Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial

• Published in: Human reproduction (Oxford) 2023-11, Vol.38 (Supplement_2), p.ii24-ii33
• Main Authors: Niu, Yue, Liu, Hong, Li, Xiufang, Zhao, Junli, Hao, Guimin, Sun, Yun, Zhang, Bo, Hu, Chunxiu, Lu, Yingli, Ren, Chun’e, Yuan, Yingying, Zhang, Jie, Lu, Yao, Wen, Qianqian, Guo, Min, Sui, Mingxing, Wang, Guili, Zhao, Dingying, Chen, Zi-Jiang, Wei, Daimin
• Format: Article
• Language: English
• Subjects: Embryo Transfer; Female; Humans; Infant, Newborn; Infertility, Female; Lipopolysaccharides; Luteal Phase; Pregnancy; Progesterone
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/deac266

Abstract STUDY QUESTION Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11–12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): −2.6%; 95% CI: −9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: −6.4%; 95% CI: −12.6% to −0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show