Automated Sperm Selection
Primary Purpose
Infertility
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Automated sperm selection software
Sponsored by
About this trial
This is an interventional basic science trial for Infertility focused on measuring In Vitro Fertilization, Embryology, Oocyte, Sperm, Automated Sperm Selection, DNA Fragmentation Index
Eligibility Criteria
Inclusion Criteria:
- Patients undergoing ICSI
- Female partner between 19-43 years of age using own or donor oocytes
Exclusion Criteria:
- Patients who do not provide informed consent
- Patients with less than 6 mature eggs collected
- Patients undergoing IVF without ICSI
- Morphology <4% normal forms
- 100% immotile sperm
- Cases where surgically-retrieved sperm is used for ICSI
Sites / Locations
- CReATe Fertility CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Standard sperm selection
Automated sperm selection
Arm Description
In the control group the oocytes will be injected with sperm that is selected by embryologists using conventional methods in the IVF lab.
The only intervention is the additional sperm selection step using software immediately prior to ICSI.
Outcomes
Primary Outcome Measures
Fertilization rate
Fertilization is defined as the visualization of 2 pronuclear at day 1 post ICSI. The proportion of fertilized eggs for each patient will be calculated as fertilization rate. Each patient's data will be aggregated to calculate the overall fertilization rate for all patients.
Blastocyst formation rate
The proportion of fertilized embryos classified as blastocysts at day 5 or day 6 of development.
Embryo morphology grade as evaluated by the SART grading system
The morphology grade (good, fair, poor) for each embryo will be evaluated. Grades for all embryos of each patient will be summarized.
Secondary Outcome Measures
Differences in early embryo cleavage divisions and late developmental (blastocyst) morphokinetics.
Embryo morphokinetic parameters will be calculated from time-lapse embryo development videos using an EmbryoScope embryo culture system. The evaluated morphokinetic parameters for each embryo include:
time of pronuclei formation
time of cleavage to a two-cell embryo
time of cleavage to a three-cell embryo
time of cleavage to a four-cell embryo
time of cleavage to a six-cell embryo
time of cleavage to a eight-cell embryo
time to full blastocyst
Differences in the proportion of euploid and aneuploid embryos between the two groups
Embryo ploidy will be evaluated by preimplantation genetic testing technique for aneuploidy.
Evaluation of patient demographic and stimulation cycle characteristics for confounding variables.
We will also compare primary outcome measures (fertilization rate, PGT-A results, blastocyst formation rate, embryo grade) of all embryos in the study (control and study group) to the overall rates in the clinic as a measure of quality assurance of the study.
Full Information
NCT ID
NCT05240469
First Posted
October 15, 2021
Last Updated
May 5, 2022
Sponsor
Create Fertility Center
Collaborators
University of Toronto
1. Study Identification
Unique Protocol Identification Number
NCT05240469
Brief Title
Automated Sperm Selection
Official Title
A Prospective, Parallel-group, Non-inferiority Study to Compare the Efficacy of an Automated Sperm Selection Method Versus Manual Sperm Selection for ICSI
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Create Fertility Center
Collaborators
University of Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Intracytoplasmic sperm injection (ICSI) is one of the standard clinical treatments for infertility. ICSI involves the injection of a single sperm into an oocyte with a sharp micropipette. Injecting a sperm with DNA fragmentation (i.e., physical breakage of the DNA double strands) into the oocyte deterministically lowers the IVF fertilization rate [1][2] and increases the miscarriage rate [3][4]. Since the invention of ICSI in 1992, single sperm selection in ICSI has been made manually by embryologists, who select sperm by qualitatively choosing sperm with "good" motility and/or morphology based on their empirical experience. This involves significant subjectivity and inconsistency. We have developed a robotic system to select sperm with low sperm DNA fragmentation. Automated sperm selection also eliminates the subjectivity and inconsistency in manual sperm selection. The system consists of a camera to acquire images of sperm and a software to analyze the images. Embryologists select sperm by observing the same sperm characteristics as in the software criteria (e.g., speed etc.), but the software provides a more accurate and quantitative measure of sperm characteristics, thus ensuring the selected sperm have low DNA fragmentation.
Detailed Description
Intracytoplasmic sperm injection (ICSI) is one of the standard clinical treatments for infertility. ICSI involves the injection of a single sperm into an oocyte with a sharp micropipette. Injecting a sperm with DNA fragmentation (i.e., physical breakage of the DNA double strands) into the oocyte deterministically lowers the IVF fertilization rate [1][2] and increases the miscarriage rate [3][4]. Patients with high sperm DNA fragmentation suffer from repeated IVF failures [8], causing heavy burdens on families and the healthcare system. Since the invention of ICSI in 1992, single sperm selection in ICSI has been made manually by embryologists, who select sperm by qualitatively choosing sperm with "good" motility and/or morphology based on their empirical experience. This involves significant subjectivity and inconsistency.
We have developed a robotic system to select sperm with low sperm DNA fragmentation. Automated sperm selection also eliminates the subjectivity and inconsistency in manual sperm selection. The system consists of a camera to acquire images of sperm and a software to analyze the images. The software automatically measures the 9 motility parameters (e.g., curvilinear speed, path linearity, etc.) and 11 morphology parameters (e.g., head ellipticity, midpiece width etc.). All these 20 parameters are defined by the WHO guidelines [9]. Embryologists select sperm by observing the same sperm characteristics as in the software criteria (e.g., speed etc.), but the software provides a more accurate and quantitative measure of sperm characteristics, thus ensuring the selected sperm have low DNA fragmentation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
In Vitro Fertilization, Embryology, Oocyte, Sperm, Automated Sperm Selection, DNA Fragmentation Index
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Care Provider
Allocation
Randomized
Enrollment
330 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard sperm selection
Arm Type
No Intervention
Arm Description
In the control group the oocytes will be injected with sperm that is selected by embryologists using conventional methods in the IVF lab.
Arm Title
Automated sperm selection
Arm Type
Experimental
Arm Description
The only intervention is the additional sperm selection step using software immediately prior to ICSI.
Intervention Type
Device
Intervention Name(s)
Automated sperm selection software
Intervention Description
The software measures both morphology and motility similar to an embryologist but provides a more accurate and consistent measure of sperm characteristics. Embryologists use their experience to qualitatively judge if an individual sperm is "suitable for injection" based on morphology and motility. Similarly, the software follows a two-step process: firstly, a computer vision algorithm measures characteristics of all sperm in a given field, including motility and morphology; secondly, the software algorithm then uses a set of quantitative criteria to categorize and identify the most developmentally competent sperm with normal characteristics. All the characteristics that the software calculate are defined by the WHO guidelines, and the software does not propose or define new parameters.
Primary Outcome Measure Information:
Title
Fertilization rate
Description
Fertilization is defined as the visualization of 2 pronuclear at day 1 post ICSI. The proportion of fertilized eggs for each patient will be calculated as fertilization rate. Each patient's data will be aggregated to calculate the overall fertilization rate for all patients.
Time Frame
1 day
Title
Blastocyst formation rate
Description
The proportion of fertilized embryos classified as blastocysts at day 5 or day 6 of development.
Time Frame
5 or 6 days
Title
Embryo morphology grade as evaluated by the SART grading system
Description
The morphology grade (good, fair, poor) for each embryo will be evaluated. Grades for all embryos of each patient will be summarized.
Time Frame
5 or 6 days
Secondary Outcome Measure Information:
Title
Differences in early embryo cleavage divisions and late developmental (blastocyst) morphokinetics.
Description
Embryo morphokinetic parameters will be calculated from time-lapse embryo development videos using an EmbryoScope embryo culture system. The evaluated morphokinetic parameters for each embryo include:
time of pronuclei formation
time of cleavage to a two-cell embryo
time of cleavage to a three-cell embryo
time of cleavage to a four-cell embryo
time of cleavage to a six-cell embryo
time of cleavage to a eight-cell embryo
time to full blastocyst
Time Frame
5 or 6 days
Title
Differences in the proportion of euploid and aneuploid embryos between the two groups
Description
Embryo ploidy will be evaluated by preimplantation genetic testing technique for aneuploidy.
Time Frame
5 or 6 days
Title
Evaluation of patient demographic and stimulation cycle characteristics for confounding variables.
Description
We will also compare primary outcome measures (fertilization rate, PGT-A results, blastocyst formation rate, embryo grade) of all embryos in the study (control and study group) to the overall rates in the clinic as a measure of quality assurance of the study.
Time Frame
5 or 6 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
43 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients undergoing ICSI
Female partner between 19-43 years of age using own or donor oocytes
Exclusion Criteria:
Patients who do not provide informed consent
Patients with less than 6 mature eggs collected
Patients undergoing IVF without ICSI
Morphology <4% normal forms
100% immotile sperm
Cases where surgically-retrieved sperm is used for ICSI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clifford L Librach, MD
Phone
416-323-7727
Email
drlibrach@createivf.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yu Sun, PhD
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
CReATe Fertility Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1N8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Research Coordinator
Phone
416-323-7727
Ext
2950
Email
researchcoordinator@createivf.com
First Name & Middle Initial & Last Name & Degree
Justin Tan
Phone
416-323-7727
Ext
2124
Email
justint@createivf.com
First Name & Middle Initial & Last Name & Degree
Clifford Librach, MD
12. IPD Sharing Statement
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Automated Sperm Selection
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