Impact of cancer therapies on ovarian reserve

Abstract

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, p<0.001; AFC: 14.55 vs. 27.20, p<0.001. In participants with an FSH<10, survivors had lower levels of AMH and AFC compared to controls. Alkylating agent dose score was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied.

Anti-Müllerian hormone: determination of ovarian reserve in early breast cancer patients

“…Increased dose of alkylating agent was associated with increased levels of FSH and decreased levels of AMH. AMH levels were not significantly different between women previously exposed to high-dose cancer therapy and 40-42-year-old controls (Gracia et al 2012).…”

“…Gracia et al (2012) carried on a cross-sectional analysis to compare measures of ovarian reserve (E 2 , FSH, inhibin B, AMH, and AFC) in young cancer survivors with those in unexposed females of similar age and with a cohort of late-reproductive-age women. A total of 71 cancer survivors (47 patients with hematological malignancy and 24 with solid tumors), 67 similarly aged unexposed controls, and 69 regularly menstruating women of late reproductive age were included.…”

Outcomes of ovarian stimulation after treatment with chemotherapy

“…While many of these drugs are curative and life saving, many types of chemotherapy are known to be gonadotoxic and may have a negative impact on ovarian reserve and future fertility for reproductive-aged women who have received them [1]. Alkylating agents, such as cyclophosphamide, are well known to cause follicular depletion, oocyte destruction, and stromal fibrosis [2][3][4], and the risk of ovarian dysfunction appears to occur in a dose-dependent fashion [5]. This effect has been demonstrated in both cancer patients [5][6][7][8] and in patients with autoimmune disease such as systemic lupus erythematosus and granulomatosis with polyangiitis [9,10].…”

Measuring ovarian volume during cesarean delivery provides valuable information about future ovarian function and reproductive capacity

“…A typical female cycle lasts 28 days; however, this can range from 21-35 days 1 . The ovarian cycle has two distinct phases: The follicular phase (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and the luteal phase (days 14-28). The follicular phase is characterized by follicle development and growth, the goal being that one follicle matures and releases an egg at the time of ovulation, around day 14 of the female cycle.…”