The enigma of unexplained subfertility

In Reproductive Medicine, when guiding couples with unexplained or mild male subfertility, there are two crucial questions. The first question is whom to treat? Which couples have favourable chances of conceiving naturally and which couples need treatment? To explore this question, we investigated whether we could improve our ability to accurately predict chances of natural conception for these couples by adding predictors to the established prediction model. We used data from a previous prospective cohort study to construct a revised prediction model and compared its performance to the established one. We concluded that the revised model performs slightly better, and this model should be externally validated. The second question is: how to treat? To study this question, we compared intrauterine insemination with ovarian stimulation, which traditionally is the first line treatment for unexplained subfertility, and in vitro fertilisation in terms of effectiveness, safety, costs and treatment compliance. We randomised 602 eligible couples with unexplained or mild male subfertility, and an unfavourable prognosis of natural conception, to in vitro fertilisation with single embryo transfer, in vitro fertilisation in a modified natural cycle and intrauterine insemination with ovarian stimulation. We chose a birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation as our primary outcome. The results of our study demonstrate that there seems to be no reason to abandon intrauterine insemination with ovarian stimulation as a first line treatment of couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception