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

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Vol. 24; no. 9; pp. 1280 - 1283
• Main Authors: Knudtson, Jennifer Flora, Tellez Santos, Marlen, Failor, Courtney M., Binkley, Peter A., Venesky, Jacob P., Tekmal, Rajeshwar R., Robinson, Randal D., Schenken, Robert S.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.09.2017; Springer International Publishing
• Subjects: Animals; Antineoplastic Agents, Alkylating - administration & dosage; Cyclophosphamide - administration & dosage; Embryology; Female; Fertility Agents, Female - administration & dosage; Fertility Preservation - methods; Gonadotropin-Releasing Hormone - administration & dosage; Gonadotropin-Releasing Hormone - analogs & derivatives; Hormone Antagonists - administration & dosage; Leuprolide - administration & dosage; Medicine & Public Health; Models, Animal; Obstetrics/Perinatology/Midwifery; Original; Original Article; Ovary - drug effects; Rats; Rats, Sprague-Dawley; Reproductive Medicine; GnRH suppression; adolescents (AYA); fertility preservation
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719116682876

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.