Clinical trial NCT04108039: Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles.
Official title: Suppression of Endogenous Luteinizing Hormone (LH) Surge With Progesterone vs GnRH Antagonist in Freeze-all IVF Cycles. A Prospective Equivalence Study With Repeated Ovarian Stimulation Cycles.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
IVF
Preimplantation Diagnosis
Lead sponsor: Fundacion Dexeus
Sponsor class: OTHER
First posted: 2019-09-27
Enrollment: 44
Sex: FEMALE
Minimum age (years): 36
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 44 women undergoing IVF treatments due to infertility, will be asked to participate in a trial in which they will undergo 2 ovarian stimulation protocols with recombinant follicle stimulating hormone (rFSH): the first one using a flexible antagonist protocol to suppress the endogenous LH rise and the second using oral micronized progesterone 200 mg/day from day 1 of stimulation.
Primary purpose: TREATMENT

Brief summary: To examine whether the number of euploid embryos following ovarian stimulation with micronized progesterone is equivalent as compared with the number of embryos after ovarian stimulation with the use of a GnRH antagonist in patients undergoing ovarian stimulation for IVF or intracytoplasmatic sperm injection (ICSI).

Detailed description: The pre-ovulatory surges of GnRH and LH are activated by increased concentrations of circulating estradiol, but ovulation is blocked when progesterone concentrations are elevated, due to a central inhibition of the GnRH surge. Although traditionally GnRH has been traditionally considered the drug of choice to control endogenous LH in controlled ovarian stimulation (COS) cycles, recently, micronized progesterone has been shown to be an effective oral alternative for preventing premature LH surges during COS in women undergoing IVF/ICSI treatments, with excellent results, whereas their safety during pregnancy is well-established. This novel protocol, has several advantages (good tolerance, user convenience, and cost reduction), that are very attractive when it comes to establishing a convenient user regimen in combination with a ''freeze all'' strategy. However, the comparative efficacy of this novel protocol with the more universal use of GnRH-antagonist protocol for the treatment of IVF patients in terms of embryo ploidy has never been evaluated up to date. The current study aims, for the first time, to examine whether the number of euploid embryos following ovarian stimulation with micronized progesterone is equivalent as compared with the number of embryos after ovarian stimulation with the use of a GnRH antagonist in patients undergoing ovarian stimulation for IVF/ICSI.

If efficacy would prove to be similar, with no impact on the chromosomal constitution of embryos, there will be obvious advantages for the preferential use of micronized progesterone over the antagonist protocol: oral administration is preferred over subcutaneous injection, and total cost of medication would be lower. This would be particularly interesting for the future in all "freeze all" protocols such as women undergoing ovarian stimulation for fertility preservation, preimplantation genetic screening and oocyte donation programs.

Eligibility criteria: Inclusion Criteria:

* Infertile patients
* Age 36-40 years old
* BMI 18-30 kg/m2
* Undergoing preimplantation genetic screening cycles
* Planned to undergo at least two treatment cycles, to accumulate embryos to increase the chance of obtaining euploid embryos for transfer
* Willing to participate in the study

Exclusion Criteria:

* Age\> 41
* Severe male factor requiring TESE (testicular sperm extraction)
* Low ovarian reserve (AMH \< 1.2 ng/ml)
* Administration of any other drug potentially interfering with the treatment.

Primary outcomes:
measure: Number of euploid embryos as compared between the 2 ovarian stimulation cycles
timeFrame: 15-45 days following oocyte retrieval procedure
Secondary outcomes:
measure: Endocrine profile at specific intervals
timeFrame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
measure: Endocrine profile at specific intervals
timeFrame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
measure: Endocrine profile at specific intervals
timeFrame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
measure: Duration of stimulation
timeFrame: 9-20 days from initiation of ovarian stimulation
measure: Incidence of premature LH rise
timeFrame: 9-20 days from initiation of ovarian stimulation
measure: Total dose of gonadotropins
timeFrame: 9-20 days from initiation of ovarian stimulation
measure: Number of mature oocytes
timeFrame: 9-20 days from initiation of ovarian stimulation
measure: Ultrasound ovarian follicles diameter measurement
timeFrame: 9-20 days from initiation of ovarian stimulation
measure: Fertilization rate
timeFrame: 1 day after oocyte retrieval
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Institut Universitari Dexeus
state: Catalunya
Study officials:
References:
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