Vitrification Versus Slow Cooling of Human Cleavage Stage Embryos

Study Overview
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Brief Summary
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Human embryos can be preserved for later transfers by freezing. Traditionally the slow cooling method has been used. About 70% of the embryos remain fully intact after thawing. However, the remaining 30% of the embryos become (partially) damaged, and this freezing damage reduces their chance to implant. Recently an ultra rapid freezing method, called vitrification has been developed. During vitrification no damaging ice crystals are formed and the embryo freezes in a glass like state. It appears that the freezing damage is reduced when embryos are vitrified. Observational studies in humans indicate that embryos are successfully preserved by vitrification, as indicated by promising pregnancy rates following thawing. However, the effectiveness of vitrification in relation to slow cooling with respect to pregnancy rates has so far not been evaluated by a randomised, controlled trial. The aim of this study is to investigate whether vitrification significantly improves embryo survival and ongoing pregnancy rates when compared to embryos frozen by slow cooling.

Detailed Description
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time of allocation: following embryo selection type of embryos: cleavage stage -, morula stage or early blastocyst stage embryo (day3 - day4 after oocyte collection) cryoprotectants: sucrose, dimethylsulfoxide, ethyleneglycol vitrification storage device: high security vitrification straws

Official Title
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A Double Blinded, Randomised Controlled Trial Comparing the Effectiveness of Vitrification to Slow Cooling in Cryopreserving Human Preimplantation Embryos

Conditions
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Infertility

Intervention / Treatment
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* Other: embryo vitrification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patient age 35 years or less embryos are obtained by in vitro fertilization (IVF) or intra cytoplasmatic spermatozoon injection (ICSI) single embryo transfer 1rst IVF/ICSI treatment with an embryo transfer availability of cryopreservable embryos Exclusion Criteria: female patient age is 36 years or older participants of oocyte donation program participants of percutaneous spermatozoon aspiration (PESA) program couples with a finite source of spermatozoa absence of cryopreservable embryos

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Vitrification<br>The embryos of patients allocated to this arm will be cryopreserved by vitrification. | Other: embryo vitrification<br>* Ultra rapid cooling of embryos by immersion in liquid nitrogen. The formation of potentially damaging ice crystals is prevented by briefly incubating the embryos in high concentrations of a mix of cryoprotectants.<br>* Other names: high security vitrification straws;|
| No Intervention: Slow cooling<br>The embryos of patients allocated to this arm will be cryopreserved by the slow cooling method, which is the standard method (=no intervention) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent change of the ongoing pregnancy rate per patient/couple who use their thawed embryos (following a fesh embryo transfer which did not result in an ongoing pregnancy) from baseline (slow cooling) to end point (vitrification). |  | ongoing pregnancy is established 10 weeks following the transfer of a frozen embryo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| post-thaw embryo survival rate |  | 1 hour after thawing | 
| ongoing pregnancy rate per patient using their thawed embryos (independent of whether they became pregnant following a fresh embryo transfer or not |  | 10 weeks following transfer of frozen thawed embryo | 
| implantation rate per thawed embryo |  | 10 weeks after transfer of thawed embryo | 
| implantation rate per transferred thawed embryo |  | 10 weeks after transfer of thawed embryo | 
| cumulative implantation rate per cryopreservation |  | 10 weeks after thawed embryo transfer | 
| ongoing pregnancy rate per frozen-thaw cycle |  | 10 weeks following thawed embryo transfer | 
| average number of frozen-thawed cycles per patient |  | is variable | 
| post thaw development (categorial) per thawed embryo |  | 24 hours following thawing | 
| average number of cryo-thaw cycles to ongoing pregnancy |  | variable, up to 3 years | 
| average number of thawed embryos to ongoing implantation |  | variable, up to 3 years | 
| Life birth rate |  | 9 month after pregnancy test | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, embryo cryopreservation, vitrification, slow cooling, slow freezing, surplus embryos, Human Reproduction