University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam.
Hum Reprod. 2021 Jun 18;36(7):1821-1831. doi: 10.1093/humrep/deab093.
Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone?
Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone.
Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET.
STUDY DESIGN, SIZE, DURATION: Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks' gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints.
The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99-1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01-1.68), P = 0.042), with a statistically significant lower rate of miscarriage at <12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32-0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group.
LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability.
Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice.
STUDY FUNDING/COMPETING INTERESTS: This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant.
NCT0399876.
在冻融胚胎移植（FET）周期中，与单独使用阴道孕酮相比，添加口服地屈孕酮作为黄体支持是否能提高妊娠结局？
与单独使用阴道孕酮相比，黄体支持添加口服地屈孕酮可提高活产率，降低流产率。
孕酮是一种重要的激素，可触发胚胎着床的子宫内膜分泌转化。在体外受精（IVF）中，给予外源性孕酮进行黄体支持。然而，通过阴道壁吸收孕酮存在广泛的个体间差异。口服地屈孕酮在新鲜胚胎移植后提供黄体支持时是有效且耐受良好的。然而，目前尚无关于在 FET 后与阴道微粒化孕酮相比，地屈孕酮与阴道微粒化孕酮联合使用的黄体支持对活产率的有效性的数据。
研究设计、规模、持续时间：2019 年 6 月 26 日至 2020 年 3 月 30 日在越南的一家学术不孕中心进行的前瞻性队列研究。
参与者/材料、设置、方法：我们研究了 1364 名接受 IVF 并进行 FET 的女性。当子宫内膜厚度达到≥8mm 时开始黄体支持。黄体支持方案为阴道微粒化孕酮 400mg 每日两次加口服地屈孕酮 10mg 每日两次（研究的第二部分）或阴道微粒化孕酮 400mg 每日两次（研究的前 4 个月）。对于妊娠试验阳性的妇女，适当的黄体支持方案将继续进行，直到 7 周妊娠。主要终点是首次 FET 后的活产，12 周内流产<12 周为次要终点之一。
阴道孕酮+地屈孕酮组和阴道孕酮组分别包括 732 名和 632 名参与者。活产率分别为 46.3%和 41.3%（比率[RR]1.12，95%CI 0.99-1.27，P=0.06；多变量分析 RR 1.30（95%CI 1.01-1.68），P=0.042），地屈孕酮+孕酮组 12 周内流产率明显低于孕酮组（3.4%比 6.6%；RR 0.51，95%CI 0.32-0.83；P=0.009）。单胎（2971.0±628.4 比 3118.8±559.2g；P=0.004）和双胞胎（2175.5±494.8 比 2494.2±584.7；P=0.002）的出生体重在孕酮加地屈孕酮组明显低于孕酮组。
局限性、谨慎的原因：该研究的主要局限性是开放性设计和研究治疗的顺序非随机化。然而，我们能够比传统的随机对照试验更快地进行两种策略的系统比较。此外，单一种族人群限制了外部的普遍性。
我们的研究结果表明，在 FET 周期中，除了阴道孕酮之外，口服地屈孕酮作为黄体支持可降低流产率并提高活产率。精心设计的、偏见有限的前瞻性队列研究可以替代随机对照临床试验，为临床实践提供信息。
研究资金/利益冲突：本研究没有外部资金。LNV 从默克、默克夏普和多姆公司获得演讲和会议费用，从默克、默克夏普和多姆公司以及 Ferring 获得演讲、会议和科学委员会费用；TMH 从 Merck、Merck Sharp and Dohme 和 Ferring 获得演讲费；R.J.N. 从 Ferring 获得科学委员会费用，并从澳大利亚国家卫生和医学研究委员会（NHMRC）获得研究资助。
NCT0399876。
