Male infertility can have many causes, both genetic and environmental. A thorough evaluation includes a history, physical exam, semen analysis, and potential hormone and imaging tests. Semen analysis evaluates parameters like volume, sperm concentration, motility, and morphology. Abnormal results on semen analysis or physical exam may indicate further tests are needed to identify potential treatable causes of infertility. The goal is to optimize the chances of natural conception or inform treatment options if needed.

1. Male infertility
Dr. Anupam Anand
PDT, NRSMC&H

2. Infertility
• “Infertility is the inability of a sexually active, non-contracepting couple to achieve
spontaneous pregnancy in one year”. (WHO)
• The disease of infertility affects approximately 15% of couples, rendering nearly one of six
childless.
• Male has 50% contribution to infertility cases.
• 18-27% of men in infertile couple group were never investigated ( American data)
• Normal fertile couples of reproductive age have a conception rate of 20% to 25% per month ,with
more than 90% conceiving within 1 year.
• Primary infertility – a couple that has never conceived
• Secondary infertility – infertility that occurs after previous pregnancy regardless of
outcome

5. •

6. • It is reasonable to initiate an evaluation after 6 months with the understanding that some couples will
still conceive shortly afterward .
• For an optimal characterization of semen, a man should be instructed to wait 1 or 2 days after an
ejaculation to submit a specimen for semen analysis.
• However, for increasing the probability of conception and pregnancy, intercourse every day around
the time of ovulation is likely the best strategy.
• On average, female fecundity declines precipitously after age 35

7. APPROACH
HISTORY
PHYSICAL EXAMINATION
SEMEN ANALYSIS
ENDOCRINE EVALUATION
UROLOGIC EXAMINATION
POST EJACULATORY SEMEN ANALYSIS
SPECIALISED TESTS

8. History
Toxins
• Endocrine Modulators -Medications may affect the ratio of estrogen to
androgen through a variety of mechanisms
• molecular similarity to estrogen
• increased estrogen synthesis
• increased aromatase activity
• dissociation of steroids from sex hormone-binding globulin (SHBG)
• decreased testosterone synthesis
• competitive and noncompetitive binding to steroid receptors
• decreased synthesis of adrenal steroids
• induction of hyperprolactinemia
Medications
• Antiandrogens -Bicalutamide, flutamide, and nilutamide
• Antihypertensive -Spironolactone
• Protease inhibitors- Indinavir
• Nucleoside reverse transcriptase inhibitors –stavudine
• Corticosteroids, especially in adolescence
• Exogenous estrogen

9. Recreational drugs
• Cannabis -decreases plasma testosterone in a dose-dependent and duration
dependent manner
• Heavy chronic alcohol intake -increase aromatization of testosterone to estradiol
• Cigarette smoking
• worsens bulk seminal parameters.
• Increased seminal oxidative stress parameters
• abnormal ratio of protamines 1 and 2 ,with evidence of atypical protamine 2
expression
Antihypertensives
• Can cause erectile dysfunction
• Calcium channel blockers
• inhibits expression of mannose-ligand binding receptors
• preventing sperm from attaching to the zona pellucida
• ACE inhibitors appear to improve sperm motility through a presumptive
effect on seminal plasma kinins
• 2.5 mg of lisinopril daily increased sperm count, motility, and morphology

10. Antipsychotics
• Most common mechanism of action for antipsychotic drugs is antagonism of dopamine
• Causes loss of libido
• Elevation of prolactin levels, most acute for risperidone and to a lesser extent olanzapine
• Selective serotonin reuptake inhibitors (SSRIs)
• anorgasmia
• delayed or absent ejaculation
Antibiotics
• Tetracycline binds mature sperm
• direct toxicity on sperm function oxidative stress mechanism
• In animals that high doses of nitrofurantoin reduced epididymal sperm density and sperm motility

11. Cytotoxic Chemotherapeutics
• Suppress briskly proliferating population of cells.
• Spermatogenic suppressive effects-dose and time dependent
• Higher doses and longer durations of therapies results in permanently impaired
fertility
• Alkylating agents such as the nitrogen mustard cyclophosphamide
• Doxorubicin, vincristine, and prednisone,
• Cisplatin, etoposide, and bleomycin
• Sperm DNA damage can be detected at least up to 2 years after chemotherapy
• Cryopreservation of sperm before treatment with cytotoxic chemotherapeutic
agents
• Bacille Calmette-Guérin into the bladder for superficial transitional cell carcinoma
resulted in a significant decrease in sperm concentration and motility

12. Thermal Toxicity
• Scrotal temperature in humans is maintained to be 2° C to 4° C below core body temperature
• Clothing, physical activity, and body posture such as whether the legs are crossed or not in a sitting position all
change scrotal temperature
• Clothing may thus confer a greater differential increase in left scrotal temperature than right scrotal temperature
• occupational exposure
• Laptop computers radiate heat, and researchers have studied the effects of these devices on scrotal temperature
Radiation
• Ionizing radiation- germ cell loss and Leydig cell dysfunction
• chances of having future offspring were lessened by radiation doses to the testes of 7.5 Gy and above
• If the radiation field is proximal to the testis and the dose is sufficient, sperm production may be diminished even if
the testis is shielded
Childhood diseases
• Hydroceles and hernias repaired during childhood
• low but discrete incidence of complications causing vasal obstruction
• rate of testis atrophy after pediatric inguinal hernia was 0.3%
• Testis Torsion
• half of men will develop adverse spermatogenic effects
• 36% to 39% of men will have sperm concentrations below 20 million/mL
• 11% of men will develop antisperm antibodies

13. I: infection and inflammation
• Infections of the testis, epididymis, prostate, and urethra may lead to male infertility through anatomic and
functional means
• Common organisms affecting the prostate include Escherichia coli, Pseudomonas aeruginosa, and Klebsiella,
Proteus, and Enterococcus species
• Typical epididymal organisms include Neisseria gonorrhoeae, Chlamydia trachomatis, and E. coli
• Infections of the testis may include the mumps, Coxsackievirus B, N. gonorrhoeae, C. trachomatis, E. coli, P.
aeruginosa, and Klebsiella, Staphylococcus, and Streptococcus species
• Mumps orchitis
• bilateral disease 36% result in Testicular atrophy
• Infertility occurs in 13%
• Mycobacterium tuberculosis may affect any reproductive organ and cause scarring of the vas deferens and
epididymis
• *vasal calcification: TB,syphilis,
gonorrhoea,schistosomiasis,chronic UTI. DM.

14. Cryptorchidism
• Dysfunction of the seminiferous epithelium
• Leydig cell steroidogenesis
• Ultrastructural defects
• Widely recognized that surgical correction of undescended testes after puberty -minimal
effect on bulk semen analysis parameters .
• Age before puberty at which orchidopexy results in optimal effect in reproductive
potential has not been definitively established.
• Prudent to recommend orchidopexy before 10 years of age from a reproductive
perspective

15. Male Reproductive Physical Examination
• Most effectively performed with the patient standing
• low examining table or chair, as some men will develop syncope during palpation of the scrotum
• Examining the Scrotum
• Visual observation
• One or both sides may be hypoplastic
• substantially larger than the other, suggesting a reactive hydrocele or tumor.
• varicocele
• Epididymis is typically difficult to appreciate
• if it is easily palpated, it is likely engorged, suggests obstruction
• Testis size
• well established to correlate with sperm production
• assessed by calipers often referred to Seager orchidometer
• long axis of the testis is gently grasped between the jaws of the calipers,
• measurement of 4.6 cm or less is associated with spermatogenic impairment
• Compare the examiner’s palpation findings with a string of ellipsoids of increasing size with marked volumes
• A volume of 20 mL or less is considered low
• directly measured by ultrasonography of the scrotum

17. Examining the Spermatic Cord
• Palpation whether the vas deferens is palpable, and whether a varicocele is present.
• Firm cordlike structure /compressibility of the vessels
• Absence of the vas can be a difficult physical sign to identify
• Meacham’ maxim -vas disappears from the examiner’s fingers three times, the clinician confident that the vas
is absent. (Randall Meacham)
• Unilateral absence of the vas deferens
• complete lack of wolffian ductal development on that side, including renal agenesis (79%)
• If both vasa are absent, high likelihood of a cystic fibrosis gene mutation
• renal agenesis in 11% of men with congenital bilateral absence of the vas deferens.
• Best modality to diagnose absence of vas deferens: clinical examination

18. Varicocele
• varicocele is the most commonly encountered nonductal surgically addressable pathologic entity
• grade I-not palpable or visible,can only be detected by radiographic evaluation such as Doppler
ultrasound
• grade II-palpable but not visible
• grade III-visible by the examining physician through the rugae of the scrotum
• the incidence of varicocele in infertile males to
be between one-third and one-half
• PENIS: abnormalities include phimosis, meatal displacement in hypospadias or epispadias, and
significant penile curvature
• semen must be deposited proximal to the cervical os for optimal chance of reproduction
• DRE: seminal vesicles cannot typically be palpated; if palpable, engorgement and possible ejaculatory
ductal obstruction
• midline cysts such as müllerian duct cysts,can obstruct the ejaculatory ducts

19. Endocrine evaluation
• Minimal evaluation includes the assessment of serum FSH and testosterone levels, which reflect germ cell
epithelium and Leydig cell status respectively
• Spermatogenesis is highly dependent on intratesticular testosterone synthesis
• Either 280 ng/dL or 300 ng/dL as a threshold for adequate androgenization in a man.
• In the healthy man,
• 30% to 44% of circulating testosterone is bound to SHBG
• 54% to 68% is loosely bound to albumin
• 0.5% to 3.0% is unbound
• bioavailable testosterone demonstrates a marked circadian rhythm in young, healthy men,
• peak in the early morning and trough in the late afternoon
• SHBG is altered in a variety of medical conditions.
• practical method of determining bioavailable testosterone is to calculate it from total testosterone, SHBG, and
albumin
• SHBG displays an opposing circadian rhythm in men of all ages, with a peak in the late afternoon and a
trough in the early morning

21. • Sertoli cell products inhibin B and activin
• regulate pituitary follicle-stimulating hormone (FSH)
• respectively inhibiting and stimulating its release
• With depopulation of Sertoli cells
• inhibin levels decrease and FSH consequently increases
• measuring inhibin B directly is a more accurate assessment of spermatogenic function
• 96% of men with obstructive azoospermia had FSH assay values of 7.6 IU/L or less and testis long axis
greater than 4.6 cm
• Ratio of total testosterone to estradiol below 10 : 1 is suggested to indicate reproductive dysfunction

23. Semen analysis
• Recommend a minimum of two analyses separated by 2 to 3 weeks for assessment .
• Historically, men were instructed to wait 2 to 5 days after an ejaculation to submit a sample for semen analysis.
• More recent studies suggest that a single day of abstinence is optimal for assessing bulk seminal parameters
When AND how?
After abstinence of 1 day.
In a clean container by masturbation or via intercourse using silastic condom or electrostimulation.
Examined with in an hour of collection.
At least two to three semen analyses should be done & spaced 2 to 3 months apart.

26. Semen volume
• the most frequently used threshold value for volume is 1.0 mL to initiate evaluation for seminal
hypovolemia.
• Aspermia, dry ejaculate, and anejaculation refer to the condition in which no fluid is discharged from the
urethra during male orgasm.
• If aspermia or seminal hypovolemia is observed, a postejaculatory urinalysis is performed to identify
retrograde ejaculation. Centrifuging the urine specimen for 10 mins at 300rpm followed by microscopic
examination of pellet at 400 magnification.
• In men with azoospermia or aspermia the presence of any sperm in post ejaculatory urinalysis suggests
retrograde ejaculation.
• In men with low ejaculate volume and oligospermia significant no. of sperms must be observed to support
diagnosis of retrograde ejaculation.
• investigation such as transrectal ultrasonography (TRUS) is conducted to evaluate whether ejaculatory
ductal obstruction may be present .
• Seminal hypervolemia with an ejaculate volume exceeding 5 mL

27. Normospermia
Aspermia
Hypospermia
Hyperspermia
Azoospermia
Oligospermia
Polyzoospermia
Asthenozoospermia
Teratozoospermia
Leukospermia
Hematospermia
Necrozoospermia
- Normal semen volume
- No semen volume
- Semen volume < 1.5 ml
- Semen volume > 5.0 ml
- No spermatozoa in semen
- Sperm concentration <15 M/ml
- High sperm concentration, >200M/ml
- <40% grade (A&B) or < 32 PR%
- <4% spermatozoa
- Leukocytes present in semen, >1M/ml
- Red blood cell present in semen
- “dead” sperm
OAT =Oligo-astheno-teratozoospermia

28. Secondary Semen Assays
• assay for antisperm antibodies :
• Conditions associated with antisperm antibody formation include vasectomy, testis trauma, orchitis,
cryptorchidism, testis cancer, and varicocele.
• Two direct assays are available:
• 1.the mixe antiglobulin reaction (MAR) test.
• 2.the immunobead assay
Pyospermia Assays:
• The Papanicolaou stain may be used to differentiate leukocytes from immature
germ cells based on nuclear morphology .
• The current consensus threshold for leukocytes according to the WHO
laboratory manual is 1 million/mL

29. Tertiary and Investigational Sperm Assays
• Sperm DNA Integrity Assays :
Sperm DNA is six times more compact than in somatic cells.
fragmentation or disturbances in DNA arrangement lead to aberrations in sperm function, fertilization, implantation,
and pregnancy.
TUNELAssay.
The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
• detect sperm head DNA fragmentation .
• ratio of TUNEL-positive sperm to all sperm and expressed as a percentage.
• Comet Assay: Like the TUNEL assay, the comet assay, also referred to as the single-cell gel electrophoresis
assay.
Denatured Sperm DNAAssays:
• Assay for sperm head DNA structure is the Sperm Chromatin Structure Assay (SCSA)

30. Sperm Ultrastructural Assessment:
• Sperm motility is dependent on the ultrastructural arrangement of microtubules in the tail with a peripheral
array of nine pairs and a central two microtubules connected by dynein arms.
• This “9 + 2” architecture is shared with cilia, and genetic disorders affecting it can manifest as respiratory
pathology associated with male reproductive dysfunction, referred to as the immotile cilia syndrome,
primary ciliary dyskinesia (PCD), or Kartagener syndrome.
• Sperm Fluorescence in situ Hybridization :
• employs fluorescent-labeled primers that bind specifically to each
chromosome in the sperm, allowing measurement of sperm
aneuploidies that are of major clinical importance
• *KARTAGENER SYNDROME: chronic sinusitis and bronchiectasis,situs inversus, and infertility

31. Genomic Assessment
• Karyotype:
• American Urological Association Best Practice Statement on the Optimal Evaluation of the Infertile Male
recommends that
• genetic testing including karyotype be performed in all males with azoospermia caused by
spermatogenic dysfunction
• those with severe oligospermia defined as less than 5 million sperm/mL.
Not indicated if-
Normal testis volume.
Palpable vasa on physical examination and strong suspicion for obstruction
Normal serum FSH and normal semen volume
Y Chromosome Microdeletion Testing
• region in the long arm of the Y chromosome was critical to the formation of sperm in man
• known as AZF (azoospermia factor)
• microdeletions of AZFc appear to be associated with spermatogenic impairment but not failure
• AZFa and AZFb microdeletions cause significant pathology of the testis resulting in diminishing low
likelihood of sperm retrieval .
• Genetic screening of the CFTR in men with CBAVD and their partners identifies the presence of severe
mutations such as ΔF508 that may result in clinically overt cystic fibrosis in offspring

32. • The presence of a supernumerary X chromosome yielding 47,XXY, or Klinefelter syndrome, is the most
commonly identified genetic cause of male infertility.
• hypergonadotropic hypogonadism, primary hypogonadism, and primary hypoandrogenism refer to impaired
testosterone synthesis caused by Leydig cell dysfunction.
• identified by elevated LH levels and decreased circulating testosterone.
• Hypogonadotropic hypogonadism refers to the condition of decreased pituitary hormonal secretion.
• Kallmann described anosmia associated with decreased pituitary function .
• Male infertility associated with AR insensitivity is characterized by increased testosterone, estradiol, and LH to
variable degrees with typical FSH levels; significantly elevated testosterone in the presence of impaired male fertility
should consequently raise the suspicion of AR resistance

36. IMAGING IN THE EVALUATION OF MALE INFERTILITY
• TRUS:
• Employs the 5- to 7-MHz endocavitary probe .
• Diagnosis of ejaculatory ductal obstruction
• azoospermia in conjunction with low seminal volume is encountered
• TRUS imaging evidence of ejaculatory duct obstruction includes
• anteroposterior seminal vesicle diameter of greater than 1.5 cm with or without a midline
prostatic cyst
• ED diameter > 2.3mm
• MRI with an endorectal coil can be used to evaluate anatomic features consistent with ejaculatory ductal
obstruction
• Abdominal imaging in the evaluation of the infertile male is primarily used to study whether renal
sequelae of congenital vasal maldevelopment is present
• Cranial MRI allows assessment of whether hyperprolactinemia is associated with an anatomic
pituitary lesion.
• distinguish between microadenomas and macroadenomas

37. Testicular biopsy
Diagnostic:
• Azoospermia with suspected obstruction as the cause
• Normal testicular size and consistency
• Normal serum FSH levels
• Suspected testicular failure (occasionally)
• Small-volume testes, High serum FSH level.
• not indicated in the initial diagnostic evaluation of the infertile man
•Specimens should be placed in a fixative solution such as Bouin’s, Zenker’s or
glutaraldehyde.
• Formalin should not be used as it may disrupt the tissue architecture.
• The most serious complication associated with testis biopsy is inadvertent biopsy of the epididymis.
•
The most common complication of testis biopsy is hematoma. Hematomas can be
large and may require drainage

39. • germ cells are lacking entirely and only Sertoli cells are visible in the germinal epithelium.
Sertoli cell–only syndrome/Germinal aplasia
• visualization of a mature sperm head is typically sufficient to confirm completion of the
stages of spermatogenesis.

40. Vasography
• Gold Standard Test for assessing the patency of vas
• Provides anatomic details of the
• Vas deferens
• Seminal vesicles
• Ejaculatory ducts
• Determination of the site of obstruction in the azoospermic patient
Ideally performed at the time of anticipated reconstruction
INDICATIONS:(Absolute)
1.Azoospermia, plus
2.Complete spermatogenesis with many mature spermatids on testis biopsy, plus
3.At least one palpable vas
1.Absence of sperm in vasal fluid indicates obstruction on the testicular side of the vasotomy site, most likely an epididymal
obstruction
2.Copious vasal fluid containing many sperm indicates vasal or ejaculatory duct obstruction.
3.Copious thick, white fluid without sperm in a dilated vas indicates secondary epididymal obstruction

41. Perform vasography only at the time of planned reconstruction.
Always sample vasal fluid first to allow cryopreservation of motile sperm if found.
Use indigo carmine instead of methylene blue to confirm patency.
Formal vasography with x-ray contrast is needed only to locate obstructions proximal to the internal inguinal ring.

44. • Retrograde Ejaculation :
• the bladder neck must first close while temporal neural sequencing first causes closure of the external sphincter to
create a high pressure compartment that is emptied with its subsequent opening.
• Primary treatment modalities include retrieval of retrograde ejaculated sperm and increasing resistance at the
bladder neck with sympathomimetic agents.
• Sympathomimetic agents such as synephrine, pseudoephedrine, ephedrine, or phenylpropanolamine
• Anejaculation : to lack of seminal emission and projectile ejaculation.
• Due to neurologic and include retroperitoneal lymph node dissection, pelvic surgery, multiple sclerosis,
transverse myelitis, congenital neural tube defects, diabetes mellitus, and spinal cord injury .
• electroejaculation, may result in sufficient sperm for IUI or IVF .
• spinal cord injuries at a level of T6 or above, stimulation may cause autonomic dysreflexia, an uninhibited
sympathetic reflex
accompanied by headache, diaphoresis, hypertension, bradycardia, and diaphoresis, which may be life threatening.
• treatment with nifedipine and during the procedure with monitoring of cardiac activity and blood pressure

45. Transrectal ultrasound-guided aspiration of the cystic or dilated ejaculatory duct.
The aspirate is examined microscopically;
if motile sperm are found, they are cryopreserved
2 to 3 mL of indigo carmine diluted with water-soluble radiographic contrast is instilled.
If a radiograph confirms a potentially resectable lesion, TURED is performed without the need for prior vasography.
If no sperm are found in the aspirate, vasography is necessary.
If no sperm are found in either vas when the vasotomy is made and vasography reveals ejaculatory duct obstruction
abandon reconstruction and plan for future IVF and ICSI.
simultaneous vasoepididymostomy and TURED - poor result
Complication-Reflux, Epididymitis, Retrograde ejaculation
TURED- TRANSURETHRAL RESECTION OF ED

46. TURED : IN EJACULATORY DUCT OBSTRUCTION

47. Sperm Retrieval Technique
Non obstructive azoospermia:
TESA- Testicular sperm aspiration
Micro-TESE- Microdissection testicular sperm extraction.
Obstructive Azoospermia
MESA- Microsurgical epididymal sperm aspiration.
PESA- Percutaneous epididymal sperm aspiration

48. SPERM RETRIEVAL TECHNIQUES

49. TESA- TESTICULAR SPERM ASPIRATION
Blind procedure
Immobilization of the testicle. By grasping it with the epididymis and cord between fingers while pulling the scrotum
skin taut. performed with a 23-gauge needle or angiocath from superior pole of testes

51. MESA (microsurgical epididymal sperm aspiration)
Invasive.
Provides retrieval of many sperm.
Less epididymal damage.
Can be cryopreserved and used for future procedures.
A median raphe approach through two small transverse scrotal incisions.
After delivery of the testis, the tunica vaginalis is opened and the epididymis inspected under operating
microscope.
The epididymal tunica is incised over a dilated tubule .
A dilated tubule is isolated and incised
.The fluid is touched to a slide, and the fluid examined.
If no sperm are obtained, the epididymal tubule and tunica are closed, and an incision is made more proximally in the
epididymis until motile sperm are obtained.
As soon as motile sperm are found, Sperm are drawn into the micropipette by simple capillary action.

52. EPIDYDIMAL SPERM RETRIEVAL

53. Varicocelectomy
• Varicocelectomy is by far the most commonly performed operation for the treatment of male
infertility.
• Varicocele is found in approximately 15% of the general population.
• 35% of men with primary infertility and in 75% to 81% of men with secondary infertility.
• Variococelectomy can also improve Leydig cell function resulting in increased testosterone levels .
• Hydrocele formation is the most common complication due to lymphatic obstruction

56. Artificial insemination
Indications
Oligospermia
Asthenospermia
Premature or retrograde ejaculation
Sperm autoantibodies & cervical factors
Unexplained infertility
Sex selection in genetic & chromosomal anomalies
Hypospadias

57. Procedures in Artificial reproductive techniques
• Intra Uterine Insemination (IUI): Involves injecting processed sperm using a small catheter through the cervix into
the uterine cavity
• In Vitro Fertilization (IVF): sperm and ovum are mixed outside the body and transfer into the uterus
afterfertilization.
• Intracytoplasmic Sperm Injection ( ICSI)
• Sperm preparation Methods: Simple washing
Swim-up technique
Density gradient
*Motile sperm organelle morphology examination (MSOME) :is a nondestructive method of assessing sperm nuclear
morphology, and a sperm chosen by this
method of high magnification visual inspection could be subsequently used in IVF techniques

58. Donor sperm
INDICATIONS
1) Azoospermia
2)Immunological factors not correctable
3)Genetic disease in husband
Guideline for sperm donation
Semen analysis- donors are selected if the post thaw semen parameters meet a minimum standard.
Genetic evaluation- genetic screening for heritable diseases.
Testing for cystic fibrosis carrier status.
Every 6 months screening – while remaining an active donor, donors should undergone a complete physical
examination and every 6 monthly for STD.

59. THANK YOU