This document discusses male infertility, including its causes, diagnosis, and treatment options. It begins with an introduction to male infertility and why evaluation is important. Diagnosis involves obtaining a medical history, performing a semen analysis and physical exam, and testing for endocrine, genetic, and other underlying factors if initial tests are abnormal. Treatment may include medical therapies for correctable issues, assisted reproductive technologies like intrauterine insemination or ICSI, or surgery to address problems like varicocele. While male infertility often cannot be cured medically, techniques like ICSI have revolutionized treatment.

1. MALE INFERTILITY
Abdulmagid Sarhan
MD, FRCOG
Professor Obstetrics & Gynecology,
Zagazig University

2. MALE INFERTILITY
INTRODUCTION
25
2525
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Female Factor
Male Factor
Female + Male Factor
Unexplained Factor

3. MALE INFERTILITY
INTRODUCTION
WHY?
TO IDENTIFY:
➢Specific cause & correct it
➢Individuals who can be offered IUI & ART
➢Infertility that can neither be corrected nor overcome with ART
➢Genetic abnormality that may affect offspring conceived by ART
➢Underlying Medical condition

4. MALE INFERTILITY
INTRODUCTION
WHEN?
Should begin at the same time as in the female partner.
Earlier evaluation:
with any obvious infertility risk factor,
those whose partner is age 35 or older and
men who have reason to question their fertility.

5. MALE INFERTILITY
INTRODUCTION
THIS PRESENTATION CONSIDERS
 Regulation of testicular function,
 The causes of male infertility,
 Semen analysis and other tests of sperm function,
 Current concepts regarding its treatment.

6. MALE INFERTILITY
DIAGNOSIS

7. MALE INFERTILITY
HISTORY
 Duration of infertility and previous fertility.
 Sexual dysfunction.
 Previous evaluation or treatment for infertility.
 Childhood illnesses
 Previous surgery,
 Systemic medical illnesses (diabetes mellitus, upper respiratory disease).
 Sexually transmitted infections.
 Environmental toxins, including heat.
 Medications and allergies.
 Occupations and use of tobacco, alcohol, and other drugs

8. MALE INFERTILITY
SEMEN ANALYSIS
SEMEN COLLECTION:
➢ When?
➢ How?
➢ Where?

9. MALE INFERTILITY
SEMEN ANALYSIS
Collection:
oAfter 2-7 d of sexual abstinence
oAt the doctor's office
oMasturbation Or
oCondoms without chemical additives
oDelivered to the laboratory within 1 h
At least 2 samples collected 1-2 w apart & not more than 3 months
apart. {marked variation of sperm production within one individual}
Any systemic disease during sperm generation time (72 days for
spermatogenesis & 14 days for transport through the epididymis& vas):
±negative impact.

10. MALE INFERTILITY
SEMEN ANALYSIS
Normal Reference Values:
Volume 1.5-5 ml
pH >7.2
Viscosity < 3 (scale 0-4)
Sperm concentration >15 million/ml
Total sperm number >40 million/ejaculate
Percent motility > 50%
Forward progression >2 (scale 0-4)
Normal morphology >50%, >30%, >14%
Round cells < 5 million/ml
Sperm agglutination <2 (scale 0-3)

11. MALE INFERTILITY
SEMEN ANALYSIS

12. MALE INFERTILITY
DIAGNOSIS

13. MALE INFERTILITY
SEMEN ANALYSIS
Prediction of fertility
▪The likelihood of infertility
✓increased with decreases in any of the 3 parameters:
✓M, NM, C
▪Normal morphology had the greatest discriminatory power.

14. MALE INFERTILITY
SEMEN ANALYSIS
Comment 5: Men whose semen characteristics fall below the lower limits
given here are not necessarily infertile; their semen characteristics are
below the reference range for recent fathers—as are, by definition, those
of 5% of the fertile men
who provided data used in the calculation of the reference range.
Comment 6: A man’s semen characteristics need to be interpreted in
conjunction with clinical information.
Comment 7: There may be regional differences in semen quality, or
differences between laboratories; laboratories should consider preparing
their own reference ranges, using the techniques described in this manual.
Comment 8: Time to pregnancy is also affected by the female partner’s
fertility status.

15. MALE INFERTILITY
SEMEN ANALYSIS

16. MALE INFERTILITY
SEMEN ANALYSIS
Sperm autoantibodies
▪4 to 8%of subfertilemen.
▪Agglutination: Stick of motile spermatozoa to each other.
▪≥10%:
▪suggestive but not conclusive of immunological infertility.
▪should be confirmed by
❖ Mixed antiglobulin reaction (MAR)
❖ Immunobead test
both of which detect sperm surface antibodies.

17. MALE INFERTILITY
SEMEN ANALYSIS
Semen biochemistry
▪Rarely useful in clinical practice.
▪Fructose marker of seminal vesicle function. Low or non-
detectable:
❖Congenital absence of the vas deferens
❖Ejaculatory duct obstruction
Post ejaculatory urinalysis - Retrograde ejaculation

18. MALE INFERTILITY
SEMEN ANALYSIS
Semen culture
▪Indicated: semen samples contain inflammatory cells
▪Results: usually not diagnostic.
▪Precautions during sample collection to prevent skin
contamination.
▪The yield of semen culture may be improved by
performing a prostatic

19. MALE INFERTILITY
SEMEN ANALYSIS
Computer-assisted sperm analysis: CASA
▪Assess:
1.sperm concentration
2.morphology.
3.Motility:
Quantitative measurement = sperm kinematics
✓sperm velocity (curvilinear, straight line, average path)
✓Amplitude of lateral displacement
✓other derived functions.
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20. MALE INFERTILITY
SEMEN ANALYSIS
Accuracy depend upon:
✓technology and
✓technical training of the operators.
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21. MALE INFERTILITY
SPERM FUNCTION TESTS
Evaluates four specific sperm functions:
 Capacitation,
 Acrosome reaction
 Fusion with the oolemma,
 Decondensation within the egg cytoplasm.

22. MALE INFERTILITY
SPERM FUNCTION TESTS
Sperm Penetration Assay
Human Zona Binding Assay
Computer-Assisted Sperm Analysis
Acrosin and the Acrosome Reaction
Biochemical Tests of sperm function
 Sperm creatine phosphokinase
 Reactive oxygen species.

23. MALE INFERTILITY
SPERM CHROMATIN INTEGRITY TEST (SCD)
• Intact DNA: Sperm with “Halo”
Represents dispersed chromatin without breaks
• Absent/small “Halo”: Damaged DNA
Represents DNA strand breaks
• Quantitative Test:
• Normal: <20% sperm with fragmented DNA
Feijo & Esteves Fertil Steril 2013


24. MALE INFERTILITY
PHYSICAL EXAMINATION
➢Abnormal History
➢Abnormal Semen Analysis

25. MALE INFERTILITY
PHYSICAL EXAMINATION
✓Examination of penis, location of urethral meatus
✓Palpation of testes & size
✓Presence & consistency of vas & epididymis
✓Secondary sexual characteristics, habitus, hair & breast
development
✓Digital rectal examination

26. MALE INFERTILITY
PHYSICAL EXAMINATION
Urologic Evaluation
Ultrasound
Testicular Biopsy
Genetic Evaluation
Sperm Chromatin Structure

27. MALE INFERTILITY
ENDOCRINE EVALUATION
Indications:
▪ Abnormal semen analysis
▪ Sexual dysfunction
▪ Specific endocrinopathy
▪ Tests :
▪ Sr. FSH
▪ Total testosterone
▪ Sr. Free Testosterone
▪ LH
▪ PRL, TSH
▪ Serum estradiol

28. MALE INFERTILITY
GENETIC EVALUATION
➢Mutations within the cystic fibrosis transmembrane
conductance regulator (CFTR) gene associated with
(CABVD).
➢Chromosomal anomalies resulting in testicular dysfunction
(Klinefelter syndrome; 47, XXY
➢Y chromosome microdeletions associated with abnormalities
of spermatogenesis

29. MALE INFERTILITY
AZOOSPERMIA

30. MALE INFERTILITY
AZOOSPERMIA

31. MALE INFERTILITY
OBSTRUCTIVE AZOOSPERMIA

32. MALE INFERTILITY
NON-OBSTRUCTIVE AZOOSPERMIA

33. MALE INFERTILITY
AZOOSPERMIA

34. MALE INFERTILITY
REACTIVE OXYGEN SPECIES (ROS)

35. MALE INFERTILITY
REACTIVE OXYGEN SPECIES (ROS)

36. MALE INFERTILITY
REACTIVE OXYGEN SPECIES (ROS)

37. MALE INFERTILITY
REACTIVE OXYGEN SPECIES (ROS)
Idiopathic oxidative stress contributes to defective spermatogenesis
leading to male factor infertility
Uncontrolled & excessive production of ROS overwhelms the limited
antioxidant defenses in semen resulting in seminal oxidative stress
Seminal oxidative stress correlates negatively with sperm concentration,
motility and function.
Superoxide anion, hydroxyl radical and hydrogen peroxide are major reactive oxygen species
(ROS) present in seminal plasma.

38. MALE INFERTILITY
TREATMENT
❖ MEDICAL TREATMENT
❖ ART
❖ SURGICAL TREATMENT

39. MALE INFERTILITY
TREATMENT
❖ MEDICAL TREATMENT

40. MALE INFERTILITY
TREATMENT
Hypogonadotropic Hypogonadism
• Hyperprolactinoma- Dopamine agonists
• Cong hypogonadotropic hypogonadism- hCG or exogenous testosterone
• Adult onset hypogonadotropin hypogonadism- hCG 2000-5000 IU 3 times per
week.
Start alone with hCG (as LH) as
hCG stimulate Leydig cells to produce testosterone
hCG alone can stimulate spermatogenesis
Annual costs lower than hMG (both FSH & LH)
Sr. Ts every 1-2 mth for 1st 3-4 mth level 400-900 ng/dl

41. MALE INFERTILITY
TREATMENT

42. MALE INFERTILITY
TREATMENT

43. MALE INFERTILITY
TREATMENT
Antioxidants in the therapy of male infertility
Because ROS have been associated with sperm DNA
damage, investigators have studied possible protective
roles of antioxidants in preventing or treating sperm DNA
damage.

44. MALE INFERTILITY
TREATMENT
Antioxidants in the therapy of male infertility
✓ 82% trials showed an improvement in either sperm quality or
pregnancy rate after antioxidant therapy.
✓ 10 trials examined pregnancy rate and 6 showed a significant
improvement after antioxidant therapy.
A systematic review of the effect of oral antioxidants on male infertility by C. Ross et al, 2010

45. MALE INFERTILITY
TREATMENT
Antioxidants in the therapy of male infertility
 Ubidecarenone
 Carotenoids (Lycopene)
 Omega 3 fatty acids
 Carnitine
 Vitamin E & Vitamin C
 Selenium
 Glutathione
 N-acetyl cysteine
 Pentoxifylline
 Trace Metals like Zinc
 Vitamin B12

46. MALE INFERTILITY
TREATMENT
❖ ART

47. MALE INFERTILITY
TREATMENT
INTRA UTERINE INSEMINATION
Indications:
• Oligospermia,
• Asthenospermia,
• Premature or retrograde ejaculation,
• Sperm autoantibodies & cervical factors,
• Unexplained infertility
• Hypospadias
• HIV positive
Advantages:
I. Overcome limitation of decreased sperm density or motility. Better than Cervical insemination
II. With washed sperm concentrate delivers more no. of sperms
III. IUI yields better results than cervical insemination.

48. MALE INFERTILITY
TREATMENT
INTRA UTERINE INSEMINATION
Cycle fecundity 3-10% infertile partner sperm
Processed motile sperm count at least 1 million
Best results when no. of TOTAL MOTILE SPERMS > 10 million
Success rates
• Highest > 14% sperm have normal morphology
• Intermediate 4-14%
• Poor <4% (advised IVF & ICSI)

49. MALE INFERTILITY
TREATMENT
ICSI
1. ICSI removes many natural barriers to fertilization,
2. Theoretically requires only a single sperm,
3. Can be successful even with nonmotile sperm.
4. Patients with Sertoli cell-only often have microscopic foci of
spermatogenesis.

50. MALE INFERTILITY
TREATMENT
❖ SURGICAL TREATMENT

51. MALE INFERTILITY
SURGICALTREATMENT

52. MALE INFERTILITY
VARICOCELE

53. MALE INFERTILITY
VARICOCELE

54. MALE INFERTILITY
VARICOCELE
Report on varicocele and infertility: a committee opinion
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Practice Committee of the American Society for Reproductive Medicine
Summary
•The diagnosis of varicoceles is based primarily on physical examination.
•Imaging studies are not indicated for the standard evaluation unless physical examination is
inconclusive.
•Only clinically palpable varicoceles have been clearly associated with infertility.
•Adolescents and young men not actively trying to conceive who have a varicocele and
objective evidence of reduced ipsilateral testicular size may be offered varicocele repair.
•Although data are limited and of lower quality, most studies show improvement in semen
parameters and fertility after repair of varicocele.
•Time to improvement in semen parameters is approximately 3 to 6 months.

55. MALE INFERTILITY
VARICOCELE
Report on varicocele and infertility: a committee opinion
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Practice Committee of the American Society for Reproductive Medicine
Conclusions
Treatment of a clinically palpable varicocele may be offered to
the male partner of an infertile couple when there is evidence of
abnormal semen parameters and minimal/no identified female
factor, including consideration of age and ovarian reserve.

56. MALE INFERTILITY
VARICOCELE
BMJ best practice (2015)
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Conclusions
I. Occurs in 15% of adolescent boys and adult men; 90% of cases on left side;
10% are bilateral.
II. May impede adolescent testicular growth and affect adult sperm parameters
and testosterone production.
III. 40% of men being evaluated in a male fertility clinic will have a varicocele.
IV. Diagnosis is usually clinical; ultrasound may be helpful where there is doubt.
V. Surgical correction may reverse testicular growth arrest in adolescents and
improve semen findings in adults.

57. MALE INFERTILITY
VARICOCELE
NICE guidance
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Do Not Do Recommendation Details
Recommendation:
Men should not be offered surgery for varicoceles as a form of fertility
treatment because it does not improve pregnancy rates.
Interventions: surgery
Source guidance details
Guidance: (CG156)
Published date: December 2016
Paragraph number: 1.4.2.2 Page number: 17

58. MALE INFERTILITY
CONCLUSION
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Male factors are the sole cause of infertility in
approximately 25% of infertile couples and are an
important contributing factor in another 20-40% .

59. MALE INFERTILITY
CONCLUSION
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Evaluation of the male partner should begin at the
same time as in the female partner.
It should start with history and semen analysis, the
abnormalities of which should call for further evaluation .

60. MALE INFERTILITY
CONCLUSION
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
With a few specific and important exceptions, male
infertility generally is not amenable to medical
treatment.

61. MALE INFERTILITY
CONCLUSION
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
Although constantly debated, only clinical varicoceles
associated with abnormal semen analysis are clearly
linked to male infertility.
The surgical correction of clinical varicocele may be of
value in the treatment of male infertility?.

62. MALE INFERTILITY
CONCLUSION
American Society for Reproductive Medicine and Society for Male Reproduction and Urology, Birmingham, Alabama
ICSI has been a revolution in the treatment of
male infertility. It overcomes even its most
severe forms.