Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 4, pp 571–581 | Cite as

Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists

  • Lisa C. Hickman
  • Natalia C. Llarena
  • Lindsey N. Valentine
  • Xiaobo Liu
  • Tommaso FalconeEmail author
Fertility Preservation



To evaluate the available randomized controlled trials (RCTs) in the literature investigating the use of gonadotropin-releasing hormone agonist (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy.


A systematic review of the literature was performed from 1960 through 2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer, or breast cancer. The primary outcome was the proportion of women who retained ovarian function after chemotherapy. Extracted data points included study design, patient characteristics, and proportion of women who developed premature ovarian failure (POF). A risk of bias assessment was performed according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The pooled odds ratio was calculated, and outcomes of individual studies were compared using the random-effects model with the inverse-variance method and the DerSimonian-Laird estimator.


Twenty-nine RCTs were identified, and 10 met criteria for inclusion in the meta-analysis. An analysis of patients who did not develop POF after chemotherapy revealed eight studies supporting the use of GnRHa (OR 1.83; 95% CI 1.34–2.49). The duration of benefit of GnRHa is unclear. An analysis of three studies with outcome data at 2 years revealed a non-significant OR of 0.53 (95% CI 0.22–1.30) for the preservation of ovarian function with GnRHa treatment.


GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study.


Chemotherapy Gonadotropin-releasing hormone Ovarian function Premature ovarian failure Systematic review 



The authors would like to acknowledge Ms. Lorelei Woody and Ms. Gretchen Hallerberg, the librarians who assisted with the literature search, as well as Mr. James Bena, a statistician who assisted with a portion of the data analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lisa C. Hickman
    • 1
  • Natalia C. Llarena
    • 1
  • Lindsey N. Valentine
    • 1
  • Xiaobo Liu
    • 2
  • Tommaso Falcone
    • 1
    Email author
  1. 1.Department of Obstetrics/GynecologyCleveland Clinic FoundationClevelandUSA
  2. 2.Department of Quantitative Health ScienceCleveland Clinic FoundationClevelandUSA

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