The total number of oocytes (follicles) declines continuously after birth such that, by the time of menarche, only a quarter of a million follicles remains, or even fewer in girls prone to premature ovarian failure. In this chapter, attention has been drawn to ovarian ageing as an inexorable process, which has sometimes been simplistically compared to an hourglass. It focuses on the factors regulating the primordial-to-primary follicle growth transition. The number of follicles established at birth and the subsequent rate of loss determines the time of follicle depletion and hence menopause. The mechanism of the primordial-to-primary follicle transition has been evolutionarily conserved, as expected with a process that crucially affects fertility and the reproductive lifespan. The number of oocytes in the ovary is fixed early in life and not renewable in adulthood but a contrary view came to the fore, namely that oocytes are continually replaced from germline stem cells.

Endometrial receptivity to embryo implantation has been an enduring bottleneck of the reproductive system in humans. The advent of in vitro fertilization (IVF) opened the possibility to revert to donated oocytes for cases of infertility linked to premature ovarian failure (POF). For being effective, however, donor egg IVF required that the endometrium was rendered receptive with the sole use of the exogenous hormones E2 and progesterone. It is likely that part of the benefit of luteal support with exogenous progesterone is mediated by an effect on the myometrium. The luteal phase is characterized by a state of uterine quiescence that is brought by progesterone secreted by the corpus luteum after ovulation. The impact of uterine contractility on IVF outcome stresses the role of precautions that need to accompany ET in an attempt to minimize the impact the measures themselves have on uterine contractions (UC).

Premature ovarian failure (POF), sometimes termed premature menopause, is an enigmatic disorder. Among the various causes of POF that now have been identified, it is clear that some are present only in those who have no oocytes remaining, whereas others may be associated with remaining follicles and offer the potential for ovulation and spontaneous pregnancy. The causes of POF include cytogenetic abnormalities of the X chromosome, enzymatic defects, defective gonadotropin secretion or action, environmental insults, and autoimmune disorders. The objectives of the evaluation of young women with hypergonadotropic amenorrhea are to identify any treatable causes and any potentially dangerous associated disorders. It is important to make the diagnosis in a timely fashion. In vitro fertilization with donor oocytes is the most effective way of providing a pregnancy for any affected woman, but should be used with caution in women with Turner syndrome and the fragile X premutation.