Progesterone Luteal Support in Natural Cycles for Unexplained Infertility: A Randomised Controlled Trial (The PiNC Trial)

TL;DR

This study tested if adding progesterone during the luteal phase in natural cycles improves live birth rates for couples with unexplained infertility.

Contribution

The study is the first to evaluate luteal-phase progesterone supplementation in natural cycles for unexplained infertility in a randomized controlled trial.

Findings

Livebirth rates were higher in the progesterone group (15.3%) compared to the control group (7.0%), though not statistically significant.

Progesterone treatment showed a trend toward lower total miscarriage rates, including biochemical losses.

The study highlights the potential of a simple, low-cost treatment for unexplained infertility that merits further investigation.

Abstract

To compare the effect of luteal‐phase progesterone supplementation in natural cycles to expectant management on live birth rates in women with unexplained infertility (UI).

An open‐label, parallel‐arm, single‐centre randomised controlled trial.

One tertiary NHS‐funded fertility unit.

Couples with UI for at least 1 year.

A comparison of luteal phase micronised vaginal progesterone treatment (400 mg bd) with timed intercourse and timed intercourse alone for 3 cycles.

Primary outcome: Livebirth rate. Secondary Outcomes: Biochemical pregnancy, clinical pregnancy, mid‐luteal serum progesterone and pregnancy loss.

One hundred and forty‐three couples were randomised. Livebirth rates were 11/72 (15.3%) in the treatment group versus 5/71 (7.0%) in the control group (RR 2.17, 95% CI 0.79–5.93). Biochemical pregnancy rates were 15/72 (20.8%) versus 10/71 (14.1%), (RR 1.48, 95% CI 0.72–3.07) and clinical pregnancy rates were 14/72 (19.4%) versus 9/71 (12.7%), (RR 1.53, 95% CI 0.71–3.31) in the treatment and control groups respectively. Pregnancy losses: 4/15 treatment group versus 5/10 control group (RR 0.53, 95% CI 0.19–1.51). One biochemical pregnancy loss in each group and 2/15 miscarriages in the treatment group versus 3/10 in the control group. Total miscarriage rates including biochemical losses were 3/15 (20%) versus 4/10 (40%) (RR 0.5, 95% CI 0.14–1.77).

The results did not reach statistical significance. However, the difference in livebirth rates warrants further investigation as this simple, noninvasive, inexpensive treatment would be a very attractive option for affected couples. A larger trial using the effect size from this study to guide sample size is planned.

The PiNC trial was registered with the EU Clinical Trials Register on 29/11/2019 www.clinicaltrialsregister.eu/ctr‐search/search?query=homerton. The first participant was recruited on 25/2/2020.

Figures