TRAP Study: Testosterone for Androgen Receptor Polymorphism

NCT06195163 | Not Yet Recruiting Phase 4

• 1 other identifier: IBMR46
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

To determine whether pretreatment with transdermal testosterone increases the number of cumulus-oocyte complexes (COCs) obtained after ovarian stimulation by more than 1.5 in patients with low ovarian reserve and androgen receptor polymorphism undergoing intracytoplasmic sperm injection (ICSI).

Conditions

Fertility Disorders

Keywords

ovarian stimulation; testosterone

Outcome Measures

Primary Outcomes (1)

• Number of COC (cumulus-oocyte complexes)

  If number of COC is higher at least by 1.5 in the experimental group.

  Egg collection day (between 8 and 14 days after starting of ovarian stimulation)

Study Arms (2)

Study group

EXPERIMENTAL

Daily 10 mg transdermal testosterone for 21 days prior to the start of ovarian stimulation.

Drug: Transdermal Gel in Sachet Dosage Form

Control group

ACTIVE COMPARATOR

No pre-treatment prior to ovarian stimulation.

Drug: No pretreatment

Interventions

Transdermal Gel in Sachet Dosage Form DRUG

Transdermal testosterone gel application prior to ovarian stimulation in the study group.

Study group

No pretreatment DRUG

No pretreatment prior to the ovarian stimulation in the control group.

Control group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with low ovarian reserve according to Bologna criteria: at least two of the following three:
• Age equal to or greater than 40 years.
• Previous cycle with less than 4 oocytes retrieved.
• Low ovarian reserve markers (antral follicle count \<5-7; AMH \<0.5-1.1 ng).
• Carriers of androgen receptor polymorphism: between 22 and 24 CAG repeats.
• Body Mass Index (BMI) less than 32.
• Indication for in vitro fertilization.
• Presence of both ovaries.
• Absence of ovarian cysts.
• Absence of endometriosis.
• Normal karyotype and fragile X study.
• Absence of severe male factor.
• Semen sample from ejaculate.
• Ability to comply with the study protocol.
• To have given written consent.

You may not qualify if:

• Non-compliance with instructions or non-formalization of informed consent.
• Concurrent participation in another study.

Sponsors & Collaborators

• Instituto Bernabeu: lead

Study Sites (1)

Instituto Bernabeu

Alicante, Alicante, 03016, Spain

Location

Related Publications (13)

• Barbieri RL, Sluss PM, Powers RD, McShane PM, Vitonis A, Ginsburg E, Cramer DC. Association of body mass index, age, and cigarette smoking with serum testosterone levels in cycling women undergoing in vitro fertilization. Fertil Steril. 2005 Feb;83(2):302-8. doi: 10.1016/j.fertnstert.2004.07.956.

  PMID: 15705366 BACKGROUND

• Bosdou JK, Venetis CA, Dafopoulos K, Zepiridis L, Chatzimeletiou K, Anifandis G, Mitsoli A, Makedos A, Messinis IE, Tarlatzis BC, Kolibianakis EM. Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial. Hum Reprod. 2016 May;31(5):977-85. doi: 10.1093/humrep/dew028. Epub 2016 Mar 7.

  PMID: 26956551 BACKGROUND

• Bosdou JK, Venetis CA, Kolibianakis EM, Toulis KA, Goulis DG, Zepiridis L, Tarlatzis BC. The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update. 2012 Mar-Apr;18(2):127-45. doi: 10.1093/humupd/dmr051. Epub 2012 Feb 3.

  PMID: 22307331 BACKGROUND

• Drakopoulos P, Bardhi E, Boudry L, Vaiarelli A, Makrigiannakis A, Esteves SC, Tournaye H, Blockeel C. Update on the management of poor ovarian response in IVF: the shift from Bologna criteria to the Poseidon concept. Ther Adv Reprod Health. 2020 Jul 31;14:2633494120941480. doi: 10.1177/2633494120941480. eCollection 2020 Jan-Dec.

  PMID: 32844159 BACKGROUND

• Duffy JMN, Bhattacharya S, Bhattacharya S, Bofill M, Collura B, Curtis C, Evers JLH, Giudice LC, Farquharson RG, Franik S, Hickey M, Hull ML, Jordan V, Khalaf Y, Legro RS, Lensen S, Mavrelos D, Mol BW, Niederberger C, Ng EHY, Puscasiu L, Repping S, Sarris I, Showell M, Strandell A, Vail A, van Wely M, Vercoe M, Vuong NL, Wang AY, Wang R, Wilkinson J, Youssef MA, Farquhar CM; Core Outcome Measure for Infertility Trials (COMMIT) initiative. Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study. Fertil Steril. 2021 Jan;115(1):201-212. doi: 10.1016/j.fertnstert.2020.11.013. Epub 2020 Nov 30.

  PMID: 33272619 BACKGROUND

• Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.

  PMID: 21505041 BACKGROUND

• Laisk T, Haller-Kikkatalo K, Laanpere M, Jakovlev U, Peters M, Karro H, Salumets A. Androgen receptor epigenetic variations influence early follicular phase gonadotropin levels. Acta Obstet Gynecol Scand. 2010 Dec;89(12):1557-63. doi: 10.3109/00016349.2010.526182. Epub 2010 Nov 5.

  PMID: 21050150 BACKGROUND

• Lledo B, Llacer J, Ortiz JA, Martinez B, Morales R, Bernabeu R. A pharmacogenetic approach to improve low ovarian response: The role of CAG repeats length in the androgen receptor gene. Eur J Obstet Gynecol Reprod Biol. 2018 Aug;227:41-45. doi: 10.1016/j.ejogrb.2018.06.001. Epub 2018 Jun 4.

  PMID: 29886316 BACKGROUND

• Lledo B, Llacer J, Turienzo A, Ortiz JA, Guerrero J, Morales R, Ten J, Bernabeu R. Androgen receptor CAG repeat length is associated with ovarian reserve but not with ovarian response. Reprod Biomed Online. 2014 Oct;29(4):509-15. doi: 10.1016/j.rbmo.2014.06.012. Epub 2014 Jul 9.

  PMID: 25131556 BACKGROUND

• Lledo B, Ortiz JA, Llacer J, Bernabeu R. Pharmacogenetics of ovarian response. Pharmacogenomics. 2014 Apr;15(6):885-93. doi: 10.2217/pgs.14.49.

  PMID: 24897293 BACKGROUND

• Subira J, Algaba A, Vazquez S, Taroncher Dasi R, Molla Robles G, Monzo Fabuel S, Baydal V, Ruiz Herreros A, Garcia Camunas N, Rubio Rubio JM. Testosterone does not improve ovarian response in Bologna poor responders: a randomized controlled trial (TESTOPRIM). Reprod Biomed Online. 2021 Sep;43(3):466-474. doi: 10.1016/j.rbmo.2021.05.021. Epub 2021 May 30.

  PMID: 34312088 BACKGROUND

• Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.

  PMID: 21558332 BACKGROUND

• Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998 Jun 15;101(12):2622-9. doi: 10.1172/JCI2081.

  PMID: 9637695 BACKGROUND

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: September 30, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)