Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01940653
Recruitment Status : Unknown
Verified May 2014 by Arne van de Vijver, Universitair Ziekenhuis Brussel.
Recruitment status was:  Recruiting
First Posted : September 12, 2013
Last Update Posted : May 21, 2014
Sponsor:
Information provided by (Responsible Party):
Arne van de Vijver, Universitair Ziekenhuis Brussel

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Progesterone Supplementation Drug: Progesterone Phase 4

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2012
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Progesterone

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:
  • oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany)
  • progesterone (Utrogestan®, Besins International, France)

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.
Drug: Progesterone

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:
  • oestradiol valerate (Progynova®, Bayer-Schering Pharma AG, Berlin, Germany)
  • progesterone (Utrogestan®, Besins International, France)




Primary Outcome Measures :
  1. clinical pregnancy rate [ Time Frame: 7 weeks of pregnancy ]

Secondary Outcome Measures :
  1. live birth rate [ Time Frame: 9 months after embryo transfer ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 39 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01940653


Contacts
Layout table for location contacts
Contact: Arne van de Vijver avandevijver@hotmail.com

Locations
Layout table for location information
Belgium
UZ Brussel Recruiting
Brussels, Belgium, 1090
Contact: Arne van de Vijver       avandevijver@hotmail.com   
Principal Investigator: Arne van de Vijver, medical doctor         
Sponsors and Collaborators
Universitair Ziekenhuis Brussel

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Arne van de Vijver, Medical Doctor, Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT01940653     History of Changes
Other Study ID Numbers: PROFETA-3
First Posted: September 12, 2013    Key Record Dates
Last Update Posted: May 21, 2014
Last Verified: May 2014

Additional relevant MeSH terms:
Layout table for MeSH terms
Progesterone
Estradiol
Estrogens
Polyestradiol phosphate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Progestins
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female