IVF Outcomes
Conditions
Keywords
Natural cycle, Artificial cycle, Frozen embryo transfer
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.
Interventions
DRUGhormone replacement therapy (HRT) group
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.
Sponsors
Malihe Mahmoudinia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rate | 6 weeks post-transfer | presence of gestational sac on ultrasound at 6 weeks |
| Chemical pregnancy rate | 12-16 days post embryo transfer | Positive BHCG test greater than 25 mIU/ml after 12-16 days of embryo transfer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Late Miscarriage Rate | up to 24 weeks gestation | loss of a fetus after 12 weeks and before 24 weeks |
| Live Birth Rate | At delivery, After 24 weeks gestation | Birth of at least one live neonate after 24 completed weeks of gestation |
| Ongoing Pregnancy Rate | At 20 weeks after embryo transfer | Pregnancy sustained beyond 20 weeks gestation |
| Pregnancy Complications | through study completion, an average of 1 year | Incidence of pregnancy-related complications, including: Preeclampsia: Onset of hypertension after 20 weeks of gestation, Gestational Diabetes, Placental Abruption,Placenta Previa |
| Cycle Cancellation Rate | Up to the day of embryo transfer | Proportion of treatment cycles canceled before embryo transfer |
| Early Miscarriage Rate | Up to 12 weeks after embryo transfer | loss of a fetus before 12 weeks of gestation |
Contacts
Primary ContactMalihe Mahmoudinia, Prof
Outcome results
None listed