gardner DK, Lane M, Stevens J, et al. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer[J]. Fertil Steril, 2000, 73(6): 1155-1158.
[16] 中国女医师协会生殖医学专业委员会专家共识编写组. 辅助生殖领域拮抗剂方案标准化应用专家共识[J]. 中华生殖与避孕杂志, 2022, 42(2): 109-116.
[17] Xu DF, Liu PP, Fan L, et al. GnRH antagonist weakens endometrial stromal cells growth ability by decreasing c-kit receptor expression[J]. Reprod Biol Endocrinol, 2022, 20(1): 29. doi: 10.1186/s12958-021-00886-y.
[18] Rivier J, Jiang GC, Lahrichi SL, et al. Dose relationship between GnRH antagonists and pituitary suppression. Human reproduction[J]. 1996, 11(Suppl 3): 133-147.
[19] Yang WJ, Hwang YC, Lin CS, et al. Embryonic early-cleavage rate is decreased with aging in GnRH agonist but not in antagonist protocols[J]. J Assist Reprod Genet, 2015, 32(5): 789-795.
[20] Bahçeci M, Ulug U, Erden HF, et al. Frozen-thawed cleavage-stage embryo transfer cycles after previous GnRH agonist or antagonist stimulation[J]. Reprod Biomed Online, 2009, 18(1): 67-72.
[21] Abbara A, Clarke SA, Dhillo WS. Novel concepts for inducing final oocyte maturation in in vitro fertilization treatment[J]. Endocr Rev, 2018, 39(5): 593-628.
[22] Wu Q, Li H, Zhu Y, et al. Dosage of exogenous gonadotropins is not associated with blastocyst an-euploidy or live-birth rates in PGS cycles in Chinese women[J]. Hum Reprod, 2018, 33(10): 1875-1882.
[23] Kyrou D, Verpoest W, Staessen C, et al. No relationship between the type of pituitary suppression for IVF and chromosomal abnormality rates of blastomeres: an observational study[J]. Fertil Steril, 2011, 95(2): 563-567.
[24] Labarta E, Bosch E, Mercader A, et al. A higher ovarian response after stimulation for IVF Is related to a higher number of euploid embryos[J]. Biomed Res Int, 2017, 2017: 5637923. doi: 10.1155/2017/5637923.
[25] La Marca A, Capuzzo M, Longo M, et al. The number and rate of euploid blastocysts in women undergoing IVF/ICSI cycles are strongly dependent on ovarian reserve and female age[J]. Hum Reprod, 2022, 37(10): 2392-2401.

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