Transdermal Testosterone Pretreatment in Poor Responders Undergoing IVF

NCT01961336 | Completed Phase 3

• 1 other identifier: UHR-9
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Ιt has been suggested that the accumulation of androgens in the micro milieu of the primate ovary, plays a critical role in early follicular development and granulosa cell proliferation. Increased intraovarian concentration of androgens seems to augment follicle stimulating hormone (FSH) receptor expression in granulosa cells and thus, potentially leading to enhanced responsiveness of ovaries to FSH. In addition, androgen excess has been shown to stimulate early stages of follicular growth and increase the number of pre-antral and antral follicles. On the basis of these data, it has been hypothesized that increasing androgen concentration in the ovarian micro milieu in poorly responding patients might lead to an increase in the number and the maturity of oocytes after ovarian stimulation for IVF. Hence, recent efforts have been focused on the potential benefit of androgen administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF. Pretreatment with transdermal testosterone has been suggested as a safe and effective way of increasing the intraovarian androgen concentration. Recently, published, randomized control trials (RCTs) have evaluated transdermal testosterone in poor responders undergoing ovarian stimulation for IVF, with inconclusive results. In view of the conflicting or inconclusive data regarding the efficacy of the proposed intervention, this study will attempt to explore the role of transdermal testosterone pretreatment in poor responders undergoing IVF through a properly designed RCT. The lack of a universal definition of poor responders has been identified previously and recently, in an attempt to address this issue, universal criteria for the definition of poor ovarian response have been proposed following a consensus meeting in Bologna. In the present study, the Bologna criteria will be used on the contrary to previous studies. Despite the advancement in assisted reproduction technologies, poor ovarian response (POR) is still considered to be one of the most challenging tasks in reproductive medicine. Poor ovarian response is considered to be an inadequate response to ovarian stimulation, defined usually by a low number of oocytes retrieved or a low number of developing follicles in a previous or in the running, respectively, in vitro fertilization (IVF) cycle. Given the severely diminished probability of pregnancy after IVF in these patients, the identification of an indisputably efficacious treatment, such as testosterone pretreatment, would be a promising alternative for poor responders undergoing IVF.

Conditions

Subfertility

Keywords

IVF, poor responder, testosterone

Outcome Measures

Primary Outcomes (1)

• Total number of retrieved oocytes

  36 h after triggering of final oocyte maturation

Secondary Outcomes (2)

• Clinical pregnancy rate (evidence of intrauterine sac with fetal heart activity at 6-8 weeks of gestation)

  At 6-8 weeks of gestation

• Proportion of patients reaching embryo transfer

  2 days following oocyte retrieval

Study Arms (2)

Testosterone

EXPERIMENTAL

Long depot follicular GnRH agonist protocol. On day 21 initiation of ovarian stimulation with recombinant FSH for ICSI. If necessary downregulation will be achieved with additional daily agonist s.c. 10 mg of testosterone gel applied on the external side of the thigh for 21 days starting from the first day of menstruation prior to initiation of ovarian stimulation with rFSH for IVF/ICSI.

Drug: Testosterone

Control

NO INTERVENTION

Long depot follicular GnRH agonist protocol. On day 21 initiation of ovarian stimulation with recombinant FSH for ICSI. If necessary downregulation will be achieved with additional daily agonist s.c.

Interventions

Testosterone DRUG

10 mg of testosterone gel applied on the external side of the thigh for 21 days starting from the first day of menstruation prior to initiation of ovarian stimulation with rFSH for IVF/ICSI

Testosterone

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced maternal age (≥40 years) or any other risk factor for POR
• A previous POR (≤3 oocytes with a conventional stimulation protocol)
• An abnormal ovarian reserve test (i.e. AFC \< 5-7 follicles or AMH \< 0.5- 1.1 ng/ml)

You may not qualify if:

• History of previous ovarian surgery
• Women with endocrine or metabolic disorders
• Women with active cancer disease
• Women with Stage III-IV Endometriosis
• Women with known hypersensitivity or allergy in any of the components of the drug
• Sperm only by ejaculation and not from FNA, TESE or refrigeration

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• University of Thessaly: collaborator

Study Sites (1)

Unit for Human Reproduction, 1st Dept of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki

Thessaloniki, Greece

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Efstratios M Kolibianakis, MD, MSc, PhD

  Unit for Human Reproduction, 1st Dept. of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 11, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 28, 2016

Record last verified: 2016-06

Locations

GR (1)