Evaluating Piezo-ICSI. - The EPI Study.

Study Overview
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Brief Summary
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Intracytoplasmic sperm injection (ICSI) has successfully been used to treat both severe male infertility and fertilization failure since its introduction in the early 1990´s. During the procedure a single sperm is injected into the cytoplasm of an oocyte to achieve fertilization. This technique is intrusive, has a relatively long learning curve and variable operator performance. A new injection technique called piezo-ICSI has recently been introduced. During piezo-ICSI, a piezo-electric effect is generated through the conversion of electric energy to mechanical energy. This causes a smooth movement of the injection pipette, which allows for steady, controlled microinjections with less psychical stress applied on the oocytes than by the conventional technique. A recent analysis, based on data from 9 different studies comparing conventional ICSI and piezo-ICSI (17500 cases), showed a benefit of piezo. Unfortunately, proper randomized trials are missing from this analysis. The proposed study is a randomized controlled study carried out at two private IVF clinics. Eligible participants are patients undergoing ICSI treatment, with a minimum of 6 oocytes. The participants will act as their own controls, with their oocytes randomly and equally divided between injection by the investigated and the conventional technique. Whether piezo-ICSI is associated with improved success rates or reduction in adverse outcomes is at present unclear. Patients with fragile oocytes may benefit more from piezo-ICSI. In patients above 35 years, piezo-ICSI has been associated with a lower oocyte degeneration rate and an increased blastocyst rate. The aim of the study is to investigate whether the piezo-ICSI technique will result in more oocytes becoming normally fertilized compared to conventional ICSI. Another proposed benefit of piezo-ICSI lies in the standardization and simplification of the ICSI procedure. Making the injection procedure more independent of operator skill may result in a more robust and predictable laboratory output.

Official Title
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Will Piezo-ICSI Increase Fertilization Rates Compared to Conventional ICSI? A Prospective Randomized Sibling Study.

Conditions
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Infertility, IVF

Intervention / Treatment
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* Device: Piezo-ICSI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients receiving controlled ovarian stimulation with gonadotrophins needing ICSI for fertilizing oocytes. Availability of at least six mature oocytes (MII) after oocyte pick-up. Planned blastocyst culture. Exclusion Criteria: Intention to perform any form of preimplantation genetic testing The use of IMSI or polarized light in the ICSI process The use of assisted hatching prior to randomization. Surgical sperm retrieval (SSR) patients. Previous participation in this RCT Concurrent participation in another investigation that can affect the primary outcome of this study. Sperm sample with <0.1million/ml or motility of <2% after preparation. Fertility preservation cycles. If a day 2-4 transfer is planned Use of vitrified oocytes.
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
Interventional Model Description: A sibling study randomizing oocytes to 2 study groups.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: ICSI<br>Traditional microinjection (ICSI) is performed on oocytes. | |
| Experimental: Piezo-ICSI<br>Microinjection (ICSI) is performed using the Piezo-ICSI technique. | Device: Piezo-ICSI<br>* During piezo-ICSI, a piezo-electric effect is generated through the conversion of electric energy to mechanical energy. This causes a smooth movement of the injection pipette, which allows for steady, controlled microinjection of a sperm with less psychical stress applied on the oocytes than by the conventional technique.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fertilization rate | Number of normally fertilized oocytes per injected oocytes | Oocytes will be observed over a period of 26 hours after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of degenerated oocytes | Number of oocytes that have degenerated after the procedure | Oocytes will be observed over a period of 26 hours after the intervention | 
| Percentage of 0 PN oocytes | Number of oocytes not fertilized (0 PN) after the procedure. | Oocytes will be observed over a period of 26 hours after the intervention | 
| Percentage of 1 PN oocytes. | Number of oocytes fertilized with one pronuclei (1 PN) after the procedure. | Oocytes will be observed over a period of 26 hours after the intervention | 
| Percentage of >2PN oocytes. | Number of oocytes fertilized with more than 2 pronuclei (>2PN) after the procedure. | Oocytes will be observed over a period of 26 hours after the intervention | 
| Differences in KID scores. | Embryo development will be analysed using a mathematical models called KID (0-10 scale). | Embryos will be observed over a period of 6 days after the procedure | 
| Differences in iDA scores. | Embryo development will be analyzed using a artificial intelligence model, called iDA (0-10 scale). | Embryos will be observed over a period of 6 days after the procedure | 
| Blastocyst rate (number of grade 3 or higher). | Number of blastocysts with a morphological score of grade 3 or higher. | Embryos will be observed over a period of 6 days after the procedure | 
| Percentage of cryopreserved blastocysts on day 5 and 6. | Number of blastocysts cryopreserved on day 5 and day 6. | Embryos will be observed over a period of 6 days after the procedure | 
| 8. Utilization rate (Number of transferred and cryopreserved blastocysts). Utilization rate | Number of transferred and cryopreserved blastocysts | Embryos will be observed over a period of 6 days after the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICSI, Fertilization, Piezo-ICSI, Oocyte, Blastocyst rate