Frozen Embryo Transfer (FET)COPSNCT07461909
Comparison of Two Vaginal Progesterone Forms in Frozen Embryo Transfer
An observational study of Frozen Embryo Transfer (FET) and Infertility, run by Instituto Valenciano de Infertilidade de Lisboa at 1 site in Portugal.
Trial summary
The goal of this observational study is to compare two commonly used vaginal progesterone formulations - soft capsules versus pessaries - in women undergoing frozen embryo transfer (FET). Read more about this study
- Who is it for?
- Ages 18 to 48 years, women only
- Conditions the study is for
- Frozen Embryo Transfer (FET), Infertility, Artificial Cycle
- What is being tested?
- Vaginal progesterone soft capsules and Vaginal progesterone pessaries
- Type of treatment
- Pill or oral medicine
- How many people
- 400 participants
- Where
- 1 sitePortugal
- Study dates
- 8 Nov 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 48 years
- Women only
- No healthy volunteers
- Adult
Study population: The study population consists of women aged 18 to 48 years undergoing frozen embryo transfer (FET) at IVI Lisboa. Eligible participants must have a BMI between 18.5 and <30 kg/m², be scheduled for a single blastocyst-stage transfer, and be prescribed vaginal progesterone for luteal phase support, either soft capsules (400 mg every 12 hours) or pessaries (400 mg every 12 hours). Both artificial cycle (AC-FET) and natural proliferative phase (NPP-FET) protocols are included. The study population reflects real-world patients receiving routine clinical care.
Who may be able to join
- Age: ≥18 and <49 years old;
- Body Mass Index (BMI) ≥18.5 Kg/m2 and <30 Kg/m2;
- Planned for single blastocyst stage transfer;
- Has been prescribed two vaginal 200mg soft capsules or one 400mg pessary of progesterone, each 12hours before and after FET;
- Either AC-FET or NPP-FET.
Who cannot join
- Women who have previously enrolled in this study;
- Those unable to comprehend the investigational nature of the proposed study;
- Rank of FET>3;
- Use of oral/injectable corticoids.
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 (IVI Lisboa)
Lisbon, 1800-282
Samuel Ribeiro, +351 218 503 210, Samuel.Ribeiro@ivirma.com
About this study
Official title: Comparison of Patient Satisfaction, Convenience and Tolerability Between Two Vaginal Progesterone Formulations During Frozen Embryo Transfer
The goal of this observational study is to compare two commonly used vaginal progesterone formulations - soft capsules versus pessaries - in women undergoing frozen embryo transfer (FET). The main question it aims to answer is:
- Do soft vaginal progesterone capsules provide similar or better patient satisfaction, convenience, and tolerability compared with vaginal progesterone pessaries during preparation for frozen embryo transfer?
Participants undergoing FET who are prescribed vaginal progesterone as part of their endometrial preparation and luteal phase support will use one of the two formulations and complete patient-reported assessments regarding satisfaction, convenience, and tolerability. The study will also measure serum progesterone levels on the day of embryo transfer and evaluate pregnancy outcomes, including clinical pregnancy and live birth rates.
Read the detailed description
Over the past few decades, assisted reproductive technology (ART) treatments have seen their protocols updated by advances in cryopreservation methods, leading to the mainstream use of the frozen embryo transfer (FET) strategy (Nagy, Shapiro, \& Chang, 2020). FET protocols are generally subdivided in either natural cycle (NC-FET) or artificial cycle (AC-FET), with several centers preferring the latter due to its flexibility in scheduling and ease of monitoring. Nonetheless, previous reports positing that AC-FET may be associated with an increased risk of miscarriage and hypertensive disorders during pregnancy have put this preference into question (Roelens, et al., 2022). Having said that, the natural proliferative phase frozen embryo transfer protocol (NPP-FET) has recently be proposed as a strategy which potentially allows for easier cycle scheduling while potentially maintaining the benefits of the natural cycle in terms of safer pregnancy outcomes (Godinho, Soares, \& Ribeiro, 2021). Both AC-FET and NPP-FET protocols rely immensely on the use exogenous progesterone for luteal phase support (LPS), with the vaginal route being the most common in Europe due to its ease of use compared to intramuscular or subcutaneous alternatives.
Progesterone is a natural hormone produced mainly by the theca cells of the corpus luteum. When supplemented vaginally, endometrial progesterone concentrations reach a steady-state within 5 hours after administration, while serum progesterone levels remain elevated for about 48 hours with prolonged bioavailability (Bulletti, et al., 1997). In a systematic review of 18 randomized clinical trials comparing vaginal preparations for LPS, all tested preparations seemed to be equally effective and safe for assisted reproductive technology cycles (Child, Leonard, Evans, \& Lass, 2018). However, studies assessing patient satisfaction are lacking (Beltsos, et al., 2014). Hence, the main objective of this study is to assess the level of satisfaction as well as understand the convenience and tolerability of two of the most common vaginal LPS formulations (soft capsules versus pessaries). The study will compare satisfaction levels, convenience and tolerability, serum progesterone levels on the FET day and pregnancy rates between the two therapeutic formulations.
- Being tested
- Vaginal progesterone soft capsules, Vaginal progesterone pessaries
- Keywords
- Progesterone, Natural cycle, Natural proliferative phase (NPP-FET), Artificial cycle (AC-FET), Patient satisfaction, Frozen embryo transfer, Assisted reproduction, Endometrial preparation, Treatment tolerability
- Medical subject headings
- Infertility, Patient Satisfaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal progesterone soft capsulesOther
Whenever the endometrium is above 7 mm and serum progesterone is determined and if <1.5ng/ml, vaginal micronized progesterone soft capsules is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (two 200 mg soft capsules). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient.
Vaginal progesterone pessariesOther
Whenever the endometrium is above 7 mm and serum progesterone is determined and if <1.5ng/ml, vaginal progesterone pessaries is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (one 400 mg pessary). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - vaginal progesterone soft capsules | Women undergoing FET who receive soft vaginal progesterone capsules (micronized progesterone 200 mg x 2 capsules every 12 h = 400 mg/12h) for endometrial preparation/luteal support as per routine care. Receives: Other: Vaginal progesterone soft capsules | |
| Cohort 2 - vaginal provesterone pessaries (ovules) | Women undergoing FET who receive vaginal progesterone pessaries (400 mg x 1 pessary every 12 h) for endometrial preparation/luteal support as per routine care. Receives: Other: Vaginal progesterone pessaries |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the patients' satisfaction, convenience and tolerability of two common vaginal progesterone formulations: soft capsules versus pessaries
Satisfaction levels, convenience and tolerability will be collected using a GDPR compliant online survey tool, filled by participants
Measured: 5 days after starting progesterone supplementation
Secondary outcomes (3)
Serum Progesterone(P4) level
Serum P4 levels collected via blood sample (as standard of care)
Measured: 5 days after starting progesterone supplementation
Clinical pregnancy rates
Clinical pregnancy confirmation at 7 - 8 weeks gestational age, via transvaginal ultrasound
Measured: 7 - 8 weeks of gestational age
Livebirth rates
Live birth rate, defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age
Measured: Livebirth after 22 completed weeks of gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start8 Nov 2024
- Primary completionAug 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 Transfer (FET)Studies 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
- Prospective
- Enrolment
- 400 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
- Samuel Ribeiro, Principal investigator, Instituto Valenciano de Infertilidade de Lisboa (IVI Lisboa)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07461909
- Sponsor's protocol ID
- 2306-LIS-122-SS
- Acronym
- COPS
- Status last verified
- Mar 2026
- First submitted
- 18 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Patient Satisfaction, Convenience and Tolerability Between Two Vaginal Progesterone Formulations During Frozen Embryo Transfer
- ClinicalTrials.gov ID
- NCT07461909
- Acronym / sponsor ID
- COPS / 2306-LIS-122-SS
- Keywords
- Progesterone, Natural cycle, Natural proliferative phase (NPP-FET), Artificial cycle (AC-FET), Patient satisfaction, Frozen embryo transfer, Assisted reproduction, Endometrial preparation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Instituto Valenciano de Infertilidade de LisboaResearch network
- Collaborators
- Gedeon Richter Ltd.
- Study start
- 8 Nov 2024 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 Mar 2026 (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.
The goal of this observational study is to compare two commonly used vaginal progesterone formulations - soft capsules versus pessaries - in women undergoing frozen embryo transfer (FET). The main question it aims to answer is:
- Do soft vaginal progesterone capsules provide similar or better patient satisfaction, convenience, and tolerability compared with vaginal progesterone pessaries during preparation for frozen embryo transfer?
Participants undergoing FET who are prescribed vaginal progesterone as part of their endometrial preparation and luteal phase support will use one of the two formulations and complete patient-reported assessments regarding satisfaction, convenience, and tolerability. The study will also measure serum progesterone levels on the day of embryo transfer and evaluate pregnancy outcomes, including clinical pregnancy and live birth rates.
Detailed description
Over the past few decades, assisted reproductive technology (ART) treatments have seen their protocols updated by advances in cryopreservation methods, leading to the mainstream use of the frozen embryo transfer (FET) strategy (Nagy, Shapiro, \& Chang, 2020). FET protocols are generally subdivided in either natural cycle (NC-FET) or artificial cycle (AC-FET), with several centers preferring the latter due to its flexibility in scheduling and ease of monitoring. Nonetheless, previous reports positing that AC-FET may be associated with an increased risk of miscarriage and hypertensive disorders during pregnancy have put this preference into question (Roelens, et al., 2022). Having said that, the natural proliferative phase frozen embryo transfer protocol (NPP-FET) has recently be proposed as a strategy which potentially allows for easier cycle scheduling while potentially maintaining the benefits of the natural cycle in terms of safer pregnancy outcomes (Godinho, Soares, \& Ribeiro, 2021). Both AC-FET and NPP-FET protocols rely immensely on the use exogenous progesterone for luteal phase support (LPS), with the vaginal route being the most common in Europe due to its ease of use compared to intramuscular or subcutaneous alternatives.
Progesterone is a natural hormone produced mainly by the theca cells of the corpus luteum. When supplemented vaginally, endometrial progesterone concentrations reach a steady-state within 5 hours after administration, while serum progesterone levels remain elevated for about 48 hours with prolonged bioavailability (Bulletti, et al., 1997). In a systematic review of 18 randomized clinical trials comparing vaginal preparations for LPS, all tested preparations seemed to be equally effective and safe for assisted reproductive technology cycles (Child, Leonard, Evans, \& Lass, 2018). However, studies assessing patient satisfaction are lacking (Beltsos, et al., 2014). Hence, the main objective of this study is to assess the level of satisfaction as well as understand the convenience and tolerability of two of the most common vaginal LPS formulations (soft capsules versus pessaries). The study will compare satisfaction levels, convenience and tolerability, serum progesterone levels on the FET day and pregnancy rates between the two therapeutic formulations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - vaginal progesterone soft capsules | – | Other: Vaginal progesterone soft capsulesWomen undergoing FET who receive soft vaginal progesterone capsules (micronized progesterone 200 mg x 2 capsules every 12 h = 400 mg/12h) for endometrial preparation/luteal support as per routine care. |
| Cohort 2 - vaginal provesterone pessaries (ovules) | – | Other: Vaginal progesterone pessariesWomen undergoing FET who receive vaginal progesterone pessaries (400 mg x 1 pessary every 12 h) for endometrial preparation/luteal support as per routine care. |
Who may qualify
- Ages
- 18 to 48 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study population consists of women aged 18 to 48 years undergoing frozen embryo transfer (FET) at IVI Lisboa. Eligible participants must have a BMI between 18.5 and <30 kg/m², be scheduled for a single blastocyst-stage transfer, and be prescribed vaginal progesterone for luteal phase support, either soft capsules (400 mg every 12 hours) or pessaries (400 mg every 12 hours). Both artificial cycle (AC-FET) and natural proliferative phase (NPP-FET) protocols are included. The study population reflects real-world patients receiving routine clinical care.
Key inclusion criteria (5 listed)
- Age: ≥18 and <49 years old;
- Body Mass Index (BMI) ≥18.5 Kg/m2 and <30 Kg/m2;
- Planned for single blastocyst stage transfer;
- Has been prescribed two vaginal 200mg soft capsules or one 400mg pessary of progesterone, each 12hours before and after FET;
- Either AC-FET or NPP-FET.
Key exclusion criteria (4 listed)
- Women who have previously enrolled in this study;
- Those unable to comprehend the investigational nature of the proposed study;
- Rank of FET>3;
- Use of oral/injectable corticoids.
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 |
|---|---|---|
| Vaginal progesterone soft capsulesWhenever the endometrium is above 7 mm and serum progesterone is determined and if <1.5ng/ml, vaginal micronized progesterone soft capsules is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (two 200 mg soft capsules). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient. | Other | Cohort 1 - vaginal progesterone soft capsules |
| Vaginal progesterone pessariesWhenever the endometrium is above 7 mm and serum progesterone is determined and if <1.5ng/ml, vaginal progesterone pessaries is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (one 400 mg pessary). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient. | Other | Cohort 2 - vaginal provesterone pessaries (ovules) |
Primary outcome
Compare the patients' satisfaction, convenience and tolerability of two common vaginal progesterone formulations: soft capsules versus pessaries
Time frame: 5 days after starting progesterone supplementation
Satisfaction levels, convenience and tolerability will be collected using a GDPR compliant online survey tool, filled by participants
3 secondary outcomes
Serum Progesterone(P4) level
Time frame: 5 days after starting progesterone supplementation
Clinical pregnancy rates
Time frame: 7 - 8 weeks of gestational age
Livebirth rates
Time frame: Livebirth after 22 completed weeks of gestational age
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 10 Mar 2026.
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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.
Samuel Ribeiro principal investigator
Instituto Valenciano de Infertilidade de Lisboa (IVI 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 (FET) and Infertility, 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 5 inclusion and 4 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 10 Mar 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 Samuel Ribeiro (+351 218503210, Samuel.Ribeiro@ivirma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare the patients' satisfaction, convenience and tolerability of two common vaginal progesterone formulations: soft capsules versus pessaries (time frame: 5 days after starting progesterone supplementation). 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 10 Mar 2026.