A comparison of progesterone via vaginal oil capsules versus pessaries for luteal phase support in assisted reproduction treatment - a multicentre cohort study of 42 291 cycles

Q: What was the study question regarding progesterone for luteal phase support (LPS) in ART?

The study assessed the effect of progesterone given via vaginal oil capsules versus pessaries on clinical outcomes for LPS in assisted reproduction treatment.

Q: How many ART cycles and what timeframe were analyzed?

A total of 42,291 cycles were analyzed from January 2017 to December 2022 across 14 Care Fertility clinics in the UK.

Q: What were the key findings for live birth and miscarriage rates?

Live birth rates were higher with vaginal oil capsules than with pessaries in both IVF/ICSI and HRT-FET groups. Miscarriage rates were lower for oil capsules in crude analyses across both cycle types, with a statistically significant difference for miscarriage in adjusted analysis specifically for HRT-FET cycles.

Q: What limitation did the authors identify for interpreting the results?

The study was retrospective, so despite extensive adjustment for confounding, residual confounding could remain. A randomized controlled trial directly comparing the two methods was recommended.

Sep 29, 2026

Uploaded by Ophelia

Clinical outcomes of luteal phase support (LPS) in assisted reproduction were compared between progesterone delivered via vaginal oil capsules and vaginal pessaries in a retrospective multicentre cohort. Data from 42,291 ART cycles across 14 UK clinics (2017–2022) evaluated fresh IVF/ICSI and HRT-FET cycles separately. Results showed higher live birth with oil capsules in both fresh and frozen cycles, with a reduced miscarriage risk observed particularly for frozen cycles. Analyses adjusted for major confounders, including age and prior reproductive history.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Study question and summary answer

What is known already

Study design, size, duration

Participants, setting, methods

Main results

Limitations and wider implications

Human Reproduction, 2026, 41(1), 59–68 [https://doi.org/10.1093/humrep/deaf219](https://doi.org/10.1093/humrep/deaf219) Advance Access Publication Date: November 21, 2025 Original Article Infertility A comparison of progesterone via vaginal oil capsules versus pessaries for luteal phase support in assisted reproduction treatment: a multicentre cohort study of 42 291 cycles R.K. Dhillon-Smith 1,2,†, M. Khairy3,†, T. Bamford 4, V. Sephton5, A. Richardson 6, A.H. Balen7, and A. Coomarasamy 1,8, 􀀃 1Department of Metabolism and Systems Science, School of Medical Sciences, Tommy’s National Centre for Miscarriage Research, University of Birmingham, Edgbaston, UK 2National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Birmingham, UK 3Care Fertility Birmingham, Birmingham, UK 4Care Fertility Manchester, Manchester, UK 5Care Fertility Group, Nottingham, UK 6Care Fertility Northampton, Northampton, UK 7Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK 8Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK 􀀃 Correspondence address. Nuffield Department of Women’s and Reproductive Health, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. E-mail: [arri.coomarasamy@wrh.ox.ac.uk](arri.coomarasamy@wrh.ox.ac.uk) https://orcid.org/0000-0002-3261-9807 †The authors consider that the first two authors should be regarded as joint first authors. 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 ofluteal 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)

FAQs

What was the study question regarding progesterone for luteal phase support (LPS) in ART?

The study assessed the effect of progesterone given via vaginal oil capsules versus pessaries on clinical outcomes for LPS in assisted reproduction treatment.

How many ART cycles and what timeframe were analyzed?

A total of 42,291 cycles were analyzed from January 2017 to December 2022 across 14 Care Fertility clinics in the UK.

What were the key findings for live birth and miscarriage rates?

Live birth rates were higher with vaginal oil capsules than with pessaries in both IVF/ICSI and HRT-FET groups. Miscarriage rates were lower for oil capsules in crude analyses across both cycle types, with a statistically significant difference for miscarriage in adjusted analysis specifically for HRT-FET cycles.

What limitation did the authors identify for interpreting the results?

The study was retrospective, so despite extensive adjustment for confounding, residual confounding could remain. A randomized controlled trial directly comparing the two methods was recommended.

Sep 29, 2026

Uploaded by Ophelia