Long-term effects of childhood cancer treatment on hormonal and ultrasound markers of ovarian reserve

To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer. An expert panel and a writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature from 1987 to 2005 was performed, and included a search of online databases and consultation with content experts. The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer. Fertility preservation methods are used infrequently in people with cancer. As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise. Fertility preservation is often possible in people undergoing treatment for cancer. To preserve the full range of options, fertility preservation approaches should be considered as early as possible during treatment planning.

To investigate the relationship between clinical markers of ovarian reserve and the true ovarian reserve as determined by the ovarian primordial follicle number. Prospective investigation. Academic medical center. Forty-two healthy women (aged 26-52 years) undergoing oophorectomy for benign gynecologic indications. Transvaginal ultrasound examination for the determination of the ovarian antral follicle count (AFC) and serum measurements of clinical markers of ovarian reserve. All measurements were obtained within 2 weeks of surgery, irrespective of cycle day. Ovarian primordial follicle count was then determined using a validated fractionator/optical disector method. Univariate and partial correlations between ovarian reserve markers and ovarian primordial follicle count. There were significant correlations between the ovarian primordial follicle count and AFC (r=0.78), anti-Müllerian hormone (AMH; r=0.72), FSH (r=-0.32), inhibin B (r=0.40), and chronological age (r=-0.80). After adjusting for age, significant correlations were identified between the ovarian primordial follicle count and AFC (r=0.53) and AMH (r=0.48). The ovarian AFC and serum levels of AMH correlate with the ovarian primordial follicle number even after adjustment for chronological age. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

These studies were undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on ovarian function and reproductive outcomes. We reviewed the frequency of acute ovarian failure, premature menopause, live birth, stillbirth, spontaneous and therapeutic abortion and birth defects in the participants in the Childhood Cancer Survivor Study (CCSS). Acute ovarian failure (AOF) occurred in 6.3% of eligible survivors. Exposure of the ovaries to high-dose radiation (especially over 10 Gy), alkylating agents and procarbazine, at older ages, were significant risk factors for AOF. Premature nonsurgical menopause (PM) occurred in 8% of participants versus 0.8% of siblings (rate ratio = 13.21; 95% CI, 3.26 to 53.51; P < .001). Risk factors for PM included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score, and a diagnosis of Hodgkin's lymphoma. One thousand two hundred twenty-seven male survivors reported they sired 2,323 pregnancies, and 1,915 female survivors reported 4,029 pregnancies. Offspring of women who received uterine radiation doses of more than 5 Gy were more likely to be small for gestational age (birthweight < 10 percentile for gestational age; 18.2% v 7.8%; odds ratio = 4.0; 95% CI, 1.6 to 9.8; P = .003). There were no differences in the proportion of offspring with simple malformations, cytogenetic syndromes, or single-gene defects. These studies demonstrated that women treated with pelvic irradiation and/or increasing alkylating agent doses were at risk for acute ovarian failure, premature menopause, and small-for-gestational-age offspring. There was no evidence for an increased risk of congenital malformations. Survivors should be generally reassured although some women have to consider their potentially shortened fertile life span in making educational and career choices.