The Fertility Clinic, Skive Regional Hospital, Skive, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
The Fertility Clinic, Skive Regional Hospital, Skive, Denmark.
Fertil Steril. 2024 Jun;121(6):1000-1009. doi: 10.1016/j.fertnstert.2024.04.006. Epub 2024 Apr 10.
To study whether midluteal serum estradiol (E2) levels are associated with the live birth rate in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles in patients with optimal midluteal serum progesterone (P4) levels.
Observational prospective cohort study.
Public fertility clinic.
A total of 412 women had an HRT-FET cycle single blastocyst transfer from January 2020 to November 2022.
The HRT-FET cycle priming regimen included oral E2 (6mg/24 h) administered in the evening, followed by vaginal P4 (400mg/12 h). Serum E2 and P4 levels were measured using a standardized method, 2-4 hours after the latest P4 administration and 9-14 hours after E4 administration on the day of blastocyst transfer, day 6 of P4 administration. Patients with serum P4 levels (<11 ng/mL [35 nmol/L]) on the day of transfer received additional rectal P4 (400mg/12 h). No additional E2 dose was administered.
The primary outcome was the live birth rate (LBR) in relation to E2 levels at blastocyst transfer day.
The optimal serum E2 levels correlating with ongoing pregnancy were ≥292 pg/mL and <409 pg/mL (≥1,070 pmol/L and <1,500 pmol/L). The LBR was 59% (60/102) when E2 levels were within this range, whereas a significantly lower LBR of 39% (101/260) was seen in patients when E2 levels were <292 pg/mL (<1,070 pmol/L) and of 28% (14/50) when E2 levels were ≥409 pg/mL (≥1,500 pg/mL). In a logistic regression analysis, adjusting for serum P4 level ≥11 ng/mL or <11 ng/mL (≥35 nmol or <35 nmol/L) on the day of transfer, body mass index, age at oocyte retrieval, day 5 or 6 vitrified blastocysts, and blastocyst score, the adjusted risk difference of live birth was -0.21 (-0.32; -0.10) when the E2 level was <292 pg/mL (<1,070 pmol/L) and -0.31 (-0.45; -0.18) when the E2 level was ≥409 pg/mL (≥1,500 pmol/L) compared with E2 levels ≥292 pg/mL and <409 pg/mL (≥1,070 and <1,500 pmol/L). Importantly, only 25% of patents had optimal levels.
The study shows a significant association between serum E2 levels and reproductive outcomes in an HRT-FET cohort in which optimal serum P4 levels were secured. Midluteal serum E2 levels are associated with the LBR in HRT-FET cycles, and E2 levels should neither be too high nor too low.
EudraCT No.: 2019-001539-29.
研究在孕激素（P4）水平最佳的黄体中期血清雌二醇（E2）水平是否与激素替代治疗冻融胚胎移植（HRT-FET）周期中的活产率相关。
观察性前瞻性队列研究。
公共生育诊所。
2020 年 1 月至 2022 年 11 月期间，共有 412 名妇女进行了 HRT-FET 周期单囊胚移植。
HRT-FET 周期的启动方案包括每天晚上口服 E2（6mg/24 h），随后阴道给予 P4（400mg/12 h）。使用标准化方法测量血清 E2 和 P4 水平，即在移植当天，即 P4 给药第 6 天，在最后一次 P4 给药后 2-4 小时和 E4 给药后 9-14 小时测量血清 E2 和 P4 水平。如果患者在移植当天的血清 P4 水平（<11ng/mL [35nmol/L]），则给予额外的直肠 P4（400mg/12 h）。不给予额外的 E2 剂量。
主要结局是与胚胎移植日 E2 水平相关的活产率（LBR）。
与持续妊娠相关的最佳血清 E2 水平为≥292pg/mL 和 <409pg/mL（≥1070pmol/L 和 <1500pmol/L）。当 E2 水平在该范围内时，LBR 为 59%（60/102），而当 E2 水平<292pg/mL（<1070pmol/L）时，LBR 显著降低至 39%（101/260），当 E2 水平≥409pg/mL（≥1500pmol/L）时，LBR 降至 28%（14/50）。在调整了移植当天血清 P4 水平≥11ng/mL 或 <11ng/mL（≥35nmol 或 <35nmol/L）、体重指数、取卵时年龄、第 5 或 6 天冷冻的囊胚和囊胚评分的逻辑回归分析中，与 E2 水平≥292pg/mL 和 <409pg/mL（≥1070 和 <1500pmol/L）相比，E2 水平<292pg/mL（<1070pmol/L）时活产的调整风险差异为-0.21（-0.32；-0.10），E2 水平≥409pg/mL（≥1500pmol/L）时为-0.31（-0.45；-0.18）。重要的是，只有 25%的患者有最佳水平。
该研究表明，在孕激素水平最佳的 HRT-FET 队列中，血清 E2 水平与生殖结局有显著关联。黄体中期血清 E2 水平与 HRT-FET 周期的活产率相关，E2 水平既不能过高也不能过低。
EudraCT 编号：2019-001539-29。
