Subject : APPLIED PATHOLOGY 2

Lecture : MALE INFERTILITY AND ERECTILE DYSFUNCTION

Date : 22/11/2018
Professor : G. Franco
Sbobinatore : Georgios Anthymiadis
Reviewer : Veronica Paterna

DEFINITION AND INTRODUCTION

Today 40% of infertility is related to male factor, another 40% to female one and the rest 20% to both or idiopathic
factor. We have very good way to assess male fertility, in case of female fertility is more complicated cause we
must rely on history and specific tests. In male we just can assess a semen analysis that show the likelihood of
paternity, in minimal cases the genetic factor can be associated with infertility. Semen analysis provide 3
important parameters for fertility: the concentration of sperm per ml, motility and morphology of sperm. Important
definitions are the following:
ANORGASMIA: Absence of orgasm. This phenomenon is more common in females and very rare in men.
Anorgasmia means that the patients doesn’t reach the plateau and the contraction which are linked to the
pleasure feeling.

ANEJACULATION: Absence of anejaculation with normal orgasm. The difference with the anorgasmia is that
the patient reaches the plateau and the contractility but no sperm coming out. When no sperm is coming out the
2 options are:
• Either there is retrograde ejaculation meaning that the sperm (seminal fluid) is going back to the bladder,
this can be a result due to some diseases like diabetes or some other neurological diseases. Its very
common that retrograde ejaculation occurs as a complication after surgery (ex. bladder neck surgery,
BPH surgery). Good news is that is still possible to have children, because we can retrieve sperm from
the bladder by asking a patient to drink a lot of water at the day of retrieval and to takes some bicarbonate
to alkalinize the urine, the urine is centrifuged, and sperm retrieve from the urine. Another option is to fill
the bladder with culture media for sperm before the retrieval.
• Other option is anejaculation when no sperm pass form ejaculatory ducts. It can be due to congenital
reasons (ejaculatory duct atresia) or some stone or inflammation that block the passage. There are
surgical approaches to solve this problem.

AZOOSPERMIA: Absence of sperm in the ejaculate even after centrifugation. It doesn’t mean that there is no
sperm, a lot of azoospermic patients have sperm in the testis or the seminal tract. It can occur due to the
obstruction and we called it Obstructive Azoospermia. Its very easy to retrieve sperm from the testis or the
epididymis, sometimes with a simple butterfly needle (aspiration). In majority of azoospermic patients
unfortunately we have a problem with the production. In those instances, we need to perform a testicular biopsy.
In half of the patients with non-obstructive azoospermia we can still find some sperm in the testis after performing
the biopsy. How its possible to have production of sperm and still having azzospermia? Cause it depends on the
amount of sperm, we need to have at least 3 sperm per tubule on average to have sperm in the ejaculate to be
able to complete the trip. Prevalence of azoospermia in male populations is around 1% and in infertile males
10-15%.

CRIPTOZOOSPERMIA: Rare sperm in the ejaculate (but when you centrifuge you can find less than
500.000/ml).
OLIGOASTHENOTERATOSPERMIA (OAT): Reduced sperm concentration, motility and morphology. This is
the most common cause of male infertility. According to the last WHO publishing in 2010 related to male infertility
the last hundred of years there is a significant decrease in the sperm count.
AZOOSPERMIA causes:

• OBSTRUCTIVE AZOOSPERMIA (OA)

-Rete testis obstruction: is quite rare
-Epididymal obstruction: the most common one, because of it small diameter its very easily damaged
from various diseases such as sexual transmitted diseases such ex. Chlamydia etc.
-Vas Deferens obstruction: very important cause Cystic fibrosis is linked to the congenital absence of
Vas Deferens even in patients with mild form of cystic fibrosis that’s not affect the lungs. People with cystic
fibrosis have very low volume of ejaculate (even less than 1 ml) because there is a congenital absence of vas
deferens and ejaculatory duct and seminal vesicle are atresic. Low volume ejaculate is mainly due to atresic
seminal vesicle that provide almost 80% of the ejaculate fluid the rest 20% provided from testis and prostate. In
these patients is very easy to retrieve sperm from epididymal head using butterfly gauge.
-Ejaculatory duct obstruction
• NONOBSTRUCTIVE AZOOSPERMIA (NOA)
-Idiopathic-50% of the cases
-Cryptorchidism- Because germ cells didn’t develop properly, and temperature is not suitable for proper
spermatogenesis. Surgical procedure should occur at very young age to avoid additional damage.
-Varicocele- dilation of veins that may cause rise of temperature in the scrotum
-Cord torsion
-Infection (viral orchitis typically due to mumps virus)
-Toxics and drug exposure (chemotherapy)- after chemotherapy we usually as the patient to wait 2 years
because chemotherapeutic drugs can be harmful for the genes and spermatogenesis. Also, it usually reduce the
production of sperm.
-Genetic – Klinefelter syndrome that is linked to the karyotype XXY, microdeletion of Y chromosome that
is related to azoospermia or oligospermia.

Question: Is it important to retrieve some sperm before performing radiotherapy or chemotherapy? Yes, I will
say its mandatory. Cryopreservation of sperm is very important, but it requires time in order to perform various
tests, due to that reason sometimes is dismissed. Cryopreserved sperm can be used in he future in case the
patient become permanently azoospermic.

Most common site of obstruction:

• Epididymis 70-80%
• Vas Deferens 10% (it can be due to
Vasectomy for birth control or during Hernia
surgical repair)
• Ejaculatory duct 10-20% (may be due to
aplasia as a cause of congenital malformation,
Mullerian cyst or lateral cyst which is Wolffian
duct cyst)
SPERM RETRIEVAL TECHNIQUES:

Today we use more often the percutaneous techniques for obstruction, by using butterfly gauge needle we
puncture the testis in the region of head of epididymis. While in a non-obstructive azoospermia (NOA) I always
need to perform biopsy. For NOA we have either TESE (testicular sperm extraction), which is actually a surgical
biopsy of the testis or microTESE which is basically operation done with operating microscope (opening testis in
two as a book and from both sides I try to find larger tubules as possible using a microscope, because larger
tubules have more chances to have sperm). If nothing is found more cuts may be required in order to find a
normal tubule with sperm. MicroTESE may still impair the hormonal production of the testis but the sperm
retrieval rates are higher than in TESE. According to his experience as a surgeon the best way to perform
microTESE is by using a stepwise approach. Another technique is TESA (testicular sperm aspiration), which is
performed by sticking a needle in the testis and aspirating fluid and tissue with negative pressure.
Testicular aspiration is even easier technique as what it need is just to puncture a needle inside a testis and then
move it several times inside to retrieve a fluid. The procedure is performed under local anesthesia and as much
as 20 punctures can be performed in single testis with a minimal to zero damage. But the same procedure in
epididymis – PESA (percutaneous epididymal sperm
aspiration) is more dangerous cause the damage to the tubule
can be severe.

ISCE and IVF:

ICSI (intracytoplasmic sperm injection) is very similar to conventional IVF (in vitro fertilization) in that gametes
(eggs and sperm) are collected from each partner. The difference between the two procedures is the method of
achieving fertilisation. In conventional IVF, the eggs and sperm are mixed together in a dish and the sperm
fertilises the egg 'naturally'. In conventional IVF, the eggs and sperm are mixed together in a dish and the sperm
fertilises the egg ‘naturally’. However, to have a chance that this will occur, large numbers of actively swimming
normal sperm are required. ICSI refers to the laboratory procedure where a single sperm is picked up with a fine
glass needle and is injected directly into each egg. ISCE is much more indicated for male factor. A single sperm
selection is relying on factors such as motility and structure.

What is the situation related to Klinefelter patients? Klinefelter patients are one of the examples of NOA, but
there is still chance to find some normal sperm in the testis. Those sperm cells can be used in ISCE technique.
But in case of patients with Y microdeletion situation is different, because we can be sure that the child will have
the same chromosomal abnormality, so child will be infertile.