Background
There is a lack of consensus on the optimal dose and form of progesterone supplementation during frozen‐thawed embryo transfer with hormone replacement therapy.

Aims
We aim to identify the serum progesterone concentration on day 16 most likely to result in positive pregnancy outcomes.

Materials and methods
We undertook a retrospective study of 4582 women who underwent frozen embryo transfer with hormone replacement therapy, or natural frozen embryo transfer, over 14 years at a multi‐site private in vitro fertilisation clinic. Embryos were 3–5 days of age at time of transfer. We extracted data on serum progesterone concentrations and outcomes, as well as dose and form of progesterone supplementation, from patient and pharmacy records.

Results
Increased live birth rates for frozen embryo transfer with hormone replacement therapy were seen with day 16 serum progesterone concentrations >50 nmol/L (26.4% vs 11.3% for <50 nmol/L; adjusted odds ratio (OR) 3.14 (95% CI 2.21–4.48)). Similarly, a decreased pregnancy loss rate was seen in this group (14.3% vs 32.6% for ≤50 nmol/L; adjusted OR 0.26 (95% CI 0.12–0.58)). There was a positive correlation between live births and the number of progesterone doses per day (r = 0.119, P = 0.026) and day 16 progesterone concentrations (r = 0.128, P = 0.011). Conclusion Improved pregnancy outcomes are seen with day 16 serum progesterone concentrations >50 nmol/L. There is a statistically significant correlation between live births, number of progesterone doses per day and day 16 serum progesterone concentrations in this study.