Letrozole-stimulated Cycle Strategy Versus Artificial Cycle Strategy (LETSACT)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-42
SponsorMỹ Đức Hospital
About this trial
The goal of this randomized clinical trial is to evaluate the effectiveness of the letrozole-stimulated cycle strategy versus the artificial cycle strategy for endometrial preparation in women with irregular menstrual cycles after one cycle of endometrial preparation. The primary question it aims to answer is:
• Does the letrozole-stimulated cycle strategy for endometrial preparation result in a higher live birth rate compared to the artificial cycle strategy in women with irregular menstrual cycles after one cycle of endometrial preparation?
Participants will undergo screening before endometrial preparation for frozen embryo transfer, following which they will be randomly assigned to one of two groups: LETS or AC. In the LETS group, investigators will prescribe letrozole 5 milligrams/day for 5 days to stimulate follicular development and micronized progesterone 800 milligrams/day for luteal phase support. In contrast, the AC group will receive oral estradiol valerate 6-12 milligrams/day and micronized progesterone 800 milligrams/day. Researchers will compare the LETS and AC groups to determine if there are differences in live birth rates.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Aged between 18 - 42.
Irregular menstrual cycle (< 21 days or > 35 days or < 8 cycles/years).
Indicated for endometrial preparation.
Transfer of only one blastocyst.
Disqualifiers
Allergy to letrozole or Ovitrelle or oral estradiol valerate or micronized progesterone
Having embryos from either oocyte donation or PGT (pre-implantation genetics testings) cycles.
Ovarian cysts that are unrelated to the oocyte pick-up.
Confirmed diagnosis with recurrent pregnancy loss (RPL) according to ESHRE guideline 2023, recurrent implantation failure (RIF) according to ESHRE 2023 good practice recommendations.
Trial design
Design model
Parallel
Treatments tested in this trial
Letrozole-stimulated cycle strategy
Procedure/SurgeryLetrozole (Femara® 2.5 milligrams, Novartis, Switzerland or Lezra® 2.5 milligrams, Actavis, Rumani) 5 milligrams/day for 5 days, starting on the second to fourth day of the menstrual cycle. Post-letrozole, ultrasound checks follicle growth. If ≥18mm, Ovitrelle® 250 mcg (Merck, Kenilworth, New Jersey, USA) induces ovulation. Luteal phase support with vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day starting two days post-hCG. Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: no follicle development on day 21 from the day of starting letrozole, spontaneous ovulation, letrozole intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome.
Artificial cycle strategy
Procedure/SurgeryOral estradiol valerate (Progynova® 2 milligrams, Bayer Pharma AG, Germany or Valiera® 2 milligrams, Laboratories Recalcine, Chile) 6 milligrams/day for 10 days, starting on the second to fourth day of the menstrual cycle. Post-estradiol, ultrasound checks endometrial thickness. If ≥7mm, start vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day. If \<7mm, increase the dose of oral estradiol valerate to 8 milligrams/day (5-6 days) and 12 milligrams/day (5-6 days). Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: endometrial thickness \<7mm on day 21 of using estradiol, spontaneous ovulation, oral estradiol valerate intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome.
Treatment groups
790 Participants
are divided into 2 treatment groupsGroup A: Letrozole-stimulated cycle strategy (LETS)Active comparator 1 intervention
Group B: Artificial cycle strategy (AC)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Live birth rate after one cycle of endometrial preparation
Live birth will be defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is atached. A birth weight of 500 grams or more can be used if gestational age is unknown. Twin and higher multiple births will be reported as a single live birth event.
Time frame
After 22 completed weeks of gestational age.Secondary outcomes
1
Positive pregnancy test after one cycle of endometrial preparation
Defined as serum human chorionic gonadotropin level greater than 25 mIU/mL.
Time frame
At 11 days after blastocyst transfer.2
Clinical pregnancy after one cycle of endometrial preparation
Diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy at 6 weeks or more after the onset of last menstrual period. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy.
Time frame
First ultrasound before 6 weeks of gestational age.3
Ongoing pregnancy after one cycle of endometrial preparation
Defined as pregnancy with a detectable heart rate at 12 weeks gestation or beyond.
Time frame
After 12 weeks of gestational age.4
Multiple pregnancy after one cycle of endometrial preparation
Defined as the presence of more than one gestational sac at early pregnancy ultrasound (6-9 weeks gestation) (Hecher and Diehl, 2009).
Time frame
Ultrasound at 6-9 weeks of gestational age.Sponsors and contacts
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Source ClinicalTrials.gov