BACKGROUND: Pro-alphaC inhibins are luteal derived analytes peaking in the maternal serum as early as Day 16 after conception. We set out to verify a previous post hoc analysis which suggested that pro-alphaC levels measured this early are extremely sensitive in predicting clinical pregnancy success after unstimulated IVF with ovulatory cycles. METHODS: Prospective observational study of 246 women undergoing frozen embryo transfer with ovulatory cycles. Serum pro-alphaC and beta-HCG levels at 14-17 days after conception were measured by enzyme-linked immunosorbent assay and grouped according to whether a clinical pregnancy occurred (demonstrable cardiac activity at > or =6 weeks gestation). RESULTS: Of 34 (13.8 ) women who achieved a clinical pregnancy, median (25th-75th centile) Days 14-17 pro-alphaC levels were 995 pg/ml (758-1463), 6- to 7-fold higher than levels observed in the remainder who did not fall pregnant (112.8 pg/ml (104-121); P <0.0001). At a fixed 95 specificity, pro-alphaC was 100 sensitive in predicting clinical pregnancy. The best specificities achieved at 100 sensitivity were; 94.8 for pro-alphaC, 96.7 for beta-HCG and 98.1 when both analytes were combined. CONCLUSIONS: Clinical pregnancy is always associated with a release of luteal derived pro-alphaC 14-17 days after conception. Pro-alphaC may play a possible biological role and be a useful clinical biomarker of luteal health.