CryopreservationPhase 4PROFETA-5NCT02032797
Optimal Length of Progesterone Supplementation Before the Transfer of Cryopreserved(Frozen)-Thawed Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone.
A Phase 4 study testing Progesterone in people with Cryopreservation and Embryo Implantation, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
The aim of the study is to determine whether 5 or 7 days of progesterone supplementation before transfer of a day 5 cryopreserved thawed embryos in an artificial cycle results in a significant higher pregnancy rate. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Cryopreservation, Embryo Implantation, Progesteron
- What is being tested?
- Progesterone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2012to Sep 2019
- 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 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Artificial cycles, in which a frozen-thawed day 5 embryo is replaced.
- Signed informed consent.
- Normal transvaginal ultrasound at screening, without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa.
- Embryos must be frozen by vitrification technique (cfr supra).
- Single or dual embryo transfer.
- Recipients of oocyte donation cycles may be included.
Who cannot join
- Known allergic reactions to progesterone products.
- Intake of experimental drug within 30 days prior to study start.
- Contraindication for pregnancy.
- Embryos of women above 39 years of age at the time of embryo freezing.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Centre of Reproductive Medicine CRG
Jette, Brussels Capital, 1090
About this study
The aim of the study is to determine whether 5 or 7 days of progesterone supplementation before transfer of a day 5 cryopreserved thawed embryos in an artificial cycle results in a significant higher pregnancy rate.
Read the detailed description
Cryopreserved-thawed embryos are often replaced in an artificial cycle, in which the endometrium is prepared by exogenous estrogen and progesterone with or without the use of GnRH agonist downregulation. The correct duration for exposure to progesterone is still not well established. To date, there are no prospective randomized trials available, comparing different durations of progesterone supplementation before the date of transfer, with regard to treatment outcome (Nawroth).
The purpose is to transfer the embryo during the 'window of implantation', what is defined as the period during which the uterus is receptive for implantation of the free-lying blastocyst. This has been a subject of debate since many years (Bourgain et al, 2007).
Succesful implantation requires a co-ordinated series of events allowing a timely dialogue between a receptive endometrium and the intrusive blastocyst (Tabibzadeh, 1998). The period of receptivity is thought to be 3 days in human (Rogers et al, 1989; Yoshinaga, 1988; Psychoyos, 1993; Harper, 1992). It is suggested that blastocyst apposition begins about day LH+6 and is completed by day LH+10 (Lessey, 2000).
A number of structural and functional endometrial changes have been suggested to play a role in the implantation process: the formation of luminal epithelial pinopodes (Enders et al, 1973), expression of adhesion molecules and growth factors and cytokines (Lessey, 2000). Most of them are related directly or indirectly to progesterone secretion and influence on the endometrium.
In the Centre of Reproductive Medicine of the Brussels University Hospital, we start progesterone supplementation 7 days before the transfer of a day 5 embryo. In order to mimic the natural cycle, since progesterone starts to rise 2 to 3 days before ovulation, due to the LH-stimulated production by the peripheral granulosa cells (Speroff). In fresh IVF-cycles, progesterone is started from the day of oocyte retrieval. HCG administration in fresh cycles will lead to an increase in progesterone levels and therefore, endometrium will progress quickly, compared with frozen-thawed cycles which are hormone supplemented (Nawroth).
Our approach in artificial FrET cycles results in a pregnancy rate of 26%.
In other centres, progesterone supplementation is generally started 5 days before the embryo transfer. Recent studies show pregnancy rates up to 40.5% (Givens CR et al, 2009), using this approach.
In this trial, we want to determine the optimal duration of progesterone supplementation.
- Conditions
- Cryopreservation, Embryo Implantation, Progesteron
- Being tested
- Progesterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
| Study group | Role | What they receive |
|---|---|---|
| A: 7 days of progesterone | Experimental | Transvaginal ultrasound (US) and hormone analysis for FSH, LH, E2 and P on day 2 of the cycle will be performed. The artificial preparation of the endometrium consists of 7 days oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany) 2 mg bid (bi-daily), followed by 6 days oestradiol valerate 2 mg tid (thrice daily). On day 13, the endometrium is measured. If endometrial thickness is more than 7 mm, patients are randomly assigned to group A or B.
Group A receives 7 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 5 days of micronized progesterone vaginally. On the 7th (group A) or 5th (group B) day of progesterone supplementation, the cryopreserved-thawed day 5 embryo is transferred. Receives: Drug: Progesterone |
| B: 5 days of progesterone | Placebo comparator | Transvaginal ultrasound (US) and hormone analysis for FSH, LH, E2 and P on day 2 of the cycle will be performed. The artificial preparation of the endometrium consists of 7 days oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany) 2 mg bid (bi-daily), followed by 6 days oestradiol valerate 2 mg tid (thrice daily). On day 13, the endometrium is measured. If endometrial thickness is more than 7 mm, patients are randomly assigned to group A or B.
Group A receives 7 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 5 days of micronized progesterone vaginally. On the 7th (group A) or 5th (group B) day of progesterone supplementation, the cryopreserved-thawed day 5 embryo is transferred. Receives: Drug: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical pregnancy rate
Measured: 7 weeks of pregnancy
Secondary outcomes (1)
live birth rate
Measured: 40 weeks of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2014 (estimated)
- Study startNov 2012
- Primary completionSep 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CryopreservationStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe 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
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arne van de Vijver, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02032797
- Sponsor's protocol ID
- PROFETA-5
- Acronym
- PROFETA-5
- Status last verified
- Sep 2019
- First submitted
- 8 Jan 2014
- Last updated
- 27 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Length of Progesterone Supplementation Before the Transfer of Cryopreserved(Frozen)-Thawed Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone.
- ClinicalTrials.gov ID
- NCT02032797
- Acronym / sponsor ID
- PROFETA-5 / PROFETA-5
- Conditions
- Cryopreservation, Embryo Implantation, Progesteron
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 10 Jan 2014 (estimated)
- 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 aim of the study is to determine whether 5 or 7 days of progesterone supplementation before transfer of a day 5 cryopreserved thawed embryos in an artificial cycle results in a significant higher pregnancy rate.
Detailed description
Cryopreserved-thawed embryos are often replaced in an artificial cycle, in which the endometrium is prepared by exogenous estrogen and progesterone with or without the use of GnRH agonist downregulation. The correct duration for exposure to progesterone is still not well established. To date, there are no prospective randomized trials available, comparing different durations of progesterone supplementation before the date of transfer, with regard to treatment outcome (Nawroth).
The purpose is to transfer the embryo during the 'window of implantation', what is defined as the period during which the uterus is receptive for implantation of the free-lying blastocyst. This has been a subject of debate since many years (Bourgain et al, 2007).
Succesful implantation requires a co-ordinated series of events allowing a timely dialogue between a receptive endometrium and the intrusive blastocyst (Tabibzadeh, 1998). The period of receptivity is thought to be 3 days in human (Rogers et al, 1989; Yoshinaga, 1988; Psychoyos, 1993; Harper, 1992). It is suggested that blastocyst apposition begins about day LH+6 and is completed by day LH+10 (Lessey, 2000).
A number of structural and functional endometrial changes have been suggested to play a role in the implantation process: the formation of luminal epithelial pinopodes (Enders et al, 1973), expression of adhesion molecules and growth factors and cytokines (Lessey, 2000). Most of them are related directly or indirectly to progesterone secretion and influence on the endometrium.
In the Centre of Reproductive Medicine of the Brussels University Hospital, we start progesterone supplementation 7 days before the transfer of a day 5 embryo. In order to mimic the natural cycle, since progesterone starts to rise 2 to 3 days before ovulation, due to the LH-stimulated production by the peripheral granulosa cells (Speroff). In fresh IVF-cycles, progesterone is started from the day of oocyte retrieval. HCG administration in fresh cycles will lead to an increase in progesterone levels and therefore, endometrium will progress quickly, compared with frozen-thawed cycles which are hormone supplemented (Nawroth).
Our approach in artificial FrET cycles results in a pregnancy rate of 26%.
In other centres, progesterone supplementation is generally started 5 days before the embryo transfer. Recent studies show pregnancy rates up to 40.5% (Givens CR et al, 2009), using this approach.
In this trial, we want to determine the optimal duration of progesterone supplementation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: 7 days of progesterone | Experimental | Drug: ProgesteroneTransvaginal ultrasound (US) and hormone analysis for FSH, LH, E2 and P on day 2 of the cycle will be performed. The artificial preparation of the endometrium consists of 7 days oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany) 2 mg bid (bi-daily), followed by 6 days oestradiol valerate 2 mg tid (thrice daily). On day 13, the endometrium is measured. If endometrial thickness is more than 7 mm, patients are randomly assigned to group A or B. Group A receives 7 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 5 days of micronized progesterone vaginally. On the 7th (group A) or 5th (group B) day of progesterone supplementation, the cryopreserved-thawed day 5 embryo is transferred. |
| B: 5 days of progesterone | Placebo comparator | Drug: ProgesteroneTransvaginal ultrasound (US) and hormone analysis for FSH, LH, E2 and P on day 2 of the cycle will be performed. The artificial preparation of the endometrium consists of 7 days oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany) 2 mg bid (bi-daily), followed by 6 days oestradiol valerate 2 mg tid (thrice daily). On day 13, the endometrium is measured. If endometrial thickness is more than 7 mm, patients are randomly assigned to group A or B. Group A receives 7 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 5 days of micronized progesterone vaginally. On the 7th (group A) or 5th (group B) day of progesterone supplementation, the cryopreserved-thawed day 5 embryo is transferred. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Artificial cycles, in which a frozen-thawed day 5 embryo is replaced.
- Signed informed consent.
- Normal transvaginal ultrasound at screening, without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa.
- Embryos must be frozen by vitrification technique (cfr supra).
- Single or dual embryo transfer.
Key exclusion criteria (4 listed)
- Known allergic reactions to progesterone products.
- Intake of experimental drug within 30 days prior to study start.
- Contraindication for pregnancy.
- Embryos of women above 39 years of age at the time of embryo freezing.
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 |
|---|---|---|
| Progesterone | Drug | A: 7 days of progesterone, B: 5 days of progesterone |
Primary outcome
clinical pregnancy rate
Time frame: 7 weeks of pregnancy
1 secondary outcome
live birth rate
Time frame: 40 weeks of pregnancy
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 27 Sep 2019.
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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 Progesterone in people with Cryopreservation and Embryo Implantation, run by Universitair Ziekenhuis Brussel 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 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: finished, as of the sponsor's last update on 27 Sep 2019. 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. Some participants in this study may receive a placebo. 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 (time frame: 7 weeks of pregnancy). 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 27 Sep 2019.