InfertilityNCT04744025
Microfluidics Versus Gradient Centrifugation Effect on Euploidy Rates
A study testing Microfluidics chamber and Density Gradient Centrifugation in people with Infertility and Recurrent Pregnancy Loss, run by Lawrence Engmann at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Infertility, Recurrent Pregnancy Loss
- What is being tested?
- Microfluidics chamber and Density Gradient Centrifugation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2021to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Center for Advanced Reproductive Services
Farmington, Connecticut, 06032
About this study
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
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.
Read the 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.
- Conditions
- Infertility, Recurrent Pregnancy Loss
- Being tested
- Microfluidics chamber, Density Gradient Centrifugation
- Keywords
- Microfluidics, Density gradient centrifugation, In vitro fertilization, Preimplantation genetic testing, Euploidy, Sperm processing
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microfluidics chamberDevice
Also called ZyMot Fertility (device brand name)
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.
Density Gradient CentrifugationOther
Sperm will be washed and centrifuged according to standard protocol, and these washed sperm will be used for ICSI.
| Study group | Role | What they receive |
|---|---|---|
| Microfluidics | Experimental | Half of participants eggs will be injected with sperm processed using a microfluidics chamber. Receives: Device: Microfluidics chamber |
| Density gradient centrifugation | Active comparator | Half of participants eggs will be injected with sperm processed using a density gradient centrifugation (the standard method). Receives: Other: Density Gradient Centrifugation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Euploidy rate of resulting embryos
Rate of embryos with normal chromosomes in both groups
Measured: Within 2-4 weeks of IVF cycle
Secondary outcomes (1)
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
Measured: Within 1-2 cycles of fresh IVF cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start13 Jan 2021
- Primary completion15 Aug 2022
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lawrence Engmann
- Sponsor type
- University, hospital or other
- Collaborators
- The Center for Advanced Reproductive Services, P.C., ZyMot Fertility
- Responsible party
- Sponsor-investigator, Lawrence Engmann, The Center for Advanced Reproductive Services, P.C.
- Investigators
- Lawrence Engmann, MD, Principal investigator, UConn HealthAlison Bartolucci, PhD, Principal investigator, The Center for Advanced Reproductive Services, P.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04744025
- Sponsor's protocol ID
- 21-106R-1
- Status last verified
- Sep 2022
- First submitted
- 3 Feb 2021
- Last updated
- 3 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: Undecided at this time, may be available upon request in the future
Publications
Godiwala P, Kwieraga J, Almanza E, Neuber E, Grow D, Benadiva C, Makhijani R, DiLuigi A, Schmidt D, Bartolucci A, Engmann L. The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial. Fertil Steril. 2024 Jul;122(1):85-94. doi: 10.1016/j.fertnstert.2024.02.021. Epub 2024 Feb 15.
PubMed 38367686
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04744025
- Acronym / sponsor ID
- 21-106R-1
- Conditions
- Infertility, Recurrent Pregnancy Loss
- Keywords
- Microfluidics, Density gradient centrifugation, In vitro fertilization, Preimplantation genetic testing, Euploidy, Sperm processing
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Lawrence EngmannUniversity, hospital or other
- Collaborators
- The Center for Advanced Reproductive Services, P.C., ZyMot Fertility
- Study start
- 13 Jan 2021 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 8 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Microfluidics | Experimental | Device: Microfluidics chamberHalf of participants eggs will be injected with sperm processed using a microfluidics chamber. |
| Density gradient centrifugation | Active comparator | Other: Density Gradient CentrifugationHalf of participants eggs will be injected with sperm processed using a density gradient centrifugation (the standard method). |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microfluidics chamberAlso: ZyMot Fertility (device brand name)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. | Device | Microfluidics |
| Density Gradient CentrifugationSperm will be washed and centrifuged according to standard protocol, and these washed sperm will be used for ICSI. | Other | Density gradient centrifugation |
Primary outcome
Euploidy rate of resulting embryos
Time frame: Within 2-4 weeks of IVF cycle
Rate of embryos with normal chromosomes in both groups
1 secondary outcome
Pregnancy rates after transfer of euploid embryos
Time frame: Within 1-2 cycles of fresh IVF cycle
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2022.
- Derived from this study: PubMed 38367686Godiwala P, Kwieraga J, Almanza E, Neuber E, Grow D, Benadiva C, Makhijani R, DiLuigi A, Schmidt D, Bartolucci A, Engmann L. The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial. Fertil Steril. 2024 Jul;122(1):85-94. doi: 10.1016/j.fertnstert.2024.02.021. Epub 2024 Feb 15.
- The Center for Advanced Reproductive Services WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Undecided at this time, may be available upon request in the future
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Engmann, MD principal investigator
UConn Health
Alison Bartolucci, PhD principal investigator
The Center for Advanced Reproductive Services, P.C.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Microfluidics chamber and Density Gradient Centrifugation in people with Infertility and Recurrent Pregnancy Loss, run by Lawrence Engmann at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Euploidy rate of resulting embryos (time frame: Within 2-4 weeks of IVF cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04744025, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2022.