Clinical trial NCT03378713: Clinical Trial to Assess the Effect of Testosterone in Patients With Poor Ovarian Response (TESTOPRIM)
Official title: Clinical Effect of Follicular Preparation With Testosterone in Poor Ovarian Response: a Randomized Controlled Clinical Trial (TESTOPRIM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility, Female
Keywords: Poor Ovarian Response
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
First posted: 2017-12-20
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Total number of mature oocytes obtained at follicular puncture.
timeFrame: 36 hours after induction of ovulation with recombinant HCG.
Secondary outcomes:
measure: Number of obtained embryos
timeFrame: 6 days after ovarian puncture.
measure: Number of antral follicles at the start of stimulation
timeFrame: Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)
measure: Initiation rate
timeFrame: Time E: prior to controlled ovarian stimulation (at the beginning of the third cycle after inclusion and randomization, approximately 56 days after Day 0)
measure: Number of days of stimulation duration
timeFrame: Time P (time of follicular puncture): 36 hours after the induction
measure: Number of total follicles and greater than 16 mm
timeFrame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation
measure: Total dose of gonadotrophins used
timeFrame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation
measure: Cancellation rate due to lack of ovarian response
timeFrame: Time C: 10-12 days after controlled ovarian stimulation
measure: Number of cumulus-oocyte complexes recovered on day of follicular puncture
timeFrame: Time P (time of follicular puncture): 36 hours after the induction
measure: Fertilization rate
timeFrame: 24 hours after the puncture
measure: Rate of cycles that achieve embryo transfer
timeFrame: Time ET ( day of embryo transfer): 4-5 days after the stimulation
measure: Number of good quality embryos available
timeFrame: 48-72 hours after puncture
measure: Number of embryos transferred
timeFrame: Time ET (day of embryo transfer): 4-5 days after the stimulation
measure: Number of cycles with supernumerary embryos to freeze
timeFrame: 6 days after embryo transfer
measure: Ongoing pregnancy rate per cycle started and per transfer
timeFrame: 70-75 days after embryo transfer
measure: Clinical pregnancy rate per cycle started and per transfer
timeFrame: 30-35 days after embryo transfer
measure: Miscarriage rate
timeFrame: At 11-13 weeks of pregnancy, if there is no previous news of the patient (Trial completion time)
measure: Serum hormone levels
timeFrame: 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)
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Hospital Universitari i Politècnic La Fe, Valencia, Spain
name: Jessica Subirá
role: PRINCIPAL_INVESTIGATOR
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