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Male Infertility
the IUI response as it is reflective of better zona pellucida binding capacity mitochondrial function and DNA damage can be measured.
50
It offers an
of the spermatozoa.
26
unbiased, sensitive and accurate analysis on a statistically relevant number
of cells. The main drawback of the use of FC in routine andrology is that it
Acrosin is a serine protease enzyme that exhibits a lectin-like carbohydrate requires expensive instrumentation and technical expertise.
binding activity to the zona pellucida glycoproteins. Assays for acrosin
include the gelatinolysis technique and a spectophotometric assay. Low Emerging Technologies
acrosin activity has been associated with low sperm density and motility,
poor normal morphology,
27
HOST
27,28
and increased ROS
28
in subfertile men. Microarray
This method analyses the transcriptome of cells and tissues and allows
ROS are by-products of normal sperm processes and are necessary for comparison transcriptomes at different stages of spermatogenesis. Its
hyperactivation and capacitation of spermatozoa. High levels of these primary application is in uncovering the still unknown genes, pathways
radicals are present with increased abnormal sperm and leukocytes.
29
and mechanisms in sperm production. Creation of messenger RNA
Increased ROS levels have been shown to have negative correlation with (mRNA) profiles can possibly distinguish spermatogenic infertility from
sperm concentration, motility and morphology.
30–32
There is an inverse other causes.
51
relationship between ROS and in vivo fertilisation rates,
33
and a meta-
analysis on ROS levels and IVF revealed an inverse relationship between the Metabolomics
two.
34
Chemiluminescence, which measures total seminal ROS (from WBCs, Metabolites are formed or released by cell processes that can provide both
abnormal spermatozoa and seminal fluid), is the most common method of qualitative and quantitative data for a glimpse of the network processes in
assay. Leukocytospermia is associated with increased ROS levels and can vivo.
52
In male infertility, the production of OS by-products and naturally
serve as an indirect measurement of ROS.
35
Oxidative stress (OS) indicates occurring antioxidants can serve as biomarkers to potentially differentiate
that there is greater ROS than the total antioxidant capacity (TAC). The fertile from subfertile men with idiopathic infertility.
53
The non-invasiveness
measurement of oxidative stress (ROS-TAC score) has been proposed to be of this test is its main advantage, should it be developed for use in the
a more accurate determination of the total effectual ROS, and a higher score clinical setting.
(>30) can help in the prediction of pregnancy outcomes.
36
Testing for this
remains limited in most fertility centres due to the high cost of equipment Atomic Force Microscopy
and the need for a fresh semen specimen. The main advantage of atomic force microscopy (AFM) over electron
microscopy is the 3D images it can provide and the simplicity of sample
DNA damage is positively correlated with poor semen parameters (low preparation (air drying). Studies in sperm plasma membrane during
sperm concentration and low sperm motility), leukocytospermia and high maturation and capacitation have identified new areas with phosphorylated
ROS levels.
37–40
Approximately 8% of subfertile men with normal semen proteins and large aggregates of lipid that did not cross post-acrosome and
parameters will have high abnormal DNA.
37
A DNA fragmentation index equatorial segments.
54
(DFI) of >30% has been associated with a significant decrease of in vivo
fertilisation rates.
41,42
A couple of meta-analyses show that couples are Controversies Surrounding Semen Analysis
twice as likely to become pregnant with regular IVF methods if the Clinical research has shown that a normal semen analysis may not reflect
DFI is <30%.
43,44
Direct DNA damage assays include single-cell defects in sperm function (idiopathic infertility), and men with poor sperm
electrophoresis (COMET) and terminal deoxynucleotidyl transferase- parameters may still achieve spontaneous pregnancy.
6,14
Fifty per cent of
medicated 2-deoxyuridine 5-triphosphate (TUNEL). Indirect methods include infertile men have recognisable causes, while the other half will have
the sperm chromatin structure assay (SCSA), which measures sperm intrinsic spermatogenic defects that may often be missed by the basic semen
chromatin integrity, DNA intercalating dyes (acridine orange), which analysis.
6
Studies on sperm donors with known fertility status reveal a
differentiates single- and double-stranded DNA, and sperm DNA significant overlap in the sperm characteristics between fertile and subfertile
denaturation tests. However, the use of DNA damage testing is men.
14,55,56
Studies noted that there is low sensitivity (0.48) in detecting
controversial.
45,46
A recent meta-analysis found that the small but statistically subfertile subjects using the WHO reference values for sperm concentration
significant association between sperm DNA integrity test results and and low sensitivity using WHO criteria for normal morphology.
14,57
Among
pregnancy in IVF and ICSI cycles does not provide a clinical indication for the variables, motility had the lowest overlap range and gave the best
routine use of these tests in male evaluation.
47
The current viewpoint on prediction of the subject’s fertility potential.
14
This is in contrast with an
DNA integrity testing, summarised by the ASRM Best Practice Guidelines, is earlier study where morphology was reported to provide the highest
that there are insufficient data to make DNA testing routine in infertility discriminating power in detecting subfertility among all of the semen
testing and that treatments have yet to prove their clinical value. variables.
57
Clearly, each variable alone is neither a powerful sole
discriminator nor a predictor of fertility status, and must therefore be
Electron microscopy has been employed by some to determine ultra- considered in the context of the other variables.
structural sperm details in cases of low sperm motility with high viability
(eosin-nigrosin/HOST).
48
Microtubular and mitochondrial defects are Ideally, the specimen should be collected within the premises of the
some defects that may test positive for viability.
49
laboratory in which it will be examined. Often, a small private room is
provided to patients. However, most men are uncomfortable producing a
Flow cytometry (FC) is an analytical cytological technique that has been specimen in this environment and suboptimal collection with incomplete
extensively used for decades. It allows cell-by-cell analysis of many optical or collection often occurs. Home-test kits were developed and marketed to
immunological features in the same sample at the same time.
50
Using FC, a overcome this. The first test that came out in the market was based on
variety of sperm features such as sperm count, viability, acrosomal integrity, sperm staining, and the colour intensity will test ‘positive’ when the sperm
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