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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
63
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
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.
The COS starts directly on the second day of the cycle without prior medication.
Hospital Universitario y Politécnico La Fe
Valencia, Spain
Total number of mature oocytes obtained at follicular puncture.
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.
Time frame: 36 hours after induction of ovulation with recombinant HCG.
Number of obtained embryos
Time frame: 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)
Initiation rate
Quotient between the number of patients initiating COS and the total number of patients, overall and in each group
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)
Number of days of stimulation duration
Time frame: 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
Total dose of gonadotrophins used
Time frame: Time I (Day of induction): 10-12 days after controlled ovarian stimulation
Cancellation rate due to lack of ovarian response
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Time frame: 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
Fertilization rate
Time frame: 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
Number of good quality embryos available
Time frame: 48-72 hours after puncture
Number of embryos transferred
Time frame: 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
Ongoing pregnancy rate per cycle started and per transfer
Time frame: 70-75 days after embryo transfer
Clinical pregnancy rate per cycle started and per transfer
Time frame: 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)
Serum hormone levels
Serum hormone levels of FSH, LH, E2, progesterone, testosterone, androstenedione, DHEA, SHBG and FAI
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)