Letrozole is an aromatase inhibitor that is primarily used in breast cancer. However, an off-label use by fertility specialists is to develop ovarian follicles, where clomifene has been ineffective. It may even be more successful than clomifene with higher birth rates, while having a lower chance of a multiple birth.¹⁹

Other adjuvants are used (mainly off label) in IVF treatments in an attempt to improve success rates based on theoretical but often unproven activity. These include:²⁰

• immunomodulators to enhance womb conditions including effects on endometrial natural killer cells (immunoglobulins, tumour necrosis factor alpha, corticosteroids);
• vasodilators to improve blood flow to the womb lining (eg sildenafil, nitroglycerine, nitrous oxide);
• muscle relaxants to reduce uterine contractions (eg progesterone, nitroglycerine, beta blockers);
• drugs to improve the womb lining development (eg aspirin, heparin, oestrogen);
• drugs to improve response to ovarian function (eg growth hormone, dehydroepiandrosterone/DHEA).

Metformin is licensed for use in women with PCOS, which may in turn improve the woman’s fertility, but the drug is not licensed directly to treat infertility.^18,20