Improvement of Cell Selection in Reproductive Techniques

A New Method to Improve the Selection of Zygotes in the Context of Assisted Reproductive Medicine. A Randomized Controlled Blinded Monocenter Study

It is the aim of this trial to use a new computerized cell selection method, in addition to the current and world-wide used scoring system of fertilized oocytes implemented by Scott, to determine whether this leads to an increase in pregnancy rates in women undergoing assisted reproductive techniques.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Other: Z-Score and computer algorithm; Other: Z-Score

Detailed Description

It is the aim of this trial to use a new computerized selection method, in addition to the current and world-wide used scoring system of fertilized oocytes (zygotes) implemented by Scott in 1998, to determine whether this leads to an increase in pregnancy rates in women undergoing assisted reproductive techniques. If successful this could in the future lead to a reduction in the numbers of embryos required to achieve a pregnancy. Transferring only one embryo means minimizing the incidence of high order multiple pregnancies.

Regularly couples gain several fertilized oocytes (zygotes) due to artificial reproductive techniques. As a routine, these cells are archived using pictures and videos for quality and safety reasons in different stages of development. Because it is planned to transfer only one or two developed embryos to the uterus, investigators have to select the zygotes with the highest potential for implantation and pregnancy. The remaining cells are preserved using vitrification.

In the study, investigators use in addition to the established Zygote-score (Z-score) by Scott a new selection method for one group of patients: The quality of the zygotes of all patients is classified according to the described Scott system. Patients are randomized to two groups. Group 1 is the control group without any further intervention. If needed for selection, the quality of the zygotes of the patients of group 2 is additionally scored with a new method. The pictures of the cells, already taken for quality and safety reasons, are taken and the cells surface is analysed using a computer algorithm.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jürgen Weiss, Professor; Phone Number: +41 41 205 36 06; Email: juergen.weiss@luks.ch
• Study Contact Backup: Name: Roger Getzmann; Phone Number: +41 41 205 28 40; Email: roger.getzmann@luks.ch

Study Locations

• Switzerland
  • Luzern, Switzerland, 6000 Luzern 16
    • Recruiting
    • Neue Frauenklinik
    • Contact: Roger Getzmann; Phone Number: +41 41 205 28 40; Email: roger.getzmann@luks.ch
    • Contact: Jürgen Weiss, Professor; Phone Number: +41 41 205 36 08; Email: juergen.weiss@luks.ch
    • Principal Investigator: Jürgen Weiss, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria (for both male and female, couples):

• Woman with age 18 years or older
• Man with age 18 years or older
• Couples who could gain fertilized cells after In vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI) after hormonal stimulation due to sterility treatments
• Couples presenting negative blood samples of human immunodeficiency virus (HIV) and Hepatitis B/C
• Signed routine contracts between hospital and patient wanting assisted reproductive technology (ART)
• Signed informed study consent
• Expectation of life more than 18 years
• No medical contraindication to become pregnant (female)
• Routine criteria for assisted reproductive techniques

Exclusion criteria (for female):

• Poor health status acc. to Investigator's judgement
• Expectation of life below 18 years
• Risk of ovarian hyperstimulation syndrome
• Avital cells (cells that do not further develop or die)
• Treatment due to fertility preservation, e.g. in case of cancer
• Problems after stimulation and follicle puncture
• Endometrial pathologies like polyps, submucous fibroids, etc.
• Any preceding stimulation cycle with endometrial thickness below 6mm
• Less than 4 fertilized oocytes
• Patient (and partner) wishes single embryo Transfer
• Failure to become pregnant with new zygote selection method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Z-Score and computer algorithm	Other: Z-Score and computer algorithm; In addition to the routine Z-score for zygote selection, if needed, the photographs of the zygotes already taken for quality and safety reasons are analysed using the new computer algorithm. Within a few minutes it generates a score, determining the quality of the cells. The two best cells upon Z-score result and new computer algorithm result are selected for first transfer.
ACTIVE_COMPARATOR: Z-Score	Other: Z-Score; After fertilisation pronuclei and nucleoli can be seen inside the cells by microscope. Routinely, the alignment of nucleoli can be used generating a score, the Z-score 1-4, established by Scott. Two zygotes getting the best Z-score are selected for cell culture and the cells that develop to embryo stage are used for first transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	Clinical pregnancy is defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.	min. 4 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing clinical pregnancy	Clinical pregnancy is defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.	min. 9 weeks after embryo transfer
Life Birth	A live birth is defined as the complete expulsion or extraction from its mother of a product of fertilization, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscle, irrespective of whether the umbilical cord has been cut or the placenta is attached.	through study completion, an average of 40 weeks after last menstrual period

Collaborators and Investigators

• Sponsor: Jürgen Weiss
• Investigators: Study Chair: Jürgen Weiss, Professor, Luzerner Kantonsspital, Neue Frauenklinik

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): November 1, 2018

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (ESTIMATE): November 20, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Infertility; Assisted reproductive technology (ART); zygotes; Z-score (Zygote Score)
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: REPROLUKS 002