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促性腺激素释放激素激动剂扳机时机对卵巢过度刺激综合征高风险患者卵母细胞成熟率的影响

Is oocyte maturation rate associated with triptorelin dose used for triggering final oocyte maturation in patients at high risk for severe ovarian hyperstimulation syndrome?

机构信息

Unit of Human Reproduction, First Department of OB/Gyn, Medical School, Aristotle University, Thessaloniki, Greece.

Eugonia Unit of Assisted Reproduction, Athens, Greece.

出版信息

Hum Reprod. 2019 Sep 29;34(9):1770-1777. doi: 10.1093/humrep/dez105.

Abstract

STUDY QUESTION

Are oocyte maturation rates different among 0.1, 0.2 and 0.4 mg triptorelin used for triggering final oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS) undergoing ICSI?

SUMMARY ANSWER

A dose of 0.1 mg triptorelin results in similar oocyte maturation rates compared to higher doses of 0.2 and 0.4 mg in patients at high risk for OHSS undergoing ICSI.

WHAT IS KNOWN ALREADY

The GnRH agonist triptorelin is widely used instead of hCG for triggering final oocyte maturation, in order to eliminate the risk of severe OHSS in patients undergoing ovarian stimulation for IVF/ICSI. However, limited data are currently available regarding its optimal dose use for this purpose in patients at high risk for OHSS.

STUDY DESIGN, SIZE, DURATION: A retrospective study was performed between November 2015 and July 2017 in 131 infertile patients at high risk for severe OHSS undergoing ovarian stimulation for ICSI. High risk for severe OHSS was defined as the presence of at least 19 follicles ≥11 mm in diameter on the day of triggering final oocyte maturation.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian stimulation was performed with recombinant FSH and GnRH antagonists. Patients received 0.1 (n = 42), 0.2 (n = 46) or 0.4 mg (n = 43) triptorelin for triggering final oocyte maturation. Hormonal evaluation of FSH, LH, estradiol (E2) and progesterone (PRG) was carried out on the day of triggering final oocyte maturation, 8 and 36 hours post triggering and 3, 5, 7, and 10 days after triptorelin administration. During this period, all patients were assessed for symptoms and signs indicative of severe OHSS development. Primary outcome measure was oocyte maturation rate, defined as the number of metaphase II (MII) oocytes divided by the number of cumulus-oocyte-complexes retrieved per patient. Results are expressed as median (interquartile range).

MAIN RESULTS AND THE ROLE OF CHANCE

No significant differences in patient baseline characteristics were observed among the 0.1 mg, the 0.2 mg and the 0.4 mg groups. Regarding the primary outcome measure, no differences were observed in oocyte maturation rate among the three groups compared [82.6% (17.8%) versus 83.3% (18.8%) versus 85.1% (17.2%), respectively, P = 0.686].In addition, no significant differences were present among the 0.1 mg, 0.2 mg and 0.4 mg groups, regarding the number of mature (MII) oocytes [21 (13) versus 20 (6) versus 20 (11), respectively; P = 0.582], the number of oocytes retrieved [25.5 (13) versus 24.5 (11) versus 23 (12), respectively; P = 0.452], oocyte retrieval rate [81.0% (17.7%) versus 76.5% (23.5%) versus 75.0% (22.5), respectively; P = 0.088], the number of fertilized (two pronuclei) oocytes [12.5 (9) versus 14.5 (7) versus 14.0 (8), respectively; P = 0.985], fertilization rate [71.7% (22%) versus 77.1% (19.1%) versus 76.6% (23.3%), respectively; P = 0.525] and duration of luteal phase [7 (1) versus 8 (2) versus 7 (1) days, respectively; P = 0.632]. Moreover, no significant differences were present among the three triptorelin groups regarding serum levels of LH, FSH, E2 and PRG at any of the time points assessed following triggering of final oocyte maturation.

LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study, and although there were no differences in the baseline characteristics of the three groups compared, the presence of bias cannot be excluded.

WIDER IMPLICATIONS OF THE FINDINGS

Based on the results of the current study, it appears that triggering final oocyte maturation with a lower (0.1 mg) or a higher dose (0.4 mg) of triptorelin, as compared to the most commonly used dose of 0.2 mg, does not confer any benefit in terms of oocyte maturation rate in patients at high risk for severe OHSS.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest.

摘要

研究问题

在接受 ICSI 的高风险卵巢过度刺激综合征 (OHSS) 患者中,用于触发卵母细胞最终成熟的 0.1、0.2 和 0.4mg 曲普瑞林的剂量是否会导致卵母细胞成熟率不同?

总结答案

与较高剂量的 0.2 和 0.4mg 相比,在接受 ICSI 的高风险 OHSS 患者中,使用 0.1mg 曲普瑞林可获得相似的卵母细胞成熟率。

已知情况

促性腺激素释放激素激动剂曲普瑞林已广泛用于替代 hCG 触发最终卵母细胞成熟,以消除接受 IVF/ICSI 卵巢刺激的患者发生严重 OHSS 的风险。然而,目前关于在高风险 OHSS 患者中使用该药物进行此目的的最佳剂量的数据有限。

研究设计、规模、持续时间:这是一项回顾性研究,于 2015 年 11 月至 2017 年 7 月在 131 名接受 ICSI 的高风险严重 OHSS 不孕患者中进行。严重 OHSS 的高风险定义为在触发最终卵母细胞成熟的当天,有至少 19 个直径≥11mm 的卵泡。

参与者/材料、设置、方法:使用重组 FSH 和 GnRH 拮抗剂进行卵巢刺激。患者接受 0.1mg(n=42)、0.2mg(n=46)或 0.4mg(n=43)曲普瑞林触发最终卵母细胞成熟。在触发最终卵母细胞成熟的当天、触发后 8 小时和 36 小时以及曲普瑞林给药后 3、5、7 和 10 天,对 FSH、LH、雌二醇 (E2) 和孕酮 (PRG) 的激素评估。在此期间,对所有患者进行评估,以确定严重 OHSS 发展的症状和体征。主要观察指标是卵母细胞成熟率,定义为每个患者获得的成熟 (MII) 卵母细胞数量除以卵丘-卵母细胞复合物的数量。结果以中位数(四分位距)表示。

主要结果和机会因素

0.1mg、0.2mg 和 0.4mg 组患者的基线特征无显著差异。关于主要观察指标,三组之间的卵母细胞成熟率无差异[分别为 82.6%(17.8%)、83.3%(18.8%)和 85.1%(17.2%),P=0.686]。此外,三组之间的成熟 (MII) 卵母细胞数量[分别为 21(13)、20(6)和 20(11),P=0.582]、卵母细胞数量[分别为 25.5(13)、24.5(11)和 23(12),P=0.452]、卵母细胞回收率[分别为 81.0%(17.7%)、76.5%(23.5%)和 75.0%(22.5%),P=0.088]、受精 (两个原核) 卵母细胞数量[分别为 12.5(9)、14.5(7)和 14.0(8),P=0.985]、受精率[分别为 71.7%(22%)、77.1%(19.1%)和 76.6%(23.3%),P=0.525]和黄体期持续时间[分别为 7(1)、8(2)和 7(1)天,P=0.632]也无显著差异。此外,三组之间在触发最终卵母细胞成熟后的任何时间点,血清 LH、FSH、E2 和 PRG 水平均无显著差异。

局限性、谨慎的原因:这是一项回顾性研究,尽管三组之间的基线特征没有差异,但不能排除存在偏倚的可能性。

研究结果的意义

根据当前研究的结果,与最常用的 0.2mg 剂量相比,在高风险严重 OHSS 患者中使用较低 (0.1mg) 或较高剂量 (0.4mg) 的曲普瑞林触发最终卵母细胞成熟似乎不会在卵母细胞成熟率方面带来任何益处。

研究资金/利益冲突:本研究未获得外部资金。没有利益冲突。

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