Clinical trial NCT04744025: Microfluidics Versus Gradient Centrifugation Effect on Euploidy Rates
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility
Recurrent Pregnancy Loss
Keywords: Microfluidics
Density gradient centrifugation
In vitro fertilization
Preimplantation genetic testing
Euploidy
Sperm processing
Lead sponsor: UConn Health
Sponsor class: OTHER
Collaborators: name: The Center for Advanced Reproductive Services, P.C.
name: ZyMot Fertility
First posted: 2021-02-08
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sibling oocyte study: Participants will have their oocytes (eggs) divided into two groups. Half of the eggs will be injected with sperm processed in the normal way, and half will be injected with sperm processed via a microfluidics chamber.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Euploidy rate of resulting embryos
timeFrame: Within 2-4 weeks of IVF cycle
Secondary outcomes:
measure: Pregnancy rates after transfer of euploid embryos
timeFrame: Within 1-2 cycles of fresh IVF cycle
Other outcomes:
measure: DNA fragmentation results
timeFrame: 1-2 years after initial study completed
Locations:
city: Farmington
country: United States
facility: The Center for Advanced Reproductive Services
state: Connecticut
Study officials:
affiliation: UConn Health
name: Lawrence Engmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Center for Advanced Reproductive Services, P.C.
name: Alison Bartolucci, PhD
role: PRINCIPAL_INVESTIGATOR
References: