A thorough and simplified description of the definition, prevalence, and approach to male infertiloty

1. MALE INFERTILITY
EDITED AND
PRESENTED BY:
RAKAN ALOTAIBI

2. DEFINITION
• It is the inability of a male partner to conceive his female
partner after 12 months of unprotected sexual intercourse OR
after 6 months of unprotected course if the female partner age
is 35 years or older
• Mostly, the cause is a disorder within the testicles

3. INCIDENCE OF INFERTILITY
• Infertility affects an estimated 15% of couples globally,
amounting to 48.5 million couples world-wide. Males are found
to be solely responsible for 20-30% of infertility cases and
contribute to 50% of cases overall. However, this number does
not accurately represent all regions of the world.
• On a global level, there is a lack of accurate statistics on rates
of male infertility.

4. CAUSES OF MALE INFERTILITY
• . There are multiple causes of male factor infertility, including
endocrine disorders, anatomic defects, problems with abnormal
sperm production and motility, as well as sexual dysfunction.
• Varicocele is the most common reversible cause of male factor
infertility; comprising 30% to 40% of infertility in men.
• Men with occupational or environmental exposure to chemicals, radiation, or excessive
heat are at increased risk for infertility, as are those with a history of varicocele, mumps,
hernia repair, pituitary tumor, marijuana use, anabolic steroid use, testicular injury, and
impotence. Certain medications have also been found to depress semen quantity and
quality, cause erectile dysfunction, or result in ejaculation failure

5. CAUSES OF MALE INFERTILITY
• ENDOCRINE AND SYSTEMIC DISORDERS (HYPOGONADOTROPIC HYPOGONADISM): Any hypothalamic or
pituitary disease can cause gonadotropin-releasing hormone (GnRH) or gonadotropin deficiency
(hypogonadotropic hypogonadism) and, therefore, infertility.
• Endocrine and systemic disorders with hypogonadotropic hypogonadism – 5 to 15 percent.
• Primary testicular defects in spermatogenesis– 70 to 80 percent. Klinefelter syndrome is the
most common identifiable cause of a primary testicular defect, but the majority in this category
have idiopathic dysspermatogenesis, an isolated defect in spermatogenesis without an
identifiable cause.
• Sperm transport disorders – 2 to 5 percent .
• Idiopathic male infertility – 10 to 20 percent. Idiopathic male infertility must be distinguished
from idiopathic dysspermatogenesis. Idiopathic male infertility describes an infertile man with a
normal seminal fluid analysis and no apparent cause for infertility, whereas infertile men with
idiopathic dysspermatogenesis have abnormal seminal fluid analyses.

6. CAUSES OF MALE INFERTILITY
• 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. Impaired
spermatogenesis in the undescended testis is related to
underlying genetic, hormonal, and developmental abnormalities.
• Inactivating mutation in the FSH receptor gene: A rare cause of male
infertility is an inactivating mutation in the follicle-stimulating
hormone (FSH) receptor gene. One report described five men who
were homozygous for an inactivating mutation of the FSH
receptor. These men had variably low sperm counts and serum
inhibin B concentrations and high serum FSH concentrations.

7. ACQUIRED CAUSES OF MALE
INFERTILITY
• Virtually all acquired testicular disorders can cause infertility, often without accompanying
Leydig-cell dysfunction, these include:
• Varicocele — Varicocele is a dilatation of the pampiniform plexus of the spermatic veins in the
scrotum. Left-sided varicoceles are 10 times more common than right-sided ones. Most men
with varicocele and infertility have abnormal semen parameters, including low sperm
concentration and abnormal sperm. Varicocele is the most common cause of male infertility.
• Infection — Viral orchitis, especially mumps, is a well-recognized cause of infertility. Some,
but perhaps not all, of these men become infertile, due either to germinal cell damage,
ischemia, or the immune response to the infection. In mumps and other viral causes of
orchitis (echovirus and arbovirus), germ cell failure is much more common than androgen
deficiency.

8. ACQUIRED CAUSES OF MALE
INFERTILITY
• Drugs and radiation :
• Many drugs are associated with impaired spermatogenesis or Leydig
cell dysfunction. Among them, 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.
• Ionizing radiation exposure leads to impaired spermatogenesis.
Doses above 600 rads usually cause irreversible azospermia causing
permanent infertility, but lower doses causes reversible infertility

9. EVALUATION
The approach for the evaluation of male infertility should include assessment by the
following:
1-History taking
2-physical examination
3- Laboratory evaluation
4- Imaging if needed

10. HISTORY TAKING
A thorough history taking must be done with asking the
following:
Age, Duration of infertility, any chronic illnesses, constitutional
symptoms, a complete systemic review, previous urological
procedures or surgeries, previously fathered children, smoking,
radiation exposure, previous testicular infections, medications,
family history of infertility, and allergies

11. PHYSICAL EXAMINATION
The physical examination should include a examination to determine signs of
endocrinopathies that are uncommon causes of male infertility (eg, thyroid dysfunction
or Cushing's syndrome). the examination should also focus on findings suggestive of
androgen deficiency. Examination must include:
1-loss of secondary sex characteristics (scant axillary and pubic hair, gynecomastia, and testicular atrophy)
2- Skin – Men with iron overload syndromes as the cause of infertility may have diffuse or patchy
hyperpigmentation. Men with Cushing's syndrome may have thin skin, ecchymoses, and/or broad purple
striae. Loss of pubic, axillary, and facial hair, decreased oiliness of the skin, and fine facial wrinkling suggest
longstanding testosterone deficiency.
3- External genitalia – Several abnormalities that affect fertility can be recognized by examination of the
external genitalia: Incomplete sexual development can be recognized by examining the phallus and testes
and finding small testes and micropenis and other findings of incomplete pubertal development (Tanner
stage less than 5).

12. LABORATORY EVALUATION- SPERM
ANALYSIS
• The first-line investigation for either couple infertility or male infertility is
sperm analysis. Sperm analysis should be collected after at least two days of
ejaculatory abstinence, preferably through masturbation. Due to the high
variability of the sperm concentrations, at least two samples must be collected,
at least one week apart.
• The following table demonstrates the normal sperm parameters.
• For patient with congenital bilateral absence of the vas deferens
which is most commonly caused by cystic fibrosis (it can also be
caused by unilateral renal agenesis), a sperm sample can be
collected through the following methods:
-Micro-Epididymal Sperm Aspiration (MESA) -Testicular Sperm Extraction (TESE)

13. LABORATORY EVALUATION- ENDOCRINE
TESTING
All men found to have abnormal sperm analysis should undergo endocrine
assessment which includes serum total testosterone, serum LH, FSH, and
prolactin.
The interpretation is as follows:
1-Low testosterone, and high FSH and LH – Primary (hypergonadotropic) hypogonadism (affecting both
spermatogenesis and Leydig cell function). These men should have a karyotype performed.
2-Normal testosterone and LH, and high FSH – Primary (hypergonadotropic) hypogonadism (seminiferous
tubule damage without Leydig cell dysfunction).
3-Low testosterone, but FSH and LH not elevated (normal or low) – Secondary (hypogonadotropic)
hypogonadism
4- Elevated serum prolactin may suggest a pituitary adenoma secreting prolactin (known as prolactinoma). A
male patient
who has elevated serum prolactin must undergo pituitary MRI.

14. IMAGING
•Scrotal and transrectal ultrasound: If a patient has
normal testicular volumes, palpable vasa deferentia on examination,
normal serum testosterone, FSH, and LH, and azoospermia, the
likely diagnosis is obstructive azoospermia. Ejaculatory duct
obstruction can be diagnosed by a scrotal or transrectal ultrasound
showing dilated seminal vesicles. Transrectal ultrasound might be
modestly more sensitive in detecting obstructive azoospermia

15. IMAGING
• Imaging is rarely needed except if varicocele is suspected in which
Ultrasound is needed to confirm the diagnosis. The other indication
for Ultrasound is the presence of azoospermia in which testicular
Ultrasound is needed to detect obstructive azoospermia
• Ultrasound is indicated if varicoceles is suspected, clinical findings
suggesting varicocele include: the presence of a dull, aching
testicular pain especially in the left side, small left testis, palpation of
the spermatic cord reveal a bag of worms sensation, worsened
symptoms upon valsalva maneuver, and negative transillumination
test

16. GENETIC TESTING
• Karyotyping is recommended for infertile men with elevated serum
FSH and LH concentrations and a sperm concentration less than 10
million/mL. Klinefelter syndrome is the most common sex
chromosome anomaly. These men typically have small, firm testes.
• Testing for cystic fibrosis transmembrane conductance regulator
(CFTR) gene can be done in patient with suspected cystic fibrosis, as
cystic fibrosis is a common cause of obstructive azoospermia.

17. APPROACH BASED UPON DIAGNOSIS:
The treatment of male infertility is directed towards the cause:
1-Endocrine disorders: all endocrine disorders must undergo
a cause-directed therapy, this may result in eugonadism and
improved sperms production. An example is prolactinoma which
can initially be shrunk through bromocriptine or cabergoline
therapy. If However, conception is needed currently or serum
testosterone doesn’t normalize upon treating the cause, then
gonadotropin replacement therapy is indicated to improve
fertility chances.

18. CONTINUE
2-Varicocele:
-Varicocele is the most common cause of male infertility, the treatment
is laparoscopic or open varicocelectomy, this therpay provides 60%
improvement of sperm parameters
3-Cryptochidism:
-Cryptochidism is the most common congenital anomaly of the
genitourinary tract, treatmemt aims to place and fix a viable undescended
testes in a normal scrotal position or to remove nonviable testis for the fear of
testicular carcinoma, surgical treatment is recommended within 4 months of
the diagnosis. The surgical procedure of choice is orchiopexy.

19. CONTINUE
4-Medications: all medications proven to cause infertility (mentioned in the
previous slides) must be stopped, or replace by other agents with similar
benefits.
5-Infections: all bacterial and viral infections (such as viral orchitis, and
urinary tract infection) must be treated. However, viral orchitis is usually self-
limiting and is treated supportively.
6-Lifestyle modification: obesity, smoking, and excessive alcohol intake are
known to contribute in
causing infertility. Therefore, weight loss, regular exercise, smoking cessation,
and decreasing alcohol consumption may optimize sperm production.

20. UNEXPLAINED INFERTILITY
• Definition: Unexplained infertility refers to the absence of a definable cause for a couple's failure
to achieve pregnancy after 12 months of attempting conception despite a thorough evaluation, or
after six months in women 35 and older.
• The management of couples with unexplained infertility should balance the efficacy,
cost, safety, and risks of various treatment alternatives. A common approach is to
start with treatments that consume few resources and are patient-directed (eg,
lifestyle changes or timed intercourse), and then move sequentially to treatments
requiring greater resources.

21. CONTINUE UNEXPLAINED INFERTILITY
• For asymptomatic women, gonadotropin ovulation induction and intrauterine
insemination (IUI) is offered because this approach is established in the treatment of
unexplained infertility and has higher rates of conception compared with IUI alone.
•Intrauterine insemination: The intrauterine insemination (IUI) procedure
consists of washing an ejaculated semen specimen to remove prostaglandins and
semen proteins that would promote an allergic reaction if injected into the uterus,
concentrating the sperm in a small volume of culture media, and then injecting the
sperm suspension directly into the upper uterine cavity using a small catheter
threaded through the cervix.

22. ASSISTED REPRODUCTIVE
TECHNOLOGY (ART)
• ARTs have advanced the treatment of infertility by allowing to successfully
bypassing the normal mechanisms of gamete transportation and
fertilization.
• The efficacy of ART varies from center to center, but in some centers it may
reach up to 80% of successful pregnancy
• The Method of ART that is proven to be effective in male infertility is
intracytoplasmic sperm injection.

23. INTRACYTOPLASMIC SPERM
INJECTION (ICSI)
• Intracytoplasmic sperm injection (ICSI) refers to a technique in which a single sperm
is injected directly into the cytoplasm of a mature oocyte. Also, it provides an effective
method for assisting fertilization in men with suboptimal semen parameters.
• ICSI is indicated mainly for male infertility that can’t be treated
medically or has failed medical therapy. It is also indicated in
unexplained infertility unresponsive to In-vitro fertilization. The
pregnancy rate for ICSI ranges from 50-80%, this efficacy rate
varies from center to center.

24. THANK YOU