Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Failure to preserve fertility in patients with Hodgkin's disease. Single-dose GnRH agonist administration in the luteal phase of GnRH antagonist cycles: a prospective randomized study.
To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not.
                Prospective randomized controlled study.
                Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt.
                Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out.
                Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment.
                In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels.
                GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required. The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility. This study was designed to evaluate the effect of luteal-phase administration of single-dose gonadotrophin-releasing hormone (GnRH) agonist on pregnancy, implantation and live birth rates in patients who received GnRH antagonist for pituitary suppression. The study population consisted of 164 patients who underwent intracytoplasmic sperm injection (ICSI) after ovulation induction by gonadotrophins and GnRH antagonist for the prevention of a premature LH surge. For luteal-phase support, all the cases received intravaginal 600 mg micronized progesterone. In this prospective study, patients were randomly assigned to two groups. In one group, patients received an additional single dose of GnRH agonist (0.5 mg leuprolide acetate) subcutaneously on day 6 after ICSI, whereas the patients in the other group did not. Although the number of embryos transferred and the grade of the embryos were similar in the two groups, the patients in the luteal-phase agonist group had significantly higher rates of implantation and clinical pregnancy rates ( P < 0.05). When the two groups were compared, there were also statistically significant differences in multiple pregnancy and live birth rates ( P < 0.05). Administration of single-dose GnRH agonist as a luteal-phase support in ovarian stimulation-GnRH antagonist cycles in addition to standard luteal support seems to be effective in all cycle outcome parameters.
The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen.