What should be the first-line treatment for unexplained infertility in women over 40 years of age – ovulation induction and IUI, or IVF?

The tendency to postpone childbearing in developed countries and the relatively high rate of infertility in older women contribute to an increase in the portion of women aged 40 years and older opting for infertility treatments. The main factor for infertility in this group is oocyte senescence, but since this process does not have a specific diagnosis many of those will be classified as having ‘unexplained infertility’. The efficacy of the traditional clinical approach for ‘unexplained infertility’ in older women is questionable. Reviewing the current literature, clomiphene citrate seems to be inefficient in this group of patients, while delivery rates of gonadotrophins and intrauterine insemination cycles are less than 5%. Although low in absolute terms, IVF is more efficient. The chance for delivery, however, diminishes with each year of age above 40. Therefore, after a short trial of gonadotrophins and intrauterine insemination, women aged 40–41 years should be quickly referred to IVF. At an older age, IVF is the primary treatment option.