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NCT Number: NCT07425990

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

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.

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Key information

Conditions

Infertility Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Frozen Embryo Transfer (FET) Genital Diseases Genital Diseases, Female Infertility Infertility, Female Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Specialized Gynecological Hospital "Ferona" Novi Sad

Novi Sad, 21000, Serbia

Location contact

Stevan Milatović, Associate Professor

CONTACT

[email protected]

+38121 3000220

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Letrozole (Aromatase Inhibitors)

Drug

Letrozole 2.5 mg administered orally twice daily from cycle days 3-7 during the early follicular phase.

Choriogonadotropin alpha (r-hCG)

Drug

Recombinant human chorionic gonadotropin (hCG) 250 mcg administered subcutaneously to trigger ovulation when follicular and endometrial criteria are met.

Progesterone

Drug

Luteal phase support with either vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily, initiated after ovulation (or 2 days after hCG trigger) and continued until 12 weeks of gestation if pregnancy occurs.

Primary outcomes

  1. Clinical Pregnancy Rate

    Time frame: Approximately 4-6 weeks after embryo transfer.

    Number of pregnancies with an ultrasound-confirmed gestational sac per embryo transfer.

Secondary outcomes

  1. Biochemical Pregnancy Rate

    Time frame: Two weeks after embryo transfer.

    Number of pregnancies with elevated serum beta-human chorionic gonadotropin (β-hCG) levels measured two weeks after embryo transfer, per embryo transfer.

  2. Implantation Rate

    Time frame: Approximately 4-6 weeks after embryo transfer.

    Number of ultrasound-confirmed gestational sacs divided by the number of embryos transferred.

  3. Miscarriage Rate

    Time frame: Up to 23 weeks of gestation.

    Pregnancy loss before 23 completed weeks of gestation, expressed per embryo transfer.

Study contacts

Contact information is provided by the study sponsor or research team.

Jelena Vukovic, MD

CONTACT

[email protected]

+381643070647

Sponsors and collaborators

Lead sponsor

University of Novi Sad

Other

Registry information

Official study title

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

Acronym: FET-LET-2x2

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Feb 23, 2026
Registry last updated
Feb 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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