IVF OutcomesNCT07003373
Comparison of Two Protocols in Frozen Embryo Transfer
A study testing hormone replacement therapy (HRT) group in people with IVF Outcomes, run by Malihe Mahmoudinia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 42 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- IVF Outcomes
- What is being tested?
- hormone replacement therapy (HRT) group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- No sites listed yet
- Study dates
- 5 Jul 2025to 5 Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Comparison of the Pregnancy Outcomes of Frozen Embryo Transfer in the Natural Cycle vs. Artificial Cycle
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.
Read the 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.
- Conditions
- IVF Outcomes
- Being tested
- hormone replacement therapy (HRT) group
- Keywords
- Natural cycle, Artificial cycle, Frozen embryo transfer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hormone replacement therapy (HRT) groupDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| natural cycle group | No intervention | 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 |
| Hormone Replacement Therapy (HRT) | Experimental | Not described Receives: Drug: hormone replacement therapy (HRT) group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
presence of gestational sac on ultrasound at 6 weeks
Measured: 6 weeks post-transfer
Chemical pregnancy rate
Positive BHCG test greater than 25 mIU/ml after 12-16 days of embryo transfer
Measured: 12-16 days post embryo transfer
Secondary outcomes (6)
Ongoing Pregnancy Rate
Pregnancy sustained beyond 20 weeks gestation
Measured: At 20 weeks after embryo transfer
Early Miscarriage Rate
loss of a fetus before 12 weeks of gestation
Measured: Up to 12 weeks after embryo transfer
Late Miscarriage Rate
loss of a fetus after 12 weeks and before 24 weeks
Measured: up to 24 weeks gestation
Live Birth Rate
Birth of at least one live neonate after 24 completed weeks of gestation
Measured: At delivery, After 24 weeks gestation
Cycle Cancellation Rate
Proportion of treatment cycles canceled before embryo transfer
Measured: Up to the day of embryo transfer
Pregnancy Complications
Incidence of pregnancy-related complications, including: Preeclampsia: Onset of hypertension after 20 weeks of gestation, Gestational Diabetes, Placental Abruption,Placenta Previa
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2025
- Study start5 Jul 2025 (estimated)
- Primary completion5 Jul 2026 (estimated)
- Study completion5 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for IVF OutcomesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Malihe Mahmoudinia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Malihe Mahmoudinia, Mashhad University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07003373
- Sponsor's protocol ID
- IR.MUMS.IRH.REC.1403.221
- Status last verified
- May 2025
- First submitted
- 25 Apr 2025
- Last updated
- 4 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Pregnancy Outcomes of Frozen Embryo Transfer in the Natural Cycle vs. Artificial Cycle
- ClinicalTrials.gov ID
- NCT07003373
- Acronym / sponsor ID
- IR.MUMS.IRH.REC.1403.221
- Conditions
- IVF Outcomes
- Keywords
- Natural cycle, Artificial cycle, Frozen embryo transfer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Malihe MahmoudiniaUniversity, hospital or other
- Study start
- 5 Jul 2025 (estimated)
- Primary completion
- 5 Jul 2026 (estimated)
- Study completion
- 5 Jul 2026 (estimated)
- First posted
- 4 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| natural cycle group | No intervention | –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 |
| Hormone Replacement Therapy (HRT) | Experimental | Drug: hormone replacement therapy (HRT) group |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hormone replacement therapy (HRT) groupEstradiol 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. | Drug | Hormone Replacement Therapy (HRT) |
Primary outcome
Clinical pregnancy rate
Time frame: 6 weeks post-transfer
presence of gestational sac on ultrasound at 6 weeks
Chemical pregnancy rate
Time frame: 12-16 days post embryo transfer
Positive BHCG test greater than 25 mIU/ml after 12-16 days of embryo transfer
6 secondary outcomes
Ongoing Pregnancy Rate
Time frame: At 20 weeks after embryo transfer
Early Miscarriage Rate
Time frame: Up to 12 weeks after embryo transfer
Late Miscarriage Rate
Time frame: up to 24 weeks gestation
Live Birth Rate
Time frame: At delivery, After 24 weeks gestation
Cycle Cancellation Rate
Time frame: Up to the day of embryo transfer
Pregnancy Complications
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing hormone replacement therapy (HRT) group in people with IVF Outcomes, run by Malihe Mahmoudinia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Malihe Mahmoudinia, Prof (09153047813, mahmoudiniam@mums.ac.ir), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate (time frame: 6 weeks post-transfer). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.