Hum Reprod. 2025 Nov 21:deaf219. doi: 10.1093/humrep/deaf219. Online ahead of print.
ABSTRACT
STUDY QUESTION: What is the effect of progesterone administered via vaginal oil capsules versus pessaries, on clinical outcomes, when used for luteal phase support (LPS) in ART?
SUMMARY ANSWER: Our study findings indicate a higher live birth rate with vaginal oil capsules compared with pessaries, in both fresh and frozen cycles. In the frozen cycles, a lower miscarriage rate was observed with vaginal oil capsules compared with pessaries.
WHAT IS KNOWN ALREADY: Sufficient LPS, with exogenous progesterone, is essential during ART to improve implantation and pregnancy rates. Micronized vaginal progesterone (MVP) is the most commonly used form of luteal support worldwide. There are no head-to-head comparisons of vaginal oil capsules versus pessaries, with a focus on clinical efficacy, for LPS.
STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of patients who completed ART cycles with either only vaginal oil capsules 600-800 mg/day or only pessaries 800 mg/day for LPS. Primary outcomes were live birth and miscarriage. Data for fresh IVF/ICSI cycles and frozen embryo transfer cycles with hormone replacement therapy (HRT-FET) were analysed separately. Multivariable regression analyses were performed with adjustment for female age, BMI, ethnicity, ovarian reserve, duration and cause of subfertility, stimulation protocol, number of previous cycles, number of oocytes, number of embryos transferred, previous live births, and previous miscarriages.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Our study population consisted of women undergoing treatment across 14 Care Fertility clinics in the UK, from January 2017 to December 2022. We included women with stimulated IVF/ICSI cycles with fresh embryo transfer and autologous HRT-FET cycles. A total of 42 291 cycles were analysed; vaginal oil capsules were exclusively used in 25 738 cycles and pessaries exclusively in 16 553 cycles.
MAIN RESULTS AND THE ROLE OF CHANCE: In the IVF/ICSI group, the live birth rate was higher in those taking vaginal oil capsules compared with pessaries: 34.3% vs 27.8%; adjusted risk ratio (aRR) 1.11 (95% CI 1.04-1.19; P < 0.001). In the HRT-FET group, the live birth rate was also higher in those taking vaginal oil capsules compared to pessaries: 36.7% vs 32.9% (aRR 1.09; 95% CI 1.04-1.14; P < 0.001). The miscarriage rate was lower in those taking vaginal oil capsules compared to pessaries for both IVF/ICSI (13.4% vs 14.5%, P < 0.05) and HRT-FET cycles (17.2% vs 19.7%, P < 0.001) in the crude analysis. The adjusted analysis for miscarriage found a statistically significant difference only for HRT-FET cycles (aRR 0.87; 95% CI 0.82-0.93).
LIMITATIONS, REASONS FOR CAUTION: This is a retrospective cohort study. Whilst we have extensively adjusted for confounding, there can still be residual confounding.
WIDER IMPLICATIONS OF THE FINDINGS: An appropriately powered randomized controlled trial directly comparing the two drugs, focusing on clinical efficacy, is required to determine if one is superior to the other.
STUDY FUNDING/COMPETING INTEREST(S): This study has been delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC). R.K.D.S. is in receipt of honoraria for lectures and presentations from Ferring Pharmaceuticals and Besins Healthcare UK. R.K.D.S. has received travel support from IBSA Pharma and Theramex UK and payment for participation on an advisory board for educational meetings for Ferring Pharmaceuticals and IBSA Pharma. A.C. has contributed to the scientific advisory boards of Ferring Pharmaceuticals, Theramax UK, Besins Healthcare UK, and Organon Pharma UK. M.K. has received travel support from Besins Healthcare UK and Merck. A.H.B. is on an advisory board and has received speaker fees from NovoNordisk Pharmaceuticals and is a shareholder at Care Fertility UK and Care Fertility Leeds. T.B. is in receipt of honoraria for lectures and presentations from Merck and Gedeon Richter. T.B. has received travel support from IBSA Pharma, Vitrolife, and Theramex and payment for participation on an advisory basis for IBSA Pharma and Conceivable Life Sciences. A.R. has received honoraria for lectures and presentations from Gedeon Richter. A.R. has received travel support from Gedeon Richter and payment for participation on an advisory board for educational meetings for Ferring Pharmaceuticals. V.S. has received travel support from IBSA Pharma and payment for educational meetings and participation in an advisory role for Theramex.
TRIAL REGISTRATION NUMBER: n/a.
PMID:41270285 | DOI:10.1093/humrep/deaf219
