SubfertilityPhase 3NCT01961336
Transdermal Testosterone Pretreatment in Poor Responders Undergoing IVF
A Phase 3 study testing Testosterone in people with Subfertility, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 years and older, women only
- Conditions the study is for
- Subfertility
- What is being tested?
- Testosterone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteGreece
- Study dates
- Oct 2013to Jun 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Greece1 site
Unit for Human Reproduction, 1st Dept of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki
Thessaloniki
About this study
Official title: The Effect of Transdermal Testosterone Pretreatment in Poor Responders Undergoing Ovarian Stimulation for In-vitro Fertilization (IVF)
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.
Read more
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
- Being tested
- Testosterone
- Keywords
- IVF, poor responder, testosterone
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of retrieved oocytes
Measured: 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)
Measured: At 6-8 weeks of gestation
Proportion of patients reaching embryo transfer
Measured: 2 days following oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Collaborators
- University of Thessaly
- Responsible party
- Principal investigator, E.M. Kolibianakis, Aristotle University Of Thessaloniki
- Investigators
- Efstratios M Kolibianakis, MD, MSc, PhD, Principal investigator, Unit for Human Reproduction, 1st Dept. of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961336
- Sponsor's protocol ID
- UHR-9
- Status last verified
- Jun 2016
- First submitted
- 10 Oct 2013
- Last updated
- 28 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26956551
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Transdermal Testosterone Pretreatment in Poor Responders Undergoing Ovarian Stimulation for In-vitro Fertilization (IVF)
- ClinicalTrials.gov ID
- NCT01961336
- Acronym / sponsor ID
- UHR-9
- Conditions
- Subfertility
- Keywords
- IVF, poor responder, testosterone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Collaborators
- University of Thessaly
- Study start
- Oct 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 11 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone | Experimental | Drug: TestosteroneLong 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. |
| 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. |
Who may qualify
- Ages
- 25 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Testosterone10 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 |
Primary outcome
Total number of retrieved oocytes
Time frame: 36 h after triggering of final oocyte maturation
2 secondary outcomes
Clinical pregnancy rate (evidence of intrauterine sac with fetal heart activity at 6-8 weeks of gestation)
Time frame: At 6-8 weeks of gestation
Proportion of patients reaching embryo transfer
Time frame: 2 days following oocyte retrieval
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2016.
- Derived from this study: PubMed 26956551Bosdou 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Efstratios M Kolibianakis, MD, MSc, PhD principal investigator
Unit for Human Reproduction, 1st Dept. of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Testosterone in people with Subfertility, run by Aristotle University Of Thessaloniki at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total number of retrieved oocytes (time frame: 36 h after triggering of final oocyte maturation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01961336, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2016.