Clinical trial NCT05978947: Microfluidic Chip Method Versus Density Gradient Centrifugation Method on Semen Parameters
Official title: Effect of Sperm Preparation by a Microfluidic Chip Method Versus a Density Gradient Centrifugation Method on Semen Parameters
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
Keywords: Semen parameters
Microfluidic chip
Density Gradient Centrifugation
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2023-08-07
Enrollment: 80
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: DNA fragmentation by Comet assay
timeFrame: 1 months
Secondary outcomes:
measure: Sperm count
timeFrame: 1 months
measure: Forward motility
timeFrame: 1 months
measure: Sperm velocities measured by CASA
timeFrame: 1 months
measure: Morphology
timeFrame: 1 months
measure: Sperm aneuploidy
timeFrame: 1 months
measure: Calcium ionophore A23187 -induced acrosome reaction assay
timeFrame: 1 months
measure: Artificial intelligence analysis
timeFrame: 1 months
measure: Intact oocyte/hemizona binding assay
timeFrame: 1 months
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Department of Obstetrics and Gynaecology
state: Hong Kong
Study officials:
References: