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

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ClinicalTrials.gov Identifier: NCT03378713
Recruitment Status : Recruiting
First Posted : December 20, 2017
Last Update Posted : August 13, 2018
Sponsor:
Information provided by (Responsible Party):
Instituto de Investigacion Sanitaria La Fe

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.

Condition or disease Intervention/treatment Phase
Infertility, Female Drug: GROUP 1: Long testosterone Drug: GROUP 2: Short testosterone Drug: GROUP 3: Control Phase 3

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  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Clinical Effect of Follicular Preparation With Testosterone in Poor Ovarian Response: a Randomized Controlled Clinical Trial (TESTOPRIM)
Actual Study Start Date : August 7, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : January 7, 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of obtained embryos [ Time Frame: 6 days after ovarian puncture. ]
  2. 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) ]
  3. 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

  4. Number of days of stimulation duration [ Time Frame: Time P (time of follicular puncture): 36 hours after the induction ]
  5. Number of total follicles and greater than 16 mm [ Time Frame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation ]
  6. Total dose of gonadotrophins used [ Time Frame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation ]
  7. Cancellation rate due to lack of ovarian response [ Time Frame: Time C: 10-12 days after controlled ovarian stimulation ]
  8. Number of cumulus-oocyte complexes recovered on day of follicular puncture [ Time Frame: Time P (time of follicular puncture): 36 hours after the induction ]
  9. Fertilization rate [ Time Frame: 24 hours after the puncture ]
  10. Rate of cycles that achieve embryo transfer [ Time Frame: Time ET ( day of embryo transfer): 4-5 days after the stimulation ]
  11. Number of good quality embryos available [ Time Frame: 48-72 hours after puncture ]
  12. Number of embryos transferred [ Time Frame: Time ET (day of embryo transfer): 4-5 days after the stimulation ]
  13. Number of cycles with supernumerary embryos to freeze [ Time Frame: 6 days after embryo transfer ]
  14. Ongoing pregnancy rate per cycle started and per transfer [ Time Frame: 70-75 days after embryo transfer ]
  15. Clinical pregnancy rate per cycle started and per transfer [ Time Frame: 30-35 days after embryo transfer ]
  16. Miscarriage rate [ Time Frame: At 11-13 weeks of pregnancy, if there is no previous news of the patient (Trial completion time) ]
  17. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   the trial treats female infertility
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03378713


Contacts
Contact: Maria Cortell 0034961246611 investigacion_clinica@iislafe.es

Locations
Spain
Hospital Universitario y Politécnico La Fe Recruiting
Valencia, Spain, 46026
Contact: Maria Cortell    0034961246611    investigacion_clinica@iislafe.es   
Sponsors and Collaborators
Instituto de Investigacion Sanitaria La Fe
Investigators
Principal Investigator: Jessica Subirá Hospital Universitari i Politècnic La Fe, Valencia, Spain

Publications:

Responsible Party: Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier: NCT03378713     History of Changes
Other Study ID Numbers: TESTOPRIM
First Posted: December 20, 2017    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Instituto de Investigacion Sanitaria La Fe:
Poor Ovarian Response

Additional relevant MeSH terms:
Infertility, Female
Infertility
Genital Diseases, Male
Genital Diseases, Female
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents