LONG-TERM EVALUATION OF OVARIAN FUNCTION AND FOLLICULAR RESERVE IN

ANALIA FREIRE; REY RA; ANDREA ARCARI; BEDECARRÁS , PATRICIA; GRINSPON R P; GRYNGARTEN MIRTA

Florianopolis

Congreso; XXVIII latin american congress of pediatric endocrinology; 2019

SLEP

Introduction: The survival rate of youngpatients with cancer has greatly improved in the last decades, in part due tothe introduction of new therapeutic agents and protocols.Chemotherapymay be associated with risk of ovarian dysfunction, permanent or transientamenorrhea, symptoms of ovarian insufficiency and infertility. It has beensuggested that prepubertal ovary is less susceptible to deleterious effect of chemotherapy.Pre-clinicalstudies suggested that hormonal suppression of thehypothalamic-pituitary-ovarian axis could minimize the impact of cytotoxicagents on the ovary. The effectiveness of gonadotropin-releasing hormoneagonists (GnRHa) in preventing the impairment of ovarian function due toexposure to cytotoxic agents in pubertal girl is still controversial.AMH isexpressed by the ovarian granulosa cells of primary, preantral and smallfollicles. It is independent of gonadotropins, representing an ideal surrogatefor ovarian reserve.Objective: To evaluate long-term ovarian function infemale adolescents with history of malignant diseases treated with chemotherapyat prepubertal or pubertal stage.Material and methods: Female adolescent patients withhistory of malignancy who required chemotherapy were analyzed at least twoyears after menarche. A transversal study was conducted to evaluate gonadalfunction measuring gonadotropins (ECLIA) and AMH (ELISA) levels after at leasttwo-year treatment withdrawal. Patientswere divided into two groups, group A: patients treated at pubertal stage whoreceived chemotherapy concomitant with GnRHa; group B: patients treated atprepubertal stage only with chemotherapy. Results: Thirty-nine patients were enrolled.    Group A (n=21)  Group B (n=18) P value Chronological age at diagnosis (years) 14.3 (9.2-18.1) 6 (0.5-10.5) <0.001  Age of evaluation (years) 17.5 (17-30) 17 (13.6-22.9) ns  Menarcheal age (years) 12.4 (10-15) 12.0 (10.2-14.7) ns  Regular menses (n) 20/21 18/18 ns  Hot flushes (n) 1/21 0/18 ns LH mUI/ml 5.7 (1.23-65.7) 6.4 (6.8-14.8) ns FSH mUI/ml 6.5 (0.11-200) 5.7 (3.6-9.4) ns AMH (pmol/L) 16.2 (1.2-57.6) 26.0 (9.1-76) 0.02 Median andrange. Serum LHand FSH were within normal levels in both group except in one patient fromgroup A, who had hypergonadotropic hypogonadism. AMH levels were significantlylower in group A. Two patients from group A achieved fertility.Conclusion:  In thislong term follow up study prepubertal girls who received chemotherapy andpubertal girls who received chemotherapy concomitantly with GnRHa showed lowrates of ovarian dysfunction. However, the decline of AMH levels in patientswho received chemotherapy in pubertal stage could indicate a decreasedfollicular reserve, although the effect of age cannot be ruled out.