Maureen Prewitt

Impact of cancer therapies on ovarian reserve

OBJECTIVE To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age. DESIGN Cross-sectional analysis of data from a prospective cohort study. SETTING University medical center. PATIENT(S) Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression. RESULT(S) In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls. CONCLUSION(S) Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.

Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy

OBJECTIVE To identify factors associated with ovarian reserve impairment during and immediately after chemotherapy. DESIGN Prospective cohort study. SETTING Four university hospitals. PATIENT(S) Forty-six adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Measurements of ovarian reserve via levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, and antimüllerian hormone (AMH) as well as antral follicle counts and mean ovarian volume at 3-month intervals. RESULT(S) Changes in ovarian reserve were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed-effects models adjusted for baseline ovarian reserve, use of alkylating agent, and hormone use. The women had at least one pretreatment and two posttreatment study visits (mean follow-up interval: 12 months). All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy. Alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment, and pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. In adjusted models, participants with a pretreatment AMH level > 2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤ 2 ng/mL recovered at a rate of 2.6% per month after therapy. CONCLUSION(S) Baseline ovarian reserve and alkylating agent exposure effect the magnitude of acute changes in ovarian reserve from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling.

Thyroid function during controlled ovarian hyperstimulation as part of in vitro fertilization

OBJECTIVE To determine the exact nature and timing of alterations in thyroid function throughout controlled ovarian hyperstimulation (COH). DESIGN Prospective cohort study. SETTING University fertility clinic. PATIENT(S) Fifty-seven women undergoing COH as part of planned in vitro fertilization. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Timing and magnitude of change in serum thyroid hormones, including TSH, total and free T(4), E(2), and thyroxine-binding globulin (TBG), measured at six time points from before stimulation to 2 weeks after serum pregnancy test. RESULT(S) Geometric mean serum TSH increased during stimulation, peaking 1 week after hCG administration compared with baseline (2.44 vs. 1.42 mIU/L), as did free T(4) (1.52 vs. 1.38 ng/dL) and TBG (32.86 vs. 21.52 μg/mL). Estradiol levels increased, peaking at hCG administration (1743.21 vs. 71.37 pg/mL). Of 50 women with baseline TSH ≤ 2.5 mIU/L, 22 (44.0%) had a subsequent rise in TSH to >2.5 during or after COH. The pattern of change over time in TSH concentrations was significantly influenced by baseline hypothyroidism and whether pregnancy was achieved. CONCLUSION(S) COH led to significant elevations in TSH, often above pregnancy appropriate targets. These findings were particularly evident in women with preexisting hypothyroidism and may have important clinical implications for screening and thyroid hormone supplementation.

Pregnancy after cancer: results from a prospective cohort study of cancer survivors.

Future fertility is an important concern for many cancer survivors. Cancer therapies have been shown to adversely impact reproductive function. However, it is difficult to predict the extent to which reproductive dysfunction will occur. The purpose of this study was to compare measures of ovarian reserve (MOR) and pregnancy rates in young female cancer survivors and similar‐aged controls.

Quantification of anti-Müllerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve

BACKGROUND Biological markers of ovarian reserve have the potential to advance research on fecundability, infertility and reproductive aging. Anti-Müllerian hormone (AMH) has emerged as a clinically useful measure of ovarian reserve, but the requirement for venous blood is an obstacle to application in non-clinical settings. This paper validates a new method for quantifying AMH in dried blood spot (DBS) samples--drops of whole blood collected on filter paper following a simple finger stick. METHODS Matched serum and DBS samples were obtained from n=101 women of reproductive age, and AMH values were compared using regression analyses and scatter plots. The precision, reliability, linearity, recovery and lower detection limit of the DBS assay were evaluated, as well as the stability of AMH in DBS across a range of storage conditions. RESULTS There was a strong agreement between AMH concentrations measured in DBS and serum samples across the entire assay range. Analysis of within-assay (percent coefficient of variation, 4.7-6.5%) and between-assay (3.5-7.2%) variability indicated a high level of assay precision and reliability, respectively. The minimum detectable dose of AMH was 0.065 ng/ml. Concentrations of AMH remained stable in DBS samples stored for 2 weeks at room temperature, and for 4 weeks when refrigerated. CONCLUSIONS The DBS assay performs at a level that is comparable to serum-based methods, with the advantage of lower burdens and costs associated with blood collection that may be advantageous for research in clinical as well as non-clinical settings on the causes and consequences of variation in ovarian reserve.