Preservation of fertility and ovarian function and minimizing chemotherapy-induced gonadotoxicity in young women

BACKGROUND: After the improved long-term survival in young women with lymph oma and leukemia undergoing chemotherapy, the preservation of future fertil ity has been the focus of recent interest. AREAS OF REVIEW: Three major topics are reviewed. They include the followin g: (1) the role of chemotherapy in the treatment of malignant and nonmalign ant disease in young women, the types of chemotherapy and their gonadal eff ects (differing between ovaries and testes) in both human and other species , and the reasons for differences in the outcomes of various studies; (2) t he human experience with GnRH-agonist therapy for minimizing chemotherapy-a ssociated gonadotoxicity; and (3) inhibin measurements in young women treat ed for chemotherapy and in perimenopausal patients and those with impending premature ovarian failure (POF). Whereas egg retrieval for in vitro fertil ization (IVF) and embryo cryopreservation is a valid assisted reproductive technology (ART) for married couples, it may be unacceptable for the young single woman. The investigational endeavors of ovarian cryopreservation awa its the clinical experience of in vitro maturation of thawed primordial fol licles, their IVF, and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of mal ignant stem cells with the thawed cryopreserved ovary has been raised after animal observations. Therefore, until these innovative endeavors prove suc cessful, and in parallel with them, an attempt was made to minimize the gon adotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic an alogue (GnRH-a) to induce a temporary prepubertal milieu, because prepubert al ovaries were found mole resistant to alkylating agents' effect than the ovaries of older women. To characterize the correlation with ovarian functi on after gonadotoxic chemotherapy for Hodgkin or non-Hodgkin lymphoma in yo ung women, the immunoreactive inhibin-A concentrations in the sera of these patients were measured before, during, and after the gonadotoxic chemother apy. CONCLUSIONS: The GnRH-a cotreatment should be considered in every woman in the reproductive age receiving chemotherapy, in addition to ART and the inv estigational attempts of ovarian cryopreservation age future in vitro matur ation or reimplantation. If these preliminary data are confirmed in a large r group of patients, inhibin-A concentrations may serve as a prognostic fac tor for predicting the resumption of ovarian function in addition to the le vels of FSH, LH, estradiol. Copyright (C) 1999 by the Society for Gynecolog ic Investigation.