Premature ovarian failure

Abstract

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.

Development of mammalian ovary

“…Similarly alterations in ovarian development, particularly affecting establishment of the ovarian reserve, i.e. the number of primordial follicles formed by the time of birth or during the early post-natal period, have been implicated as one pathway to establish an ovary predisposed to POF (Goswami & Conway 2005). Changes in regions of the X chromosome defined as POF loci (Therman et al 1990) are thought to result in a blockage of germ cell meiosis leading to oocyte apoptosis (Burgoyne & Baker 1984).…”

“…The concept that pre-or perinatal alterations in environment can lead to permanent alterations in the structure and function of a number of organs has important implications for human health and the livestock industry. With respect to the ovary, pre-natal exposure to contaminants has been implicated in human polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility in women, as well as premature ovarian failure (POF) (Goswami & Conway 2005). In addition, gestational nutrition and infection are thought to have direct effects on the ovary, leading to impaired post-natal fertility; an important issue in domestic livestock.…”

Genetic Etiology of Primary Premature Ovarian Insufficiency

“…X chromosome alterations are the most frequent genetic causes of PPOI, accounting for 12% of cases 6,[11][12][13] . Th ese alterations comprise complete monosomy or partial deletion, duplication or translocation of the X chromosome, as follows: a) Turner syndrome (45X0) -the prevalence of X monosomy is 1:2500.…”

Genes involved in human premature ovarian failure

“…However, in most of the cases, including a subset associated with PA and gonadal dysgenesis (Reynaud et al 2004, Fechner et al 2006, ovarian insufficiency occurs because of an anticipated depletion of the primordial follicular pool. The etiological causes that may activate such mechanisms are highly heterogeneous and include chromosomal, genetic, autoimmune, metabolic, infectious, and iatrogenic factors (Goswami & Conway 2005). At present, about 25% of all forms of POF can be classified as iatrogenic and are related to cancer treatment, but more than 50% of the cases remain idiopathic, so that the origin of POI is still largely unknown.…”