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

Instituto de Investigacion Sanitaria La Fe

Status and phase: Completed; Phase 3

Conditions: Infertility, Female

Treatments: Drug: GROUP 2: Short testosterone; Drug: GROUP 3: Control; Drug: GROUP 1: Long testosterone

Study type: Interventional

Funder types: Other

Identifiers

NCT03378713

TESTOPRIM

Details and patient eligibility

About

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.

Full 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.

Enrollment: 63 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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63 participants in 3 patient groups

GROUP 1: Long testosterone

Experimental group

Description:

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.

Treatment:

Drug: GROUP 1: Long testosterone

GROUP 2: Short testosterone

Active Comparator group

Description:

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.

Treatment:

Drug: GROUP 2: Short testosterone

GROUP 3: Control

Active Comparator group

Description:

The COS starts directly on the second day of the cycle without prior medication.

Treatment:

Drug: GROUP 3: Control