This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Slide 1
Presented by Omar Chahal MD. Supervised by Dr Khaled El Sayyid
Updates on the evaluation and management of Azoospermia
Slide 2
Definition of Infertility Inability to conceive after 1 year of
unprotected sexual intercourse Affects approximately 15% of couples
40% of cases involve a male 40% of cases involve a female 20 %
involve both sexes
Slide 3
The Hypothalamic Pituitary Gonadal Axis
Slide 4
FSH & LH In the testis, LH stimulates steroidogenesis
within Leydig cells by inducing the mitochondrial conversion of
cholesterol to pregnenolone and testosterone FSH binds to sertoli
cells and spermatogonial membranes within the testis and is the
major stimulator of seminiferous tubule growth during development
& is essential for the initiation of spermatogenesis at
puberty
Normal Sperm parameter ParametersNormal values Abnormalities
Volume>2.0 ml*4: prolonged sexual abstinence
PH7.2-7.8*Acidic(6.5-7): Ejaculatory duct obstruction *Acidic with
low volume & non coagulation: CBAVD ColorWhitish-gray
Pearl-white *Yellowish: jaundice, carotenemia, drugs *Reddish:
hematospermia (secondary to urethral bleeding or inflammation of
the seminal vesicles or genitourinary tumors) Motility>50%Low:
if sexual abstinence >5 days Concentration>20 000
000/mlPolyspermia: associated with poor sperm quality
Morphology>30% with Normal morphology Normal sperm possess an
oval head with well-defined acrosomal region composing 40% to 70%
of the head area
Slide 7
AZOOSPERMIA Azoospermia is defined as complete absence of sperm
from the ejaculate for at least two separate centrifuged semen
samples It is present in about 1% of all men and in approximately
15% of infertile men Azoospermia is different from aspermia, in
that aspermia is the complete absence of seminal fluid emission
upon ejaculation
Slide 8
Causes of Azoospermia 1)Pretesticular: also called secondary
testicular failure, usually endocrine in nature 2)Testicular:
boardly termed as primary testicular failure, these are intrinsic
disorders of spermatogenesis 3)Posttesticular: includes Ejaculatory
dysfunction or obstruction of the genital tract, it constitute 40%
of cases of azoospermia Pretesticular and post-testicular causes
are often amenable to treatment, which may restore fertility,
whereas the success rates for intervention in testicular pathology
are much more modest
Posttesticular 1- Reproductive tract obstruction a. Congenital
blockages: Congenital absence of the vas deferens (CAVD), example:
Cystic Fibrosis Young syndrome (triad of chronic sinusitis,
bronchiectasis, and obstructive azoospermia) Idiopathic epididymal
obstruction PKD (secondary to obstructing cysts in the epididymis
or seminal vesicle) Ejaculatory duct obstruction b. Acquired
blockages: Vasectomy (performed for contraception) Groin surgery
(iatrogenic injury of inguinal vas from hernia repair) Infection
(which may involve the epididymis, with scarring and Obstruction)
c. Functional blockages: Sympathetic nerve injury or medications
that impair the contractility of seminal vesicle or Vasal
musculature
Slide 13
Posttesticular 2- Disorders of sperm function or motility a.
Immotile cilia syndromes (Men have nonmotile but viable sperm in
normal numbers) b. Maturation defects (due to epididymal
dysfunction after vasectomy induced Blockage) c. Immunollogic
infertility (may result from an abnormal exposure to sperm antigens
after testicular injury)
Slide 14
Although both primary and secondary testicular failure will be
associated with marked reduction in testicular volume, these
entities can be distinguished by serum endocrine testing to include
FSH, LH, testosterone, and prolactin levels High serum FSH levels,
typically greater than two times normal, are indicative of primary
testicular failure, and diagnostic testicular biopsy is not
required to rule out obstructive etiologies Primary testicular
failure in conjunction with azoospermia, commonly termed
nonobstructive azoospermia (NOA), is best managed with testicular
sperm harvest for eventual ICSI Azoospermic patients with normal
testicular size, palpable vas deferens, and normal serum FSH levels
require a diagnostic testicular biopsy to differentiate genital
tract obstruction from disorders of spermatogenesis such as
maturation arrest
Slide 15
Evaluation of specific conditions associated with azoospermia .
Absence of the vasa deferentia (vasal agenesis): The most common
cause of congenital bilateral absence of the vas deferens (CBAVD)
is a mutation of the cystic fibrosis transmembrane conductance
regulator (CFTR) gene About 95% of males with clinical cystic
fibrosis have CBAVD, and approximately 70% of men with CBAVD and no
clinical evidence of a cystic fibrosis have an identifiable
abnormality of CFTR gene The diagnosis of vasal agenesis, either
bilateral or unilateral, is made by physical examination Imaging
studies and surgical exploration are not necessary to confirm the
diagnosis, but may be useful for diagnosing abnormalities
associated with vasal agenesis
Slide 16
Due to the embryological association between the vasa and
seminal vesicles, most patients with vasal agenesis also have
seminal vesicle hypoplasia or agenesis. Since the majority of semen
is derived from the seminal vesicles, almost all patients with
CBAVD have low semen volume In the azoospermic patient who has
unilateral vasal agenesis, radiologic imaging with transrectal
ultrasonography (TRUS) may be useful to evaluate the ampullary
portion of the contralateral vas deferens and the seminal vesicles,
because unilateral vasal agenesis can be associated with
contralateral segmental atresia of the vas deferens or seminal
vesicle, resulting in obstructive azoospermia.
Slide 17
An abdominal ultrasound or CT scan should be obtained to assess
anomalies such as renal agenesis In 1 study, 26% of men with
unilateral CAVD and 11% with CBAVD had Renal agenesis. This
association between unilateral vasal agenesis and ipsilateral renal
anomalies is due to their common embryological origin However,
since a man with CBAVD most likely has mutations in the CFTR gene,
the Guidelines recommend genetic testing for CFTR mutations in the
female partner before using sperm of a man with CBAVD
Slide 18
. Ductal Obstruction: a) Patients with normal ejaculate volume
The serum FSH of a patient with normal semen volume is a critical
factor in determining whether a diagnostic testicular biopsy is
needed to establish the presence or absence of normal
spermatogenesis In fact, FSH values in the upper normal range
usually indicate impaired spermatogenesis while marked elevation of
serum FSH is diagnostic of abnormal spermatogenesis usually
nonobstructive azoospermia Although a diagnostic testicular biopsy
will determine if spermatogenesis is impaired, it does not provide
accurate prognostic information as to whether or not sperm will be
found on future sperm retrieval attempts for patients with
nonobstructive azoospermia In addition, in cases of nonobstructive
azoospermia, the presence or absence of sperm in a diagnostic
testicular biopsy specimen does not absolutely predict whether
sperm are present elsewhere in that or the opposite testis
Slide 19
Therefore, a testicular biopsy is not necessary to either
establish the diagnosis or to gain clinically useful prognostic
information for patients with clinical findings consistent with the
diagnosis of nonobstructive azoospermia (i.e. testicular atrophy or
markedly elevated FSH) Conversely, patients who have a normal serum
FSH should undergo a diagnostic testicular biopsy The
recommendation of the Male Infertility of AUA is to use the
diagnostic testicular biopsy to distinguish between obstructive and
non- obstructive causes of Azoospermia in patients with normal
testicular size, at least 1 palpable vas deferens and a normal
serum FSH level
Slide 20
If the testicular biopsy is normal, obstruction at some level
in the reproductive system must be present and the location of the
obstruction may then be determined Most men with obstructive
azoospermia, palpable vasa and no history suggesting iatrogenic
vasal injury have bilateral epididymal obstruction Epididymal
obstruction can be identified only by surgical exploration
Slide 21
Testicular biopsy can be performed by a standard open incision
technique or by percutaneous methods A routine open testicular
biopsy, performed under local anesthesia, is the most common method
This should be performed through a small scrotal incision without
delivering the testis outside the skin or tunica vaginalis This
minimizes postoperative scarring and therefore facilitates
subsequent scrotal reconstructive surgery
Slide 22
Vasography may be utilized to determine whether there is an
obstruction in the vas deferens or ejaculatory ducts The use of
this technique is highly selective and should only be performed by
urologists with microsurgical experience, who can proceed with
reconstruction in the same setting, as obstruction can develop at
the site of vasography
Slide 23
Slide 24
b) Patients with low ejaculate volume Low ejaculate volume
(< 1.0 ml) that is not caused by hypogonadism or CBAVD can be
caused by ejaculatory dysfunction, but is most likely caused by
ejaculatory duct obstruction (EDO) Ejaculatory dysfunction rarely,
if ever, causes low ejaculate volume with azoospermia, although it
is a well-known cause of aspermia or low ejaculate volume with
oligospermia Additional seminal parameters that can be helpful in
determining the presence of EDO are seminal pH and fructose, since
the seminal vesicle secretions are alkaline and contain fructose
However, the results of semen pH and fructose testing may be
misleading when these tests are not properly performed and,
therefore, many experts tend to give less weight to these
parameters over other clinical findings
Slide 25
grossly dilated left seminal vesicle with wide intravesicular
spaces Transrectal ultrasonography (TRUS) is indicated for the
diagnosis of EDO in men with low ejaculate volume and palpable vasa
While vasography is an alternative diagnostic test for EDO, TRUS is
minimally invasive and avoids the risk of vasal injury associated
with vasography
Slide 26
The finding of midline cysts, dilated ejaculatory ducts and/or
dilated seminal vesicles (greater than 1.5 cm in anteroposterior
diameter) on TRUS is suggestive, but not diagnostic, of ejaculatory
duct obstruction Conversely, normal seminal vesicle size does not
completely rule out the possibility of obstruction
Slide 27
Therefore, seminal vesicle aspiration (SVA) and seminal
vesiculography may be performed under TRUS guidance to make a more
definitive diagnosis of EDO The presence of large numbers of sperm
in the seminal vesicle of an azoospermic patient is highly
suggestive of EDO
Slide 28
Recommendation : Transrectal ultrasonography with or without
seminal vesicle aspiration and seminal vesiculography, should be
considered as an initial minimally invasive diagnostic choice to
identify ejaculatory duct obstruction in azoospermic men with low
ejaculate volume and bilateral palpable vasa In patients with
ejaculatory duct obstruction demonstrated by TRUS, testis biopsy
may be considered if needed to confirm normal spermatogenesis
Vasography with or without testicular biopsy should be considered a
second line choice to identify the site of reproductive tract
obstruction in these patients, and should not be done unless
reconstructive surgery is undertaken at the same surgical
procedure
Slide 29
Surgical management TURED is the standard treatment of ED
obstruction In a series of 46 men with low semen volume azoospermia
or severe oligospermia, Schroeder- printzen et al used TURED to
treat, 46% had improvement in semen quality and 20% initiated a
pregnancy. A concern of this study is that 4% of patients who had
sperm in the preoperative ejaculation specimen became azoospermic
after treatment Futhermore, 20% of treated patients experienced
complications. Including watery, high volume ejaculate, prolonged
cathetherization for gross hematuria, UTI, chronic epididymitis
with recurrent pain, post-void dribbling and premature
ejaculation
Slide 30
Although the success rate is not impressive and complications
are not negligible, TURED may allow select patients to undergo
assisted reproductive techniques with ejaculated sperm Given the
potential complications of urinary sphincter injury, rectal injury
and reflux of urine into the reproductive tract with the use of
TURED An alternative treatment for ED obstruction was proposed. In
1995 jarow and zagoria published a report on the use of antergrade
balloon dilatation of the ED with the patient under general
anesthesia to recanalize an obstructed ED The authors preferred the
antegrade approach as it is often difficult to catheterize the
orifice of the ED transurethrally, especially with distortion of
the anatomy that may be present with obstruction
Slide 31
Microsurgical reconstruction of the reproductive tract
(vasovasostomy & vasoepididymostomy) It is successful in
patients with obstructive azoospermia Following vasectomy reversal,
for example, return of sperm to the ejaculate occurs in 70-95% of
patients, and pregnancies are obtained without the need for
assisted reproduction in 30-75% of couples
Slide 32
A very important factor influencing the likelihood of sperm
returning to the semen and of pregnancy after vasectomy reversal
is: The number of years between vasectomy and attempted
reconstruction The length of the obstructive interval the presence
or absence of sperm in the intraoperative vas fluid; the gross
appearance and quality of the sperm in the vas fluid The length of
the vas segment between the epididymis and the vasectomy site The
presence or absence of a sperm granuloma at the vasectomy site The
likelihood of pregnancy after vasectomy reversal is also heavily
influenced by the age of the female partner
Slide 33
Intra Cytoplasmic Sperm Injection: The sperm requirement for
egg fertilization has dropped from hundreds of thousands for IVF to
1 viable sperm for ICSI This has led to the development of
aggressive new surgical techniques to provide sperm for egg
fertilization from men with apparent azoospermia Clinical pregnancy
rates reported in the recent literature range from 26- 57% and
delivery rates range from 18- 75%