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A Combination of a GnRH Antagonist and Agonist for Fertility Preservation in an Adolescent Female Murine Model

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Abstract

Recent studies have suggested that GnRH agonists (GnRHags) protect ovarian function following chemotherapy. Here, we study the effect of a combination of GnRH antagonist (GnRHan) and GnRHag for gonadal protection from gonadotoxic chemotherapy in adolescent female rats. Cycling Sprague Dawley rats were treated at adolescent age. Thirty female rats were randomized to 5 treatment groups (n = 6/group): (1) placebo, (2) cyclophosphamide (CPA) alone, (3) GnRHan followed by GnRHag with placebo, (4) GnRHan followed by GnRHag with CPA, and (5) GnRHag with CPA. The main outcome measure was live birth rate (LBR), and secondary measures included rat weight, ovarian volume, and follicles. Group 2 had decreased LBR compared to all other groups. Group 4 and 5 had LBR similar to placebo. There was no difference in the ovarian volume. The CPA-alone group had decreased number of antral follicles compared to control. These studies demonstrate that the combination of GnRHan and GnRHag and GnRHag alone preserved fertility in female adolescent rats following gonadotoxic chemotherapy treatment. The addition of a GnRHan to a GnRHag does not confer a greater protective effect.

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References

  1. Barton SE, Najita JS, Ginsburg ES, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2013;14(9):873–881.

    Article  Google Scholar 

  2. Robinson RD, Knudtson JF. Fertility preservation in patients receiving chemotherapy or radiotherapy. Mo Med. 2014;111(5):434–438.

    PubMed  PubMed Central  Google Scholar 

  3. Cakmak H, Rosen MP. Ovarian stimulation in cancer patients. Fertil Steril. 2013;99(6):1476–1484.

    Article  Google Scholar 

  4. Moore HC, Unger JM, Phillips KA, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372(10):923–932.

    Article  CAS  Google Scholar 

  5. Lambertini M, Boni L, Michelotti A, et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA. 2015;314(24):2632–2640.

    Article  CAS  Google Scholar 

  6. Blumenfeld Z, Evron A. Preserving fertility when choosing chemotherapy regimens—the role of gonadotropin-releasing hormone agonists. Expert Opin Pharmacother. 2015;16(7):1009–1020.

    Article  CAS  Google Scholar 

  7. Li X, Kang X, Deng Q, Cai J, Wang Z. Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatininduced toxicity: a controlled experimental animal study. Reprod Biol Endocrinol. 2013;11:16.

    Article  CAS  Google Scholar 

  8. Lemos CN, Reis FM, Pena GN, Silveira LC, Camargos AF. Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophospha-mide. Reprod Biol Endocrinol. 2010;8:51.

    Article  Google Scholar 

  9. Montz FJ, Wolff AJ, Gambone JC. Gonadal protection and fecundity rates in cyclophosphamide-treated rats. Cancer Res. 1991;51(8):2124–2126.

    CAS  PubMed  Google Scholar 

  10. Blumenfeld Z. How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embryo, oocytes, or ovaries. Oncologist. 2007;12(9):1044–1054.

    Article  Google Scholar 

  11. Ozcelik B, Turkyilmaz C, Ozgun MT, et al. Prevention of pacli-taxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist. Fertil Steril. 2010;93(5):1609–1614.

    Article  CAS  Google Scholar 

  12. Ataya K, Ramahi-Ataya A. Reproductive performance of female rats treated with cyclophosphamide and/or LHRH agonist. Reprod Toxicol. 1993;7(3):229–235.

    Article  CAS  Google Scholar 

  13. Ataya KM, McKanna JA, Weintraub AM, Clark MR, LeMaire WJ. A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Res. 1985;45(8):3651–3656.

    CAS  PubMed  Google Scholar 

  14. Meirow D, Assad G, Dor J, Rabinovici J. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Human reproduction (Oxford, England). 2004;19(6):1294–1299.

    Article  CAS  Google Scholar 

  15. Danforth DR, Arbogast LK, Friedman CI. Acute depletion of murine primordial follicle reserve by gonadotropin-releasing hormone antagonists. Fertil Steril. 2005;83(5):1333–1338.

    Article  CAS  Google Scholar 

  16. Potolog-Nahari C, Fishman A, Cohen I. Protection of ovarian function and fertility using a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in young females. Gynecol Endocrinol. 2007;23(5):290–294.

    Article  CAS  Google Scholar 

  17. Whitehead J, Toledo MG, Stern CJ. A pilot study to assess the use of the gonadotropin antagonist cetrorelix in preserving ovarian function during chemotherapy. Aust N Z J Obstet Gynaecol. 2011;51(5):452–454.

    Article  Google Scholar 

  18. Elgindy EA, El-Haieg DO, Khorshid OM, et al. Gonadotropin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial. Obstet Gynecol. 2013;121(1):78–86.

    Article  CAS  Google Scholar 

  19. Tek M, Cayan S, Yilmaz N, Oguz I, Erdem E, Akbay E. The effect of vascular endothelial growth factor on spermatogenesis and apoptosis in experimentally varicocele-induced adolescent rats. Fertil Steril. 2009;91(5 suppl):2247–2252.

    Article  Google Scholar 

  20. Sengupta P. The laboratory rat: relating its age with human’s. Int J Prev Med. 2013;4(6):624–630.

    PubMed  PubMed Central  Google Scholar 

  21. Bokser L, Szende B, Schally AV. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats. Br J Cancer. 1990;61(6):861–865.

    Article  CAS  Google Scholar 

  22. Jarrell J, Lai EV, Barr R, McMahon A, Belbeck L, O’Connell G. Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat. Cancer Res. 1987;47(9):2340–2343.

    CAS  PubMed  Google Scholar 

  23. Levine JM, Kelvin JF, Quinn GP, Gracia CR. Infertility in reproductive-age female cancer survivors. Cancer. 2015;121(10):1532–1539.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Jennifer Flora Knudtson MD, Marlen Tellez Santos BS, Courtney M. Failor MD, Peter A. Binkley BS, Jacob P. Venesky MD, Rajeshwar R. Tekmal PhD, Randal D. Robinson MD & Robert S. Schenken MD

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  1. Jennifer Flora Knudtson MD
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  2. Marlen Tellez Santos BS
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  3. Courtney M. Failor MD
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  4. Peter A. Binkley BS
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  5. Jacob P. Venesky MD
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  6. Rajeshwar R. Tekmal PhD
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  7. Randal D. Robinson MD
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  8. Robert S. Schenken MD
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Correspondence to Jennifer Flora Knudtson MD.

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Knudtson, J.F., Santos, M.T., Failor, C.M. et al. A Combination of a GnRH Antagonist and Agonist for Fertility Preservation in an Adolescent Female Murine Model. Reprod. Sci. 24, 1280–1283 (2017). https://doi.org/10.1177/1933719116682876

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  • DOI: https://doi.org/10.1177/1933719116682876

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