A Randomized Controlled Intervention Trial with Danazol to Improve Telomeric and Fertility Parameters in Women with Diminished Ovarian Reserve: A Pilot Study

Data de publicació: 04/07/2023 Data Ahead of Print: 04/07/2023

Autors de IIS La Fe

Autors aliens a IIS La Fe

Kohls, Graciela
Iglesias, Carlos
Toribio, Monica
Garcia-Velasco, Juan A.

Grups d'Investigació

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Biomarcadores, Medicina Genómica, Estadística y Análisis masivo de datos en Reproducción humana asistida

Investigador Principal

Marcos Meseguer Escrivá
Endocrinología Reproductiva e Infertilidad

Leader

José Remohí Giménez
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

Background: Most women who are treated at in vitro fertilization (IVF) clinics have trouble conceiving due to ovarian failure (OF), which seems to be associated to short telomeres and reduced or absent telomerase activity in their granulosa cells. Indeed, telomere pathways are involved in organ dysfunction. However, sexual steroids can stimulate the expression of the telomerase gene and have been successfully used to prevent telomere attrition. Thus, a strategy to improve IVF outcomes in women with OF could be telomerase reactivation using sexual steroids.Methods: We conducted a double-blind, placebo-controlled study. Patients with diminished ovarian reserve were randomized to Danazol or placebo for 3 months. We included patients with normal ovarian reserve in the study as untreated controls. Patients and controls underwent several ovarian stimulations (OSs). Telomere and IVF parameters were assessed.Results: We found that the mean telomere length in blood and the percentage of short and long telomeres were similar throughout the 3 months of treatment with Danazol. Remarkably, while the number of cells with one telomeric repeat-containing RNA (TERRA) focus decreased (p = 0.04) after the first month of Danazol treatment, the number of cells with 2 to 4 TERRA foci increased (p = 0.02). Regarding fertility, no differences were found in the antral follicle count. Interestingly, in OS performed after the trial, all Danazol-treated patients had a better MII oocyte rate compared to OS performed before the pilot study.EudraCT number: 2018-004400-19.Conclusions: Danazol treatment seemed to affect telomere maintenance, since both the number of TERRA foci and the ratio of MII oocytes changed. However, further research is needed to confirm these results.

Dades de la publicació

ISSN/ISSNe:: 2688-4844, 2688-4844
Tipus:: Article
Pàgines:: 305-318
DOI:: 10.1089/whr.2023.0013
PubMed:: 37476605

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Mètriques

Filiacions

Cordova-Oriz, Isabel:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain
Kohls, Graciela:: IVIRMA Madrid, Madrid, Spain
Iglesias, Carlos:: IVIRMA Madrid, Madrid, Spain
Polonio, Alba M.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain
Chico-Sordo, Lucia:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain
Toribio, Monica:: IVIRMA Madrid, Madrid, Spain
Meseguer, Marcos:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain

IVIRMA Valencia, Lab Vitro Fertilizat, Valencia, Spain
Varela, Elisa:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain

Rey Juan Carlos Univ, Dept Med Specialties & Publ Hlth, Madrid, Spain

Rey Juan Carlos Univ, Dept Med Specialties & Publ Hlth, Edificio Dept 2 Av Atenas S-N, Madrid 28922, Spain
Pellicer, Antonio:: IVIRMA Rome, Rome, Italy

Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain

Univ Valencia, Sch Med, Dept Obstet & Gynecol, Valencia, Spain
Garcia-Velasco, Juan A.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Valencia, Spain

IVIRMA Madrid, Madrid, Spain

Rey Juan Carlos Univ, Dept Med Specialties & Publ Hlth, Madrid, Spain