title: A Combination of a GnRH Antagonist and Agonist for Fertility Preservation in an Adolescent Female Murine Model.
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.
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Jennifer Flora
authors.initials: JF
authors.lastname: Knudtson
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Marlen
authors.initials: M
authors.lastname: Tellez Santos
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Failor
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Binkley
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Venesky
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Rajeshwar R
authors.initials: RR
authors.lastname: Tekmal
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Randal D
authors.initials: RD
authors.lastname: Robinson
authors.affiliation: 1 Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Schenken
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D059247:Fertility Preservation / Q000379:methods*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D016729:Leuprolide / Q000008:administration & dosage*; D023421:Models, Animal; D010053:Ovary / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide; D016729:Leuprolide; C062876:cetrorelix
keywords: GnRH suppression; adolescents (AYA); fertility preservation