Elsevier

Fertility and Sterility

Volume 99, Issue 2, February 2013, Pages 477-483.e1
Fertility and Sterility

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

https://doi.org/10.1016/j.fertnstert.2012.09.039Get rights and content

Objective

To identify factors associated with ovarian reserve impairment during and immediately after chemotherapy.

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.

Section snippets

Materials and methods

This study is part of a collaboration between the University of Pennsylvania (Penn), Children's Hospital of Philadelphia (CHOP), Children's Memorial Hospital in Chicago (CMH), and the University of North Carolina at Chapel Hill (UNC). Institutional review board approval was obtained at each site, and informed consent was obtained from all participants. The study included a visit before initiation of cancer therapy and then visits every 3 months from chemotherapy initiation. Study visits

Results

Eighty-one women between the ages of 15 and 35 years were enrolled in this study. Forty-six women had sufficient visits to be included in this report. Thirty eligible women were recruited from Penn, seven from CMH, six from CHOP, and three from UNC.

Baseline characteristics are presented in Table 1. Most participants were Caucasian, unmarried, normal weight, nulligravid, and college graduates. Nineteen (41%) of 46 participants were diagnosed with breast cancer and 37% with hematologic

Discussion

Cancer therapies have been shown to impair reproductive function in cancer survivors, but the acute impact of therapies on ovarian function in postpubertal adolescents and young women is not well documented. Future fertility is an important consideration for young women newly diagnosed with cancer, and better methods are needed to predict long-term reproductive potential in individual patients so that they can be counseled regarding fertility preservation strategies 12, 13.

Our study completed a

References (23)

  • J.M. Letourneau et al.

    Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer

    Cancer

    (2011)
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      AMH recovery after gonadotoxic damage depends not only on the type of gonadotoxic agent but also the age and size of the ovarian reserve [23,26]. AMH values at the time of gonadotoxic treatment are also predictive of fertility recovery after gonadotoxic damage since there is a greater likelihood of menstrual cycle and fertility resumption with higher pretreatment AMH values [17,25]. AMH has also been investigated as a predictor of the impact of ovarian surgery on ovarian reserve, as in the case of ovarian endometriosis.

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    K.E.D. has nothing to disclose. M.D.S. has nothing to disclose. M.P. has nothing to disclose. J.P.G. has nothing to disclose. D.W. has nothing to disclose. J.E.M. has nothing to disclose. Y.G. has nothing to disclose. C.R.G. has nothing to disclose.

    Supported by NIH Grant K01 L:1-CA-133839–03 (CG); 1R01HD062797 (CG), and the Doris Duke Clinical Research Fellowship (KED).

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