The Dynamics of Serum Levels of AMH - as a Predictor of Ovarian Reserve in Oncologic Female Patients Treated by Chemotherapy. A Prospective Analytic Research

 

Dr. Muhammad Fatum

Background:

Damage to the ovary by chemotherapy is a major concern following cancer treatment. Moreover, this appears to increase during the last decade, due to a significant raise in survival rates post chemotherapy owing to improvements in early detection and aggressive treatment protocols. A precise ability to predict POF would facilitate informed choice of therapy and individualized approach to fertility preservation.

Analyses of ovarian function following cancer therapy have mostly described the prevalence of ovarian failure following treatment. Follicular depletion may occur despite maintenance of regular menstrual cycles. Ovarian reserve testing has become established in the fertility setting where it is used to predict outcome in assisted reproduction. These tests have the potential to estimate the reproductive lifespan of the ovaries, which would allow an accurate estimation of fertility status and the risk of premature ovarian failure. Several hormonal and ultrasound-based tests are therefore used, including follicular stimulating hormone (FSH), inhibin B, ovarian volume, ovarian blood flow and antral follicle count (AFC). Such tests must be validated in patients with cancer, so that the function of their ovaries is quantified enabling appropriate measures to be taken to improve fecundity and overall quality of life.

Gonadal function is usually measured in follow-up studies of long-term survivors of childhood cancer by analysis of gonadotropins. However, neither the luteinizing hormone (LH) nor FSH correctly reflects the ovarian reserve. In recent years, two new markers for ovarian function became available. Inhibin B, which is solely produced by granulosa cells of small antral follicles, is decreased in women with known fertility problems (e.g. premature ovarian failure) and undetectable in postmenopausal women. Inhibin B is one of the first endocrine markers to change in perimenopausal women, even before changes in FSH levels can be detected. The second new marker is anti-Mullerian hormone (AMH) [aka: ‘Müllerian-inhibiting substance, MIS'] a member of the transforming growth factor (TGF) superfamily. This hormone is produced by granulosa cells of early developing preantral follicles of the ovary, and levels decrease when the number of follicles decreases with age. AMH concentrations in the circulation declines with age and show good prediction of the ovarian response to FSH treatment. AMH was shown to be a more sensitive marker of ovarian reserve in patients treated for hodgkin's disease.

Aim of study:

The aim of this study is to compare various markers of ovarian reserve to assess ovarian function in young women treated by different protocols of chemotherapy, irradiation and bone marrow transplantation.

Materials & Methods: Type of study

This is a prospective observational study of ovarian function in premenopausal women with newly diagnosed malignant disease.

Ethics: The study is submitted to Hadassah Ethics committee and will be NIH    registerd.

Inclusion criteria: Any premenopausal female patient planned for chemotherapy or radiotherapy 

Exclusion criteria: Patient refusal to be followed

Endpoints measured

1.    Menstrual history

2.    Hormones: LH, FSH, estradiol, progesterone

3.    Inhibin B and AMH: commercial assay kits according to the manufacturer's sensitised assay protocol.

4.    Ovarian ultrasound for follicular count

Study design: Endpoints will be measured prior to therapy and then at 3, 6, 9 and 12 months. Thus each patient will serve as her own control.

Time length of study: Two years from study commencement