Transdermal Testosterone Pretreatment in Poor Responders Undergoing IVF

NCT ID: NCT01961336

Last Updated: 2016-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Testosterone

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.

Group Type: EXPERIMENTAL

Testosterone

Intervention Type: 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

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Testosterone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 25 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Thessaly

OTHER

Sponsor Role: collaborator

Aristotle University Of Thessaloniki

OTHER

Sponsor Role: lead

Responsible Party

E.M. Kolibianakis

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Efstratios M Kolibianakis, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Thessaloniki, , Greece

Countries

Greece

References

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.

Reference Type: DERIVED

PMID: 26956551 (View on PubMed)

Other Identifiers

UHR-9

Identifier Type: -

Identifier Source: org_study_id