Frozen Embryo TransferNCT06307184
Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer
An observational study of Frozen Embryo Transfer, run by Instituto Valenciano de Infertilidade de Lisboa at 1 site in Portugal.
Trial summary
This study will assess the convenience of the natural proliferative phase frozen embryo transfer (NPP-FET) in terms of number of number of appointments needed before cycle scheduling. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women only
- Conditions the study is for
- Frozen Embryo Transfer
- What is being tested?
- Natural proliferative phase frozen embryo transfer
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 530 participants
- Where
- 1 sitePortugal
- Study dates
- 23 Feb 2024to Dec 2026
- Phase
- Observational
- 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 49 years
- Women only
- No healthy volunteers
- Adult
Study population: The study group will include a prospectively recruited cohort of ovulatory patients undergoing their first or second FET attempt following oocyte donation in a natural proliferative phase protocol. The control group will include a retrospective cohort of ovulatory patients undergoing a natural cycle frozen embryo transfer following oocyte donation.
Who may be able to join
- Endometrial thickness ≥ 7 mm on the day of starting progesterone-based luteal phase support (LPS)
- Serum progesterone levels <1.5 ng/ml on the day of starting progesterone-based LPS
- LPS with micronized progesterone 400mg b.i.d.
- Regular cycles (>24 days, ≤ 38 days)
- IVF/ICSI with donated oocytes
- Single blastocyst stage embryo transfer
- First or second embryo transfer from the same cohort
Who cannot join
- Use of exogenous ovarian stimulation during FET
- Untreated hydrosalpinx, polyp, submucous myomas or severe adenomyosis
- Recurrent pregnancy loss (≥ 3 previous pregnancy losses)
- Recurrent implantation failure with embryos from oocyte donation (≥ 3 previous failed embryo transfers)
- Personalized initiation of exogenous progesterone according to a previous endometrial receptivity assay test
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal1 site, 1 recruiting
- Recruiting
Instituto Valenciano de Infertilidade
Lisbon
Samuel Santos-Ribeiro, MD PhD
About this study
Official title: Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer: an Ambispective Cohort Study
This study will assess the convenience of the natural proliferative phase frozen embryo transfer (NPP-FET) in terms of number of number of appointments needed before cycle scheduling.
Read the detailed description
Frozen embryo transfer (FET) is increasingly used nowadays in Assisted Reproductive Techniques (ART) clinics. Several factors account for this uprising. Among them, the concept of ovarian hyperstimulation syndrome (OHSS)-free clinic, the increasing use of preimplantation genetic testing (PGT), the improved vitrification systems, and the growing evidence regarding similar, or even better, pregnancy rates when FET are compared to fresh embryo transfers.
In the last few years, research has focused on the selection of the best protocol for endometrial preparation in patients undergoing FET cycles. Despite the accumulating evidence suggesting similar reproductive outcomes following both artificial cycle (AC-FET) and natural cycle (NC-FET) protocols, AC-FET is frequently adopted in ART centers due to its convenience in terms of cycle scheduling. However, a role for the corpus luteum in the maternal vasodilatory changes of early pregnancy has recently been associated with a decreased risk of pre-eclampsia. In fact, several large cohort studies have reported a higher risk of hypertensive diseases of pregnancy, macrosomia, post-term delivery and cesarean section following AC-FET.
The NPP-FET protocol is a strategy that potentially allows for cycle scheduling while maintaining the benefits of the natural cycle in terms of pregnancy outcomes. The main goal of the present study is to analyze its convenience in terms of the number of appointments needed before FET scheduling by comparing it with the NC-FET protocol. Additionally, the investigators aim to compare the reproductive outcomes between the two strategies and to analyze whether NPP-FET patients undergo ovulation.
Briefly, the study group will prospectively recruit ovulatory patients who will perform vaginal ultrasound monitoring will be performed on cycle day 8-12, depending on the length of the patients' menstrual cycle. When the endometrial thickness is at least 7 mm and the dominant follicle is at least 13 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. The control group will include a retrospective cohort of ovulatory patients who underwent NC-FET.
- Conditions
- Frozen Embryo Transfer
- Being tested
- Natural proliferative phase frozen embryo transfer
- Keywords
- Endometrial preparation, Natural cycle, Progesterone, Pregnancy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Natural proliferative phase frozen embryo transferProcedure or surgery
When endometrial thickness is above 7 mm, vaginal micronized progesterone will be administered 400mg 12/12h when the dominant follicle is at least 13 mm, serum estradiol (E2) levels are >80 pg/ml, and serum progesterone levels are <1.5ng/ml. Embryo transfer will be performed on the fifth day of progesterone.
| Study group | Role | What they receive |
|---|---|---|
| Natural proliferative phase frozen embryo transfer (NPP-FET) | When the endometrial thickness is at least 7 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours, as per standard clinical practice, when the dominant follicle is at least 13 mm, serum estradiol (E2) levels are >80 pg/ml, and serum progesterone levels are <1.5ng/ml. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. Progesterone will be continued until the 11th week of pregnancy. Receives: Procedure: Natural proliferative phase frozen embryo transfer | |
| Natural cycle frozen embryo transfer (NC-FET) | When the mean dominant follicle diameter was at least 17 mm and the endometrial thickness was at least 7 mm, serum E2, progesterone and luteinizing hormone (LH) were evaluated. If a spontaneously LH peak was detected (E2>80 pg/ml, LH peak >18 mIU/mL with progesterone level <1.5 ng/mL), vaginal micronized progesterone was started from the evening of ovulation at a dose of 200 mg every 12 hours. Conversely, whenever a LH peak was not detected (E2>80 pg/ml, LH <18mIU/ml and progesterone <1,5 ng/ml), r-hCG 250µg (Ovitrelle®) was administered subcutaneously, followed, 48 hours later, by daily administration of 200 mg micronized vaginal progesterone every 12 hours. One embryo was transferred 7 days after r-hCG administration or 6 days after LH peak detection. Progesterone was continued until the 8th week of pregnancy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of appointments needed before cycle scheduling
Number of visits for cycle monitoring until embryo transfer scheduling
Measured: Up to three weeks
Secondary outcomes (6)
Cycle duration until embryo transfer (days)
Number of days since the first day of menstrual bleeding until the day of embryo transfer
Measured: Up to four weeks
Proportion of patients with low progesterone values on the day of embryo transfer
Percentage of patients with low serum progesterone levels on the day of embryo transfer
Measured: One day
Human corionic gonadotropin (hCG) positive rate
Proportion of patients with a positive hCG test
Measured: 10-14 days after ET
Miscarriage rate
Proportion of patients with spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age
Measured: Up to 20 weeks after ET
Ongoing pregnancy rate
Proportion of patients with a pregnancy beyond the 11th week
Measured: 9-11 weeks after ET
Live birth rate
Proportion of patients with a live birth
Measured: 40 weeks after ET
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start23 Feb 2024
- Primary completionSep 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frozen Embryo TransferStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 530 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Valenciano de Infertilidade de Lisboa
- Sponsor type
- Research network
- Collaborators
- Gedeon Richter Ltd.
- Responsible party
- Sponsor
- Investigators
- Ana R Neves, MP, Principal investigator, Instutito Valenciano de Infertilidade de Lisboa (IVI-RMA Lisboa)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06307184
- Sponsor's protocol ID
- 2301-LIS-007-AN
- Status last verified
- May 2025
- First submitted
- 17 Feb 2024
- Last updated
- 23 Feb 2026
- 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 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer: an Ambispective Cohort Study
- ClinicalTrials.gov ID
- NCT06307184
- Acronym / sponsor ID
- 2301-LIS-007-AN
- Conditions
- Frozen Embryo Transfer
- Keywords
- Endometrial preparation, Natural cycle, Progesterone, Pregnancy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 530 participants (estimated)
- Lead sponsor
- Instituto Valenciano de Infertilidade de LisboaResearch network
- Collaborators
- Gedeon Richter Ltd.
- Study start
- 23 Feb 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Mar 2024 (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 study will assess the convenience of the natural proliferative phase frozen embryo transfer (NPP-FET) in terms of number of number of appointments needed before cycle scheduling.
Detailed description
Frozen embryo transfer (FET) is increasingly used nowadays in Assisted Reproductive Techniques (ART) clinics. Several factors account for this uprising. Among them, the concept of ovarian hyperstimulation syndrome (OHSS)-free clinic, the increasing use of preimplantation genetic testing (PGT), the improved vitrification systems, and the growing evidence regarding similar, or even better, pregnancy rates when FET are compared to fresh embryo transfers.
In the last few years, research has focused on the selection of the best protocol for endometrial preparation in patients undergoing FET cycles. Despite the accumulating evidence suggesting similar reproductive outcomes following both artificial cycle (AC-FET) and natural cycle (NC-FET) protocols, AC-FET is frequently adopted in ART centers due to its convenience in terms of cycle scheduling. However, a role for the corpus luteum in the maternal vasodilatory changes of early pregnancy has recently been associated with a decreased risk of pre-eclampsia. In fact, several large cohort studies have reported a higher risk of hypertensive diseases of pregnancy, macrosomia, post-term delivery and cesarean section following AC-FET.
The NPP-FET protocol is a strategy that potentially allows for cycle scheduling while maintaining the benefits of the natural cycle in terms of pregnancy outcomes. The main goal of the present study is to analyze its convenience in terms of the number of appointments needed before FET scheduling by comparing it with the NC-FET protocol. Additionally, the investigators aim to compare the reproductive outcomes between the two strategies and to analyze whether NPP-FET patients undergo ovulation.
Briefly, the study group will prospectively recruit ovulatory patients who will perform vaginal ultrasound monitoring will be performed on cycle day 8-12, depending on the length of the patients' menstrual cycle. When the endometrial thickness is at least 7 mm and the dominant follicle is at least 13 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. The control group will include a retrospective cohort of ovulatory patients who underwent NC-FET.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Natural proliferative phase frozen embryo transfer (NPP-FET) | – | Procedure: Natural proliferative phase frozen embryo transferWhen the endometrial thickness is at least 7 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours, as per standard clinical practice, when the dominant follicle is at least 13 mm, serum estradiol (E2) levels are >80 pg/ml, and serum progesterone levels are <1.5ng/ml. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. Progesterone will be continued until the 11th week of pregnancy. |
| Natural cycle frozen embryo transfer (NC-FET) | – | –When the mean dominant follicle diameter was at least 17 mm and the endometrial thickness was at least 7 mm, serum E2, progesterone and luteinizing hormone (LH) were evaluated. If a spontaneously LH peak was detected (E2>80 pg/ml, LH peak >18 mIU/mL with progesterone level <1.5 ng/mL), vaginal micronized progesterone was started from the evening of ovulation at a dose of 200 mg every 12 hours. Conversely, whenever a LH peak was not detected (E2>80 pg/ml, LH <18mIU/ml and progesterone <1,5 ng/ml), r-hCG 250µg (Ovitrelle®) was administered subcutaneously, followed, 48 hours later, by daily administration of 200 mg micronized vaginal progesterone every 12 hours. One embryo was transferred 7 days after r-hCG administration or 6 days after LH peak detection. Progesterone was continued until the 8th week of pregnancy. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study group will include a prospectively recruited cohort of ovulatory patients undergoing their first or second FET attempt following oocyte donation in a natural proliferative phase protocol. The control group will include a retrospective cohort of ovulatory patients undergoing a natural cycle frozen embryo transfer following oocyte donation.
Key inclusion criteria (7 listed)
- Endometrial thickness ≥ 7 mm on the day of starting progesterone-based luteal phase support (LPS)
- Serum progesterone levels <1.5 ng/ml on the day of starting progesterone-based LPS
- LPS with micronized progesterone 400mg b.i.d.
- Regular cycles (>24 days, ≤ 38 days)
- IVF/ICSI with donated oocytes
Key exclusion criteria (5 listed)
- Use of exogenous ovarian stimulation during FET
- Untreated hydrosalpinx, polyp, submucous myomas or severe adenomyosis
- Recurrent pregnancy loss (≥ 3 previous pregnancy losses)
- Recurrent implantation failure with embryos from oocyte donation (≥ 3 previous failed embryo transfers)
- Personalized initiation of exogenous progesterone according to a previous endometrial receptivity assay test
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 |
|---|---|---|
| Natural proliferative phase frozen embryo transferWhen endometrial thickness is above 7 mm, vaginal micronized progesterone will be administered 400mg 12/12h when the dominant follicle is at least 13 mm, serum estradiol (E2) levels are >80 pg/ml, and serum progesterone levels are <1.5ng/ml. Embryo transfer will be performed on the fifth day of progesterone. | Procedure or surgery | Natural proliferative phase frozen embryo transfer (NPP-FET) |
Primary outcome
Number of appointments needed before cycle scheduling
Time frame: Up to three weeks
Number of visits for cycle monitoring until embryo transfer scheduling
6 secondary outcomes
Cycle duration until embryo transfer (days)
Time frame: Up to four weeks
Proportion of patients with low progesterone values on the day of embryo transfer
Time frame: One day
Human corionic gonadotropin (hCG) positive rate
Time frame: 10-14 days after ET
Miscarriage rate
Time frame: Up to 20 weeks after ET
Ongoing pregnancy rate
Time frame: 9-11 weeks after ET
Live birth rate
Time frame: 40 weeks after ET
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 23 Feb 2026.
- 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.
Ana R Neves, MP principal investigator
Instutito Valenciano de Infertilidade de Lisboa (IVI-RMA Lisboa)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Frozen Embryo Transfer, run by Instituto Valenciano de Infertilidade de Lisboa at 1 site in Portugal.
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 7 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Ana R Neves, MD, PhD (218 503 210 ext. 00351, ana.neves@ivirma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of appointments needed before cycle scheduling (time frame: Up to three weeks). 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 23 Feb 2026.