Progesterone SupplementationPhase 4PROFETA-3NCT01940653
Optimal Length of Progesterone Supplementation Before the Transfer of Cryopreserved (Frozen)-Thawed Day 3 Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone
A Phase 4 study testing Progesterone in people with Progesterone Supplementation, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Progesterone Supplementation
- What is being tested?
- Progesterone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2012to Dec 2017
- 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 Up to 39 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Artificial cycles, in which a frozen-thawed day 3 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.
About this study
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).
In this trial, the investigators want to determine the optimal duration of progesterone supplementation: 3 or 5 days before embryo transfer.
Read the detailed description
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, the investigators start progesterone supplementation 5 days before the transfer of a day 3 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).
In other centres, progesterone supplementation is generally started 3 days before the embryo transfer.
In this trial, the investigators want to determine the optimal duration of progesterone supplementation: 3 or 5 days before embryo transfer.
- Conditions
- Progesterone Supplementation
- Being tested
- Progesterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany), progesterone (Utrogestan®, Besins International, France)
Procedures 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. All patients with an endometrium less than 7 mm on day 13 of estrogen stimulation, are excluded.
Group A receives 5 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 3 days of micronized progesterone vaginally. On the 5th (group A) or 3rd (group B) day of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred.
| Study group | Role | What they receive |
|---|---|---|
| Progesterone | Other | Group A receives 5 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International). On the 5th (group A) of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred. Receives: Drug: Progesterone |
| progesterone 3 days | Active comparator | Group B receives 3 days of micronized progesterone vaginally. On the 3rd day of progesterone supplementation, the cryopreserved-thawed day 3 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: 9 months after embryo transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2013 (estimated)
- Study startNov 2012
- Primary completionDec 2017
- Study completionDec 2017
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 Progesterone SupplementationStudies 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
- NCT01940653
- Sponsor's protocol ID
- PROFETA-3
- Acronym
- PROFETA-3
- Status last verified
- Sep 2019
- First submitted
- 9 Sep 2013
- Last updated
- 27 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
van de Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, De Vos M, Tournaye H, Blockeel C. What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. Hum Reprod. 2016 May;31(5):1097-104. doi: 10.1093/humrep/dew045. Epub 2016 Mar 22.
PubMed 27005893
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 Day 3 Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone
- ClinicalTrials.gov ID
- NCT01940653
- Acronym / sponsor ID
- PROFETA-3 / PROFETA-3
- Conditions
- Progesterone Supplementation
- 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
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 12 Sep 2013 (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.
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).
In this trial, the investigators want to determine the optimal duration of progesterone supplementation: 3 or 5 days before embryo transfer.
Detailed description
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, the investigators start progesterone supplementation 5 days before the transfer of a day 3 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).
In other centres, progesterone supplementation is generally started 3 days before the embryo transfer.
In this trial, the investigators want to determine the optimal duration of progesterone supplementation: 3 or 5 days before embryo transfer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Progesterone | Other | Drug: ProgesteroneGroup A receives 5 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International). On the 5th (group A) of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred. |
| progesterone 3 days | Active comparator | Drug: ProgesteroneGroup B receives 3 days of micronized progesterone vaginally. On the 3rd day of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred. |
Who may qualify
- Ages
- Up to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Artificial cycles, in which a frozen-thawed day 3 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 |
|---|---|---|
| ProgesteroneAlso: oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany), progesterone (Utrogestan®, Besins International, France)Procedures 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. All patients with an endometrium less than 7 mm on day 13 of estrogen stimulation, are excluded. Group A receives 5 days of micronized progesterone vaginally (Utrogestan® ((Utrogestan, Besins International), 3x200mg daily), group B receives 3 days of micronized progesterone vaginally. On the 5th (group A) or 3rd (group B) day of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred. | Drug | Progesterone, progesterone 3 days |
Primary outcome
clinical pregnancy rate
Time frame: 7 weeks of pregnancy
1 secondary outcome
live birth rate
Time frame: 9 months after embryo transfer
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.
- Derived from this study: PubMed 27005893van de Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, De Vos M, Tournaye H, Blockeel C. What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. Hum Reprod. 2016 May;31(5):1097-104. doi: 10.1093/humrep/dew045. Epub 2016 Mar 22.
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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 Progesterone Supplementation, 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. 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?
On the ClinicalTrials.gov record for NCT01940653, 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 27 Sep 2019.