Evaluating prognosis in unexplained infertility

Importance: The diagnosis of unexplained infertility presents a dilemma as it signifies both uncertainty about the cause of infertility and the potential for natural conception. Immediate treatment of all would result in overtreatment. Prediction models estimating the likelihood of natural conception and subsequent live birth can guide treatment decisions. Objective: To evaluate if in couples with unexplained infertility, prediction models are effective in guiding treatment decisions. Evidence review: This review examines 25 studies that assess prediction models for natural conception in couples with unexplained infertility in terms of derivation, validation, and impact analysis. Findings: The largest prediction models have been integrated in the synthesis models of Hunault, which includes female age and infertility duration, having been pregnant before and motile sperm percentage. Despite its limited discriminative capacity, this model demonstrates excellent calibration. Importantly, the impact of the Hunault model has been evaluated in randomized clinical trials, and shows that in couples with unexplained infertility and 12-month natural conception chances exceeding 30%, immediate treatment with intrauterine insemination (IUI) and controlled ovarian hyperstimulation is not better than expectant management for 6 months. Below the threshold of 30%, treatment with IUI is superior over expectant management, but immediate in vitro fertilization was not better than IUI. Conclusion: In couples with unexplained infertility and a good prognosis for natural conception, treatment can be delayed, whereas in couples with a poor prognosis, immediate treatment (with IUI-controlled ovarian hyperstimulation) is warranted. Relevance: These data indicate that in couples with unexplained infertility, integration of prediction models into clinical decision making can optimize treatment selection and maximize fertility outcomes while limiting unnecessary treatment.