TRAP Study: Testosterone for Androgen Receptor Polymorphism

Fertility Disorders Clinical Trial

— TRAP  

Official title:

Transdermal Testosterone Pretreatment in Poor Responders With Androgen Receptor Polymorphism Undergoing ICSI: A Randomized Clinical Investigation.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06195163
• Other study ID #: IBMR46
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 30, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: December 2023
• Source: Instituto Bernabeu
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 31, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Patients with low ovarian reserve according to Bologna criteria: at least two of the following three:

1. Age equal to or greater than 40 years.

2. Previous cycle with less than 4 oocytes retrieved.

3. 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.

Exclusion Criteria:

• Non-compliance with instructions or non-formalization of informed consent.

• Concurrent participation in another study.

Related Conditions & MeSH terms

• Fertility Disorders

Intervention

Drug:
• Transdermal Gel in Sachet Dosage Form
Transdermal testosterone gel application prior to ovarian stimulation in the study group.
• No pretreatment
No pretreatment prior to the ovarian stimulation in the control group.

Locations

Country	Name	City	State
Spain	Instituto Bernabeu	Alicante

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Bernabeu

Country where clinical trial is conducted

Spain, 

References & 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. — View Citation

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 R — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)