鑽石舞台

系統綜述問題

對於接受冷凍胚胎或來自供體卵母細胞的胚胎進行胚胎移植的女性，最有效的子宮內膜準備方法是什麼？

（圖片來自Medical bag）

研究背景

夫妻因男方因素、女方因素或不明原因不孕而接受相關治療。在新鮮胚胎移植周期失敗後，可以在有冷凍胚胎時進行凍融胚胎移植。子宮內膜的充分激素製備對於卵子捐贈者和冷凍胚胎更換周期而言至關重要，以提供最佳懷孕機會。一些研究者已經嘗試了許多藥物和各種給藥方式，以優化植入率，從而提高胚胎移植程序的成功率：刺激周期（產生內源性雌二醇）、程序周期（使用外源性雌二醇）或自然周期（允許卵巢在沒有刺激的情況下產生雌二醇）是一些選擇；使用促性腺激素釋放激素（gonadotropin-releasing hormone, GnRH）激動劑和拮抗劑避免自發排卵可能會產生一些影響；或使用其他一些可能增強子宮內膜容受性的藥物，如阿司匹林或類固醇也進行了評估。

研究特徵

我們發現31項隨機對照試驗比較了不同的干預措施，例如總共有5426名女性，雌激素和孕激素的劑量和給藥途徑、使用阻止患者過早排卵的藥物（GnRH激動劑）以及使用其他藥物改善子宮內膜。證據截至2020年6月。

主要結果

我們不確定刺激周期（用來曲唑）與程序周期相比，用於子宮內膜準備是否能改善活產。有證據表明，如果假設程序化周期後的活產幾率為24%，那麼刺激周期後的活產幾率將在13%到51%之間。我們也不確定對流產率和子宮內膜厚度的影響。刺激周期可提高臨床妊娠率。關於多胎妊娠、月經取消和其他不良反應的數據缺乏。

我們不確定自然周期與程序周期相比是否能提高活產率、妊娠率、流產率和子宮內膜厚度。缺乏其他所有結局的數據。

我們不確定經皮給藥（經皮膚給藥）雌激素與口服（經口給藥）雌激素相比是否能提高臨床妊娠率和流產率。在此比較中，缺乏所有其他結局的數據。

在供體取卵當天或取卵後的第二天開始注射孕激素，可能會增加臨床妊娠率並可能降低取消誘導排卵率。我們不確定它是否能降低流產率。缺乏其他所有結局的數據。

與不使用GnRH激動劑相比，使用GnRH激動劑的周期可提高活產率。我們不確定GnRH周期與無GnRH周期對臨床妊娠率、流產率和子宮內膜厚度的影響。在此比較中，沒有研究報告其他結局。

我們不確定是否有任何GnRH激動劑比其他藥物更好：每天服用亮丙瑞林或沉積色氨酸可提高臨床妊娠率，或者每天服用醋酸亮丙瑞林或每日服用那法瑞林可降低流產率。沒有研究報告其他結局。

與激動劑相比，GnRH拮抗劑可能提高臨床妊娠率。對流產率和多胎妊娠率的影響尚不確定。沒有研究報告其他結局。

我們不確定服用阿司匹林的周期與不服用阿司匹林的周期相比，是否能改善活產、臨床妊娠率或子宮內膜厚度。缺乏其他所有結局的數據。

我們也不確定使用類固醇的周期與不使用類固醇的周期相比，是否能提高活產率、臨床妊娠率或流產率。沒有研究報告其他結局。

證據質量

證據質量為中等到極低。證據的主要局限性是研究方法報告不佳，以及活產結果缺乏精確性。

作者:Glujovsky D, Pesce R, Sueldo C, Quinteiro Retamar AM, Hart RJ, Ciapponi A；譯者：趙志慧，武漢大學；審校：靳英輝，武漢大學中南醫院循證與轉化醫學中心；編輯排版：索于思，北京中醫藥大學循證醫學中心

相關文章鏈接

【Cochrane簡語概要】孕前生活方式建議真的能幫助不孕症患者懷孕嗎？

【Cochrane Plain Language Summary】

Endometrial preparation for egg donor recipients or for frozen embryo transfers

Review question

What is the most effective method for endometrial preparation in women undergoing embryo transfers with frozen embryos or embryos derived from donor oocytes?

Background

Couples undergo infertility treatments due to male factor, female factors or unexplained infertility. After an unsuccessful fresh embryo transfer cycle, a frozen-thawed embryo transfer can be performed when frozen embryos are available. Adequate hormonal preparation of the endometrium is of utmost importance for both egg donor and frozen embryo replacement cycles to provide the optimal chances of pregnancy. Many drugs and various modes of administration have been tried by several investigators in order to optimise implantation rates and consequently improve the success rates of the embryo transfer procedures: stimulated cycles (to generate endogenous oestradiol), programmed cycles (administering exogenous oestradiol) or natural cycles (allowing the ovaries to produce oestradiol without stimulation) are some of the options; avoiding spontaneous ovulation with gonadotropin-releasing hormone (GnRH) agonists and antagonists could have some impact; or using some other drugs such as aspirin or steroids that could potentially enhance the endometrial receptivity were also evaluated.

Study characteristics

We found 31 randomised controlled trials comparing different interventions such as the dose and route of administration of oestrogens and progestogen, the use of drugs that stop the patient from ovulating prematurely (GnRH agonists), and the use of other medications to improve the endometrium in a total of 5426 women. The evidence is current to June 2020.

Key results

We are uncertain whether a stimulated cycle (with letrozole) compared to a programmed cycle, for endometrial preparation, improves live birth. The evidence suggests that if the chance of live birth following a programmed cycle is assumed to be 24%, the chance following a stimulated cycle would be between 13% and 51%. We are also uncertain of the impact on miscarriage rate and endometrial thickness. A stimulated cycle may improve clinical pregnancy rate. Data were lacking on multiple pregnancy, cycle cancellation and other adverse effects.

We are uncertain whether a natural cycle improves the live birth rate, pregnancy rate, miscarriage rate and endometrial thickness in comparison with a programmed cycle. Data were lacking for all other outcomes.

We are uncertain if transdermal (delivered via the skin) oestrogens compared with oral (by mouth) oestrogens improve clinical pregnancy rate and miscarriage rate. Data were lacking for all other outcomes in this comparison.

Starting progestogen on the day of the donor oocyte retrieval or the day after probably increases the clinical pregnancy rate and probably reduces the cycle cancellation rate. We are uncertain if it reduces the miscarriage rate. Data were lacking for all other outcomes.

A cycle with GnRH agonist compared to without may improve live birth rate. We are uncertain of the effect of a GnRH cycle compared to no GnRH for the outcomes of clinical pregnancy rate, miscarriage rate, and endometrial thickness. No study reported on the other outcomes for this comparison.

We are uncertain if any GnRH agonist is better than other: a cycle with daily leuprolide or with deposit tryptorelin improves clinical pregnancy rate, or if daily acetate leuprolide or daily nafarelin reduces the miscarriage rate. Other outcomes were not reported.

GnRH antagonists compared to agonists probably improve clinical pregnancy rate. We are uncertain of the effect on miscarriage rate and multiple pregnancy rate. No study reported the other outcomes.

We are uncertain whether a cycle with aspirin compared to a cycle without improves live birth, clinical pregnancy rate or endometrial thickness. Data were lacking for all other outcomes.

We are also uncertain whether a cycle with steroids compared to a cycle without steroids improves live birth rate, clinical pregnancy rate or miscarriage rate. No study reported on the other outcomes.

Quality of the evidence

The evidence was of moderate to very low-quality. The main limitations in the evidence were poor reporting of study methods, and lack of precision in the findings for live birth.