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.