Microfluidics Versus Gradient Centrifugation Effect on Euploidy Rates

A Double-blind Prospective Randomized Clinical Trial Comparing Euploidy Rates Among Embryos Created From Sibling Oocytes Injected With Sperm Processed by Microfluidics or by Density Gradient Centrifugation

This research is being done to determine if using a microfluidics chamber, a device used to process sperm, will be effective in improving the rates of embryos with normal chromosomes (structures that carry genetic information) during in vitro fertilization (IVF) treatment. The investigators hypothesize that this device is effective at improving rates of normal chromosomes among embryos.

Study Overview

• Status: Active, not recruiting
• Conditions: Infertility; Recurrent Pregnancy Loss
• Intervention / Treatment: Device: Microfluidics chamber; Other: Density Gradient Centrifugation

Detailed Description

As part of the in vitro fertilization (IVF) process, eggs are removed from the ovaries and are inseminated (mixed) or injected with sperm. In order for fertilization to occur, the sperm cells must be separated from the semen before introducing them to the eggs. Currently, sperm are isolated from the semen using a series of wash steps in a centrifuge (device to spin and concentrate the sperm). This requires processing at high speeds in order to separate motile sperm from the other parts of the semen. Although it is common practice, it is possible that this method of processing the semen may cause damage to the sperm cells.

Alternatively, a microfluidics chamber can be used to choose the best sperm. A microfluidics chamber is a small device in which the unwashed sperm can be placed at one end. Sperm that are moving forward will swim through the chamber and come out the other end. Dead sperm are left behind and the sperm with the best motility (how normally they move forward) and normal morphology (how the sperm looks) will make it to the other end of the chamber. These sperm can then be chosen for injection into the egg. This device is FDA-approved for this purpose and is commercially available and is currently routinely used in the IVF lab utilized by the investigators as well as most labs in the country.

Some small initial studies showed that a higher number of embryos with higher quality were made with sperm selected from a microfluidics chamber. In another recent study, the chances of creating an embryo with a normal number of chromosomes (structures that carry genetic information) was also slightly higher if a microfluidics chamber was used to process the sperm. This might be because sperm that have the highest motility and normal morphology may also be more likely to be genetically normal. However, there are no good-quality studies looking at the rates of embryos with normal chromosomes created from using a microfluidics chamber to process sperm.

The purpose of this research study is to determine whether using a microfluidics chamber to process sperm for injection into eggs increases the rates of embryos with normal chromosomes. At the time of egg retrieval, participants will have their eggs randomized (like the flip of a coin) into two groups. Half of the eggs will be injected with sperm processed using gradient centrifugation, the standard method. The other half of the eggs will be injected with sperm processed using a microfluidics chamber. The goal is to determine the rate of embryos with normal chromosomes in each group. Other goals include looking at how many embryos develop to good quality blastocysts and are biopsied and how many patients get pregnant after embryo transfer.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • The Center for Advanced Reproductive Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

• Subjects are nonpregnant females ≥ 18 years and ≤ 42 years of age.
• Subjects obtain ≥ 6 mature oocytes at the time of oocyte retrieval or at the time of ICSI.
• Subjects are utilizing ICSI for fertilization.
• Subjects are utilizing PGT-A (PGT for aneuploidy).
• Subjects are able to understand, read, and write in English at a fifth-grade level.
• Subjects are willing to comply with study protocol and procedures and provide written informed consent.

Exclusion criteria:

• Subjects are utilizing donor oocytes, donor sperm, or gestational carrier.
• Subjects have a diagnosis of severe male factor infertility (sperm concentration < 5 mil/mL at semen analysis).
• Subjects are utilizing surgically removed sperm (e.g. via testicular sperm aspiration [TESA] or microsurgical epididymal sperm aspiration [MESA]).
• Subjects are utilizing frozen/thawed sperm.
• Subjects are utilizing frozen/thawed oocytes.
• Subjects are undergoing a day 3 (cleavage stage) embryo transfer.
• Subjects obtain < 6 mature oocytes at the time of oocyte retrieval or at the time of ICSI.
• Subjects obtain ≥ 6 mature oocytes but choose to fertilize fewer than 6 of them.
• Sperm sample parameters are low on the day of oocyte retrieval (semen volume < 1.0 mL or concentration < 1 million motile/mL).
• Male partner has an infectious disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microfluidics; Half of participants eggs will be injected with sperm processed using a microfluidics chamber.	Device: Microfluidics chamber; Unwashed sperm will be placed into the inlet chamber of the microfluidics device. The most motile sperm will swim to the outlet chamber, and these sperms will be used for intracytoplasmic sperm injection (ICSI) into the eggs.; Other Names: ZyMot Fertility (device brand name)
Active Comparator: Density gradient centrifugation; Half of participants eggs will be injected with sperm processed using a density gradient centrifugation (the standard method).	Other: Density Gradient Centrifugation; Sperm will be washed and centrifuged according to standard protocol, and these washed sperm will be used for ICSI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Euploidy rate of resulting embryos	Rate of embryos with normal chromosomes in both groups	Within 2-4 weeks of IVF cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy rates after transfer of euploid embryos	Pregnancy rate after one euploid embryo (from either experimental or control group) is transferred back into the participant in a subsequent cycle	Within 1-2 cycles of fresh IVF cycle

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA fragmentation results	Compare DNA fragmentation results between groups	1-2 years after initial study completed

Collaborators and Investigators

• Sponsor: Lawrence Engmann
• Collaborators: The Center for Advanced Reproductive Services, P.C.; ZyMot Fertility
• Investigators: Principal Investigator: Lawrence Engmann, MD, UConn Health; Principal Investigator: Alison Bartolucci, PhD, The Center for Advanced Reproductive Services, P.C.

Publications and helpful links

Helpful Links

• The Center for Advanced Reproductive Services Website

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Actual): August 15, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: In vitro fertilization; Microfluidics; Euploidy; Density gradient centrifugation; Preimplantation genetic testing; Sperm processing
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 21-106R-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Undecided at this time, may be available upon request in the future

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes