Study of the ZyMōt Sperm Selection Method and Its Effect on Embryo Ploidy. (ZYMOT2)

It has been described that 11% of men with semen values within the normal range established by the World Health Organization (WHO) have sperm DNA fragmentation. This has been associated with a lower fertilization rate, lower embryo development and, therefore, lower reproductive success. Focusing on the study of the integrity of the male genome can provide us information to diagnose infertility in the couple. The use of conventional sperm selection methods such as swim-up or density gradients has been a great advance in the improvement of male fertility. However, these methods use centrifugation in their protocol, a procedure that has been associated with sperm DNA damage. The ZyMōt is a chip based on microfluidic properties that allows the recovery of spermatozoa with lower DNA fragmentation rate without centrifugation of the semen sample. This new sperm selection method maintains all the advantages of conventional techniques, but decreasing DNA fragmentation associates to sperm recoveries techniques eventually improving reproductive rates. This quality would be beneficial for patients with unexplained infertility, recurrent pregnancy loss or clinical varicocele, factors that have been associated with a higher index of DNA fragmentation. However up to date there is evidence-based data supporting such improvement. The main objective of the present project is to evaluate the ZyMōt as a new non-invasive sperm selection device and to see its impact on the euploidy rate, comparing it with a sperm selection technique that is routinely used in the clinic: swim-up. At the same time, the effect that this new chip may have on sperm and other reproductive variables will be analyzed clinically, and molecularly with immunohistochemical and transcriptomic analyses in order to observe the impact of SDF(sperm DNA fragmentation) at the molecular and genomic level in oocytes with low reparative potential oocytes.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Male; Sperm Count, Low
• Intervention / Treatment: Procedure: Swim-up; Device: Sperm capacitation through the ZyMōt®Sperm Separation Device®

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: MARIA LUISA PARDIÑAS, Pre-Doc; Phone Number: +34 963.05.90.00; Email: marialuisa.pardiñas@ivirma.com

Study Locations

• Spain
  • Madrid, Spain, 28023
    • Recruiting
    • IVIRMA MADRID
    • Contact: MONICA TORIBIO; Phone Number: +34 651 79 10 00; Email: IVESMADRID@IVIRMA.COM
    • Sub-Investigator: Alberto Pacheco, PhD
    • Sub-Investigator: Lucía Sánchez, MSc
  • Valencia, Spain, 46015
    • Recruiting
    • IVIRMA Valencia
    • Principal Investigator: Maria Jose Delossantos, PhD
    • Contact: Maria Jose Delossantos, PhD; Phone Number: 34963050900; Email: mariajose.delossantos@ivi.es
    • Contact: Laura Caracena, Mrs; Phone Number: 11054 34963050900; Email: laura.caracena@ivirma.com
    • Sub-Investigator: José María Delosantos, PhD
    • Principal Investigator: Angel Martín, MSc
    • Principal Investigator: David Ortega, MSs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Couples undergoing an ICSI cycle with PGT-A (Preimplantational Genetic Test for Aneuploidy).
• Males over 18 years of age whose semen sample meets the basic conditions predetermined by the ZyMōt Multi 850µL chip.
• Fresh semen samples.
• Embryos are to be deposited in a time-lapse incubator.
• Women over 37 years of age who have obtained in follicular puncture a number of MII oocytes greater than or equal to 4.

Exclusion Criteria:

• Males with severe asthenozoospermia (<10% progressively motile spermatozoa), globozoospermia (spermatozoa with morphological alterations and lack of acrosome) and/or azoospermia (absence of spermatozoa in the ejaculate).
• Seminal samples obtained by testicular biopsy.
• Samples incubated with calcium ionophore.
• Males and females with previously known abnormal karyotype.
• Oocytes coming from the oocyte donation program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SWIM-UP; Half of the sample from the same patient will be processed by the capacitation technique routinely used in the clinic, swim-up: this is a sperm capacitation technique in which the motile spermatozoa in the seminal sample, after centrifugation and incubation, move to the top of the medium. In this way, spermatozoa with good progressive motility will remain in the supernatant.	Procedure: Swim-up; The swim-up is a sperm capacitation technique in which the motile spermatozoa of the seminal sample, after centrifugation and incubation, move to the upper part of the medium. In this way, spermatozoa with good progressive motility will remain in the supernatant.; Other Names: Sperm capacitation throught swim-up technique
Experimental: ZYMOT; Half of the semen sample will be processed through the ZyMōt® Sperm Separation Device sperm separation chip: This chip based on microfluidic properties will help us to separate and recover the semen sample with an improvement in the quality of the spermatozoa, the capacitated spermatozoa with better motility will be selected.	Device: Sperm capacitation through the ZyMōt®Sperm Separation Device®; This chip based on microfluidic properties will help us to separate and recover the semen sample with improved sperm quality. It is composed of two microwells, one initial and one final, and a porous membrane through which the sample will be filtered and the capacitated spermatozoa with better motility will be selected. Syringe 850µL of the initial seminal sample into the first well and 750µL of seminal wash medium into the second well. The device is incubated at 37°C for up to 30 minutes. During this incubation, the sample will travel by microfluidic properties from the first well through the porous membrane to the second well. This membrane will filter those spermatozoa with a higher motility. Thus, at the end of the established incubation time, the medium with the selected spermatozoa from the second well (final well) will be collected with a syringe. After this, the sample will be processed and ready for the following procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EUPLOIDY RATE	Evaluate euploidy rate and compare it between both groups	1 YEAR

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MOBILITY RATE	Evaluate and compare mobility between both groups	1 year
VITALITY RATE	Evaluate and compare vitality between both groups	1 year
DNA FRAGMENTATION RATE	Evaluate and compare DNA fragmentation between both groups	1 YEAR
SPERM RETRIEVAL RATE	Evaluate and compare sperm retrieval rate between both groups	1 years
FERTILIZATION RATE	Evaluate the effect of ZyMōt on the fertilization rate	1 year
USEFUL BLASTOCYS RATE	To evaluate number of useful blastocyst per number of MII oocyte injected and fertilized.	1 year

Collaborators and Investigators

• Sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Collaborators: IVI Madrid
• Investigators: Principal Investigator: MARIA JOSE DE LOS SANTOS, PhD, IVIRMA Valencia

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Embryo development; Euploidy; ZyMöt; Sperm fragmentation
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Infertility; Infertility, Male; Oligospermia
• Other Study ID Numbers: 2211-VLC-157-MD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No