Human Reproduction Department, IVI RMA Valencia, Valencia 46015, Spain.
IVI Foundation, Health Research Institute La Fe, Valencia 46026, Spain.
Hum Reprod. 2021 Feb 18;36(3):683-692. doi: 10.1093/humrep/deaa322.
Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced?
Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles.
We previously found that serum P levels <9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin.
STUDY DESIGN, SIZE, DURATION: This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET.
Women with serum P levels <8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P < 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels <8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml.
LIMITATIONS, REASONS FOR CAUTION: Only women with MVP were included. Extrapolation to other P administration forms needs to be validated.
This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient.
STUDY FUNDING/COMPETING INTEREST(S): None.
NCT03272412.
在人工子宫内膜准备周期中，胚胎移植（ET）日血清孕激素（P）阈值低于该值是否会降低持续妊娠的机会？
ET 日血清 P 水平<8.8ng/ml 会降低自身或捐赠卵周期的持续妊娠率（OPR）。
我们之前发现，在 211 名接受卵子捐赠的接受者中，ET 日血清 P 水平<9.2ng/ml 显著降低 OPR。在这里，我们评估了这些结果是否适用于所有接受人工子宫内膜准备周期的不孕患者，无论卵母细胞来源如何。
研究设计、大小、持续时间：这是一项前瞻性队列研究，于 2017 年 9 月至 2018 年 11 月进行，纳入了 1205 名接受人工子宫内膜准备周期（戊酸雌二醇和米诺孕素阴道栓 400mg 每日两次）后进行 ET 的患者。
参与者/材料、地点、方法：年龄≤50 岁的患者，子宫内膜三层≥6.5mm，行单个或两个囊胚移植。共分析了 1150 名接受自身卵母细胞治疗且未进行非整倍体胚胎植入前遗传学检测（PGT-A）的患者（n=184）、接受自身卵母细胞 PGT-A 治疗的患者（n=308）或接受捐赠卵母细胞治疗的患者（n=658）。主要终点是基于 ET 前即刻测量的血清 P 水平，在妊娠 12 周后持续妊娠率。
血清 P 水平<8.8ng/ml（第 30 百分位）的患者 OPR（36.6% vs 54.4%）和活产率（35.5% vs 52.0%）明显低于其余患者。多变量逻辑回归显示，血清 P<8.8ng/ml 是总体人群和三组治疗中影响 OPR 的独立因素。血清 P 水平与 BMI、体重和末次孕激素剂量与血液检查之间的时间呈显著负相关，与年龄、身高和 HRT 天数呈正相关。多变量逻辑回归显示，只有体重是血清 P 水平<8.8ng/ml 的独立因素。无论血清 P 水平是否高于/低于 8.8ng/ml，持续妊娠的患者的产科和围产期结局均无差异。
局限性、谨慎的原因：仅纳入接受米诺孕素治疗的患者。需要验证其在其他孕激素给药形式中的外推。
本研究确定了在接受自身或捐赠卵的人工子宫内膜准备周期中，ET 日血清 P 阈值为 8.8ng/ml，以优化结局。三分之一接受米诺孕素治疗的患者血清 P 水平不足，这反过来又影响了 ART 周期的成功。建议在使用米诺孕素时监测黄体中期的 P 水平，以根据患者的需要调整剂量。
研究资金/利益冲突：无。
NCT03272412。
