Premature ovarian failure: etiology and prospects

Abstract

A search of past and current articles on ovarian physiology and premature ovarian failure (POF) using MEDLINE was performed in order to present an overview of clinical manifestations, necessary laboratory investigations, possible etiologies and treatments for POF. POF is defined as gonadal failure before the age of 40 years. Initially, POF was thought to be permanent, but it is now believed that spontaneous remissions and even pregnancies are possible in affected women. In most cases, the etiology of POF remains elusive, but several rare specific causes have been identified. Although the etiology of POF is heterogenic, the treatment principles are the same. Hormone replacement therapy (HRT) is still the cornerstone of treatment. The only proven method of obtaining a pregnancy in patients with POF is fertilization of a donor oocyte. Cryopreservation of oocytes has worked well in animals but awaits refinement before it can be applied routinely to humans with prodromal POF, or to patients before chemotherapy or irradiation in order to save their oocytes for future fertilization. New alternatives to traditional HRT and methods of fertility preservation are under development, but understanding of the basic pathophysiology of POF is necessary for the development and use of innovative treatments.

Ovarian Preservation by GnRH Agonists during Chemotherapy: A Meta-Analysis

“…The rate of ovarian failure depends largely on the type of chemotherapy, the cumulative dose, and the age of the woman receiving the treatment. 16,17 Among women < age 40 with early stage breast cancer, amenorrhea occurred in 54% of women after 6-12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF ). Menses resumed in 23% of these young women.…”

Premature Ovarian Failure

“…POF may occur due to chromosomal, genetic, autoimmune, metabolic (galactosaemia), infectious (mumps), and iatrogenic (anticancer treatments) causes but a large proportion of cases remain idiopathic [10, 11] despite diagnostic advances.…”

Gonadotrophin Releasing Hormone Analogues for Ovarian Function Preservation in Young Females Undergoing Chemotherapy

“…Six studies were prospectively randomized (Cobleigh et al, 1995;Laml et al, 2000;Dada et al, 2001;Walshe et al, 2006;Maltaris et al, 2007;Megan et al, 2009) and six were case series with control (Bonadonna et al, 1985;Kreuser et al, 1990;Ortin et al, 1990;Ataya et al, 1993;Shalev et al, 2003;Lamar et al, 2009). The randomized controlled studies included 340 patients (173 in the study group and 167 in the control group).…”

“…The rate of ovarian failure depends largely on the age of the woman receiving the treatment, type of chemotherapy and cumulative dose (Laml et al, 2000). The risk of ovarian failure increases with increasing patient's age at the time of therapy.…”