Idealizing Pregnancy Outcome With Single Blastocyst Transfer in a FET Cycle

Pregnancy Clinical Trial

Official title:

Idealizing Pregnancy Outcome With Single Blastocyst Transfer in a Frozen Embryo Transfer (FET) Cycle; Array Comparative Genome Hybridization (aCGH) Euploid Screened Versus Morphology Selected Blastocyst.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01987856
• Other study ID #: aCGH vs blastocyst morphology
• Secondary ID: Ideal blastocyst
• Status: Withdrawn
• Phase: N/A
• First received: November 13, 2013
• Last updated: May 25, 2016
• Start date: January 2014
• Est. completion date: September 2017

Study information

• Verified date: May 2016
• Source: Antalya IVF
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Single embryo transfer (SET) has been advocated as a means of reducing the risk of multiple pregnancies, but has meant a reduction in pregnancy risk per embryo transfer. Embryo aneuploidy has been cited as the primary reason for the low embryo implantation achieved in human IVF. In the majority of IVF programs embryo selection has mainly been based on the microscopic assessments embryo. Culturing embryos to the blastocyst stage as a selection mechanism has seen an increase in implantation rates, presumably indicating that morphologically normal blastocysts formed by day 5 of culture may have a reduced aneuploidy rate. Morphological normality does, however, not completely preclude aneuploidy, with many transferred and cryopreserved embryo bearing factors that may hold an increased risk for implantation failure and miscarriage.

To select the conditions for single blastocyst transfer that will significantly improve reproductive outcomes; increased implantation, reduced pregnancy loss and increased live birth rates.

Description:

Methodology

Patients: Patients less 40 years of age with a normal ovarian reserve (>10 antral follicle count), normal BMI (>18 and <30) and who have had no more than 3 previous IVF cycles consulted to have elective single embryo transfer (eSET) will be presented with the conditions of the trial. Patients that accept the conditions of the trial will be randomly allocated to the two groups of the study; Group 1; no blastocysts (N-blastocyst) aneuploidy screened before vitrification and cryostorage, Group 2; patients will have at least 2 blastocysts biopsied for aCGH aneuploidy screening (S-blastocysts) before all blastocysts, are vitrified and cryostored.

Controlled ovarian stimulation (COS): All patients will be stimulated for multiple follicular development using a fixed antagonist protocol with recombinant follicle stimulating hormone (rFSH) and human menopausal gonadotropin (HMG). Final oocyte maturation will be triggered using a bolus dose of gonadotropin releasing hormone (GnRH) agonist.

Intracytoplasmic sperm injection (ICSI): all oocyte inseminations will be done by ICSI, 2-4 hours after oocyte collection. All resulting 2 pronuclei (PN) zygotes will be cultured to day 5.

Blastocyst scoring and selection; Blastocyst will be scored on 3 criteria; on a scale of 1 (morula/early blastocyst) to 6 (hatched blastocyst) for expansion and on a scale of A to C (A for good, B for fair, and C for poor) for inner cell mass (ICM) and trophectoderm (TE) morphology. Patients to be included in the study must have at least 2 blastocysts with expansion grade 3 on day 5 of culture.

Exclusion criteria: All patients with less than 5 oocytes collected at the time of oocyte pickup (OPU) will be excluded from the study. All patients with <2 blastocysts with expansion grade 3 on day 5 of culture will be excluded from the study.

Vitrification: All suitable blastocyst will be vitrified using the Kitazato cryotop method, a single blastocyst per device.

aCGH: An external laboratory will be used for the screening of the selected blastocyst. All biopsies will be performed on day 5 of culture to remove between 3-5 cells from the TE. Harvested TE cells will be washed placed in a tube, as directed by the genetic laboratory, before being transported to the genetics laboratory.

Frozen embryo transfer (FET): A natural cycle programmed with the use of E2 and P4 supplementation to determine time (progesterone day 6) for blastocyst warming and transfer.

Outcomes measured: pregnancy rate (positive βhCG per blastocyst transfer), implantation rate (fetal sac per blastocyst transfer), ongoing pregnancy rate (fetal heart per blastocyst transfer), single normal live delivery (baby per blastocyst transfer and baby per positive βhCG).

Setting: Antalya IVF It is advised that before attempting to perform embryo aneuploid screening the IVF laboratory should have proven extended embryo (to day 6) culture and embryo vitrification proficiency. At Antalya IVF more than 70% of cycles are extended culture cycles with a more than acceptable implantation rate of 42% for fresh and 44% for vitrified-warmed blastocysts. These reproductive outcomes have been maintained over the last calender year.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

Inclusion Criteria:

Patients less than 40 years of age with a normal ovarian reserve (>10 antral follicle count), normal BMI (>18 and <30) and who have had no more than 3 previous IVF cycles

Exclusion Criteria:

All patients with less than 5 oocytes collected at the time of OPU will be excluded from the study.

All patients with <2 blastocysts with expansion grade 3 on day 5 of culture will be excluded from the study.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pregnancy

Intervention

Procedure:
• Blastocyst morphology
microscopic examination only

Locations

Country	Name	City	State
Turkey	Antalya IVF	Antalya

Sponsors (1)

Lead Sponsor	Collaborator
Antalya IVF

Country where clinical trial is conducted

Turkey, 

References & Publications (1)

Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients:results from a randomized pilot study. Molecular Cytogenetics 2012, 5:24 Ly KD, Agarwal A, Nagy ZP. Preimplantation genetic screening: does it help or hinder IVF treatment and what is the role of the embryo? J Assist Reprod Genet 2011; 28:833-849. Forman EJ,Upham KM, Cheng M, Zhao T, Hong KH, Nathan R. Treff NR, Scott Jr. RT. Comprehensive chromosome screening alters traditional morphology-based embryo selection: a prospective study of 100 consecutive cycles of planned fresh euploid blastocyst transfer. Fertil Steril 2013; 100 (3): 718-724.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Euploid rate	the percentage of biopsied blastocyst that are chromosomally euploid	24 months	No
Primary	Live birth rate	single live birth per blastocyst transfer	24 months	No
Secondary	Pregnancy rate	the percentage of cycles with a beta human chorionic gonadotropin (ßhCG) value of greater than 30 IU on day 14 of cycle	24 months	No
Secondary	Ongoing pregnancy rate	the percentage of cycles with a 7 week ultrasound confirmed fetal heart	24 months	No