What are the indications for using ovulation induction therapy in women with infertility?

Ovulation induction therapy is indicated primarily for women with anovulatory infertility due to ovulation disorders classified by the World Health Organization (WHO) into three groups: Group 1 (hypothalamic-pituitary failure), Group 2 (hypothalamic-pituitary-ovarian dysfunction, predominantly polycystic ovary syndrome [PCOS]), and Group 3 (ovarian failure) ¹.

For women with WHO Group 1 ovulation disorders, ovulation induction is indicated when lifestyle modifications such as increasing body weight (if BMI <19) and moderating excessive exercise fail to restore ovulation; these women should be offered pulsatile gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity to induce ovulation ¹.

In women with WHO Group 2 ovulation disorders (mainly PCOS), ovulation induction is indicated when weight loss in women with BMI ≥30 does not restore ovulation. First-line pharmacological treatments include clomifene citrate, metformin, or a combination of both, with treatment choice guided by BMI, side effect profile, and monitoring requirements ¹. Clomifene citrate treatment should be monitored by ultrasound during the first cycle to minimize risks of multiple pregnancy and should not exceed six months ¹.

For women with WHO Group 2 ovulation disorders who are resistant to clomifene citrate, second-line ovulation induction options include laparoscopic ovarian drilling, combined clomifene citrate and metformin therapy if not previously used, or gonadotrophins ¹. Gonadotrophin therapy requires careful ultrasound monitoring to reduce risks of ovarian hyperstimulation and multiple pregnancy, and patients should be informed of these risks prior to treatment ¹.

Women with ovulatory disorders due to hyperprolactinaemia should be treated with dopamine agonists such as bromocriptine, which can restore ovulation and fertility ¹.

Ovulation induction is not routinely indicated for women with unexplained infertility, as oral ovarian stimulation agents like clomifene citrate do not increase pregnancy or live birth rates in this group; instead, IVF is recommended after two years of unsuccessful conception attempts ¹.

Recent literature supports the use of exogenous gonadotropins for ovulation induction in anovulatory women, particularly those resistant to first-line agents, emphasizing individualized treatment plans to optimize outcomes and minimize risks (Practice Committees of the American Society for Reproductive Medicine and Society for Reproductive Endocrinology and Infertility, 2020). Emerging evidence also explores novel approaches such as hormone-free or follicle-stimulating hormone-primed treatments in PCOS, though these remain investigational (Vuong et al., 2025). Fertility preservation considerations may influence ovulation induction strategies in specific clinical contexts (Hussein et al., 2020) ¹.