冻胚移植前较高剂量的阴道微粒化黄体酮是否增加活产率？

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Study question

探讨的问题

Does a higher daily dose of micronized vaginal progesterone (MVP) increase live birth rates (LBR) or diminishes risk of early pregnancy loss (EPL)?

每日较高剂量的阴道微粒化黄体酮（MVP）是否增加活产率（LBR）或降低早期流产率（EPL）？

Summary answer

总结回答

An increased dose of MVP does not affect reproductive outcomes.

增加MVP的剂量并不影响生殖结局。

What is known already

已知内容

Endometrial preparation in frozen embryo transfer (FET) cycles can be achieved either in a natural cycle (NC), a stimulated cycle or an artificial cycle (AC). Despite growing advocacy for utilization of NC for FET mainly because of pregnancy complications, there are still numerous indications and strengths of AC, such as convenient monitoring and planning. In AC-FET cycles exogenous estradiol (E2) and progesterone (P) are administered consecutively in order to mimic a natural cycle. Although MVP still being the most widely used medication for LPS in AC-FET cycles, dose finding studies are lacking.

冷冻胚胎移植（FET）周期中的子宫内膜准备方案包括自然周期（NC）、促排周期及人工周期（AC），由于妊娠并发症少，越来越多的人提倡FET周期使用NC准备内膜，但AC方案仍有其适应症和优势，如方便监测和规划。在AC-FET中，需要外源性雌二醇（E2）和孕酮(P)连续给药，从而模拟一个月经周期。尽管MVP仍然是人工周期中使用最广泛的黄体支持药物，但仍缺乏剂量方面的研究。

Study design, size, duration

研究设计、大小、持续时间

This is a retrospective study performed at a university-affiliated centre including patients performing a single blastocyst transfer from January 2016 till June 2021. Pregnancy outcomes were compared between patients receiving 600mg (3x200mg) or 800mg (2x200mg) of MPV in the second phase of an AC-FET cycle. The time period was chosen to incorporate the empiric change made in the inner guidelines regarding artificial cycles LPS in autumn 2018.

这是一项在一个大学附属生殖中心进行的回顾性研究，包括从2016年1月至2021年6月进行单囊胚FET患者。比较AC-FET的第二阶段，接受600mg（3x200mg）或800mg（2x200mg）MPV的患者的妊娠结局。选择这样的时间段是为了纳入2018年秋季关于AC-FET黄体支持的内部指南中的经验变化。

Participants/materials, setting, methods

参与者/材料、环境、方法

Patients aged 19-39, who underwent the first frozen single blastocyst transfer were included. Only HRT cycles, where after exogenous estradiol endometrium preparation LPS was started with MVP 600mg or 800mg were included. Patients lost to follow-up, with missing data, with known uterine pathology, recurrent miscarriages, with switch to MNC, with more than one progesterone route planned or modified LPS were excluded.

年龄在19-39岁之间，接受首次冷冻单囊胚移植的患者。只纳入激素替代周期（HRT），在外源性E2进行内膜准备后，黄体支持开始使用MVP 600mg或800mg。排除随访失败、数据缺失、已知子宫病变、复发性流产、改用改良自然周期（MNC）方案、同时使用其他黄体支持途径或更改黄体支持方案的患者。

Main results and the role of chance

主要结果和分析

1825 artificial cycles for FET were included. 827 supplemented with 600mg of MVP -MVP600 group and 998 with 800mg of MVP – MVP800 group. The MVP600 and MVP800 groups did not differ in BMI 24.02 (SD 4.73) vs 23.81 (SD 4.6) (p = 0.37), rank of embryo transfer 1.93 (SD 1.41) vs 1.77 (SD1.19) (p = 0.11), or the thickness of the endometrium at planning 8.67mm (SD1.79) vs 8.51mm (SD 1.7) (p = 0.06). Yet, MVP 800mg group was slightly older than MVP600 group 31.99 (SD 3.72) vs 30.84 (SD 3.9) (p < 0.001). Positive hCG was 58.65% (485 out of 827) for MVP600 and in 62.12% (620 out of 998) for MVP800 group (p = 0.13). LBR per positive hCG 64.18% (292 out of 455) in MVP600 and 67.17% (397 out of 591) in MVP800 group (p = 0.31). Early pregnancy loss per positive hCG did not differ between the groups, and including biochemical losses, was 32.75% in MVP600 (149 out of 455) vs 30.8% in MVP800 (182 out of 591) (p = 0.5). Multivariable regression analysis adjusting for relevant confounders (eg. BMI, endometrium thickness) revealed that the dose of MVP 600mg vs 800mg is not significantly associated with EPL OR 0.92 (95% CI 0.71-1.22) p > 0.592.

纳入了1825个AC-FET。827个周期MVP 600mg（MVP600组），998个周期MVP800mg（MVP800组）。两组在BMI[24.02（SD 4.73）和23.81（SD 4.6）（p=0.37）]、胚胎移植等级[1.931.93（SD1.41）和1.77（SD1.1.19）（p=0.11）]、子宫内膜厚度[8.67mm(SD1.51mm（SD1.7）（p=0.06）]等方面无明显差异。然而，MVP 800mg组年龄略大于MVP600组[31.99（SD 3.72）vs 30.84（SD 3.9）（p < 0.001）]。MVP600组hCG阳性率为58.65%（827中485人），MVP800组为62.12%（998中620人）（p=0.13）。每组hCG阳性后的早期流产率（包括生化妊娠）在两组之间没有差异，MVP600组为32.75%分析校正相关混杂因素（如：BMI，子宫内膜厚度）后显示，MVP 剂量600mg和800mg与流产之间无明显相关性（OR=0.92，95%可信区间CI （0.71-1.22）， p > 0.592）。

Limitations, reasons for caution

局限性分析

The main limitation is the retrospective design of our study, with an inherent risk of bias. Furthermore, we could not compare the blood progesterone values at the day of the transfer as in MVP600 they were not routinely performed, so the need for additional LPS could not be compared.

主要的局限性是我们研究的回顾性设计，存在固有偏倚风险。此外，因为MVP600没有常规进行检测，不能比较移植当天的血清孕酮水平，也不能比较需要额外的黄体支持的概率。

Wider implications of the findings

研究的深远意义

This is the largest study dose finding study comparing the two progesterone administration doses. The higher dose of MVP does not improve reproductive outcomes, but might be more convenient due to a twice daily application.

这是比较两种孕酮给药剂量的最大的研究剂量的研究。结果表明增加MVP剂量并不能改善生殖结局，但由于每天应用两次，可能更为方便。

文章来源：

E Bumbul-Mazurek, C Roelens, S Mackens, L Van Landuyt, P Drakopoulos, H Tournaye, C Blockeel, O-021 The dose of micronised vaginal progesterone prior to frozen embryo transfer in artificially prepared cycles: the more the better?, Human Reproduction, Volume 38, Issue Supplement_1, June 2023, dead093.021, https://doi.org/10.1093/humrep/dead093.021