- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01940653
Optimal Length of Progesterone Supplementation Before the Transfer of Cryopreserved (Frozen)-Thawed Day 3 Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone (PROFETA-3)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Brussels, Belgium, 1090
- UZ Brussel
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Progesterone
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.
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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.
Other Names:
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Active Comparator: progesterone 3 days
Group B receives 3 days of micronized progesterone vaginally.
On the 3rd day of progesterone supplementation, the cryopreserved-thawed day 3 embryo is transferred.
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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clinical pregnancy rate
Time Frame: 7 weeks of pregnancy
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7 weeks of pregnancy
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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live birth rate
Time Frame: 9 months after embryo transfer
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9 months after embryo transfer
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PROFETA-3
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