Clinical Trial to Assess the Effect of Testosterone in Patients With Poor Ovarian Response (TESTOPRIM)

NCT03378713 | Completed Phase 3

• 1 other identifier: TESTOPRIM
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Trial to determine the absolute and relative efficacy of two follicular preparation regimens with transdermal testosterone during the cycle (s) prior to the initiation of COS (controlled ovarian stimulation) in patients diagnosed with POR (poor ovarian response) for the increase in the number of mature oocytes recovered.

Conditions

Infertility, Female

Keywords

Poor Ovarian Response

Outcome Measures

Primary Outcomes (1)

• Total number of mature oocytes obtained at follicular puncture.

  Determining whether a Follicular preparation with transdermal testosterone increases the number of mature oocytes retrieved in patients diagnosed with Poor Ovarian Response and which testosterone administration regimen is more effective for this purpose.

  36 hours after induction of ovulation with recombinant HCG.

Secondary Outcomes (17)

• Number of obtained embryos

  6 days after ovarian puncture.

• Number of antral follicles at the start of stimulation

  Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)

• Initiation rate

  Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)

• Number of days of stimulation duration

  Time P (time of follicular puncture): 36 hours after the induction

• Number of total follicles and greater than 16 mm

  Time I (Day of induction): 10-12 days after controlled ovarian stimulation

Study Arms (3)

GROUP 1: Long testosterone

EXPERIMENTAL

Application of testosterone in transdermal gel during the 2 cycles prior to initiation of controlled ovarian stimulation and until the onset of second menstruation (approximately 56 days). The COS begins the day after the last testosterone application.

Drug: GROUP 1: Long testosterone

GROUP 2: Short testosterone

ACTIVE COMPARATOR

Application of testosterone in transdermal gel begins on day 21 of menstrual cycle, from the luteal phase of the cycle prior to initiation of controlled ovarian stimulation and until menstruation (approximately 10 days). The COS begins the day after the last testosterone application.

Drug: GROUP 2: Short testosterone

GROUP 3: Control

ACTIVE COMPARATOR

The COS starts directly on the second day of the cycle without prior medication.

Drug: GROUP 3: Control

Interventions

GROUP 1: Long testosterone DRUG

Application of testosterone in transdermal gel during the 2 cycles prior to initiation of controlled ovarian stimulation and until the onset of second menstruation (approximately 56 days). The COS begins the day after the last testosterone application

GROUP 1: Long testosterone

GROUP 2: Short testosterone DRUG

Application of testosterone in transdermal gel begins on day 21 of menstrual cycle, from the luteal phase of the cycle prior to initiation of controlled ovarian stimulation and until menstruation (approximately 10 days). The COS begins the day after the last testosterone application.

GROUP 2: Short testosterone

GROUP 3: Control DRUG

The COS starts directly on the second day of the cycle without prior medication.

GROUP 3: Control

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: the trial treats female infertility
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed consent prior to the completion of any procedure related to the clinical trial.
• Female older than 18 years old at the time of randomization.
• Prior diagnosis of poor ovarian response (POR) according to ESHRE Bologna criteria. Patients must meet at least 2 of the following:
• Advanced maternal age (40 years or more) or any other risk factor for POR.
• A previous POR (3 oocytes or less) with a conventional ovarian stimulation protocol.
• Abnormal ovarian reserve test (RFA \<5-7 or AMH 3.3-7.9 pmol / l).

You may not qualify if:

• Presence of uterine malformations, corrected or not.
• Presence of uterine pathology defined as submucous myomas or endometrial polyps, documented by transvaginal ultrasound.
• Couples with severe male factor defined as REM \<1 or azoospermia.
• Hydrosalpinx unilateral or bilateral uncorrected.
• Perimenopausal patients with irregular menstrual cycles.
• Concurrent untreated endocrine disorders.
• Patients who have participated in a clinical trial in a period of less than one month.
• Known allergy to the drug.
• BMI\> 35 kg / m2

Sponsors & Collaborators

• Instituto de Investigacion Sanitaria La Fe: lead

Study Sites (1)

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Related Publications (27)

• Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update. 2003 Jan-Feb;9(1):61-76. doi: 10.1093/humupd/dmg007.

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• Gorgy A, Naumann N, Bates S, Craft IL. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol. 1997 Dec;104(12):1420-1. doi: 10.1111/j.1471-0528.1997.tb11020.x. No abstract available.

  PMID: 9422028 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

• Kyrou D, Kolibianakis EM, Venetis CA, Papanikolaou EG, Bontis J, Tarlatzis BC. How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2009 Mar;91(3):749-66. doi: 10.1016/j.fertnstert.2007.12.077. Epub 2008 Jul 21.

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• Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S. Interventions for 'poor responders' to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010 Jan 20;(1):CD004379. doi: 10.1002/14651858.CD004379.pub3.

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• Jeve YB, Bhandari HM. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis. J Hum Reprod Sci. 2016 Apr-Jun;9(2):70-81. doi: 10.4103/0974-1208.183515.

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• Bastu E, Buyru F, Ozsurmeli M, Demiral I, Dogan M, Yeh J. A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response. Eur J Obstet Gynecol Reprod Biol. 2016 Aug;203:30-4. doi: 10.1016/j.ejogrb.2016.05.027. Epub 2016 May 24.

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• Ertzeid G, Storeng R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod. 2001 Feb;16(2):221-5. doi: 10.1093/humrep/16.2.221.

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• Van der Auwera I, D'Hooghe T. Superovulation of female mice delays embryonic and fetal development. Hum Reprod. 2001 Jun;16(6):1237-43. doi: 10.1093/humrep/16.6.1237.

  PMID: 11387298 BACKGROUND

• Baker VL, Brown MB, Luke B, Smith GW, Ireland JJ. Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. Fertil Steril. 2015 Nov;104(5):1145-52.e1-5. doi: 10.1016/j.fertnstert.2015.07.1151. Epub 2015 Aug 18.

  PMID: 26297646 BACKGROUND

• Escriva AM, Diaz-Garcia C, Monterde M, Rubio JM, Pellicer A. Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM). J Clin Endocrinol Metab. 2015 Jul;100(7):2597-605. doi: 10.1210/jc.2015-1194. Epub 2015 May 8.

  PMID: 25955224 BACKGROUND

• Fanchin R, Cunha-Filho JS, Schonauer LM, Kadoch IJ, Cohen-Bacri P, Frydman R. Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens. Fertil Steril. 2003 Feb;79(2):316-21. doi: 10.1016/s0015-0282(02)04574-0.

  PMID: 12568840 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

• Massin N, Cedrin-Durnerin I, Coussieu C, Galey-Fontaine J, Wolf JP, Hugues JN. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study. Hum Reprod. 2006 May;21(5):1204-11. doi: 10.1093/humrep/dei481. Epub 2006 Feb 13.

  PMID: 16476678 BACKGROUND

• Balasch J, Fabregues F, Penarrubia J, Carmona F, Casamitjana R, Creus M, Manau D, Casals G, Vanrell JA. Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poor-responder IVF patients with normal basal concentrations of FSH. Hum Reprod. 2006 Jul;21(7):1884-93. doi: 10.1093/humrep/del052. Epub 2006 Mar 3.

  PMID: 16517559 BACKGROUND

• Fabregues F, Penarrubia J, Creus M, Manau D, Casals G, Carmona F, Balasch J. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod. 2009 Feb;24(2):349-59. doi: 10.1093/humrep/den428. Epub 2008 Dec 3.

  PMID: 19054777 BACKGROUND

• Kim CH, Howles CM, Lee HA. The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders. Fertil Steril. 2011 Feb;95(2):679-83. doi: 10.1016/j.fertnstert.2010.07.1077.

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• Kim CH, Ahn JW, Moon JW, Kim SH, Chae HD, Kang BM. Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders. Dev Reprod. 2014 Sep;18(3):145-52. doi: 10.12717/DR.2014.18.3.145.

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• 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

• 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.

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• Fooladi E, Reuter SE, Bell RJ, Robinson PJ, Davis SR. Pharmacokinetics of a transdermal testosterone cream in healthy postmenopausal women. Menopause. 2015 Jan;22(1):44-9. doi: 10.1097/GME.0000000000000259.

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• National Collaborating Centre for Women's and Children's Health (UK). Fertility: Assessment and Treatment for People with Fertility Problems. London: Royal College of Obstetricians & Gynaecologists; 2013 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK247932/

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MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Officials

• Jessica Subirá

  Hospital Universitari i Politècnic La Fe, Valencia, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 20, 2017
• Study Start: August 7, 2017
• Primary Completion: February 11, 2019
• Study Completion: February 11, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-02

Locations

ES (1)