Recurrent pre-clinical pregnancy loss is unlikely to be a 'cause' of unexplained infertility

Background A proportion of women with 'unexplained' infertility may present with subfertility because their pregnancies fail before they are clinically recognized. In order to test whether pre-clinical early pregnancy losses (EPL) occur more frequently in women with unexplained infertility, serial urinary hCG concentrations were measured to compare EPL per cycle rates following spontaneous conception in patients with unexplained infertility versus healthy volunteers. Methods Sixty patients under 39 years of age with unexplained infertility and 60 healthy controls, who were trying to conceive spontaneously, participated in this study. All participants were asked to collect daily urine samples from cycle day 14 until menstruation for three consecutive cycles or until a positive pregnancy test was obtained.Urinary hCG and creatinine levels were measured by immunoassay. Implantation was detected when urinary hCG levels rose above reference levels constructed from samples obtained from 12 women not attempting to conceive. EPL rates were determined by a linear mixed model using logarithmically transformed hCG/creatinine data. Results In the 133 cycles of 60 women with unexplained infertility, just one implantation was detected, which became an ongoing pregnancy. In contrast, in 103 such cycles in 46 control patients, 30 implantations were detected (24 clinical pregnancies, 6 cases of EPL). The odds ratio for EPL/cycle in the unexplained versus control group was 0 (95 confidence interval: 00.795, P = 0.026). Conclusions Our data do not support the hypothesis that recurrent EPL may present as unexplained infertility. Post-implantation failure is therefore unlikely to contribute significantly to the presentation of subfertility.