BACKGROUND: Oral (anti-oestrogens) and injectable (gonadotrophins) ovulation induction agents have been used to increase the number of eggs produced by a woman per cycle in treatment for unexplained subfertility. It is unclear whether there are significant advantages of one type of treatment over the other in this context or in terms of fertility. OBJECTIVES: To assess the efficacy of oral versus injectable ovulation induction agents for unexplained subfertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All trials where oral ovulation induction agents were compared with injectable ovulation induction agents in treatment groups generated by randomisation, from couples with unexplained subfertility, were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Five randomised controlled trials, including a total of 231 identified couples with unexplained subfertility, were found and included in this review. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth, miscarriage, multiple birth, occurrence of ovarian hyperstimulation syndrome and cycle cancellation. MAIN RESULTS: Where trials with important co-interventions were excluded, there was no significant difference in the odds of beneficial outcomes for oral versus injectable ovulation induction agents - live birth per couple (OR 0.06, 95%CI 0.00-1.15), pregnancy per woman (OR 0.33, 95%CI 0.09-1.20); nor of detrimental outcomes for injectable versus oral agents - miscarriage (OR 0.11, 95%CI 0.00-2.84); there were no reported cases of multiple births, cases of ovarian hyperstimulation or discontinued cycles consequent upon overstimulation. Where trials with the co-intervention of a human chorionic gonadotrophin trigger injection (given only in the injectable ovulation induction agent treatment arm) were not excluded there was no significant difference in the odds of live birth per couple (OR 0.40, 95%CI 0.15-1.08). However oral ovulation induction agents had significantly reduced odds of pregnancy per woman compared to injectable ovulation induction agents (OR 0.41, 95%CI 0.17-0.80). For detrimental outcomes, there were no significant differences in the odds of miscarriage (OR 0.61, 95%CI 0.09-4.01) and multiple birth (OR 1.08, 95%CI 0.16-7.03) for injectable versus oral agents. No data were available concerning the occurrence of ovarian hyperstimulation syndrome nor cycle cancellation. REVIEWER'S CONCLUSIONS: There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.
Athaullah, N., Proctor, M., & Johnson, N. (2002). Oral versus injectable ovulation induction agents for unexplained subfertility. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd003052