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

Abstract

Objective: 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). Design: An open-label, parallel-arm, single-centre randomised controlled trial. Setting: One tertiary NHS-funded fertility unit. Population: Couples with UI for at least 1 year. Method: A comparison of luteal phase micronised vaginal progesterone treatment (400 mg bd) with timed intercourse and timed intercourse alone for 3 cycles. Main Outcome Measures: Primary outcome: Livebirth rate. Secondary Outcomes: Biochemical pregnancy, clinical pregnancy, mid-luteal serum progesterone and pregnancy loss. Results: 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). Conclusions: 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. Trial Registration: 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.