FET-LET-2x2: Clinical Pregnancy Rates After Frozen Embryo Transfer in Natural and Modified Natural Cycles

FET-LET-2x2: A Randomized Open-Label 2×2 Factorial Trial Comparing Clinical Pregnancy Rates After Frozen Embryo Transfer in True and Modified Natural Cycles With and Without Aromatase Inhibitors

The goal of this clinical trial is to learn whether different natural approaches to preparing the uterus for frozen embryo transfer (FET) can improve pregnancy success in women undergoing in vitro fertilization (IVF) treatment.

The main questions it aims to answer are:

1. Is a completely natural menstrual cycle more successful than a natural cycle in which ovulation is triggered with medication when preparing for frozen embryo transfer?
2. Does taking a medication called letrozole at the beginning of the cycle improve pregnancy success compared to not taking it?

Researchers will compare four different approaches to see which one results in the highest chance of achieving a clinical pregnancy, confirmed by ultrasound.

Participants will:

• Be randomly assigned to one of four groups
• Undergo monitoring with ultrasound and blood hormone tests during their menstrual cycle
• In some groups, take letrozole tablets for a few days early in the cycle
• In some groups, receive a hormone injection to help control the timing of ovulation
• Undergo frozen embryo transfer at the appropriate time
• Receive standard hormonal support after embryo transfer
• Researchers will compare four different approaches to see which one results in the highest chance of achieving a clinical pregnancy, confirmed by ultrasound.

Inclusion Criteria:

• Women aged 18 to 40 years
• Regular menstrual cycles (26-35 days)
• Scheduled for frozen embryo transfer (FET) in a natural menstrual cycle
• Normal gynecological ultrasound findings without clinically significant uterine abnormalities
• Ability to provide written informed consent

Exclusion Criteria:

• Use of preimplantation genetic testing (PGT) for the transferred embryo
• Use of donor oocytes
• Inadequate embryo survival after thawing, defined as loss of viability in more than 50% of blastomeres
• Irregular menstrual cycles
• Presence of clinically significant uterine abnormalities detected by ultrasound
• Inability or unwillingness to provide written informed consent