Fertility after treatment for Hodgkin's disease.
BACKGROUND
The investigational endeavors of ovarian cryopreservation await the clinical experience of auto- or xenotransplantation, in vitro maturation of thawed primordial follicles, their in vitro fertilization and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryoperserved ovary has been raised following experimental animal observations. Therefore, until these innovative endeavors prove successful, we have attempted to minimize the gonadotoxic effect of chemotherapy by the co-treatment with a gonadotropin-releasing hormone agonistic analog (GnRH-a) to induce a temporary prepubertal milieu. The immunoreactive inhibin-A and -B in these patients was measured before, during and following the gonadotoxic chemotherapy.


METHODS
A prospective clinical protocol was undertaken in 60 women aged 15-40 years with lymphoma, 10 with leukemia and 10 undergoing chemotherapeutic treatments for non-malignant diseases such as systemic lupus erythematosus or other autoimmune diseases. A monthly injection of depot D-TRP(6)-GnRH-a was administered from before starting the chemotherapy until its conclusion, up to a maximum of 6 months. Hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T, P4, insulin-like growth factor (IGF)-1, IGF-BP3 and prolactin) was taken before starting the GnRH-a/chemotherapy co-treatment, and monthly thereafter until resumtion of spontaneous ovulation. This group was compared with a control group of 60 women who have been treated with similar chemotherapy.


RESULTS
Whereas all but three (40, 36 and 34 year old) of the surviving patients within the GnRH-a/ chemotherapy co-treatment group resumed spontaneous ovulation and menses within 12 months, less than half of the patients in the 'control' group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P <0.05). The remaining 55% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by about one-third of the patients resuming cyclic ovarian function, suggesting reversible ovarian damage in a larger proportion of women than those experiencing POF. Inhibin-A and -B decreased during the GnRH-a/ chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared with low levels in those who developed POF.


CONCLUSIONS
If these preliminary data are consisent in a larger group of patients, GnRH-a co-treatment should be considered in every woman of reproductive age receiving chemotherapy, in addition to assisted reproductive technologies and the investigation into ovarian cryopreservation for future in vitro maturation, autotransplantation or xenotransplantation.
Blumenfeld
Z
Z
Department of Obstetrics/Gynecology, Hematology and Oncology, Rambam Medical Center, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. bzeev@techunix.technion.ac.il
Dann
E
E
Avivi
I
I
Epelbaum
R
R
Rowe
J M
JM
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015925:Cryopreservation / Q000379:methods; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods; D010053:Ovary / Q000637:transplantation; D010063:Ovum; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D017329:Triptorelin Pamoate / Q000008:administration & dosage
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; C422362:inhibin A; C422364:inhibin B; D017329:Triptorelin Pamoate; D007265:Inhibins