直肠孕酮给药，能提高低孕酮患者持续妊娠率？

欧洲人类生殖与胚胎学学会（ESHRE）年会是生殖医学领域规模最大、最具影响力的年度国际学术会议之一，覆盖生殖医学领域所有专业。2023年ESHRE年会已经召开，生殖医学论坛精选了众多会议精华内容进行了翻译，希望给大家带来最新鲜、最前沿的生殖医学资讯。

本篇内容由翻译志愿者南通大学附属妇幼保健院生殖医学中心朱怡医生翻译，蔡贺博士审校，供大家学习交流！

Study question

研究的问题

Can supplementation with additional rectal administration of progesterone secure high ongoing pregnancy rates (OPR) in patients with low serum progesterone (P4) at blastocyst transfer (ET)?

胚胎移植后额外以直肠给药的方式补充黄体酮，是否可以提高低血清孕酮患者的持续妊娠率？

Summary answer

概括结论

Rectally administered progesterone starting on the blastocyst transfer day secures high OPR in patients with serum P4 levels lower than 35 nmol/l (11ng/ml).

在胚胎移植后额外以直肠给药的方式补充黄体酮，可以提高低血清孕酮低于35nmol/l（11ng/ml）的患者的持续妊娠率。

What is known already

目前已知的

Low serum P4 levels at peri-implantation in HRT-FET cycles impact reproductive outcomes negatively. However, studies have shown that patients with low P4 after a standard vaginal progesterone treatment can obtain live birth rates (LBR) comparable to patients with optimal P4 levels if they receive additional subcutaneous progesterone, starting close to the day of blastocyst transfer. In contrast, increasing vaginal progesterone supplementation in low serum P4 patients does not increase LBR. Another route of administration rarely used in ART is the rectal route, although progesterone is well absorbed and serum P4 levels reach a maximum level after approximately two hours.

在人工周期内膜准备的胚胎移植过程中，低血清孕酮水平与妊娠结局呈负相关。然而，研究表明移植后标准化使用阴道黄体酮制剂的低血清孕酮患者与近移植日即开始皮下注射黄体酮制剂的患者相比，可获得相似的活产率。相反，在低血清孕酮水平的患者中，增加阴道给黄体酮制剂的剂量并不会提高活产率。ART中黄体酮制剂很少使用的另一种给药途径是直肠给药，该种给药方式黄体酮吸收效率更高，血清孕酮水平在给药2小时后可达高峰。

Study design, size, duration

研究设计、规模、持续时间

This prospective interventional study included a cohort of 488 patients treated with single blastocyst HRT-FET, in which a total of 374 patients had a serum P4 level ≥35nmol/l (11ng/ml) at ET, and 114 patients had a serum P4 level <35nmol/l (11ng/ml). The study was conducted from January 2020 to November 2022.

这项前瞻性研究纳入488名接受人工周期内膜准备的单囊胚移植患者，其中374名患者在移植日血清孕酮水平高于35nmol/l（11ng/ml），114名患者血清孕酮水平低于35nmol/l（11mg/ml）。该研究起止时间为2020年1月至2022年11月。

Participants/materials, setting, methods

参与者/材料、设置、方法

Patients undergoing HRT-FET in a public Fertility Clinic. Endometrial preparation included oral oestradiol (6mg/24hours), followed by vaginal micronized progesterone, 400mg/12hours. Single blastocyst transfer and P4 measurements were performed on the 6th day of progesterone administration and patients with serum P4 <35nmol/l (11ng/ml) additional rectal administration of progesterone (400mg/12hour) was started the same day. In pregnant patients, vaginal and rectal administration continued until week 8, and oestradiol and vaginal progesterone treatment continued until week 10.

患者均在公共生育诊所接受人工周期内膜准备的单胚胎移植。子宫内膜准备包括口服雌二醇（6mg/24小时），然后是阴道微粒化黄体酮（400mg/12小时）。在黄体酮给药的第6天进行单囊胚移植和血清孕酮的测定，血清孕酮<35nmol/l（11ng/ml）的患者在同一天开始额外以直肠给药的方式补充黄体酮（400mg/12小时）。在妊娠患者中，阴道和直肠给药持续到第8周，雌二醇联合阴道黄体酮制剂的治疗持续到第10周。

Main results and the role of chance

主要结论和偏倚

Among 488 HRT-FET single blastocyst transfers, the mean age of the patients at oocyte retrieval (OR) was 30.9 ±4.6 years and the mean BMI at ET 25.1 ±3.5 kg/m2.

The mean serum P4 level after vaginal progesterone administration on the day of blastocyst transfer was 48.9 ±21.0 nmol/l (15.4 ±6.6ng/ml), and a total of 23% (114/488) of the patients had a serum P4 level lower than 35nmol/l (11ng/ml). The overall, positive hCG rate, clinical pregnancy rate, OPR week 12, and total pregnancy loss rate were 66% (320/488), 54% (265/488), 45% (221/488), and 31% (99/320), respectively. There was no significant difference in neither OPR week 12 nor total pregnancy loss rate between patients with P4 ≥35nmol/l (11ng/ml) and patients with P4 <35nmol/l, who received rescue in terms of rectally administered progesterone, 45% vs. 46%, p = 0.77 and 30% vs. 34%, p = 0.53, respectively.

OPR did not depend on whether patients had initially low P4 and rectal rescue or were above the P4 cut-off. Logistic regression analysis showed that only age at OR and blastocyst scoring correlated with OPR week 12, independently of other factors like BMI, and vitrification day of blastocysts (day 5 or 6).

488例人工周期内膜准备的单胚胎移植患者，取卵时的平均年龄为30.9±4.6岁，平均BMI为25.1±3.5 kg/m2。

胚胎移植当天给予阴道用黄体酮后，血清孕酮水平为48.9±21.0 nmol/l（15.4±6.6ng/ml），其中23%（114/488）的患者血清孕酮水平低于35nmol/l（11ng/ml）。总的来说，hCG阳性率、临床妊娠率、孕12周的持续妊娠率和总妊娠丢失率分别为66%（320/488）、54%（265/488），45%（221/488）和31%（99/320）。血清孕酮大于35nmol/l（11ng/ml）的患者和小于35nmol/l的患者在孕12周的持续妊娠率和总妊娠丢失率方面均无显著差异，分别为45%比46%，p=0.77和30%比34%，p=0.53。

持续妊娠率并不取决于患者最初的血清孕酮水平和是否进行直肠用药来补救，或者是否高于血清孕酮的截断值。Logistic回归分析显示，孕12周的持续妊娠率只和取卵时患者年龄和囊胚评分有关，与BMI和囊胚发育天数（第5或第6天）等其他因素无关。

Limitations, reasons for caution

局限性，需要注意的地方

In this study vaginal progesterone (Cyclogest®), a solid pessary with progesterone suspended in vegetable hard fat, was used vaginally as well as rectally. It is unknown whether other vaginal progesterone products could be used rectally as easily with the same rescue effect.

这项研究中，阴道用孕酮制剂(Cyclogest®)，是一种孕酮混合在植物硬脂肪中的固体栓剂，可用于阴道也可以用于肛门。目前尚不清楚其他阴道用孕酮产品是否也能同样地用于直肠，并具有同样的疗效。

Wider implications of the findings

研究结果的更广泛含义

A substantial part of HRT-FET patients receiving vaginal progesterone treatment has low serum P4. Adding rectally administered progesterone in these patients increases the reproductive outcome. Importantly, rectal progesterone administration is considered convenient by the majority of patients; moreover, progesterone pessaries are easy to administer rectally and of low cost.

使用阴道黄体酮制剂治疗的人工周期内膜准备患者中，相当一部分患者的血清孕酮水平较低。在这些患者中增加直肠用黄体酮制剂能改善生殖结局。重要的是，大多数患者认为直肠给药很方便，此外，黄体酮栓剂易于被直肠吸收，且价格低廉。

文章来源：

B Alsbjerg, M B Jensen, B B Povlsen, H O Elbaek, R Laursen, A Mikkelsen, M C Reich, U S Kesmodel, P Humaidan, P-596 Rectal progesterone administration secures high ongoing pregnancy rate in a personalized Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) protocol - a prospective interventional study, Human Reproduction, Volume 38, Issue Supplement_1, June 2023, dead093.040, https://doi.org/10.1093/humrep/dead093.040