Clinical trial NCT02086279: AMH Levels Change During Treatment With GnRh Agonist
Official title: AMH Levels Change During Treatment With GnRh Agonist: A Prospective Observational Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Uterine Fibroids
Endometriosis
Endometriosis of Uterus
Pelvic Pain
Keywords: AMH levels
Ovarian reserve
GnRH analogue
Ovarian reserve after GnRH analogue
Ovarian reserve modification
Antral follicle count
Antral follicle count after GnRH analogue
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 67
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: To evaluate the variation of AMH levels in women undergoing treatment with GnRHa, and to assess whether this variation correlates with changes in the antral and pre-antral follicle ultrasonographic count (AFC).

Detailed description: The anti Mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of antral and preantral ovarian follicles.

Several studies have shown that the AMH levels provide a reliable indication of the size of the growing follicles pool (1). AMH is now commonly used as a biomarker for improving the ovarian reserve in women of reproductive age because it is related with outcomes of assisted reproduction cycles, chances of pregnancy and distance from menopause (2-4).

For several years GnRH agonists have been used for the purpose of preserving fertility in the course of chemotherapy in young women with cancer (5). Their effectiveness, however, isn't 100% and there is the need to monitor the ovarian reserve in the course of treatment in these young women. With the administration of GnRHa, the FSH levels (the most used hormone for improve the ovarian reserve, although it is less reliable and less manageable because of its intra-cyclic variations) cannot be used to measure the residual ovarian function due to the physiological reduction of gonadotropins induced by the treatment. AMH levels, conversely, are relatively stable both during the menstrual cycle (6) and during administration of the contraceptive pill (7,8), suggesting the gonadotrophin independence of this molecule. AMH could therefore be a useful biomarker of ovarian reserve in the course of GnRHa treatment.

The use of GnRHa for fertility preservation during chemotherapy is controversial because of inconclusive outcome data on fertility (9) and because the mechanism by which GnRHa may act to preserve fertility is unknown. The major function of GnRHa is to suppress the production of pituitary gonadotrophins, acting indirectly on the ovarian follicles, not exposing growing follicles to the toxicity of chemotherapy and thus protecting the future ovarian function.

Determine the effect of GnRHa on AMH serum level is an essential step to determine both the effectiveness of the treatment in terms of preservation of fertility and the reliability of this marker for ovarian reserve in cancer patients treated with GnRHa. Up to now, the published studies have shown extremely contrasting data. Considered that GnRHa is largely used in non-oncological patients for preoperative pharmacological preparation in various benign gynecological conditions, it is possible to exploit the high number of patients with these characteristics for the non-invasive assessment of analogue effect on the AMH levels.

Eligibility criteria: Inclusion Criteria:

* Patients waiting for surgery for benign conditions such as uterine fibroids and endometriosis, undergoing preoperative treatment with two consecutive doses of GnRHa at a dose of 11.25 every three months
* 18 to 45 years aged patients
* Regular menstrual intervals between 22 and 35 days
* Expressed written consent for the study entry

Exclusion Criteria:

* Patients who do not consent to pharmacological preparation with GnRHa
* Estrogen-progestin therapy in the 2 months before enrollment
* Autoimmune diseases, chronic , metabolic, systemic and endocrine disorders, including hyperandrogenism, hyperprolactinemia, diabetes mellitus and thyroid disease.
* Hypogonadotropic hypogonadism
* Majors clinical conditions

Primary outcomes:
measure: AMH levels change before and after GnRHa
timeFrame: At study entry and at 1, 3 and 6 months after the administration of the first vial of GnRH-a
Secondary outcomes:
measure: Preantral and antral follicles
timeFrame: At study entry and at 1, 3 and 6 months after the administration of the first vial of GnRH-a
measure: Correlation between AMH levels and preantral and antral follicles count
timeFrame: At study entry and at 1,3 and 6 months after the first vial of GnRH
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Chair of Obstetrics and Gynecology - University division - UMG
state: CZ
Study officials:
affiliation: Magna Graecia University of Catanzaro
name: Fulvio Zullo
role: PRINCIPAL_INVESTIGATOR
References: