Preimplantation Genetic Diagnosis for the Indication of Advanced Reproductive Age

Comparison of Embryo Transfer With and Without PGS for the Indication of Advanced Reproductive Age (37-42) in Patients Undergoing ART

The objective of this study is to demonstrate that Preimplantation Genetic diagnosis will significantly reduce spontaneous abortions and increase ongoing pregnancy rates in patients of advanced maternal age (37-42) undergoing IVF. We would like to test this hypothesis by a randomized trial performed with the most suitable conditions using very successful IVF laboratories capable to perform the embryo biopsy under strict controlled conditions after proper training and validation of the techniques.

Study Overview

• Status: Suspended
• Conditions: Infertility
• Intervention / Treatment: Procedure: Preimplantation Genetic Diagnosis (PGD)

Detailed Description

Indications: Patients of advanced reproductive age wishing to receive preimplantation genetic screening in ART.

Objectives: To demonstrate that Preimplantation Genetic diagnosis (PGD) will significantly reduce spontaneous abortions and increase ongoing pregnancy rates in patients of advanced maternal age (37-42) undergoing IVF.

Test Method: Preimplantation Genetic Screening through FISH Treatment: In Vitro Fertilization treatment. The resulting embryos of the test group will undergo embryo biopsy followed by PGD with FISH using a 10-probe test with "no result rescue".

Study Population: 978 infertile women undergoing ART Major Inclusions: Premenopausal infertile women wishing to conceive, aged 37 42 years, inclusive, regular menstrual cycles and screening early follicular phase FSH within normal limits.

Major Exclusions: Clinically significant systemic disease; any contraindication to pregnancy or carrying pregnancy to term; known ASRM Grade III or IV endometriosis; clinically significant abnormal findings on a transvaginal ultrasound within 6 weeks prior to the beginning of OCP treatment; extrauterine pregnancy within 3 months prior to the beginning of OCP treatment; poor response in a previous ART cycle (≤ 3 oocytes retrieved); ≥ 3 prior, initiated, consecutive ART cycles without a clinical pregnancy; prior severe OHSS; TESA and TESE patients; patients carriers of chromosomal or genetic diseases.

Randomization: Eligible patients will be randomized in a 1:1 ratio to either:

Group A: Hatching "or" Group B: Hatching + PGS Study Procedures The study will be conducted on an outpatient basis. All pre-study screening assessments will be performed prior to treatment start.

Post-treatment Oocyte retrieval and embryology procedures will be Procedures performed according to the usual practice of the study center. Test Method Hatching, embryo biopsy, fixation and Fluorescence in-situ Hybridization (FISH) will be performed strictly in line with the methodology included in this protocol and only carried out by technicians certified by Reprogenetics.

Primary Endpoint: ongoing pregnancy rate (past 2nd trimester). Secondary Endpoints: implantation rate, pregnancy rate, miscarriage rate and live birth.

• Study Type: Interventional
• Enrollment (Anticipated): 1200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • IVI Barcelona
• United States
  • California
    • Beverly Hills, California, United States, 90210
      • ART Reproductive Center,
  • Illinois
    • Highland Park, Illinois, United States, 60035
      • Fertility Centers of Illinois
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Institute for Reproductive Medicine and Science at Saint Barnabas Medical Center
    • Livingston, New Jersey, United States, 07039
      • Reprogenetics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 37 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Premenopausal infertile women wishing to conceive
• Aged 37 42 years, inclusive,
• Regular menstrual cycles (generally 25 35 days in length) and screening early follicular phase FSH within normal limits.

Exclusion Criteria:

• Clinically significant systemic disease;
• Any contraindication to pregnancy or carrying pregnancy to term;
• Known ASRM Grade III or IV endometriosis;
• Clinically significant abnormal findings on a transvaginal ultrasound within 6 weeks prior to the beginning of OCP treatment;
• Extrauterine pregnancy within 3 months prior to the beginning of OCP treatment;
• ≥ 3 prior, initiated, consecutive ART cycles without a clinical pregnancy;
• Prior severe OHSS;
• TESA and TESE patients;
• Patients carriers of chromosomal or genetic diseases.
• Egg donation cycles.
• Frozen Cycles.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 1; Control: assisted hatching, without Preimplantation Genetic Diagnosis
Experimental: 2; Test: embryo biopsy with Preimplantation Genetic Diagnosis	Procedure: Preimplantation Genetic Diagnosis (PGD); one-cell embryo biopsy on day 3 of development. The cell will be analyzed by FISH using probes for X,Y,13,15,16,17,18,21,22 chromosomes. Cells with dubious results will be reanalyzed by "no result rescue" (Colls et al. 2007); Other Names: PGS; Preimplantation Genetic Screening

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ongoing pregnancy rate (past 2nd trimester).	after 21 days, 20 weeks, and 7 month of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
spontaneous abortions	within 1st and 2nd trimester
pregnancy	one month for presence of fetal sac
implantation	first month, for presence of fetal sacs

Collaborators and Investigators

• Sponsor: Reprogenetics
• Investigators: Principal Investigator: Santiago Munne, PhD, Reprogenetics

Publications and helpful links

General Publications

• Colls P, Escudero T, Cekleniak N, Sadowy S, Cohen J, Munne S. Increased efficiency of preimplantation genetic diagnosis for infertility using "no result rescue". Fertil Steril. 2007 Jul;88(1):53-61. doi: 10.1016/j.fertnstert.2006.11.099. Epub 2007 Feb 12.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Anticipated): January 1, 2011
• Study Completion (Anticipated): April 1, 2011

Study Registration Dates

• First Submitted: March 26, 2008
• First Submitted That Met QC Criteria: March 28, 2008
• First Posted (Estimate): March 31, 2008

Study Record Updates

• Last Update Posted (Estimate): February 23, 2010
• Last Update Submitted That Met QC Criteria: February 21, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: IVF; aneuploidy; PGD; ART; miscarriage; PGS; pregnancy loss; Preimplantation Genetic Diagnosis; chromosome abnormalities
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: Reprogenetics-01