Breast Cancer Research and Treatment

, Volume 122, Issue 3, pp 803–811 | Cite as

Pharmacological interventions for fertility preservation during chemotherapy: a systematic review and meta-analysis

  • Irit Ben-Aharon
  • Anat Gafter-Gvili
  • Leonard Leibovici
  • Salomon M. StemmerEmail author
Clinical trial


The rate of chemotherapy-induced ovarian failure (CIOF) has been reported as 14–100% and is age- and agent-dependent. The role of GnRH analogs (GnRHa) and oral contraceptives (OC) in the prevention of CIOF is questionable. We performed a systematic review and a meta-analysis of studies assessing the efficacy of hormonal interventions in reducing CIOF in cancer or systemic lupus erythematosus (SLE) patients treated with chemotherapy. MEDLINE, EMBASE, and conference proceedings were searched until October 2009. From 504 potentially relevant references, 21 comparative studies were included for review and analysis. Data were collected to determine the risk ratio (RR) for amenorrhea, FSH levels, pregnancy rate, and biomarkers for ovarian reserve. Sixteen studies (SLE: 4 studies, 85 patients; malignancy: 12 studies, 596 patients) which assessed GnRHa for fertility preservation prior to chemotherapy were included in the meta-analysis. Five studies which evaluated the use of OC were systematically reviewed. Meta-analysis revealed that GnRHa are effective in reducing amenorrhea rates in all patients (RR 0.26, 95% CI 0.14–0.49). Pregnancy rate was higher in the GnRHa arm. The advantage of GnRHa was shown only in observational studies, but not in randomized controlled trials. Biomarkers for ovarian reserve were similar in both arms. Studies evaluating the efficacy of oral contraceptives in preserving ovarian function showed inconclusive results. GnRHa appears to improve menstruation resumption. Nevertheless, randomized prospective trials are less conclusive for their real value in conserving ovarian reserve and pregnancy. Large-scale prospective randomized trials are warranted to evaluate the role of GnRHa in preventing CIOF.


Ovarian failure GnRH agonists Oral contraceptives 


Conflict of interest statement


Supplementary material

10549_2010_996_MOESM1_ESM.doc (56 kb)
Supplementary Table 1 (DOC 56 kb)
10549_2010_996_MOESM2_ESM.doc (37 kb)
Supplementary Table 2 (DOC 37 kb)
10549_2010_996_MOESM3_ESM.doc (42 kb)
Supplementary Table 3 (DOC 42 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Irit Ben-Aharon
    • 1
    • 2
  • Anat Gafter-Gvili
    • 2
    • 3
  • Leonard Leibovici
    • 2
    • 4
  • Salomon M. Stemmer
    • 1
    • 2
    Email author
  1. 1.Institute of Oncology, Davidoff Center, Rabin Medical CenterPetah TiqwaIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityRamat AvivIsrael
  3. 3.Institute of Hemato-Oncology, Davidoff Center, Rabin Medical CenterPetah TiqwaIsrael
  4. 4.Department of Medicine ERabin Medical CenterPetah TiqwaIsrael

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