Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis.
OBJECTIVE
Treatment with cyclophosphamide (CYC) confers up to a 40% risk of ovarian failure in women of reproductive age. The use of GnRH agonists (GnRHa) to preserve ovarian function has been investigated in several small studies. We performed a systematic review of studies examining whether a GnRHa administered during chemotherapy is protective of ovarian function and fertility.


METHODS
We searched the English-language literature (1966-April 2007) using MEDLINE and meeting abstracts and included studies that reported an association between GnRHa and ovarian preservation in women receiving chemotherapy. Studies without a control group were excluded. Ovarian preservation was defined as the resumption of menstrual cycles and a premenopausal follicle-stimulating hormone (FSH) after chemotherapy. Fertility was determined by a woman's ability to become pregnant. We estimated the summary relative risk (RR) and associated 95% confidence intervals (95% CI) using a random-effects model.


RESULTS
Nine studies included 366 women. Three studies included women with autoimmune disease receiving CYC; six included women with hematologic malignancy receiving combination chemotherapy. In total, 178 women were treated with GnRHa during chemotherapy, 93% of whom maintained ovarian function. Of the 188 women not treated with GnRHa, 48% maintained ovarian function. The use of a GnRHa during chemotherapy was associated with a 68% increase in the rate of preserved ovarian function compared with women not receiving a GnRHa (summary RR = 1.68, 95% CI 1.34-2.1). Among the GnRHa-treated women, 22% achieved pregnancy following treatment compared with 14% of women without GnRHa therapy (summary RR = 1.65, CI 1.03-2.6).


CONCLUSIONS
Based on the available studies, GnRHa appear to improve ovarian function and the ability to achieve pregnancy following chemotherapy. Several randomized trials are underway to define the role and mechanism of GnRHa in ovarian function preservation. In the meantime, premenopausal women facing chemotherapy should be counseled about ovarian preservation options, including the use of GnRHa therapy.
Clowse
Megan E B
ME
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. megan.clowse@duke.edu
Behera
Millie A
MA
Anders
Carey K
CK
Copland
Susannah
S
Coffman
Cynthia J
CJ
Leppert
Phyllis C
PC
Bastian
Lori A
LA
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005300:Fertility Agents, Female / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000032:analysis*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D016017:Odds Ratio; D010053:Ovary / Q000187:drug effects; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D016649:Primary Ovarian Insufficiency / Q000188:drug therapy*; D011379:Prognosis; D055815:Young Adult
D018931:Antineoplastic Agents, Hormonal; D005300:Fertility Agents, Female; D007987:Gonadotropin-Releasing Hormone