Does luteal support improve outcomes in modified natural-cycle frozen embryo transfer?

Is There a Need for Luteal Support in Modified Natural Cycle Frozen Embryo Transfer Cycles: a Prospective, Multicenter, Randomized Trial

This will test whether adding progesterone (with or without hCG) during a modified natural-cycle frozen embryo transfer helps people aged 18–40 with a good frozen blastocyst get pregnant.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: Dunamenti REK Istenhegyi IVF Center (Academic / other)
• Locations: 5 sites (Budapest, Budapest and 4 other locations)
• Trial ID: NCT06875752 on ClinicalTrials.gov

What this trial studies

This is a randomized controlled trial comparing three approaches for modified natural-cycle frozen embryo transfer: no luteal support, vaginal progesterone, and progesterone plus hCG. Eligible participants planning a single good-quality blastocyst transfer are randomized and undergo a modified natural FET protocol with monitoring of follicle development. Primary outcomes include implantation and clinical pregnancy rates, with follow-up for pregnancy continuation and likely live birth. The trial is conducted at several IVF centers in Hungary and uses standard inclusion/exclusion criteria to select participants.

Who should consider this trial

Good fit: Ideal candidates are people aged 18–40 with BMI 18–35 kg/m2, a regular 21–35 day cycle, at least one good-quality frozen blastocyst, planning a single blastocyst transfer, and an intact uterine cavity.

Not a fit: Patients unlikely to benefit include those outside the age or BMI ranges, with irregular cycles, no spontaneous dominant follicle development, recurrent miscarriage, hydrosalpinx, active HIV/hepatitis infection, or those planning multiple embryo transfers.

Why it matters

Potential benefit: If successful, adding luteal support could increase implantation and live birth rates for people undergoing modified natural-cycle FET.

How similar studies have performed: Previous studies on luteal support in frozen embryo transfer have shown mixed results, with stronger evidence in stimulated or artificial cycles but inconclusive data specifically for modified natural cycles.

Eligibility criteria

Inclusion Criteria:

* Age 18-40 years at the time of vitrification
* At least one good quality blastocyst frozen
* Planned 1 blastocyst transfer
* \<3 failed previous ETs
* Cycle length between 21-35 days
* Body mass index (BMI): 18-35 kg/m2
* Intact uterine cavity based on hysteroscopy, hysteron-salpingogram, salina sonohysterogram
* Consent to participate

Exclusion Criteria:

* Age \<18 of over 40 at the time of vitrification
* BMI: \<18 kg/m2 or \>35 kg/m2
* Planned transfer of more than 1 embryo
* Irregular cycles (\<21 or \>35 days)
* Use of a protocol other than the modified natural cycle frozen embryo transfer
* Lack of good morphology blastocysts
* No evidence for spontaneous follicle development (no dominant (\>17 mm) follicle by day 20 of cycle)
* Patient with a history of recurrent miscarriages
* Presence of a hydrosalpinx
* Irregular uterine cavity
* Positive test for HIV, hepatitis B or C
* Lack of consent

Where this trial is running

Budapest, Budapest and 4 other locations

• Dunamenti REK Istenhegyi IVF Center — Budapest, Budapest, Hungary (Recruiting)
• Dunamenti REK Gyor IVF Center — Győr, Gyor, Hungary (Recruiting)
• University of Pecs, Dept. OBGYN, Reproductive Center — Pécs, Pecs, Hungary (Recruiting)
• University of Szeged, Reproductive Medicine Institute — Szeged, Szeged, Hungary (Recruiting)
• Dunamenti REK Tapolca IVF Center — Tapolca, Tapolca, Hungary (Recruiting)

Study contacts

• Study coordinator: Peter Kovacs MD medical director Dunamenti REK Istenhegyi IVF Center, MD, PhD

Conditions Luteal Support; Frozen Embryo Transfer; luteal support; frozen embryo transfer; progesterone; modified natural cycle