Phase II Study of Gonadotropin-Releasing Hormone Analog for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients

Abstract

Purpose. Premature ovarian failure occurs in 40%-70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%-100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropinreleasing hormone (GnRH) analogs, such as leuprolide, in a continuous-release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non-HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to <10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence.Patients and Methods. Eligible patients were women aged <40 years who were HSCT candidates, were premenopausal, and had both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels <20 IU/L. Two 22.5-mg leuprolide doses were delivered in 3-month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose.Results. Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow-up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function (p ‫؍‬ .66).Conclusion. Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated. The Oncologist 2012;17:233-238

Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning

“…Interestingly, of those undergoing non-myeloablative HCT (10 out of the 44 evaluable patients) only one patient had preserved ovarian function. 19 These results differ significantly from our study. This may be partly due to their more rigorous definition for ovarian failure as well as the longer duration of follow-up in our study which allows more time for ovarian function to recover.…”

Hematopoetik Kök Hücre Transplantasyonu İle Tetiklenen Ovaryan Yetmezliğe Bağlı Gelişen Labial Adezyon

“…Series reporting ovarian function and pregnancies after HSCT vary greatly in terms of endpoints, number of patients included, age at and indications for BMT, conditioning regimens and duration of follow-up. The risk of premature ovarian failure is very high, however, and increases with age and in case of HSCT conditioning treatment with total body irradiation 9,10 .…”

Perspectives on the co-treatment with GnRHa in female patients undergoing hematopoietic stem cell transplantation

“…Also, Cheng and coworkers analyzed in a phase II prospective study the effectiveness of GnRHa use in HSCT recipients ( 43 ). Among the 44 patients evaluated in the study who performed HSCT, 33 women received MA regimens and 11 non-MA regimens.…”

“…Five of the seven patients that restored COF had HL. The authors concluded that leuprolide was not able to preserve the ovarian function in patients who underwent HSCT using either MA or non-MA regimens ( 43 ). Their work was criticized by colleagues in the medical field for several reasons.…”