Purpose: 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 ¼ 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 ¼ 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.

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growing follicles and decreases the sensitivity of small pre-antral follicles to FSH. Along with its pivotal role in follicular development, AMH serves as a putative marker of ovarian reserve and of assisted reproductive technology outcome. Aromatase cytochrome P450 (encoded by the CYP19 gene) is the key enzyme in biosynthesis of estrogens from C 19 -steroid precursors. Previous animal studies suggest that AMH inhibits expression of aromatase in fetal ovaries; however, the effect of AMH on aromatase in postnatal human ovaries is not well understood. The objective of the present study was to investigate the effects of AMH on expression of aromatase in human granulosa cells (hGCs).DESIGN: Effects of AMH in the absence and presence of cAMP were studied in primary luteinized hGCs obtained during in-vitro fertilization cycles and in the immortalized human granulosa cell line, HGL5.MATERIALS AND METHODS: hGCs were cultured þ/À dibutyryl cAMP (1 mM), þ/À AMH (5-100 ng/ml) for 24-48h. RNA was isolated, reversed-transcribed and real-time PCR was performed to measure mRNA transcripts for CYP 19 IIa (ovarian specific promoter of aromatase).RESULTS: In HGL5 cells, cAMP caused a $40-fold induction of CY-P19IIa mRNA. While AMH (25 ng/ml) alone had a modest stimulatory effect ($1.5-fold), surprisingly, co-treatment with AMH þ cAMP caused a synergistic $75-fold increase in CYP19IIa mRNA levels. In primary cultures of hGCs, basal CYP19IIa mRNA levels were elevated; cAMP caused a $2.5fold increase in CYP19IIa mRNA, while AMH had a moderate stimulatory effect (1.5-fold). In cells co-treated with AMH þ cAMP, CYP19IIa mRNA levels were increased $3.5-fold.CONCLUSIONS: These novel findings suggest that AMH acts synergistically with cAMP to upregulate aromatase expression in hGCs. Since both AMH and estradiol (product of the aromatase reaction) serve as markers of oocyte quality and fertilization rate, we postulate that these hormones may interact in the selection and growth of the dominant follicle and influence folliculogenesis and oocyte quality. Further studies are needed to elucidate the mechanisms of action of AMH on aromatase and its influence on folliculogenesis.OBJECTIVE: To assess early follicular phase AMH levels as a marker of ovarian response in anonymous oocyte donors.DESIGN: Retrospective, blinded analysis of serum samples from young (<32 yrs) egg donors who donated in single-or double-recipient oocyte donation cycles (OD) at a university-based fertility program.MATERIALS AND METHODS: AMH levels were evaluated in 187 donors (meanþSD age: 26AE3 yrs) at the start of their first donation during 2004-2007. AMH levels were assayed in cryostored serum samples collected on day 2 post-menses onset after depot-leuprolide and prior to the start of injectable menotropins. AMH levels were assessed using the Beckman Coulter enzyme-linked immunosorbent assay (ELISA) kit. Cycles were evaluated for number of oocytes retrieved, IUs menotropin required and pregnancy outcome. Pearson's correlation coefficient was used to determine relations...

Objective To conduct a quantitative survey that focuses on oncologists' practice patterns and attitudes surrounding treatment-related infertility and fertility preservation, specifically among women of reproductive age. Study Design A 19-item survey was emailed to medical, pediatric, radiation and surgical oncologists at Duke University. Descriptive statistics were used. Results Most oncologists (61%) who responded always or usually discuss the impact treatment will have on fertility. Nearly half (45%) never refer women to reproductive specialists. Respondents who attended an educational session on fertility preservation were more likely to consider a patient's desire for fertility when planning her treatment than those who did not attend (45% vs. 33%). More than half (55%) of attendees were willing to consider a less aggressive regimen to preserve fertility, compared with 29% of those who did not attend. Conclusion While most oncologists recognize the importance of discussing infertility risks, many do not discuss fertility preservation routinely. Reasons for this discrepancy included poor prognosis and emergent need to start therapy. Increasing awareness through educational events may influence current practice patterns and increase collaboration between reproductive endocrinologists and oncologists.