Fertility after age 45: From natural conception to Assisted Reproductive Technology and beyond

The introduction of in vitro fertilization (IVF) in 1978 - an accomplishment awarded with the 2010 Nobel Prize in Physiology or Medicine - has revolutionized the lives of millions of couples previously unable to conceive. Though initially applied primarily to young women with blocked Fallopian tubes, over the past three decades IVF has been increasingly used to combat age-related infertility. It has become clear that the decline in fertility with increasing female age is largely due to a rapid decrease in oocyte (egg) quantity and quality, with a higher proportion of oocytes displaying genetic abnormalities. Despite significant improvements in medical stimulation and laboratory culturing of embryos, IVF success once women reach the age of 45 is exceedingly rare. It has been well established through elegant clinical studies that, unlike the ovary, the reproductive capacity of the uterus does not diminish with age, even into the late 40s and 50s. With the use of oocytes from younger donors, women who are menopausal can attain very high rates of conception. The increased obstetrical risks in this population, which has a higher risk of underlying medical co-morbidities, must be considered prior to attempts at assisted conception, often in consultation with a multidisciplinary team of physicians. Finally, attempts to reverse the age-related decline in oocyte quality through micro-manipulation of the nucleus and cytoplasm have yielded disappointing results and are fraught with ethical concerns.