Embryo TransferPhase 4NAFTNCT03642665
Natural Versus Artificial Cycle for Frozen-Thawed Embryo Transfer
A Phase 4 study testing Natural cycle, Estradiol Valerate and Micronized progesterone in people with Embryo Transfer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
This study evaluates clinical pregnancy rates, obstetrical outcome parameters, costs and patient preferences in natural cycle versus artificial cycle frozen embryo transfers (FET). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Embryo Transfer
- What is being tested?
- Natural cycle, Estradiol Valerate and Micronized progesterone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 554 participants
- Where
- 1 siteBelgium
- Study dates
- 25 Sep 2018to 1 Nov 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women undergoing FET after a first, second or third fresh IVF/ICSI cycle
- Single embryo transfer (SET) or Double embryo transfer (DET)
- Female age between 18-45 year
- Women having a natural ovulatory cycle (24-35 days)
- Normal uterine cavity (fundal indentation at the cavity <10mm)
- Written informed consent
Who cannot join
- Use of donor gametes
- BMI > or equal to 35 kg / m2
- Any contra-indication to estrogen or progesterone supplementation (e.g. history of thrombosis, prior or current hormone-sensitive malignancy…)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Frozen-thawed Embryo Transfer in a Natural Versus Artificial Cycle: a Randomized Clinical Trial
This study evaluates clinical pregnancy rates, obstetrical outcome parameters, costs and patient preferences in natural cycle versus artificial cycle frozen embryo transfers (FET).
Read the detailed description
Transfer of cryopreserved embryos can be performed in a natural cycle (NC-FET) or in an artificially prepared cycle (AC-FET). Both cycle regimens have their advantages and disadvantages. So far, most comparative studies have failed to identify the optimal protocol for FET. In this study patients undergoing FET will be randomized between an endometrial preparation by a natural cycle or by an artificial cycle (by oestradiol validate and micronized progesterone).
- Conditions
- Embryo Transfer
- Being tested
- Natural cycle, Estradiol Valerate, Micronized progesterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Natural cycleDrug
no medication
Estradiol ValerateDrug
Also called Artificial cycle
Oestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy.
Micronized progesteroneDrug
Also called Artificial cycle
Micronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| Natural cycle | Experimental | no medication Receives: Drug: Natural cycle |
| Artificial cycle | Active comparator | Oestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy.
Micronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. Receives: Drug: Estradiol Valerate; Drug: Micronized progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate with fetal heart beat
Clinical pregnancy rate with fetal heart beat diagnosed by ultrasound no later than the gestational age of 9 weeks
Measured: 9 weeks
Secondary outcomes (12)
Biochemical pregnancy rate
Measured: 9 weeks
Miscarriage rate
Measured: 12 weeks
Ectopic pregnancy rate
Measured: 9 weeks
Live birth rate
Measured: 41 weeks
Multiple pregnancy rate
Measured: 9 weeks
Adverse events
tombo-embolic events, serious side-effects (car leaflet) which require cancellation of treatment
Measured: 12 weeks
Cycle cancellation rate
Measured: 4 weeks
Endometrial thickness
Measured: 3 weeks
Endometrial pattern
Sonographic aspect of the endometrium (triple-line, no triple-line)
Measured: 3 weeks
number of center visits to monitor FET cycle
Measured: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
cost analysis per treatment cycle
Measured: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
patient satisfaction
To evaluate the effect of the different regimens on patients wellbeing/distress, Patient Reported Experience Measures (PREMS) from validated questionnaires will be used. Twenty-two questions from the Benyamini questionnaire will be used (Benyamini et al. 2005) and 10 questions from the subscales 'environment' (α=0.81) and 'tolerability' (α=0.75) of the FertilQol questionnaire (Pedro et al 2013). On the day of embryo transfer, the treating gynecologist will hand out the questionnaire to the patient. The patient will return the filled-in questionnaire on the day of the pregnancy test, before she knows the result of the pregnancy test.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start25 Sep 2018
- Primary completion1 Nov 2024
- Study completion1 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Embryo TransferStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter prospective randomized clinical trial
- Masking
- None (open label)
- Enrolment
- 554 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- GZA Ziekenhuizen Campus Sint-Augustinus, Imelda Hospital, Bonheiden, Jessa Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03642665
- Sponsor's protocol ID
- S61372
- Acronym
- NAFT
- Status last verified
- Feb 2024
- First submitted
- 17 Jul 2018
- Last updated
- 28 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Geysenbergh B, Debrock S, Lie Fong S, Vanhie A, Tomassetti C, Bafort C, Meeuwis L, Neyens S, Pelckmans S, Laenen A, Vriens J, De Loecker P, Dancet E, Peeraer K. Natural versus artificial cycle for endometrial preparation in ovulatory women undergoing frozen-thawed embryo transfer: a randomised controlled trial. Hum Reprod. 2026 Aug 1;41(8):1420-1429. doi: 10.1093/humrep/deag095.
PubMed 42315758
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frozen-thawed Embryo Transfer in a Natural Versus Artificial Cycle: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03642665
- Acronym / sponsor ID
- NAFT / S61372
- Conditions
- Embryo Transfer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 554 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- GZA Ziekenhuizen Campus Sint-Augustinus, Imelda Hospital, Bonheiden, Jessa Hospital
- Study start
- 25 Sep 2018 (actual)
- Primary completion
- 1 Nov 2024 (actual)
- Study completion
- 1 Nov 2024 (actual)
- First posted
- 22 Aug 2018 (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 evaluates clinical pregnancy rates, obstetrical outcome parameters, costs and patient preferences in natural cycle versus artificial cycle frozen embryo transfers (FET).
Detailed description
Transfer of cryopreserved embryos can be performed in a natural cycle (NC-FET) or in an artificially prepared cycle (AC-FET). Both cycle regimens have their advantages and disadvantages. So far, most comparative studies have failed to identify the optimal protocol for FET. In this study patients undergoing FET will be randomized between an endometrial preparation by a natural cycle or by an artificial cycle (by oestradiol validate and micronized progesterone).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter prospective randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Natural cycle | Experimental | Drug: Natural cycleno medication |
| Artificial cycle | Active comparator | Drug: Estradiol Valerate, Drug: Micronized progesteroneOestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. Micronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Women undergoing FET after a first, second or third fresh IVF/ICSI cycle
- Single embryo transfer (SET) or Double embryo transfer (DET)
- Female age between 18-45 year
- Women having a natural ovulatory cycle (24-35 days)
- Normal uterine cavity (fundal indentation at the cavity <10mm)
Key exclusion criteria (3 listed)
- Use of donor gametes
- BMI > or equal to 35 kg / m2
- Any contra-indication to estrogen or progesterone supplementation (e.g. history of thrombosis, prior or current hormone-sensitive malignancy…)
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 cycleno medication | Drug | Natural cycle |
| Estradiol ValerateAlso: Artificial cycleOestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. | Drug | Artificial cycle |
| Micronized progesteroneAlso: Artificial cycleMicronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. | Drug | Artificial cycle |
Primary outcome
Clinical pregnancy rate with fetal heart beat
Time frame: 9 weeks
Clinical pregnancy rate with fetal heart beat diagnosed by ultrasound no later than the gestational age of 9 weeks
12 secondary outcomes
Biochemical pregnancy rate
Time frame: 9 weeks
Miscarriage rate
Time frame: 12 weeks
Ectopic pregnancy rate
Time frame: 9 weeks
Live birth rate
Time frame: 41 weeks
Multiple pregnancy rate
Time frame: 9 weeks
Adverse events
Time frame: 12 weeks
Cycle cancellation rate
Time frame: 4 weeks
Endometrial thickness
Time frame: 3 weeks
Endometrial pattern
Time frame: 3 weeks
number of center visits to monitor FET cycle
Time frame: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
cost analysis per treatment cycle
Time frame: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
patient satisfaction
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Derived from this study: PubMed 42315758Geysenbergh B, Debrock S, Lie Fong S, Vanhie A, Tomassetti C, Bafort C, Meeuwis L, Neyens S, Pelckmans S, Laenen A, Vriens J, De Loecker P, Dancet E, Peeraer K. Natural versus artificial cycle for endometrial preparation in ovulatory women undergoing frozen-thawed embryo transfer: a randomised controlled trial. Hum Reprod. 2026 Aug 1;41(8):1420-1429. doi: 10.1093/humrep/deag095.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Natural cycle, Estradiol Valerate and Micronized progesterone in people with Embryo Transfer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 6 inclusion and 3 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: finished, as of the sponsor's last update on 28 Feb 2025. 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 Belgium. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate with fetal heart beat (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03642665, which also lists 1 linked publication.
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 28 Feb 2025.