Clinical trial NCT00646893: Preimplantation Genetic Diagnosis for the Indication of Advanced Reproductive Age
Official title: Comparison of Embryo Transfer With and Without PGS for the Indication of Advanced Reproductive Age (37-42) in Patients Undergoing ART
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Infertility
Keywords: aneuploidy
miscarriage
pregnancy loss
PGD
PGS
Preimplantation Genetic Diagnosis
chromosome abnormalities
IVF
ART
Lead sponsor: Reprogenetics
Sponsor class: INDUSTRY
First posted: 2008-03-31
Enrollment: 1200
Sex: FEMALE
Minimum age (years): 37
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ongoing pregnancy rate (past 2nd trimester).
timeFrame: after 21 days, 20 weeks, and 7 month of treatment
Secondary outcomes:
measure: spontaneous abortions
timeFrame: within 1st and 2nd trimester
measure: pregnancy
timeFrame: one month for presence of fetal sac
measure: implantation
timeFrame: first month, for presence of fetal sacs
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: ART Reproductive Center,
state: California
city: Highland Park
country: United States
facility: Fertility Centers of Illinois
state: Illinois
city: Livingston
country: United States
facility: Institute for Reproductive Medicine and Science at Saint Barnabas Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Reprogenetics
state: New Jersey
city: Barcelona
country: Spain
facility: IVI Barcelona
Study officials:
affiliation: Reprogenetics
name: Santiago Munne, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.