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 lymphoma and leukemia undergoing chemotherapy, the preservation of future fertility has been the focus of recent interest.Areas of Review: Three major topics are reviewed. They include the following: (1) the role of chemotherapy in the treatment of malignant and nonmalignant disease in young women, the types of chemotherapy and their gonadal effects (differing between ovaries and testes) in both human and other species, and the reasons for differences in the outcomes of various studies; (2) the human experience with GnRH-agonist therapy for minimizing chemotherapy-associated gonadotoxicity; and (3) inhibin measurements in young women treated by chemotherapy and in perimenopausal patients and those with impending premature ovarian failure (POF). Figure 1Longitudinal profile of inhibin-A, inhibin-B, progesterone (P₄) (bars), 17-β-estradiol (E₂), FSH, and LH in a young woman undergoing cyclophosphamide, adriamycin, oncovin, and prednisone chemotherapy (Chemotx.) and GnRH-agonist (GnRH-a) cotreatment for non-Hodgkin lymphoma. Despite a temporary increase in FSH and LH concentrations 3 months after GnRH-a/chemotherapy cotreatment, this patient spontaneously conceived 2 years after the protocol, bringing about an increase in inhibin-A and inhibin-B levels. Whereas egg retrieval for in vitro fertilization (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 awaits the clinical experience of in vitro maturation of thawed primordial follicles, their IVF, and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryopreserved ovary has been raised after animal observations. Therefore, until these innovative endeavors prove successful, and in parallel with them, an attempt was made to minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a) to induce a temporary prepubertal milieu, because prepubertal ovaries were found more resistant to alkylating agents' effect than the ovaries of older women. To characterize the correlation with ovarian function after gonadotoxic chemotherapy for Hodgkin or non-Hodgkin lymphoma in young women, the immunoreactive inhibin-A concentrations in the sera of these patients were measured before, during, and after the gonadotoxic chemotherapy.Conclusions: The GnRH-a cotreatment should be considered in every woman in the reproductive age receiving chemotherapy, in addition to ART and the investigational attempts of ovarian cryopreservation for future in vitro maturation or reimplantation. If these preliminary data are confirmed in a larger group of patients, inhibin-A concentrations may serve as a prognostic factor for predicting the resumption of ovarian function in addition to the levels of FSH, LH, and estradiol. Copyright (C) 1999 Society for Gynecologic Investigation.