InfertilityNCT05978947
Microfluidic Chip Method Versus Density Gradient Centrifugation Method on Semen Parameters
A study testing ZyMōt Multi 850µL device and Density Gradient Centrifugation Method in people with Infertility, run by Professor Ernest Hung-Yu Ng at 1 site in China.
Trial summary
Infertility affects many couples, with male infertility being a common cause. In vitro fertilization (IVF) is an effective treatment, but its success rates are not high. Semen quality can affect IVF outcomes, and the current method used to process semen can damage the sperm and DNA. Read more about this study
- Who is it for?
- Any age, men onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- ZyMōt Multi 850µL device and Density Gradient Centrifugation Method
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2023to 31 Mar 2025
- 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 Any age
- Men only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Sperm concentration of the raw semen with at least 5 million motile sperm per ml with a total volume of not less than 1.5ml.
Who cannot join
- Sperm concentration of the raw semen of less than 5 million motile sperm per ml
- Men unable to provide an ejaculated semen sample
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Department of Obstetrics and Gynaecology
Hong Kong, Hong Kong
Ernest HY NG, MD, 852-22553400, nghye@hku.hk
Ernest HY NG, MD
About this study
Official title: Effect of Sperm Preparation by a Microfluidic Chip Method Versus a Density Gradient Centrifugation Method on Semen Parameters
Infertility affects many couples, with male infertility being a common cause. In vitro fertilization (IVF) is an effective treatment, but its success rates are not high. Semen quality can affect IVF outcomes, and the current method used to process semen can damage the sperm and DNA. Scientists are now testing a new method called microfluidic chip technology, which reduces DNA damage and increases sperm movement. This study will compare the effectiveness of the chip method and the current method on semen quality in men attending a fertility clinic. The study will randomly assign semen collected to one of the two methods and assess the semen quality using different tests, as well as the difference in using two different microfluidic chip platform . The primary outcome will be DNA fragmentation, and other outcomes include sperm count and motility. Semen samples would be collected from study subjects for analysis and that both the samples and results would not be used in patients' treatment.
Read the detailed description
Infertility affects one in six couples and is getting more common as many women delay marriage and childbirth for various reasons. In vitro fertilization (IVF) is the most effective treatment for couples with long standing infertility and has treated millions of infertile couples over the world since the first birth of IVF was reported more than 40 years ago. However, despite advances in technology, the pregnancy and birth rates remain around 35% and 25% per transfer in Europe in 2018. Among all infertile couples, 20-30% are due to male infertility. Semen parameters may affect the IVF outcomes and it was hypothesized that the relative contribution of sperm to a live birth is around 10-15%.
IVF involves hormone injections to stimulate a woman's ovaries to produce a number of oocytes which are collected by a minor operation and then mixed with sperm to form embryos in the laboratory. Usually, one or two embryos are transferred to the uterus 2-5 days after oocyte retrieval. In IVF, semen samples produced by husbands are commonly processed by a density gradient centrifugation method to isolate the better spermatozoa for fertilization. The density gradient centrifugation can enrich spermatozoa with relatively good motility and normal morphology. It is possible to recover spermatozoa from semen specimens with a very low sperm density. It can provide a relatively good yield. However, it requires technical training to set up the density gradient consisting of two media with different densities. During semen processing, spermatozoa are centrifuged through the gradient. It is known that centrifugation causes considerable damage to spermatozoa by the reactive oxygen species produced during the process. Reactive oxygen species are known to be one of the major causes leading to sperm DNA fragmentation and subsequent adverse outcomes including implantation failure and miscarriage. A meta-analysis showed sperm DNA damage has a negative effect on clinical pregnancy following IVF.
A microfluidic chip, which is a miniaturized device containing channels and chambers in the microscale range for nanoparticle preparation, is being used as an alternative sperm preparation technique recently. By employing microfluidic technology, spermatozoa can go through the chip that closely simulates the natural selection in the female genital tract microenvironment. The technology enables the selection of high-quality motile spermatozoa from semen samples without the need for centrifugation, leading to reduced reactive oxygen species formation.
Studies have consistently demonstrated that the use of a microfluidic chip method greatly reduces DNA fragmentation and increases motility when compared with the density gradient centrifugation method.
This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.
Objectives:
The first objective of this randomized controlled trial is to compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation on semen parameters. The hypothesis is that the use of sperm preparation by a microfluidic chip method improves semen parameters.
The second objective is to compare the effect of two different microfluidic chip platforms on semen parameters.
Trial design:
Men attending at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital for fertility treatment will be recruited.
- Conditions
- Infertility
- Being tested
- ZyMōt Multi 850µL device, Density Gradient Centrifugation Method
- Keywords
- Semen parameters, Microfluidic chip, Density Gradient Centrifugation
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZyMōt Multi 850µL deviceDevice
The ZyMōt Multi 850µL device is a laboratory tool designed for use in assisted reproductive technology (ART) procedures such as intrauterine insemination (IUI) and in vitro fertilization (IVF). It is a sperm preparation device that uses a proprietary patented technology to isolate and select motile sperm from semen samples for use in ART procedures.
Density Gradient Centrifugation MethodDevice
Density gradient centrifugation is a laboratory technique used to separate and isolate different types of cells or particles based on their density. It is commonly used in various applications, including cell biology, immunology, and assisted reproductive technology (ART).
| Study group | Role | What they receive |
|---|---|---|
| Microfluidic Chip Method | Experimental | The Sperm Separation Device - ZyMōt Multi 850µL device (ZyMōt Fertility, Inc) will be used. The microfluidic chamber will be used based on the manufacturer's instructions. 850 μL of the semen sample will be added to the inlet port of the device and 750 μL of fertilization media will be added to the outlet port. The device will then be incubated in 6% CO2 at 37°C. After 30 minutes, 500 μL of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube. The final volume will be adjusted to 1mL for sperm counting. Receives: Device: ZyMōt Multi 850µL device |
| Density Gradient Centrifugation Method | Active comparator | After liquefaction, sperm preparation will be completed by a discontinuous density gradient centrifugation method, using Pureception (CooperSurgical, Denmark) sperm density gradient media. The resulting sperm pellet after centrifugation will be washed once with the sperm washing medium (G-IVF Plus, Vitrolife, Sweden) The washed spermatozoa will be resuspended with the same medium, adjusting the final volume to 500 μL. The final volume will be adjusted to 1mL for sperm counting. Receives: Device: Density Gradient Centrifugation Method |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA fragmentation by Comet assay
Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.
Measured: 1 months
Secondary outcomes (8)
Sperm count
Sperm count
Measured: 1 months
Forward motility
Assessment of forward motility of sperm by manual observation using the World Health Organization (WHO) criteria.
Measured: 1 months
Sperm velocities measured by CASA
Quantitative analysis of sperm velocities using computer-assisted sperm analysis (CASA) system, including assessment of forward motility, curvilinear velocity, and linearity.
Measured: 1 months
Morphology
Quantitative assessment of sperm morphology by manual observation using the Tygerberg strict criteria.
Measured: 1 months
Sperm aneuploidy
Quantitative measurement of sperm aneuploidy by fluorescence in situ hybridization (FISH) using probes for chromosomes X, Y, 13, 18, and 21.
Measured: 1 months
Calcium ionophore A23187 -induced acrosome reaction assay
Quantitative measurement of acrosome reaction in sperm induced by calcium ionophore A23187 using flow cytometry.
Measured: 1 months
Artificial intelligence analysis
Quantitative analysis of sperm morphology using artificial intelligence algorithms.
Measured: 1 months
Intact oocyte/hemizona binding assay
Quantitative measurement of sperm binding to intact oocytes or hemizona using the intact oocyte/hemizona binding assay.
Measured: 1 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2023
- Study start1 Jul 2023
- Primary completion31 Mar 2025 (estimated)
- Study completion31 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Professor Ernest Hung-Yu Ng
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Professor Ernest Hung-Yu Ng, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05978947
- Sponsor's protocol ID
- UW 23-233
- Status last verified
- Dec 2024
- First submitted
- 29 Jun 2023
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sperm Preparation by a Microfluidic Chip Method Versus a Density Gradient Centrifugation Method on Semen Parameters
- ClinicalTrials.gov ID
- NCT05978947
- Acronym / sponsor ID
- UW 23-233
- Conditions
- Infertility
- Keywords
- Semen parameters, Microfluidic chip, Density Gradient Centrifugation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Professor Ernest Hung-Yu NgUniversity, hospital or other
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 7 Aug 2023 (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.
Infertility affects many couples, with male infertility being a common cause. In vitro fertilization (IVF) is an effective treatment, but its success rates are not high. Semen quality can affect IVF outcomes, and the current method used to process semen can damage the sperm and DNA. Scientists are now testing a new method called microfluidic chip technology, which reduces DNA damage and increases sperm movement. This study will compare the effectiveness of the chip method and the current method on semen quality in men attending a fertility clinic. The study will randomly assign semen collected to one of the two methods and assess the semen quality using different tests, as well as the difference in using two different microfluidic chip platform . The primary outcome will be DNA fragmentation, and other outcomes include sperm count and motility. Semen samples would be collected from study subjects for analysis and that both the samples and results would not be used in patients' treatment.
Detailed description
Infertility affects one in six couples and is getting more common as many women delay marriage and childbirth for various reasons. In vitro fertilization (IVF) is the most effective treatment for couples with long standing infertility and has treated millions of infertile couples over the world since the first birth of IVF was reported more than 40 years ago. However, despite advances in technology, the pregnancy and birth rates remain around 35% and 25% per transfer in Europe in 2018. Among all infertile couples, 20-30% are due to male infertility. Semen parameters may affect the IVF outcomes and it was hypothesized that the relative contribution of sperm to a live birth is around 10-15%.
IVF involves hormone injections to stimulate a woman's ovaries to produce a number of oocytes which are collected by a minor operation and then mixed with sperm to form embryos in the laboratory. Usually, one or two embryos are transferred to the uterus 2-5 days after oocyte retrieval. In IVF, semen samples produced by husbands are commonly processed by a density gradient centrifugation method to isolate the better spermatozoa for fertilization. The density gradient centrifugation can enrich spermatozoa with relatively good motility and normal morphology. It is possible to recover spermatozoa from semen specimens with a very low sperm density. It can provide a relatively good yield. However, it requires technical training to set up the density gradient consisting of two media with different densities. During semen processing, spermatozoa are centrifuged through the gradient. It is known that centrifugation causes considerable damage to spermatozoa by the reactive oxygen species produced during the process. Reactive oxygen species are known to be one of the major causes leading to sperm DNA fragmentation and subsequent adverse outcomes including implantation failure and miscarriage. A meta-analysis showed sperm DNA damage has a negative effect on clinical pregnancy following IVF.
A microfluidic chip, which is a miniaturized device containing channels and chambers in the microscale range for nanoparticle preparation, is being used as an alternative sperm preparation technique recently. By employing microfluidic technology, spermatozoa can go through the chip that closely simulates the natural selection in the female genital tract microenvironment. The technology enables the selection of high-quality motile spermatozoa from semen samples without the need for centrifugation, leading to reduced reactive oxygen species formation.
Studies have consistently demonstrated that the use of a microfluidic chip method greatly reduces DNA fragmentation and increases motility when compared with the density gradient centrifugation method.
This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.
Objectives:
The first objective of this randomized controlled trial is to compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation on semen parameters. The hypothesis is that the use of sperm preparation by a microfluidic chip method improves semen parameters.
The second objective is to compare the effect of two different microfluidic chip platforms on semen parameters.
Trial design:
Men attending at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital for fertility treatment will be recruited.
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
- This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.
| Arm | Type | Receives |
|---|---|---|
| Microfluidic Chip Method | Experimental | Device: ZyMōt Multi 850µL deviceThe Sperm Separation Device - ZyMōt Multi 850µL device (ZyMōt Fertility, Inc) will be used. The microfluidic chamber will be used based on the manufacturer's instructions. 850 μL of the semen sample will be added to the inlet port of the device and 750 μL of fertilization media will be added to the outlet port. The device will then be incubated in 6% CO2 at 37°C. After 30 minutes, 500 μL of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube. The final volume will be adjusted to 1mL for sperm counting. |
| Density Gradient Centrifugation Method | Active comparator | Device: Density Gradient Centrifugation MethodAfter liquefaction, sperm preparation will be completed by a discontinuous density gradient centrifugation method, using Pureception (CooperSurgical, Denmark) sperm density gradient media. The resulting sperm pellet after centrifugation will be washed once with the sperm washing medium (G-IVF Plus, Vitrolife, Sweden) The washed spermatozoa will be resuspended with the same medium, adjusting the final volume to 500 μL. The final volume will be adjusted to 1mL for sperm counting. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Sperm concentration of the raw semen with at least 5 million motile sperm per ml with a total volume of not less than 1.5ml.
Key exclusion criteria (2 listed)
- Sperm concentration of the raw semen of less than 5 million motile sperm per ml
- Men unable to provide an ejaculated semen sample
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 |
|---|---|---|
| ZyMōt Multi 850µL deviceThe ZyMōt Multi 850µL device is a laboratory tool designed for use in assisted reproductive technology (ART) procedures such as intrauterine insemination (IUI) and in vitro fertilization (IVF). It is a sperm preparation device that uses a proprietary patented technology to isolate and select motile sperm from semen samples for use in ART procedures. | Device | Microfluidic Chip Method |
| Density Gradient Centrifugation MethodDensity gradient centrifugation is a laboratory technique used to separate and isolate different types of cells or particles based on their density. It is commonly used in various applications, including cell biology, immunology, and assisted reproductive technology (ART). | Device | Density Gradient Centrifugation Method |
Primary outcome
DNA fragmentation by Comet assay
Time frame: 1 months
Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.
8 secondary outcomes
Sperm count
Time frame: 1 months
Forward motility
Time frame: 1 months
Sperm velocities measured by CASA
Time frame: 1 months
Morphology
Time frame: 1 months
Sperm aneuploidy
Time frame: 1 months
Calcium ionophore A23187 -induced acrosome reaction assay
Time frame: 1 months
Artificial intelligence analysis
Time frame: 1 months
Intact oocyte/hemizona binding assay
Time frame: 1 months
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 5 Dec 2024.
- Individual participant dataSharing planned: No
Related trials for Infertility
RecruitingObservational study
Inherited Reproductive Disorders
Genetic Disorder, Infertility
RecruitingObservational study
Biorepository in Participants Who Undergo OTC for Gonadotoxic Therapy
Acute Ovarian Failure, Infertility
Not yet recruiting
Implementing IVM for Fertility Treatment in Clinical Practice
Infertility
Not yet recruitingObservational study
Linzagolix in Adenomyosis and Recurrent Implantation Failure
Adenomyosis of Uterus, Implantation Failure
Active, not recruitingPhase 1/2
A Novel Aromatase Inhibitor, Leflutrozole, for Treatment of Non-Obstructive Azoospermia
Infertility Due to Azoospermia, Infertility, Male
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ZyMōt Multi 850µL device and Density Gradient Centrifugation Method in people with Infertility, run by Professor Ernest Hung-Yu Ng at 1 site in China.
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 1 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 5 Dec 2024. 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 China. 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?
Contact YU WING TONG, MBBS (92707722, ptong@connect.hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA fragmentation by Comet assay (time frame: 1 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2024.