Oral dydrogesterone versus micronized vaginal progesterone for luteal phase support: a double-blind crossover study investigating pharmacokinetics and impact on the endometrium

• Published in: Human reproduction (Oxford) 2024-02, Vol.39 (2), p.403-412
• Main Authors: Loreti, S, Thiele, K, De Brucker, M, Olsen, C, Centelles-Lodeiro, J, Bourgain, C, Waelput, W, Tournaye, H, Griesinger, G, Raes, J, Vieira-Silva, S, Arck, P, Blockeel, C, Mackens, S
• Format: Article
• Language: English
• Subjects: Adult; Cross-Over Studies; Dydrogesterone; Endometrium; Female; Fertilization in Vitro - methods; Humans; Lipopolysaccharides; Luteal Phase; Ovulation Induction - methods; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic; RNA; Sperm Injections, Intracytoplasmic - methods; Triptorelin Pamoate
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/dead256

How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)? Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium. O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level. Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis. All oocyte donors were