Impact of Local Biopsy to the Endometrium Prior to Controlled Ovarian Stimulation on Clinical Pregnancy

Official Title: “Influence of Local Biopsy of the Endometrium Prior to Controlled Ovarian Stimulation for IVF or ICSI Procedure on the Rates of Embryo Implantation, Clinical Pregnancy and Live Birth in ART”

In vitro fertilization (IVF) is the only available solution for many couples with various forms of infertility. The embryo implantation step in the IVF procedure is a complex multistage process and represents the majority of the causes of the IVF failure. Several approaches have been evaluated to improve implantation rates but none has demonstrated its superiority. However, endometrial receptivity is important for pregnancy and several studies suggest that local injury to the endometrium of IVF patients improves the rates of embryo implantation, clinical pregnancy and live birth.

They are possible mechanisms by which endometrial sampling may increase receptivity and improve clinical pregnancy rate of IVF-ET. First, local injury to proliferative phase endometrium might induce the decidualization of the endometrium, and increase its implantation rate. Second, local injury to the endometrium might provoke the wound healing, involving a mass secretion of different cytokines and growth factor, which are beneficial for embryo implantation. Last, the injury might make the endometrium maturation.

This study proposes to evaluate the efficiency of an endometrial injury in the first controlled ovarian hyperstimulation cycle on the rate of clinical pregnancy, in assisted reproductive technologies. This study will compare 2 groups of patients. The first group will undergo biopsy of the endometrium before the IVF; the second will undergo the IVF alone. Inclusions will be conducted on 33 months; the patients will be in the study for a period of 36 weeks. The total duration of the study is 39 months

Intervention(s) in this Clinical Trial

• Procedure: biopsy
  • The endometrium biopsy will be done as the same time as the GnRH treatment. The biopsy is realised with a Pipette de Cornier® (CDD international, PROMIDED France) following the laboratory protocol: Apply antiseptic solution (povidone-iodine, Dakin®) on the cervix and vagina. In most cases, using Pozzi forceps is not necessary. Insert carefully the pipelle de Cornier® in the uterus through the cervix. Withdraw the piston to create a negative pression Move the pipelle de cornier® in and out while twisting. Take care to no remove the pipelle form the uterus (suction lost). Twist the pipelle de Cornier® to cover an angle of 360°. Make several "in and out" cycle in order to collect a complete sample of the endometrium. Withdraw the pipelle de Cornier® when filled with tissue Reinsert internal piston to deposit sample in cup filled with a fixative.
• Procedure: IVF
  • fresh IVF-embryo transfer treated with long protocol for the controlled ovarian hyperstimulation

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: group 1 : IVF with biopsy
  • fresh IVF-embryo transfer treated with long protocol or antagonist protocol for the controlled ovarian hyperstimulation plus local injury to the endometrium of patients one menstrual cycle before the IVF
• Active Comparator: group 2
  • fresh IVF-embryo transfer treated with long protocol or antagonist protocol for the controlled ovarian hyperstimulation alone

Primary Measures

• Rate of clinical pregnancy
  • Time Frame: 5 weeks after the embryo implantation in an IVF procedure
    Safety Issue?: No

Secondary Measures

• Rate of clinical pregnancy
  • Time Frame: 3 months after the IVF implantation
    Safety Issue?: No
• Rate of embryo implantation
  • Time Frame: 5 weeks after the embryo implantation
    Safety Issue?: No
• Rate of miscarriage/extra-uterine pregnancy/multiple pregnancy
  • Time Frame: first trimester after the IVF
    Safety Issue?: Yes
• Adverse effects during the local injury (biopsy) to the endometrium
  • Time Frame: during the biopsy
    Safety Issue?: Yes
• Evaluation of the patients pain intensity and type from the biopsy.
  • Time Frame: during and after the biopsy
    Safety Issue?: Yes

Inclusion Criteria:

• primary or secondary infertility
• first or second IVF attempt
• aged ≥18 and ≤38 years
• regular menstrual cycles
• FSH≤ 12IU/L
• Informed consent signed

Exclusion Criteria:

• ovocyte donor
• pathology of the uterus or annexes
• Body mass index (BMI)> 35
• ongoing vaginal infection
• undetermined vaginal bleeding
• contraindication to the Cornier pipette or to these treatments : Gonal F®, Puregon®, Ovitrelle®, Utrogestan®,
• women included in another study on medically assisted procreation
• any administrative or legal supervision

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 38 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University Hospital, Bordeaux Other

Overall Clinical Trial Officials and Contacts

Antoine Benard, Doctor Study Chair University Hospital Bordeaux, France  

Overall Contact: Sandrine Blancpain, Doctor 05 56 79 58 35 sandrine.blancpain@chu-bordeaux.fr

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01064193

Study ID Number: CHUBX 2009/12

ClinicalTrials.gov Identifier: NCT01064193

Health Authority: France: Afssaps - French Health Products Safety Agency