Ovarian rescue/protection from chemotherapeutic agents

BACKGROUND: After improved long-term survival in young women with lymphoma and leukemia undergoing chemotherapy, preservation of future fertility has been the focus of recent interest. The investigational endeavors of ovarian cryopreservation await the clinical experience of in vitro maturation of t hawed primoridal follicles, their in vitro fertilization, and embryo transf er. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cr yoperserved ovary has been raised after experimental animal observations. T herefore, until these innovative endeavors prove successful, and in paralle l with them, we attempted to minimize the gonadotoxic effect of chemotherap y by the cotreatment with a gonadotropin-releasing hormone (GnRH) agonistic analogue to induce a temporary prepubertal milieu. Whereas inhibin-B conce ntrations in serum may reflect the ovarian granulosa cell compartment, inhi bin-A reflects luteal function. Immunoreactive inhibin-A and -B in these pa tients before, during, and after gonadotoxic chemotherapy were measured. METHODS: A prospective clinical protocol was undertaken in 44 women with ly mphoma, aged 15-40 years, ten with leukemia and eight undergoing chemothera peutic treatments for nonmalignant diseases such as systemic lupus erythema tosus or other autoimmune diseases. A monthly injection of depot D-TRP6-GnR H-a was administered from before the start of chemotherapy until its conclu sion, up to a maximum of 6 months. A hormonal profile was taken before star ting the GnRH-a/chemotherapy cotreatment, and monthly thereafter until the women resumed spontaneous ovulation. This group was compared with a control group of 55 women who had been treated with similar chemotherapy. Inhibin- A and -B immunoactivity was measured. RESULTS: Whereas all but one (40-year-old) of the surviving patients with G nRH-a/chemotherapy cotreatment group resumed spontaneous ovulation and mens es within 6 months, fewer than half of the patients in the control group (c hemotherapy without GnRH-A cotreatment) resumed ovarian function and regula r cyclic activity (P < .05). The remaining 60% experienced premature ovaria n failure (POF). Temporary increased follicle-stimulating hormone (FSH) con centrations were experienced by almost a third of the patients resuming cyc lic ovarian function, suggesting a reversible ovarian damage in a larger pr oportion of women than those experiencing POF. Inhibin-A and -B decreased d uring GnRH-a/chemotherapy cotreatment but increased to normal levels in pat ients who resumed regular ovarian cyclicity and/or spontaneously conceived, compared with low levels in those who developed POF. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, inhibin-A or -B concentrations may serve as prognostic factors to predict the resumption of ovarian function, in addition to the levels of F SH, luteinizing hormone, and estradiol. GnRH-a cotreatment should be consid ered for every woman of reproductive age who receives chemotherapy, in addi tion to assisted reproductive technology and the investigational attempts o f ovarian cryopreservation for future in vitro maturation. (J Soc Gynecol I nvestig 2001;8:S60-S64) Copyright (C) 2001 by the Society for Gynecologic I nvestigation.