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Hum. Reprod. Advance Access published online on October 14, 2008
Human Reproduction, doi:10.1093/humrep/den337
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Does controlled ovarian stimulation prior to chemotherapy increase primordial follicle loss and diminish ovarian reserve? An animal study

E. Maman, K. Prokopis, J. Levron, A. Carmely, J. Dor and D. Meirow1

IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel- Hashomer, Israel

1 Correspondence address. Tel: +972-3-5302882; Fax: +972-3-5341589; E-mail: meirow{at}post.tau.ac.il

BACKGROUND: Storage of embryos for fertility preservation before chemotherapy is widely practiced. For multiple oocyte collection, the ovaries are hyperstimulated with gonadotrophins that significantly alter ovarian physiology. The effects of ovarian stimulation prior to chemotherapy on future ovarian reserve were investigated in an animal model.

METHODS: Cyclophosphamide (Cy) in doses of 0, 50 or 100 mg/kg was administered to 38 adult mice (control, unstimulated). A second group of 12 mice were superovulated with equine chorionic gonadotrophin (eCG, 10 IU on Day 0) before Cy administration; hCG (10 IU) was administered (Day 2) followed by 0, 50 or 100 mg/kg Cy (Day 4). In both groups ovaries were removed, serially sectioned (7-day post-Cy), primordial follicles were counted and differences between groups evaluated.

RESULTS: Follicle number dropped from 469 ± 24 (mean ± SE) to 307 ± 27 and 234 ± 19 with 50 or 100 mg/kg Cy, respectively (P < 0.0001). In the eCG pretreated group, follicle count dropped from 480 ± 31 to 345 ± 16 and 211 ± 26 when 50 or 100 mg/kg Cy were administered (P < 0.0001). There were no significant differences in follicle count between the pretreated eCG group and controls for each chemotherapy dose.

CONCLUSIONS: This animal study indicates that ovarian stimulation before administration of Cy does not adversely affect ovarian reserve post-treatment. These results provide support for the safety of fertility preservation using ovarian stimulation and IVF–embryo cryopreservation procedures prior to chemotherapy.

Key words: fertility preservation/chemotherapy/IVF/ovarian stimulation/primordial follicles

Submitted on June 25, 2008; resubmitted on July 27, 2008; accepted on July 30, 2008.


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