Male Infertility

1. The three tiers are the hypothalamus, the anterior pituitary, and the testes
2. The hypothalamus produces GNRH which is transported to the anterior pituitary
via hypothalamohypophysial shunt
3. GNRH acts on the gonadotropes of the anterior pituitary stimulating release of
FSH and LH (The book mentions a second secretory molecule called Secretin
that is produced locally by the pituitary and causes the selective release of FSH)
4. FSH and LH travel via the circulatory system to the testes where LH acts on
Leydig cells stimulating testosterone production and FSH acts on the Sertoli
cells which then support spermatogenesis within the seminiferous tubules.

1. Testosterone and other androgens (estradiol and DHT) exert negative feedback
at both the level of the hypothalamus (decreased GNRH) and pituitary
(decreased LH). This activity is mediated by the androgen receptors located at
both the hypothalamus and AP
2. Inhibin, a protein produced by the Sertoli cells, acts on the anterior pituitary
causing decreased release of FSH. Another group of proteins called Activins are
also produced by the Sertoli cells and exert positive feedback on the AP causing
increased FSH release.

1. The first step is migration of primordial germ cells from the yolk sac into the
medullary cords where they are surrounded by Sertoli cell precursors
2. 7 weeks after conception

LH pulsatility is blunted along with age-related decline in leydig cell
steroidogenesis, although basal levels of LH actually increase

After penetrating the tunica albugenia, the testicular arteries run inferiorly along
the posterior surface of the parenchyma sending penetrating branches anteriorly
along the way. The vessels then sweep over the inferior pole passing anteriorly
and branching out over the surface of the testis. Because of this arrangement, the
medial and lateral midsection of the testis has fewer vessels compared with
anterior or inferior sections.
2. Because of this, testicular biopsy should be done in the medial or lateral surface
of the upper pole, where risk of vascular injury is minimal.

1. Internal spermatic testicular artery which branches off abdominal aorta just
below renal artery; Artery of the vas which branches from the internal iliac;
External spermatic (cremasteric) artery which branches off the inferior
epigastric (external iliac)
2. Pampiniform plexus facilitates heat exchange and exchange of small molecules
directly between inflowing arterial blood and outflowing venous blood,
including testosterone.
3. Delivers blood to the testes that is 2-4 C degrees lower than rectal temperature;
this is important for sperm development and ultimately fertility.

1. The first peak occurs in utero between 12 and 18 weeks gestation and causes the
differentiation of the fetal reproductive tract
2. The second peak occurs at 2 months of age and “imprints” androgen-dependent
target tissues ensuring their appropriate response later in life
3. Finally the overall peak occurs during the 2nd or 3rd decade causing
masculinization of the male at puberty and maintenance and growth of
androgen-dependent organs.

1. They create a specialized environment with the adluminal compartment of the
seminiferous tubule which is distinct from the interstitial environment (part of
blood-testis barrier)
2. They support germs cells directly via gap junctions
3. They facilitate migration of differentiating germ cells within the tubule itself

the tight junctions between Sertoli cells that segregate pre-meiotic germ cells
from other germ cells; the endothelial cells in capillaries with in the testis; and
the peritubular myoid cells
2. It shields haploid male gametes which are not recognized as “self” from the
immune system thus preventing the formation of anti-sperm antibodies
3. If breakdown of the barrier by some testicular insult such as torsion or trauma
occurs after puberty when male gametes become antigenic, immune recognition
may occur allowing the formation of anti-sperm antibodies that may adversely
affect future fertility.

1. Proliferative phase: spermatogonia divide and either replace their number (stem
cell renewal) or produce daughter cells committed to become spermatocytes
2. Meiotic phase: spermatocytes undergo reduction division resulting in haploid
spermatids
3. Spermiogenic phase: spermatids undergo maturation and metamorphosis to
mature spermatozoa
4. This takes ~64 days

1. Although the mechanisms are not clearly understood, the epididymis seems to
exert a maturing effect on transiting spermatozoa such that they reach full
functional capacity and are capable of fertilizing oocytes by the end by the end
2. Caput, corpus, and cauda
3. Testicular artery and deferential artery (with collaterals in between)

1. 2-12 days
2. Rhythmic contractions of contractile cells surrounding the epididymal duct
3. Distal corpus or proximal cauda epididymis

1. About 50% in the proximal vas and 50% in the epididymis
2. A 10:1 muscle-lumen ratio in the vas (the greatest of any hollow viscus in the
human body)

1. The chance of a normal couple conceiving is estimated to be 20% to 25% per
month, 75% by 6 months, and 90% by 1 year.
2. Most conceptions occur when intercourse takes place within 6 days before and
including the day of ovulation.
3. Age 24

Approximately 20% of cases of infertility are caused entirely by a male factor,
with an additional 30% to 40% of cases involving both male and female factors.
Therefore, a male factor is present in one half of infertile couples.
2. No. Although, in the past, couples were not evaluated until 12 months of
attempted conception, with the advancing age of infertile couples, the authors do
not recommend deferring an initial evaluation. A basic, simple, cost-effective
evaluation of both the male and the female should be initiated at the time of
presentation.

1. Identify reversible conditions
2. Identify irreversible conditions amenable to ARTs
3. Identify irreversible conditions that lead to adoption
4. Identify significant underlying medical pathology
5. Identify genetic or chromosomal abnormalities that may affect the kids

1. Although there is some controversy, most experts advise vaginal intercourse
every 2 days, which ensures that viable sperm are present during the 12- to
24-hour period in which the oocyte is within the fallopian tube and is capable of
being fertilized.

1. There is both experimental and clinical evidence that the timing of orchidopexy
does not appear to affect the findings of spermatogenic abnormalities in these
testes as long as the testes were brought down before puberty.
2. False
3. There is no scientific evidence that the type of underwear worn affects
spermatogenesis

1. There have been no controlled studies demonstrating improved pregnancy rates
after the diagnosis and treatment of subclinical varicoceles. We therefore do not
recommend evaluating patients for the presence of subclinical varicoceles.

1. No. Patients should have 2-3 properly collected specimens examined over
several weeks
2. Except in cases of azoospermia, the semen analysis does not allow for the
definitive separation of patients into sterile and fertile groups. As semen
parameters decrease in quality, the statistical chance of conception decreases but
does not reach zero.

1. The seminal vesicles secrete the substance responsible for coagulation. Patients
with CBAVD usually have absent or hypoplastic seminal vesicles. Semen in
these patients does not coagulate, is acidic, and has a low volume.
2. PSA causes semen liquefaction
3. In cases in which the semen demonstrates nonliquefaction or hyperviscosity
4. The consistency of the semen may be disregarded

Small-volume ejaculates may be produced in patients with obstruction of the
ejaculatory ducts, androgen deficiency, retrograde ejaculation, sympathetic
denervation, absence of the vas deferens and seminal vesicles, drug therapy, or
bladder neck surgery.

1. 7.2 or greater
2. Acidic prostatic secretions and alkaline seminal vesicle secretions
3. Normal = 70 million – 100million/mL
4. No, a man can have a normal sperm count but be infertile, eg, because of absent
motility

1. Normal, incomplete collection, or retrograde ejaculation
2. Ejaculatory duct pathology or absent seminal vesicles

Azoospermia, low volume ejaculate, and acidic, fructose-negative semen that
does not coagulate
2. Transrectal ultrasonography is more clinically useful than fructose
determination

Elevated FSH. Elevated serum FSH level suggests a significant problem with
spermatogenesis because normally it would undergo negative feedback
inhibition by inhibin, produced by Sertoli cells. However, normal serum FSH
level does not guarantee intact spermatogenesis.

The authors recommend that all men with an indication in the history or
physical examination or a sperm density less than 10 million/ml have serum
FSH and testosterone levels measured, because endocrine abnormalities are
rarely present when the sperm concentration is greater than 10 million/ml..

Spinal cord injury
2. Aspermia - Absence of seminal fluid
3. Azoospermia - Absence of sperm within the seminal fluid
4. The evaluation of the azoospermic patient should be geared toward determining
whether
azoospermia is caused by abnormal spermatogenesis or by ductal obstruction

In patients with small testes and FSH concentrations greater than two to three
times normal, severe germ cell failure is present and the ultimate outlook is
poor. A testis biopsy should be performed in these patients only if testicular
sperm retrieval combined with IVF is being considered.

1. Oligospermia – Sperm densites of less than 20 million sperm/mL
2. Varicocele

Defects in sperm movement, referring to low levels of motility or forward
progression or both.
2. It can be caused by spermatozoal structural defects, prolonged abstinence
periods, genital tract infection, antisperm antibodies, partial ductal obstruction,
varicoceles, and idiopathic causes may be responsible for these cases.

Normal semen analyses in infertile couples suggest the possibility of a female
factor as well as immunologic infertility or incorrect coital habits. A PCT should
be obtained in these instances. If no sperm are identified, the couple must be
questioned about their coital technique.

Risk factors for the development of antisperm antibodies include conditions that
may disrupt the blood-testis barrier. Approximately 60% of men develop
antisperm antibodies after vasectomy whereas approximately one third of
patients with CBAVD are found to have antisperm antibodies present on the
sperm at the time of retrieval from the epididymis. Other causes that have been
associated with the presence of antisperm antibodies include acute epididymitis,
cryptorchidism, and genital trauma.
2. Effects: impaired penetration of the cervical mucus, inhibition of sperm
capacitation, premature induction of the acrosome reaction, impairment of zona
binding or fertilization of the egg
3. Test patients with the previously mentioned risk factors, those demonstrating
impaired sperm motility, sperm agglutination, abnormal PCT findings, and
couples with unexplained infertility

1. Vasography is indicated to determine the site of obstruction in azoospermic
patients who have active spermatogenesis documented by testis biopsy.
Vasography is best performed in conjunction with reconstructive surgery
because this procedure carries an inherent risk of vasal injury that could
complicate future reconstructive surgery if performed separately.

1. This suggests obstruction of the ejaculatory ducts
2. TURED.

Abdominal ultrasound. Ipsilateral renal anomalies are present in up to 80% of
men with unilateral absence of the vas deferens, with the most common
anomaly being renal agenesis (risk for renal anomalies much lower with
bilateral absence).

1. This is an examination of cervical mucus under a microscope to examine sperm
deposition, morphology and motility.
2. It is indicated only if the results will influence the management of the infertile
couple. Used in cases of hyperviscous semen, unexplained infertility, and lowvolume
or high-volume semen specimens with normal total sperm counts.
Because patients with very poor quality semen invariably have poor PCTs, it is
not necessary to perform PCTs in this group of patients. A persistently abnormal
PCT in the face of reasonably good semen parameters should lead the physician
to question the quality of the cervical mucus.

Nonmotile sperm may be viable but lack the ability to move or may be dead.
The finding of a predominance of viable nonmotile sperm suggests the presence
of ultrastructural defects. To differentiate these two states, sperm viability
assays are used.
2. About 6% of the time, with a prevalence that increases as the sperm count
decreases.

. Diagnostic testicular biopsy is performed only in azoospermic patients. Most
clinicians perform bilateral testicular biopsy, but, in patients with discrepant
testicular volume, some physicians perform a biopsy on the larger testis only.
The purpose of diagnostic testicular biopsy is to differentiate between
obstructive/nonobstructive azoospermia; usually done in patients in whom
ductal obstruction is suspected based on relatively normal serum FSH and
testicular volume.
2. Other role is in patients with nonobstructive azoospermia considering sperm
retrieval and IVF.

1. Patients have small to normal-sized testes associated with normal or elevated
levels of FSH
2. Pathology shows seminiferous tubules with sertoli cells only and absence of all
germ cells
3. There is no effective treatment

1. Endocrine Causes (“pretesticular causes”)
2. Disorders of Spermatogenesis
3. Sperm delivery disorders
4. Sperm function disorders

1. Congenital hypogonadotropic hypogonadism associated with anosmia. It is a
genetically heterogeneous disorder that may be inherited in an X-linked,
autosomal dominant or autosomal recessive pattern. A delay in pubertal
development is the hallmark of the syndrome. Treat with androgen replacement;
gonadotropin therapy (hCG + FSH) is required for initiation of spermatogenesis.
2. Treat Prader-Willi the same as Kallman’s syndrome.

1. Introduction of sex steroids into the circulation from a source besides the testis
has an inhibitory effect on spermatogenesis because of the resultant reduction of
both intratesticular testosterone and FSH through feedback inhibition on the
pituitary gland. Thus, the administration of exogenous testosterone is a male
contraceptive and anabolic steroids have a similar effect.

Estrogens normally suppress pituitary gonadotropin secretion. ED,
gynecomastia, testicular atrophy may be present in men with estrogen excess.
2. A state of secondary testicular failure may be induced by estrogen-secreting
tumors in the adrenal cortex. Sertoli or Leydig cell tumors in the testicles may
produce estrogen; excess estrogens may also result from hepatic dysfunction or
obesity.
3. Adipose tissue produces aromatase, which converts testosterone to estrogen

1. Because prolactin suppresses gonadotropin-releasing hormone secretion, and
subsequently levels of gonadotropins and testosterone.
2. Although surgery and radiation therapy were used in the past to treat patients
with prolactin-secreting pituitary tumors, the vast majority of patients respond to
medical therapy. The two agents most commonly used today are bromocriptine
and cabergoline.

Defined by presence of an extra X chromosome: XXY (rarely 46,XY/47,XXY).
A phenotypic male with small firm testes, gynecomastia, and elevated
gonadotropins characterizes the classic form of Klinefelter’s syndrome. There is
no therapy to improve spermatogenesis in Klinefelter’s syndrome. For the
patient with mosaic Klinefelter’s syndrome and severe oligospermia, ICSI
combined with IVF is a possibility
2. Histologically, Leydig cells are present in large clumps resembling Leydig cell
tumors

Yes. In general, there is a direct relationship between testicular position and
fertility potential: The higher the cryptorchid testis, the more severe the
testicular dysfunction. Absence of germ cells is found in 20% to 40% of
inguinal testes in contrast to 90% of intra-abdominal testes

A varicocele is an abnormal tortuosity and dilatation of the testicular veins
within the spermatic cord, and is the most common correctable cause of male
infertility. Approximately 90% of varicoceles are left-sided. Most studies report
an approximately 10% prevalence of bilateral varicoceles, although some recent
reports have reported a higher prevalence of bilaterality.
2. With unilateral right-sided varicoceles, you must consider a right renal tumor
with thrombus into the IVC, into which the right testicular vein drains (will not
collapse in the supine position).
3. No. The presence of a varicocele alone is not an indication for varicocele repair,
because the majority of men with varicoceles are fertile. The presence of a
clinically detectable varicocele associated with an abnormal semen analysis in
an infertile couple is an appropriate indication for treatment after the female
partner has been evaluated.
4. Improvements in motility are most common, occurring in 70% of patients, with
improved sperm densities in 51% and improved morphology in 44% of patients.

With cisplatin-based chemotherapy, most patients will become azoospermic;
however, the majority will recover spermatogenesis within 4 years.
2. Semen quality will usually return to baseline within 2 years after radiation
therapy for seminoma. Approximately one fourth of patients may become
permanently infertile from such radiation treatment. After radiation therapy,
most patients are advised to avoid conception for 2 years until the prognosis is
more certain.

7-12% of all infertile men

1. The currently recommended management of couples with infertility owing to
CBAVD is sperm retrieval combined with IVF using ICSI after appropriate
genetic testing and counseling of the couple regarding the risk of cystic fibrosis.

Ephedrine sulfate (25 to 50 mg qid), pseudoephedrine (60 mg qid), and
imipramine (25 mg bid) may induce ejaculation secondary to an increase in the
sympathetic tone of the internal sphincter and vas deferens.

False: it works best with upper motor neuron lesions such as spinal cord injuries
above T10.

Aseptic necrosis of the hip

Ultrastructural axonemal defects are commonly associated with identical defects
in the cilia of the respiratory tract. This condition is known as the immotile cilia
syndrome or primary ciliary dyskinesia. Chronic respiratory tract infections with
bronchiectasis are common in these patients. When these clinical findings are
combined with situs inversus, which is present in 50% of these cases, the patient
has Kartagener’s syndrome.

Up to 6%

When an azoospermic man has normal levels of FSH and testes of normal size
and consistency, or when an azoospermic man with an elevated FSH and
bilateral small nuts who desires attempted sperm retrieval and IVF with ICSI
2. False. A 95% correlation has been described between percutaneous and open
techniques, but the major disadvantage is an increased risk of injury to the
testicular artery or epididymis, plus it offers less seminiferous tubules for
examination
3. Bleeding and hematomas
4. Use an operating microscope

Grade I are palpable only with valsava, grade II are palpable without valsalva,
and grade III are visible through the scrotal skin at rest
2. Veins 3.5mm or larger, with reversal of venous flow after valsalva
3. Only when the presence of a varicocele is uncertain on exam or recurrence is
suspected

1. Four conditions must be met: the couple has known infertility, the female
partner has normal fertility, the varicocele is palpable on exam (or if suspected
is found with ultrasound, and the male has an abnormal semen analysis
2. Less complications, including testicular artery injury, hydrocele (3-39% in
nonmicrosurgical versus almost zero with microsurgical), and recurrence
(9-16% in nonmicrosurgical inguinal and 5-20% in nonmicrosurgical
subinguinal, versus 1-2% with microsurgical inguinal)
3. In a series of 1500 microsurgical varicocele repairs, over 40% after the first year
and 70% at 2 years
4. Lack of testicular atrophy, sperm density greater than 50 million/ejaculate,
motility of > 60%, and normal FSH levels

Longer time from vasectomy
2. The quality of fluid found in the proximal (testicular) vas at the time of
reversal. It should be considered when the quality is thick, pasty, and devoid of
sperm; if creamy and containing only debris; and if there is no fluid whatsoever

False, it depends on the surgeon
2. Most studies with large numbers of patients have generally found patency rates
of 75-85% and pregnancy rates of 45-70%

1. Vasal aspiration- useful if the lack of ejaculation has a neurologic cause
2. Percutaneous epididymal sperm aspiration (PESA)- quick and inexpensive, but
frequently insufficient sperm are obtained
3. Microsurgical epididymal sperm aspiration (MESA)- appropriate for men with
epididymal or vassal obstruction, allows for collection of large amount of
sperm, but is costly
4. Open testis biopsy
5. Testis sperm aspiration and needle biopsy- low cost and morbidity, but low
numbers
6. Microsurgical (or non-microsurgical) testicular sperm extraction- allows
meticulous dissection and less trauma to blood vessels, less tissue needs to be
extracted preserving more of the testis, and there appears to be a higher rate of
sperm retrieval for ICSI

1. Axial diameter greater than 1.5cm

1. Indicated in the azoospermic man who is found to have many mature
spermatozoa on testicular biopsy and who also has at least one palpable vas2. It is used to help confirm equivocal TRUS findings, or if no sperm are found on
SV aspiration.
3. Its use has been limited by the risk of vassal injury and subsequent vassal
occlusion.

Usually deep and just posterior to the veru

Reflux of urine into the ejaculatory ducts and subsequently into the SV’s, vas, or
even the epididymis, which can lead to acute or chronic epididymitis; also,
retrograde ejaculation, and rarely incontinence
2. 55% have improvement in semen parameters, and there’s a 27% pregnancy rate