Large UK cohort suggests differences in clinical outcomes between two widely used options.
Women undergoing IVF treatment may see better outcomes from taking progesterone capsules rather than pessaries, a new study has found.
A new analysis of 42,291 assisted reproduction treatment (ART) cycles across 14 fertility clinics in the UK reports that vaginal micronised progesterone given as an oil-based capsule was associated with higher live birth rates and, in some cases, lower miscarriage rates compared with vaginal pessaries. Both are widely used for luteal phase support - the hormone therapy that helps the womb lining sustain an early pregnancy.
In fresh in vitro fertilisation (IVF) cycles, live birth occurred in about 34% of patients using capsules compared with 28% using pessaries. In frozen embryo transfer cycles, the figures were 37% versus 33%. Miscarriage rates were also lower with capsules in frozen cycles.
The research, published in Human Reproduction, was led by University of Birmingham researchers and delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) alongside clinical collaborators in Care Fertility centres nationwide.
Progesterone support is essential during assisted reproduction. Our multicentre analysis indicates that, in routine UK practice, vaginal oil capsules were associated with a higher chance of live birth than pessaries, and - with frozen embryo transfers - a lower miscarriage risk.
Luteal phase support (LPS) with extra progesterone is essential in assisted reproduction, because ovarian stimulation in fresh IVF cycles can reduce the body’s natural progesterone production. In frozen embryo transfer cycles using hormone replacement therapy (HRT-FET), there is no corpus luteum - the temporary structure that forms in the ovary after ovulation and normally produces progesterone to help maintain early pregnancy - so progesterone must be provided artificially.
Micronised vaginal progesterone (MVP) is the most commonly used form of luteal support worldwide, with UK practice frequently using either an oil-based capsule (Utrogestan®) or a pessary (Cyclogest®). Until now, there has been little real-world evidence comparing their effectiveness, and the choice of product therefore varies by clinician, or clinic preference and cost.
This retrospective cohort study analysed anonymised data from 14 Care Fertility clinics in the UK and Ireland between January 2017 and December 2022. Across 23,149 women and 42,291 eligible ART cycles, capsules were used in 25,738 cycles and pessaries in 16,553 cycles. In addition to higher live birth rates, crude analysis showed lower miscarriage rates with capsules in both IVF/ICSI and HRT‑FET cycles; in adjusted analyses, a statistically significant reduction in miscarriage was observed in HRT‑FET (aRR 0.87; 95% CI 0.82–0.93).
Dr Rima Dhillon-Smith, Clinical Associate Professor of Gynaecology and Reproductive Medicine at the University of Birmingham, co-lead for the Women’s Metabolic Health research theme at the NIHR Birmingham BRC, and joint first author of the study, said:
“Progesterone support is essential during assisted reproduction. Our multicentre analysis indicates that, in routine UK practice, vaginal oil capsules were associated with a higher chance of live birth than pessaries, and - with frozen embryo transfers - a lower miscarriage risk.
“While these findings are encouraging for patients and clinicians and provide robust comparative, real-world evidence to help guide practice and future trial design, a powered randomised trial is now needed to determine whether one option is truly superior.”
Clinical Associate Professor of Gynaecology and Reproductive Medicine
Staff profile of Dr Rima Dhillon-Smith, Clinical Associate Professor of Gynaecology and Reproductive Medicine, University of Birmingham.
