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

August 12, 2019 updated by: Instituto de Investigacion Sanitaria La Fe

Clinical Effect of Follicular Preparation With Testosterone in Poor Ovarian Response: a Randomized Controlled Clinical Trial (TESTOPRIM)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

POR is a challenge for reproductive medicine because of its impact on treatment outcomes and the lack of sufficiently proven therapeutic tools. According to recent publications based on retrospective studies of large registries, there is a correlation between the number of oocytes and LBR (live birth rate), so the investigators consider that variable mature oocytes are a reasonable compromise and a solid substitute for other outcome variables such as LBR or CPR (clinical pregnancy rate).

Regarding the duration of treatment, the investigators decided to include two groups of testosterone treatment (compared to the control group) with different duration. One will explore the role of testosterone in prolonged treatments (two full menstrual cycles). The other will test the pattern most commonly used in most studies, that is, testosterone in luteal phase of the previous cycle (about 10 days in short protocol with GnRH antagonist). In this way the investigators will establish an absolute comparison with the control group and relative between both treatment groups (long testosterone vs. short testosterone) to determine if / which of the two regimen (the two, only one or none) improves the number of mature oocytes recovered.

The product under investigation is testosterone gel, transdermal administration, 50 mg / single dose (Testim®, Ferring, Madrid, Spain). Regarding the dose, the investigators decided to keep the most used in the rest of studies (12.5 mg / day).

This study population will include only patients diagnosed with POR based on ESHRE Bologna criteria, in order to homogenize the population and allow comparisons with other studies in the future.

Regarding the dose, the investigators decided to keep the most used in the rest of studies (12.5 mg/day) which so far has been the only one proven effective. It is clearly possible that lower and more physiological doses are equally effective, but this yet has to be proven in well-designed studies. The gel is self-administered by the patients who are adequately instructed by a research nurse.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valencia, Spain, 46026
        • Hospital Universitario y Politecnico La Fe

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  • Patients who have received androgen treatment within 3 months prior to inclusion in the study.
  • BMI> 35 kg / m2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: GROUP 1: Long testosterone
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
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
ACTIVE_COMPARATOR: GROUP 2: Short testosterone
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
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.
ACTIVE_COMPARATOR: GROUP 3: Control
The COS starts directly on the second day of the cycle without prior medication.
Drug: GROUP 3: Control
The COS starts directly on the second day of the cycle without prior medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of mature oocytes obtained at follicular puncture.
Time Frame: 36 hours after induction of ovulation with recombinant HCG.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of obtained embryos
Time Frame: 6 days after ovarian puncture.
6 days after ovarian puncture.
Number of antral follicles at the start of stimulation
Time Frame: Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)
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 Frame: Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)
Quotient between the number of patients initiating COS and the total number of patients, overall and in each group
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 Frame: Time P (time of follicular puncture): 36 hours after the induction
Time P (time of follicular puncture): 36 hours after the induction
Number of total follicles and greater than 16 mm
Time Frame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation
Time I (Day of induction): 10-12 days after controlled ovarian stimulation
Total dose of gonadotrophins used
Time Frame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation
Time I (Day of induction): 10-12 days after controlled ovarian stimulation
Cancellation rate due to lack of ovarian response
Time Frame: Time C: 10-12 days after controlled ovarian stimulation
Time C: 10-12 days after controlled ovarian stimulation
Number of cumulus-oocyte complexes recovered on day of follicular puncture
Time Frame: Time P (time of follicular puncture): 36 hours after the induction
Time P (time of follicular puncture): 36 hours after the induction
Fertilization rate
Time Frame: 24 hours after the puncture
24 hours after the puncture
Rate of cycles that achieve embryo transfer
Time Frame: Time ET ( day of embryo transfer): 4-5 days after the stimulation
Time ET ( day of embryo transfer): 4-5 days after the stimulation
Number of good quality embryos available
Time Frame: 48-72 hours after puncture
48-72 hours after puncture
Number of embryos transferred
Time Frame: Time ET (day of embryo transfer): 4-5 days after the stimulation
Time ET (day of embryo transfer): 4-5 days after the stimulation
Number of cycles with supernumerary embryos to freeze
Time Frame: 6 days after embryo transfer
6 days after embryo transfer
Ongoing pregnancy rate per cycle started and per transfer
Time Frame: 70-75 days after embryo transfer
70-75 days after embryo transfer
Clinical pregnancy rate per cycle started and per transfer
Time Frame: 30-35 days after embryo transfer
30-35 days after embryo transfer
Miscarriage rate
Time Frame: At 11-13 weeks of pregnancy, if there is no previous news of the patient (Trial completion time)
At 11-13 weeks of pregnancy, if there is no previous news of the patient (Trial completion time)
Serum hormone levels
Time Frame: Day 0; Time I (day of induction): 10-12 days after controlled ovarian stimulation; and Time E (prior to controlled ovarian stimulation: at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)
Serum hormone levels of FSH, LH, E2, progesterone, testosterone, androstenedione, DHEA, SHBG and FAI
Day 0; Time I (day of induction): 10-12 days after controlled ovarian stimulation; and Time E (prior to controlled ovarian stimulation: at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigacion Sanitaria La Fe

Investigators

  • Principal Investigator: Jessica Subirá, Hospital Universitari i Politècnic La Fe, Valencia, Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 7, 2017

Primary Completion (ACTUAL)

February 11, 2019

Study Completion (ACTUAL)

February 11, 2019

Study Registration Dates

First Submitted

November 30, 2017

First Submitted That Met QC Criteria

December 14, 2017

First Posted (ACTUAL)

December 20, 2017

Study Record Updates

Last Update Posted (ACTUAL)

August 13, 2019

Last Update Submitted That Met QC Criteria

August 12, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TESTOPRIM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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