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.