Improvement of Cell Selection in Reproductive Techniques

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infertility

Intervention / Treatment
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* Other: Z-Score and computer algorithm
* Other: Z-Score


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Z-Score and computer algorithm<br> | Other: Z-Score and computer algorithm<br>* 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.<br>|
| Active Comparator: Z-Score<br> | Other: Z-Score<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Assisted reproductive technology (ART), zygotes, Z-score (Zygote Score), Infertility