Clinical trial NCT07003373: Comparison of Two Protocols in Frozen Embryo Transfer
Official title: Comparison of the Pregnancy Outcomes of Frozen Embryo Transfer in the Natural Cycle vs. Artificial Cycle
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: IVF Outcomes
Keywords: Natural cycle
Artificial cycle
Frozen embryo transfer
Lead sponsor: Mashhad University of Medical Sciences
Sponsor class: OTHER
First posted: 2025-06-04
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized clinical trial evaluates two different endometrial preparation protocols-hormone replacement therapy (HRT) and natural cycle-for frozen embryo transfer (FET) in infertile women undergoing assisted reproductive technology (ART). The goal is to compare implantation, clinical pregnancy, and ongoing pregnancy outcomes.

Detailed description: This prospective, randomized controlled clinical trial is conducted on women aged 18 to 42 years undergoing frozen embryo transfer (FET) during in vitro fertilization (IVF) cycles. Eligible participants meet the inclusion criteria and provide written informed consent.

Participants are randomized into two groups using a permuted block method:

HRT Group (Control): Estradiol valerate is initiated at 4 mg/day on day 2 of the menstrual cycle and is adjusted to 8 mg/day based on endometrial thickness. Once the endometrial thickness reaches ≥8 mm, progesterone supplementation is started (400 mg vaginal suppositories twice daily and 50 mg intramuscular injections daily) for 5 days before blastocyst transfer.

Natural Cycle Group: A transvaginal ultrasound is performed on cycle day 2 or 3 to rule out ovarian cysts and confirm an endometrial thickness \<5 mm. If eligible, patients are monitored from day 8 onward. Ovulation is tracked by assessing dominant follicle growth (≥15 mm), LH surge (≥17 IU/L), and serum progesterone (\>1.5 ng/mL). Once ovulation is confirmed and endometrial thickness reaches ≥7 mm, FET is scheduled for 6 days post-LH surge or 5 days post-follicle collapse. Serum progesterone is measured one day before transfer; if \<10 ng/mL, 400 mg/day progesterone is administered.

Embryos are cultured in Blastocyst medium (Origio, Denmark) and assessed daily. High-quality embryos (Grade A) are defined by a 4-cell stage on day 2, a 7-8 cell stage on day 3, uniform cell size, and \<20% fragmentation. Blastocyst grading follows Gardner's criteria. One or two top-quality embryos are transferred using a Cook catheter under abdominal ultrasound guidance. If no blastocyst is available by day 5, the most advanced embryo is transferred.

Eligibility criteria: Inclusion Criteria:

Regular menstrual cycles

Maternal age between 18 and 42 years

Normal intrauterine cavity confirmed by pretreatment ultrasound or hysteroscopy

Body Mass Index (BMI) less than 30 kg/m²

No ovulation disorders

Exclusion Criteria:

No embryos available for transfer (no embryo thawing)

Withdrawal of patient consent to continue treatment

Failure of dominant follicle development (in natural cycle group)

Inadequate endometrial response for transfer

No endometriosis grade 3 or higher

The participant provided written informed consent

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: 6 weeks post-transfer
measure: Chemical pregnancy rate
timeFrame: 12-16 days post embryo transfer
Secondary outcomes:
measure: Ongoing Pregnancy Rate
timeFrame: At 20 weeks after embryo transfer
measure: Early Miscarriage Rate
timeFrame: Up to 12 weeks after embryo transfer
measure: Late Miscarriage Rate
timeFrame: up to 24 weeks gestation
measure: Live Birth Rate
timeFrame: At delivery, After 24 weeks gestation
measure: Cycle Cancellation Rate
timeFrame: Up to the day of embryo transfer
measure: Pregnancy Complications
timeFrame: through study completion, an average of 1 year
Other outcomes:
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