Male infertility factors.pptx

MALE INFERTILITY
FACTORS
Dr: Ekram Abdullah Nasher

• Introduction.
• Spermatogenesis and Sperm
Transport
• Prevalence of the infertility
etiologies.
• Causes.
• Evaluation.
CONTENTS

Introduction
is defined as the inability to conceive despite regular unprotected sexual intercourse
over a specific period of time, usually 1–2 years.
57% 72% 85%
Spontaneously
Conceive after three
months
Spontaneously
Conceive after six
months
Spontaneously
Conceive after one
year
93%
Spontaneously
Conceive after tow
year
Infertility:

• SUBFERTILITY: couples who exhibit decreased reproductive
efficiency.
• FECUNDABILITY: probability of achieving pregnancy within a
single menstrual cycle.
• FECUNDITY: probability of achieving live birth within a cycle.

• The seminal vesicles: are the source of fructose in the seminal plasma as
well as the prostaglandins. It has been suggested that these prostaglandins
facilitate sperm transport in the female genital tract by stimulating smooth
muscle contractions.
• The prostatic secretions: contain acid phosphatase, citric acid and a high
concentration of zinc.
• The secretions of the bulbourethral glands: have a high content of
mucopolysaccharides. The exact functions are not known.
The accessory sex organs

Spermatogenesis and Sperm Transport

Hypothalamic-Pituitary- Testicular Axis:
 FSH is secreted from the pituitary and acts
on the semineferous tubules to stimulate
spermatogenesis (it actually binds to the
Sertoli cells).
 It is thought that inhibin, a peptide secreted
by the Sertoli cells, is the main substance
exerting a negative feedback on FSH .
 LH (previously called the interstitial cell
stimulating hormone (ICSH) stimulates the
Leydig cells (interstitial cells) to produce
testosterone which is also essential for
spermatogenesis.
 Testosterone exerts a negative feedback
effect on the release of LH.

•The production of sperm takes place within the hundreds of seminiferous tubules which
account for 97 percent of the volume of the testis.
•Two classes of cells are found within the tubules: germ cells and Sertoli cells.
•The length of the spermatogenesis cycle starts every 16 days, and the whole process,
i.e. from the appearance of a type-A spermatogonium to the release of a spermatozoon ,
takes approximately 72 days .
•Adult males produce 100-200 million sperm each day.
The spermiogenesis: is a process of differentiation of newly formed spermatids.
involves the
1. formation of the acrosomal cap over the apical extremity of the nucleus,
2. relocation of the nucleus towards the periphery of the cell,
3. dense condensation of the nuclear chromatin
4. formation of the motile apparatus of the sperm.

Morphologically, the spermatozoa consist of:
 Head.
 Tail.
 Small neck.
The tail can be further subdivided into:
 Middle.
 Principal.
 End pieces.
The greater portion of the sperm head is made
up of the nucleus .

• The motor apparatus of the spermatozoon is contained within the tail. This is the
axoneme which consists of 2 central microtubules surrounded by a circle of 9 evenly
spaced pairs of microtubules .
• The microtubules has 2 arms made of dynein, a protein with ATPase activity.
Absence of the dynein arms leads to absent sperm motility (e.g. the Kartagener
syndrome).
• The energy for sperm motility is generated by mitochondria which are concentrated in
the middle piece.

• The transport is the result of the combined activity of the contractile action of the myoid
cells around the tubules and smooth muscles in the testicular tissue.
• The transit time of sperm from their detachment from the seminiferous epithelium to
storage in the tail of the epididymis or ampulla of the vas is between 7 and 10 days.
• During their passage through the epididymis, sperm acquire the ability to move
progressively forward. This process is dependent on specific glycoproteins secreted by
the epididymis and requires calcium ions.
• In the male, and during ejaculation, the sperm are pushed from the cauda epididymis
and vas deferens into the urethra, where they mingle with the secretions of the accessory
glands to form semen.
Sperm Transport, Maturation and Storage

• Although a large number of sperm are inseminated, a relative few reach the site of
fertilization at the ampullasperm can be found in the tube 5 minutes after
insemination.
• The propulsive forces for such transport is provided by contractions of the uterus
and oviducts, possibly induced by prostaglandins present in the semen.
• Movement of sperm within the ampulla appears to be caused by beating of the
ampullary cilia.
• Before mammalian spermatozoa can fertilize the ovum, they must process
capacitation which occurs in the oviduct and by which the sperm acquired ability of
sperm to undergo the acrosome reaction, to bind to the zona pellucida, and to acquire
hyperactivated motility.

This process involves:
1. Removal of the epididymal and seminal plasma proteins coating the sperm surface.
2. Alteration in the glycoproteins of the sperm plasma membrane.
The acrosome reaction is due to the modification and breakdown, followed by a merger
of the sperm cell membrane and the outer acrosomal membrane, allowing the release of
enzymes and changes in the inner acrosomal membrane, necessary for fusion with the
oocyte cell membrane.

Fusion of the sperm and oocyte
membrane to form a zygote is followed
by the cortical reaction and metabolic
activation of the oocyte, block to
penetration of the zona by other sperm
is mediated by the cortical
reaction(release of materials from the
cortical granules, lysosome-like
organelles that are found just below the
egg surface lead to the zona reaction,
the hardening of the extracellular layer.
About 4 to 22 minutes are required for
zona penetration.

Lower reference limits (5th centiles and their 95% CIs) for semen characteristic – WHO 2010

Aspermia: Failure of emission of semen (no ejaculate).
Oligospermia / oligozoospermia: Sperm count is less than 20 million per mL.
Pofyzoospermia: Count is more than 350 million/ mL.
Azoospermia: No spermatozoan in the semen.
Asthenozoospermia: Reduced sperm motility.
Leucocytospermia: Increased white cells in semen.
Necrozoospermia: Spermatozoa are dead or motionless.
Teratozoospermia: > 70% spermatozoa with abnormal morphology.
Oligoasthenoteratozoospermia: Disturbance of all 3 variables

Relative Prevalence of the etiologies of
infertility
Female factors Both Male factors Unexplained
15%
38% 27% 20%
Over 80 percent of infertile men have low sperm concentrations associated with a decrease in
sperm motility (asthenozoospermia) and spermatozoa with normal morphology.
●A small percentage of infertile men have normal sperm concentrations but poor sperm quality
with a decrease in sperm motility and/or abnormal sperm morphology (teratozoospermia).
●A small percentage of infertile men have normal sperm concentrations and normal motility and
morphology.

Categories of Male Infertility causes:
Hypothalamic
pitutary disorders
Primary gonadal
disorders
Disorders of
sperm transport
ldiopathic
10-20%
2-5% 65-80% 5%

Hypothalamic pitutary disorders
Congenital
Any hypothalamic or pituitary disease can cause gonadotropin-releasing
hormone (GnRH) or gonadotropin deficiency (hypogonadotropic hypogonadism)
and, therefore, infertility.
Systemic
disorders
Acquired

Congenital:
• idiopathic isolated gonadotropin deficiency·
• Kallmann syndrome: testicular failure due to gonadotropin deficiency(X-linked genetic
disorders The defect will be transmitted to daughters, but not to sons).
• Single gene mutations.
Acquired:
• Hypothalamic and pituitary tumors ( pituitary macroadenomas ,craniopharyngiomas ,other
sellar masses)
• Infiltrative disease (Infiltrative diseases include sarcoidosis ,histiocytosis ,tuberculosis ,
fungal infections ,iron overload syndromes (eg ,transfusion-related hemosiderosis and
hemochromatosis)
• Hyperprolactinemia ; is associated with impotence.

• Autoimmune(lymphocytic hypophysitis) Head trauma,intracrainal surgery or radiation.
• Vascular lesion as pituitary infarction and carotid aneurysm.
• Drugs (such as opioids or other central nervous system-activating drugs( including
cannabinoids).
• Chronic systemic illness and malnutrition.
• Infections.
• obesity(The obesity-associated decrease in serum SHBG contributes to the low serum total
testosterone concentrations).

• Klinefelter syndrome: One of the most common causes of primary hypogonadism with
impaired spermatogenesis and testosterone deficiency ,which may occur in up to 1 out of
500 to 700 phenotypic males and in up to 10 to 15 percent of infertile men with
azoospermia. It is aneuploidy with an extra X (XXY chromosome being the most frequent).
These patients often have very small testes and almost always have azoospermia.
• Y chromosome deletions (transmitted obligatorily to the male offspring).
• Cryptorchidism (Men with a history of undescended testes have lower sperm counts ,sperm
of poorer quality ,and lower fertility rates than men with normally descended testes .
• Varicoceles: a dilatation of the pampiniform plexus (The optimum temperature for
spermatogenesis is 29.35 °C, the presence of a varicocele leads to an increased temperature
of the testes with its suppressing effect on spermatogenesis)
Primary gonadal disorders

• FSH raised in idiopathic testicular failure with germ cell hypoplasia (Sertoli cell only
syndrome).
• Antisperm antibodies in serum or semen(occur spontaneously or after testicular injury
(This result in clumping of the spermatozoa after ejaculation).
• Infections: viral orchitis ,especially mumps , tuberculosis and leprosy may also cause
epididymal obstruction, Sexually transmitted diseases (STDs) such as gonorrhea and
chlamydia can also cause orchitis. Many HIV infected men have relatively normal
semen parameters, but some may have low sperm motility.
• Radiation: Ionizing radiation impairs spermatogenesis.
• Chronic illness: as chronic renal inffuciency,malnutrition, sickle cell anemiadiabetes,
hypothyroidism, malignancies and other debilitating diseases.

• Infections causing obstruction to vas deferns.
• Vasectomy.
• Drugs: (the most important are the alkylating drugs( cyclophosphamide and
chlorambucil (Antiandrogens( flutamide ,cyproterone ,bicalutamide ,spironolactone ,
ketoconazole ,and cimetidine may cause dysspermatogenesis by inhibiting testicular
androgen production or action also Sperm motility is inhibited by the use of
propranolol and other beta blockers, nitrofuranes, niridazole (an antischistosomal)
and ethanol.
• Environmental: gonadotoxins ,hyprethermia and smoking and its possible effect on
sperm counts are inconsistent .However ,in a meta-analysis of 20 observational studies ,
men who smoked cigarettes were more likely to have low sperm counts and Alcohol
inhibits spermatogenesis by suppressing Leydg cell synthesis of testosterone or by
suppressing gonadotropin.

• Epididymal obstruction or dysfunction: which is either congenital as in Cystic fibrosis
(CF) (there is obestraction or malformation of the ejaculatory duct, seminal vesicle, vas
deferens and distal two-thirds of the epididymis) or follow chronic infection , or traumatic.
• Kartagener syndrome: (AD) primary ciliary dyskinesia is a genetically heterogeneous
disease that affects cilia function and structure. The clinical presentations include recurrent
sinopulmonary infections, bronchiectasis, situs inversus, and male infertility (with
asthenozoospermia or oligozoospermia
• Ejacu latory dysfunction: Patients with ejaculatory duct obstruction present with a low
ejaculate volume and seminal fructose with no sperm count and/or very low sperm
motility.
• Young's syndrome: genetic defect that may lead to abnormal transport of sperm , in
which inspissated secretions within the vas and epididymis interfere with transport of
sperm, leading to obstructive azoospermia.
Disorders of sperm transport

These include:
• Low coital frequency due to excessive work, lack of interest or marital problems.
• The use of lubricants which may affect sperm motility and fertilizing capacity.
• Impotence due to organic causes (e.g. diabetic neuritis) or to psychological factors or may be
drug induced (e.g. antihypertensives, CNS depressants).
• Improper deposition of sperm (outside the vagina) due to hypospadias or premature
ejaculation. The latter may be due to organic (inflammatory congestion) or psychological
causes.
• Retrograde ejaculation: In this condition, the sperm is retrogradely ejaculated inside the
bladder rather than through the urethra. The condition arises from the loss of the
sphincteric mechanism at the bladder neck which normally contracts during
ejaculation.
(e.g. diabetic neuritis), surgical interference (e.g. prostatectomy) or ntihypertensive drugs.
Coital Defects

Error in the seminal fluid
1- un usually high or low volume of ejaculate.
2- low fructose content.
3- high prostaglandin content.
4- undue viscosity.

Evaluation of male infertility
• To Identify and correct specific cause
• To identify the individuals whose fertility cannot be corrected but could be
over come by IUI and ART.
• To identify-Genetic abnormality
• To identify any medical condition that requires specific attention
• To identify the individuals whose infertility can neither be corrected or
overcome with ART, in whom adoption or donor sperm are considered.

EVALUATION
History Investigations
Examination

HISTORY
 Duration of infertility and previous infertility.
 Coital frequency and sexual dysfunction.
 Any previous evaluation or treatment of infertility.
 Childhood illness and developmental history.
 Previous surgery and its outcome, systemic medical illness
 History of exposure to STD.
 Exposure to environmental toxins.
 Current medications and allergies.
 Occupational exposure to tobacco, alcohol and other drugs.

HISTORY
 Agents such as heat, X-rays, metals, and pesticides – evidence suggestive of a
harmful effect. Therefore, enquire about occupation; e.g., radiotherapists, engine
drivers, diggers, agricultural workers, chemists, laboratory workers, painters.

Physical examinations
• Examination of penis.
• Palpation of testes and measurement of their size.
• Presence and consistency of both vasa and epididymides.
• Presence of any varicocele.
• Secondary sexual characteristics, hair distributio n, and breast development.
• Digital rectal examination.

 Features of hypogonadism: e.g. complete or partial absence of pubertal development,
poorly developed secondary sexual characters.
 Penile abnormalities: e.g. hypospadias or phimosis.
 Testicular size: This should be measured using an orchidometer which consists of a
series of plastic ellipsoids graded for volume (1 to 25 ml). In the normal adult, testicular
size should exceed 15 ml.
 Testicular location and consistency should also be determined.
 Varicocele.
 Gynecomastia.
 Prostate: by rectal examination: This is small in patients with androgen deficiency
and may be enlarged in patients with chronic genital tract infections but
ultrasonography can now be used to measure the size of the prostate more accurately.
This may be performed suprapubically or transrectally.
Local Examination

Male infertility investigations
1. The Seminal Fluid Analysis
2. Hormonal Assays
3. Vital Staining
4. Hypo-osmotic Swelling (HOS) Test
5. Immunological Tests
6. Semen Culture
7. Measurement of Zinc, Citric Acid and Acid Phosphatase in Seminal Plasma
8. Measurement of Fructose in Seminal Plasma
9. Measurement of Neutral α- glucosidase in Seminal Plasma
10. Testicular Biopsy
11. Cytogenetic Studies
12. Sperm Function Tests
13. Vasography
14. Renal US
15. Transrectal / transurethral US

• If the first semen analysis (SA) is abnormal, repeat it in 3 months after the initial
analysis to allow time for the cycle of spermatozoa formation to be completed
(not mandatory and can be done earlier if it generates anxiety).
• A single-sample analysis will falsely identify about 10% of men as abnormal, but
repeating the test reduces this to 2%.
• If azoospermia or severe oligozoospermia is detected, repeat the test as soon as
possible (within 2–4 weeks).
semen analysis

1. Liquification
2. Apperance
3. Volume
4. Consistency-viscosity
5. pH
6. Motility
7. Agglutination
8. Morphology
9. Round cells
semen analysis

Initial Macroscopic Examination
 Liquefaction: A normal semen sample liquefies within 60 minutes at room temperature.
Delayed liquefaction may be due to chronic prostatitis or seminal vesiculitis.
 Appearance: A normal semen sample has a homogeneous, gray opalescent appearance. It
may appear less opaque if the sperm concentration is very low, or brown when red blood
cells are present.
 Volume: The normal is between 1 and 6 ml. Less than 1 ml may be due to partial
obstruction of the secretory ducts or retrograde ejaculation. Larger than 6 ml may reflect
the presence of congestion (due to a long period of abstinence) or of chronic infection in
which case the number of WBCs is increased. Inability to produce a semen sample,
despite the feeling of orgasm, is called aspermia.

 Consistency (viscosity): A normal sample leaves the pipette as small discrete drops,
while in cases of abnormal consistency, the drop will form a thread more than 2 cm long.
Increased viscosity may be due to chronic prostatitis or seminal vesiculitis or to a congenital
(e.g. Kartagener’s syndrome).
 Reaction (pH): Normally, the pH should be in the range of 7.2 to 8.0.
If the pH is less than 7.0 in a sample with azoospermia, dysgenesis of the vas deferens,
seminal vesicles or epididymis may be present.

WHO grading system for sperm motility
Using a laboratory counter, at least 200 successive spermatozoa should be counted and
graded for motility. The percentage of each motility grade is then calculated.
Grade a = rapid progressive motility (> 20 mm/sec)
Grade b = slow or sluggish progressive motility (1 to 20 mm/sec)
Grade c = non-progressive motility (<1 mm/sec)
Grade d = absence of motility
According to WHO , in normal semen, at least 25% of the spermatozoa should have
rapid progressive motility (grade a) and at least 50% should belong to grades a and b .
Diminished sperm motility is termed asthenospermia.
Sperm motility

Agglutination of spermatozoa means that motile spermatozoa stick to each other
• head to head .
• midpiece to midpiece,
• tail to tail
• mixed way, e.g. midpiece to tail.
The adherence either of immotile spermatozoa to each other or of motile spermatozoa to
mucus threads, cells other than spermatozoa, or debris is considered to be non-specific
aggregation rather than agglutination.
The presence of agglutination of 10% or more, is suggestive of, but not sufficient
evidence for, an immunological cause of infertility
Agglutination

 According to WHO, at least 30% of the spermatozoa should have normal
morphology.
 An increase in the percentage of abnormal spermatozoa is termed teratospermia.
 Oligospermia, asthenospemia and teratospermia are frequently associated and the
condition is termed oligo-terato-astheno-spermia (OTA syndrome).
 As multiple defects are sometimes observed in the same spermatozoon, a measure
called the teratozoospermia index has been devised .
 This index is calculated by dividing the number of all defects observed by the
number of abnormal sperm.
 TZI > 1.80 indicate poor sperm fertilizing ability .
Sperm morphology

Cellular elements other than spermatozoa
 Epithelial cells from the urethral tract,
 Spermatogenic cells ( spermatids, spermatocytes and spermatogonia )
 leukocytes,
The concentration of such cells can be estimated using the hemocytometer.
A normal ejaculate should not contain more than 5x106 round cells/ml , while the number
of leukocytes should not exceed 1 × 10 6/ml

Result of Semen analysis
- Normospermia: all parameter normal
- Oligospermia: reduce sperm number
- Asthenospermia: reduce sperm motility
- Teratospermia: increase abn forms of sperm
- Azoospermia: No sperm in semen
- Aspermia: ejaculation failure
- leukocytospermia : increase WBC in semen
- Necrozoospermia:all sperm non viable or non motile

Full evaluation – examination and investigations.
• If the sperm concentration is ≤ 5 × 106/ml, impaired sexual function or other clinical
findings suggestive of any specific concern from history.
• Azoospermia – complete absence of sperm from the ejaculate (1% of all men and in
approximately in 15% of infertile men).
Abnormal SA
Unexplained subfertility/ female factor
Normal SA

Once an abnormality has been found in the seminal fluid analysis, one or more
of the following test should be requested in order to find the cause of the
abnormality and plan the best management way.
Hormonal Assays
*serum FSH and LH
*prolactin
*serum testosterone
*serum T3, T4 and TSH should be measured

This test should be performed in cases of total absence of motility to differentiate between
dead spermatozoa and living but on-motile spermatozoa, as in the latter case, ICSI can be
successfully performed.
A film of semen is stained using a supravital stain (0.5% eosin Y or eosin nigrosin) and the
spermatozoa are examined under light or phase contrast microscopy . Under the light
microscope, the dead spermatozoa appear red and the living spermatozoa are unstained
(colorless). Under (negative) phase contrast microscopy, the dead spermatozoa appear yellow
and the live appear bluish.
Vital Staining

Hypo-osmotic Swelling (HOS) Test
- This test is also performed to differentiate between
dead spermatozoa and living non-motile
spermatozoa in cases of total absence of motility.
- Liquefied semen (0.1 ml) is added to 1 ml the warm
swelling solution (sodium citrate and fructose in
distilled water) and kept in 37°C for at least 30
minutes (but not more than 120 minutes).
- The sperm cells are then examined under phase-
contrast microscopy . Living spermatozoa swell by
imbibing the hypo-osmotic solution and this
produces coiling of their tails .
HOS test

* to detect Antibodies present on the sperm surface .
Immunobead test:
The MAR test: The IgG MAR test (mixed antiglobulin reaction test )
* Is performed on the semen to detect the presence of antisperm antibodies on the spermatozoa.
Kibrick’s sperm agglutinating antibodies test:
* This test detects the presence of sperm agglutinating antibodies
in the serum (of the male or the female).
Isojima test:
*This test detects the presence of sperm immobilizing antibodies in the serum of the male or
the female.
there is still controversy as to the role of these antibodies as a cause of infertility.
The most commonly performed immunological tests are:
Immunological Tests

Semen Culture
*This should be performed if infection of the male accessory glands is suspected (e.g.
in cases of leukocytospermia) in order to identify the infective agent and its sensitivity
to different antibiotics.
To detect prostate gland function.
Normal values are:-
 2.4 μmol or more of zinc per ejaculate .
52 μmol or more of citric acid per ejaculate .
200 U or more of acid phosphatase per ejaculate
Measurement of Zinc, Citric Acid and Acid Phosphatase in Seminal Plasma:
Measurement of Fructose in Seminal Plasma
To detect the secretory function of the seminal vesicles .

Measurement of Neutral α-glucosidase
in Seminal Plasma
• Neutral α-glucosidase is secreted from the epididymis and is a specific marker for
epididymal function.
• The assay is simpler, cheaper and less time consuming than the other two markers of
epididymal function, namely L-carnitine and glycerophosphocholine.
• Diminished values of α-glucosidase in seminal plasma denote distal ductal obstruction,
when used with hormonal and testicular parameters.
• Normal values are 20 mU per ejaculate or more.

Testicular Biopsy
Testicular biopsy should be performed when azoospermia or severe oligospermia exist, to
determine whether the condition is due to testicular dysfunction or to vasal obstruction.
The biopsy may be obtained by one of the following methods:
1- Needle biopsy
2- Stab biopsy
3- Full exploration: Testicular biopsy can be combined with vasography in cases of
azoospermia to check the patency of the exretory ducts.

10- Complete spermatogenesis with many spermatozoa. and a germinal epithelium
organized in a regular thickness leaving an open tubular lumen.
9 - Many spermatozoa present but germinal epithelium disorganized with marked sloughing
or obliteration of lumen.
8 -Only few spermatozoa (5-10) present
7 -No spermatozoa but many spermatids present
6- No spermatozoa and only a few spermatids (5-10) present
5 -No spermatozoa, no spermatids but several spermatocytes present
4 -Only a few spermatocytes (<5) and no spermatids or spermatozoa present
3 -Spermatogonia the only germ cells present
2 -No germ cells Sertoli cells present
1 -No cells in tubular section (complete hyalinization)
Johnsen’s method for scoring testicular biopsy

Cytogenetic Studies
Cytogenetic abnormalities in infertile men is about 2 percent .
i. Buccal smear:
To detect The presence of an additional X chromosome . in patients with Klinefelter’s
syndrome. More than one additional X chromosome or mosaicism may also be found.
ii. Karyotyping: The different chromosomes can now be examined using banding techniques
as well as the technique of fluoro in-situ hybridization (FISH).
should be reserved for patients with:-
 severe oligospermia or azoospermia
 testicular atrophy in whom the buccal smear examination is unconvincing or abnormal
 husbands of women with recurrent abortions where XXY and XYY and autosomal
translocations are particularly suspected.
iii. (PCR): to detect Single genes defect

Low FSH and testosterone
Pre-testicular – secondary testicular
failure
- Hypogonadotrophic hypogonadism.
- Bilateral testicular atrophy, low semen volume, low LH levels.
- Kallmann syndrome.
- Acquired functioning and nonfunctioning pituitary tumours.
Perform serum prolactin level and pituitary CT or MRI.

High FSH and N/L testosterone
Testicular – primary testicular failure
• Bilateral testicular atrophy, low semen volume.
• Chromosomal abnormalities found in 7% of male infertility. Sex chromosome aneuploidy is
most common (Klinefelter syndrome in 2/3 cases). Karyotype all patients with non-
obstructive azoospermia and severe oligospermia (sperm count: < 5 × 106/ml).
• Y-chromosome microdeletions – may be found in 10–15% of men with azoospermia or
severe oligozoospermia. Prognostic significance – with deletions in AZFa or AZFb regions,
sperm are normally not found, whereas up to 80% with AZFc deletions may have retrievable
sperm. (AUA)
• Counsel regarding inheritance of the compromised fertility potential in male offspring.

Normal FSH and testosterone
Post-testicular – 40%
Obstructive
erectile/ejaculatory
- Anejaculation
- Retrograde ejaculation
- Erectile dysfunction
vasal agenesis
- Epididymal/vasal obstruction
- Ejaculatory duct obstruction
Obstruction
- CBAVD
- Unilateral vasal agenesis

• 70% of men with CBAVD and no clinical evidence of cystic fibrosis have an abnormality
of CFTR gene.
(Almost all males with clinical cystic fibrosis have CBAVD).
• Seminal vesicle hypoplasia or agenesis
• Low semen volume – since majority of semen is derived from seminal vesicles.
• Both partners – genetic counselling and test for CFTR gene. Failure to identify a CFTR
abnormality in a man with CBAVD does not rule out the presence of a mutation, as many
mutations may not be detected by routine testing methods; therefore, test the spouse for
CFTR gene abnormalities because she may be a carrier.
• In patients who have CBAVD and CFTR mutations, the prevalence of renal anomalies is
extremely rare. Therefore, imaging of the kidneys with USS or CT scan is only indicated in
men with CBAVD with no mutations in CFTR.
Congenital bilateral absence of the vas deferens

Unilateral vasal agenesis
• Transrectal USS (TRUS) – to evaluate the ampullary portion of the contralateral vas
deferens and the seminal vesicles, because unilateral vasal agenesis can be associated
with contralateral atresia of the vas deferens or seminal vesicle, leading to obstruction
azoospermia.
• There is a strong association between unilateral vasal agenesis and ipsilateral renal
anomalies; therefore, organize USS or CT scan of the kidneys.

Epididymal/vasal obstruction
• Vasa and testes are normal, semen volume normal.
• If Bilateral – identified only by surgical exploration.
• Vasal obstruction – vasectomy (most common), severe genitourinary infections,
iatrogenic.
• Vasography – to diagnose whether the obstruction is in vas deferens or ejaculatory
ducts. It should not be done unless reconstructive surgery is undertaken at the same
surgical procedure.
obstruction

Ejaculatory duct obstruction
• Semen volume low (< 1.0 ml).
• Seminal pH low and fructose low, as the seminal vesicle secretions are
alkaline and contain fructose.
• TRUS – minimally invasive and avoids the risk of vasal injury associated
with vasography.
• With or without seminal vesicle aspiration and seminal vesiculography –
determine the anatomical site of the obstruction.
• Vasography.
Obstruction

Genetic evaluation
1) Mutations within cystic fibrosis transmembrane conductance regualtor (CTFR gene).
2) Chromosomal anomalies resulting testicular dysfunction-kli nefelter syndrome.
3)y chromosome deletions associated with abnormalities of spermatogeneis.

General care
● Improvement of general health , reduction of weight in obese ,avoidance of
alcohol and heavy smoking are help.
● Medication that interfere spermatogenesis should be avoided.

Pre-testicular
• Hormonal treatment (GnRH)
to replace GnRH deficiency in infertile men with hypothalamic hypogonadotropic
hypogonadism (HH) (e.g., Kallmann’s syndrome ) The most effective dose for pulsatile
GnRH is a dose between 5-20 μg every one to two hours delivered by a subcutaneous
pump or needle.
GnRH is very effective in inducing spermatogenesis as early as four months after the start
of therapy and can take up to two years.
When pulsatile GnRH treatment fails to mount a clinical response, the method of
administration, effectiveness of the dose, or other causes such as formed anti-GnRH
antibodies should be evaluated as part of the differential diagnosis.

The treatment of male infertility in men with pituitary insufficiency (e.g., pituitary adenoma,
systemic diseases such as hemochromatosis and sarcoidosis) is based on the use of
gonadotropins . (human chorionic gonadotropin (rec-hCG), FSH (rec-hFSH) and LH (rec-
hLH) or highly purified urinary gonadotropins).
Initially, hCG is administrated alone. After several months of treatment, if no sperm is
detected but adequate serum T levels are achieved, then treatment with FSH is introduced .
Gonadotropins are self-administered subcutaneous injections with dosages ranging between
75-150 IU of FSH or human menopausal gonadotropin (hMG) two to three times weekly
plus 1,500-2,500 IU of hCG twice weekly. The duration of treatment may vary from 6-24
months or more and typically continues until sperm appears in the ejaculate and/or when
pregnancy is achieved.
Gonadotropins

AI treatment of men with idiopathic OAT or azoospermia
Candidates for aromatase inhibition have usually been identified as men with serum and T
<300 ng/dL and T/E ratios >10
AIs (anastrozole 1 mg daily, or letrozole 2.5 mg daily) increase T, decrease estrogen levels,
and inhibit the peripheral metabolism of T.
is an off-label use of this medication
Aromatase inhibitor (AI) therapy

CC, like other SERMs, inhibits central estrogen feedback and up regulates the production
of LH and FSH, leading to induction of spermatogenesis.
Before the introduction of intracytoplasmic sperm injection, SERM’s where one of the few
option available for men with idiopathic infertility.
their use in the treatment of male hypogonadism and infertility is currently off-label.
Selective estrogen receptor modulators (SERMs)

secondary (hypogonadotropic) hypogonadism due to a prolactin adenoma, we suggest
dopamine agonist therapy, usually cabergoline, as this typically restores spermatogenesis
and fertility. In men with prolactin macroadenomas, lowering the serum prolactin
concentration and shrinking the adenoma may not be sufficient to increase the testosterone
concentration and sperm count (because of permanent damage to the gonadotroph cells).
In this case, we start gonadotropin therapy for induction of spermatogenesis.
Not use clomiphene citrate, aromatase inhibitors, or gonadotropin therapy for secondary
(hypogonadotropic) hypogonadism, idiopathic dysspermatogenesis, or idiopathic male
infertility

Primary testicular defects in sperm production
can divided into:
• Low serum testosterone and high serum FSH and LH concentrations.
• Normal serum testosterone and isolated elevation of serum FSH concentration
The seminiferous tubules in these men are severely damaged, so most patients are
azoospermic. There are no known effective medical therapies for these men, and
success rates with assisted reproductive technology (ART) are low compared with
men with other infertility diagnoses. Obtaining testicular tissue for histologic
examination helps to determine whether such men can conceive via ART
(Low testosterone and high FSH and LH)
(hypergonadotropic) hypogonadism

Normal serum T and LH, high FSH
Many of these men have sperm present in the ejaculate or in a testicular biopsy that can
be used for ART.
Option used:
• Surgical sperm retrieval (SSR) by TESA/TESE and ICSI.
• Donor sperm (DI).

Post-testicular
Obstructive
Microsurgical reconstruction
• Vasovasostomy – is preferable to SSR/ICSI in men with prior vasectomy if the
obstructive interval is < 15 years and no female fertility risk factors are present. Sperm
return in 70–95% of cases, and pregnancies in 30–75% of couples.
• Vasoepididymostomy – for congenital, infectious, or idiopathic epididymal
obstruction; 20–40% of couples achieve pregnancy.
• Transurethral resection of the ejaculatory ducts – sperm in 50–75% of cases and
pregnancy rate is about 25%.

Ejaculatory/erectile
Erectile dysfunction
• Treat any organic co-morbidities and psychosexual dysfunctions.
 Treatment options:
• Oral phosphodiesterase type 5 (PDE5) inhibitors.
• Intraurethral alprostadil.
• Intracavernous vasoactive drug injection.
• Vacuum constriction devices.
Anejaculation
• Serotonin reuptake inhibitors.
• SSR/ICSI.
Retrograde ejaculation
• Alkalanization of urine, sperm retrieval, and ICSI.

• Before potentially sterilising chemotherapy or radiotherapy .
• Before surgery that might interfere with fertility (e.g. bladder neck surgery in a younger
man or removal of a testicle in a man with testicular malignancy, or before vasectomy or
transgender surgery);
• For men with progressive decrease in semen quality as a result of diseases that have an
associated risk of subsequent azoospermia (i.e., pituitary macroadenoma,
craniopharyngioma, empty sella syndrome, chronic nephropathy, uncontrolled diabetes
mellitus, and multiple sclerosis);
• For men with paraplegia when sperm have been obtained by electro-ejaculation or obtained
by penile vibratory stimulation;
• For men with psychogenic anejaculation,
• After gonadotropin treatment has induced spermatogenesis in men with hypogonadotropic
hypogonadism;
Indications for cryopreservation

Indications:
• Obstructive azoospermia.
• Non-obstructive azoospermia.
• Infectious disease in the male partner (such as HIV).
• Severe rhesus isoimmunization.
• Severe deficits in semen quality in couples who do not wish to undergo ICSI.
• Certain cases where there is a high risk of transmitting a genetic disorder to the
offspring.
This should done after:
Counseling and assessment of the female partner:
Donor insemination

Infection of the accessory male reproductive glands should be treated with the
appropriate antibiotics.
Prolonged courses are necessary to eradicate the infections of the prostate and
seminal vesicles.
Cotrimoxazole (Septrin) one tablet twice daily or erythromycin 250 mg twice daily
given for 3 months have been used in these cases with some success . However,
the proper antibiotic should better be determined on the basis of culture and
sensitivity tests
Antibiotic Therapy

• Steroids have been used for the treatment of immunological infertility.
• As the maximum depression in lgG and IgA occurs in the third week after therapy,
• Shulman et al recommended methyl prednisolone 96 mg/ day for 7 days (given to the
man on days 21-28 of his wife’s menstrual cycle).
• Similarly, Hendry reported the successful use of prednisolone 5 mg three times daily for
2 to 12 months (average 6 months)
Steroids

• Screening for antisperm antibodies.
• Routine use of post-coital testing of cervical mucus.
• Routine use of sperm DNA integrity testing. (AUA).
• Routine test of reactive oxygen species (ROS).
• Complementary therapies.
• Use of anti-oestrogens, gonadotrophins, androgens, bromocriptine, or kinin-
enhancing drugs in men with idiopathic semen abnormalities.
• Use of antibiotics for men with leucocytes in their semen unless there is an
identified infection.
• Surgery for men for varicocoele.
What not to do

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