Primordial follicles maintain dormancy in the ovary and only a small number of them are activated towards ovulation every day. Several signaling pathways in oocytes and the surrounding flattened pre-granulosa cells have been shown to play crucial roles in primordial follicle activations and sex steroid hormones are also known to affect it. Intrinsic estrogen, estradiol, has been reported to suppress primordial follicle formation and the later primordial follicle activation in rodent neonatal ovaries. Conversely, some phytoestrogens and endocrine disruptors which possess intrinsic estrogen-like biological activity with different binding affinities to estrogen receptors, can activate primordial follicles. Testosterone and dehydroepiandrosterone have been used in fertility treatments in the expectation that they would activate primordial follicle, although evidence of their efficacy is inconclusive. Progesterone suppresses primordial follicle formation and the later primordial follicle activation in rodent neonatal ovaries. Synthetic progestins possess the ability to bind to steroid hormone receptors other than the progesterone receptor. Thus, progestins may regulate primordial follicle activation through other sex hormone receptors. It may be possible to regulate primordial follicle activation by sex steroid hormones in the future. However, it is not yet clear which pathway mediates the effect of these hormones on primordial follicle activation, and this will need to be studied in the future.

Anti-Müllerian hormone (AMH) was originally discovered as the factor responsible for the regression of the Müllerian duct during male sexual differentiation. Through studies of AMH knockout mice, AMH has also been found to regulate primordial follicle recruitment and FSH-dependent cyclic recruitment. However, the details of how AMH influences follicular growth have not been elucidated. Since the early 2000s, when serum AMH concentration was found to be a reliable biochemical marker of ovarian reserve, AMH has been in the spotlight in reproductive medicine. Several studies of AMH have led to new insights on the mechanism of AMH-regulated follicular growth. Here, we review from the earliest studies to the latest findings, AMH regulation of follicle growth with reference to the potential clinical uses of AMH and AMH inhibitors.

The ovaries of women of reproductive age may show specific histological structures that may relate to the maintenance of primordial follicles and the regulation of early follicular development, which are keys to understanding the dynamics of ovarian reserve. The pelvic environment of women is frequently exposed to physiological or pathological inflammatory stimuli. Endometriosis is a disorder that should be viewed as a chronic inflammatory disease manifested by pelvic pain and infertility. Inflammation surrounding the normal ovarian cortex may alter the histological structure which possesses primordial and early growing follicles. Fibrotic changes in histological niches in the nest of primordial follicles may provoke activation of dormant follicles and concomitant atresia. Along with decline in AMH, which is produced by early growing follicles, fibrotic changes may accelerate the demise of primordial follicles which has been described as “burn-out by inflammation”. As a result, women with endometriosis may suffer from diminished ovarian reserve, a possible cause of endometriosis-related infertility.

Aggressive chemotherapy and radiotherapy can cure cancer in young female patients, but they can also result in the loss of ovarian function. For these young survivors, both recovery of ovarian function and reproductive potential after treatment have become important quality of life issues. Ovarian tissue cryopreservation (OTC), followed by transplantation after cancer remission is the most commonly applied fertility restoration approach in prepubertal females and women who require immediate cancer therapy. A major concern of frozen-thawed ovarian tissues (FTOT) autotransplantation in cancer survivors is the reintroduction of malignant cells that may have metastasized to the graft. There are several detection methods for minimal residual diseases (MRD) in ovarian cortex tissues. The aim of this paper is to review the available data describing the safety of transplantation of FTOT from cancer patients, focusing on the methods used to detect tumor cells in ovarian tissues and future perspectives in this field.