Microfluidic Chip Method Versus Density Gradient Centrifugation Method on Semen Parameters

Infertility Clinical Trial

Official title:

Effect of Sperm Preparation by a Microfluidic Chip Method Versus a Density Gradient Centrifugation Method on Semen Parameters

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05978947
• Other study ID #: UW 23-233
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: August 2023
• Source: The University of Hong Kong
• Contact: YU WING TONG, MBBS
• Phone: 92707722
• Email: ptong[@]connect.hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Sperm concentration of the raw semen of less than 5 million motile sperm per ml

• Men unable to provide an ejaculated semen sample

Related Conditions & MeSH terms

• Infertility

Intervention

Device:
• ZyMot Multi 850µL device
The ZyMot 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 Method
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).

Locations

Country	Name	City	State
China	Department of Obstetrics and Gynaecology	Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Professor Ernest Hung-Yu Ng

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA fragmentation by Comet assay	Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.	1 months
Secondary	Sperm count	Sperm count	1 months
Secondary	Forward motility	Assessment of forward motility of sperm by manual observation using the World Health Organization (WHO) criteria.	1 months
Secondary	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.	1 months
Secondary	Morphology	Quantitative assessment of sperm morphology by manual observation using the Tygerberg strict criteria.	1 months
Secondary	Sperm aneuploidy	Quantitative measurement of sperm aneuploidy by fluorescence in situ hybridization (FISH) using probes for chromosomes X, Y, 13, 18, and 21.	1 months
Secondary	Calcium ionophore A23187 -induced acrosome reaction assay	Quantitative measurement of acrosome reaction in sperm induced by calcium ionophore A23187 using flow cytometry.	1 months
Secondary	Artificial intelligence analysis	Quantitative analysis of sperm morphology using artificial intelligence algorithms.	1 months
Secondary	Intact oocyte/hemizona binding assay	Quantitative measurement of sperm binding to intact oocytes or hemizona using the intact oocyte/hemizona binding assay.	1 months