From aetiology till the evidence based management for all cases of male infertility

1. Male Infertility
AHMED ELBOHOTY
MSc, MD, MRCOG, MIGSC
Reproductive Endocrinology & Infertility – Ob Gyn consultant
Assistant professor in Ain Shams University

2. ILOs
3/21/20 ELBOHOTY 2
To review the basic anatomy and physiology related to male
reproduction
To identify different etiologies of male infertility
To review the appropriate practice in the assessment and
investigation of subfertile men.
To summarize the treatment options for subfertile men.

3. Sperm journey
3/21/20 3ELBOHOTY

4. Male
Reproductive
System
3/21/20 4ELBOHOTY
Hypothalmus-
pituitary
Testis
Pathway

5. Defining infertility
INFERTILE
3/21/20 5ELBOHOTY

6. Infertility causes
3/21/20 ELBOHOTY 6
Male
30%
Ovulation
25 %
Tubal
20 %
Cervical, uterine,
endometriosis
5 %
Unexplained
20 %

7. Causes of
Male
infertility
3/21/20 7
Testicular
Pre Testicular
Obstruction
Sexual dysfunction
ELBOHOTY
Post Testicular

8. Pretesticular 5%:
• Gonadotrophin deficiency e.g. severe weight loss, Kallman
syndrome, Prader–Willi syndrome, Laurence–Moon–Biedl
syndrome
Hypothalamic disease
• Pituitary insufficiency (tumours, radiation, surgery)
• Hyperprolactinemia
• Exogenous hormones (anabolic steroids, glucocorticoid excess)
Pituitary disease
3/21/20 ELBOHOTY 8

9. Testicular:
• Chromosomal & Genetic
• Cryptorchidism
• Defective androgen synthesis or response (5a-reductase deficiency, androgen insensitivity)
Congenital
• Idiopathic 30-40% of male infertility.
• Age, environmental factors, hyperthermia, life style, obesity, Increased DNA
fragmentations
• Varicocele
• Injury (orchitis, torsion, trauma)
• Systemic disease (renal failure, liver failure)
• Chemotherapy, radiotherapy
• Infections
• Testicular tumours
Acquired
3/21/20 ELBOHOTY 9

10. Chromosomal abnormalities
3/21/20 ELBOHOTY 10
1 % in men with normal sperm count
5% of oligospermic
15% of azospermic
Azospermia with chromosomal or genetic abnormality
• 2/3 of them: Klinefelter syndrome XXY
• 10-15% of azospermic or svere oligospermic have Microdeletion of
Y chromosome abnormalities
• Others: structural abnormalities eg. Translocations, inversions, ..

11. Obesity & metabolic syndrome in men
3/21/20 ELBOHOTY 11

12. Varicocele
and fertility
ELBOHOTY 3/21/20 12
A collection of dilated refluxing veins in the spermatic
cord
11.7% of men with normal semen
25.4% of men with abnormal semen.
Varicocele may be associated with the followings
• Failure of ipsilateral testicular growth and development.
• Symptoms of pain and discomfort.
• Male subfertility.
• Hypogonadism
• Increased DNA fragmentation
The diagnosis of varicoceles is based primarily on physical
examination. (Not imaging)

13. Oxidative stress & DNA damage
Human Reproduction, Volume 26, Issue 7, 05 May 2011, Pages 1628–1640,
https://doi.org/10.1093/humrep/der1323/21/20 ELBOHOTY 13

14. Obstruction
• Cystic fibrosis (CBAVD)
Congenital
• Vasectomy
• Infection (chlamydia, gonorrhoea)
• Iatrogenic vasal injury
Acquired
3/21/20 ELBOHOTY 14

15. Sexual dysfunction
3/21/20 15
Erectile
• Neurogenic
• Spinal cord injury
• Cauda equina lesions
• Multiple sclerosis
• Parkinsons disease
• Pharmacological
• Alcohol
• Antipsychotic and antidepressants
• Alpha blockers
Ejaculation
• Neurogenic
• Bladder neck incompetence (Prostatectomy,
congenital defects,…
ELBOHOTY

16. Assessment
3/21/20 16
ELBOHOTY

17. Basic fertility work up for infertility couple
History
Physical examination
Assessment of pregnancy suitability
Semen
analysis
Ovulation evaluation Tubal patency testing
Life style modification
Optimize BMI
Folic acid supplementation
Pap smear
3/21/20 17ELBOHOTY

18. Assessment of male partner
• History
• Examination
• Semen analysis
• Indicated tests in some cases:
• Hormonal profile
• Genetic
• Testicular biopsy
• Imaging
• Not indicated:
• Screening for antisperm antibodies
• Post-coital testing of cervical mucus
3/21/20 18ELBOHOTY

19. History
3/21/20 ELBOHOTY 19
• libido, erection, ejaculation, Frequency, penetration, use of lubricant
Sexual history
• Previous pregnancies – with current and previous partners. Duration of infertility. Previous infertility treatments
Fertility history
• Recent pyrexia/ illness. Systemic illness – diabetes mellitus, cancer, infection. Genetic disorders – cystic fibrosis, Klinefelter syndrome
• Cryptorchidism, hypospadias, testicular torsion, mumps, orchitis
Medical history
• Orchidopexy. Hernia repair. Pelvic, bladder or retroperitoneal surgery
Surgical history
• Anosmia, visual field defects
• Review of systems:
• Infertility, genetic diseases
Family history:
• Anabolic steroids, Nitrofurantoin, cimetidine, sulfasalazine, spironolactone, a-blockers, methotrexate, amiodarone, antidepressants, phenothiazines, radiotherapy,
chemotherapy
Medications:
• Alcohol, smoking, recreational drugs, ionising radiation, Chronic heat exposure, Lead exposure
Social history:

20. Examination:
• General:
• BMI, General health status, Specific features of
genetic problems
• Secondary sexual characteristics: Hair distribution:
face, trunk, axilla, pubic , Muscle mass,
Gynaecomastia
• Abdomen or inguinal: scars from previous surgery
• Penis: position of meatus
• Scrotum:
• Testicular size, consistency, presence of masses,
location
• Epididymis: induration, engorgement, cyst
• Vasa deferentia: agenesis, atresia, granuloma
• Spermatic cord: varicocele
3/21/20 ELBOHOTY 20

21. Semen analysis
mandatory for any infertile couples
21
Collection: After 2-7 d of sexual abstinence
Masturbation Or Condoms without chemical additives
Delivered to the laboratory within 1 h

22. World Health Organization reference values:
Semen Volume: 1.5 ml or more
PH: 7.2 or more
Sperm concentration: 15 million spermatozoa per ml or more
Total sperm number: 39 million spermatozoa per ejaculate or more
Total motility: 40% or more motile or 32% or more with progressive motility
Vitality: 58% or more live spermatozoa
Sperm morphology (percentage of normal forms): 4% or more.
3/21/20 ELBOHOTY 22

23. Abnormalities
3/21/20 ELBOHOTY 23
Oligozoospermia:
spermatozoa < 15
million/mL
Asthenozoospermia:
<40% grade (PR+NP)
or < 32 PR%
Teratozoospermia: <
4% normal forms.
Oligo-asteno-
teratozoospermia
(OAT)
Hypospermia –
semen volume < 1.5
ml
Aspermia – no
semen volume
Azospermia: No
sperms
Cryptospermia:
Detection of sperms
after centrifuging of
seminal fluid

24. 3/21/20
ELBOHOTY
24
Semen analysis
Normal
one test is sufficient
Mild/ moderate
abnormality
Repeat after 3 months
with life style changes+/-
medicines
Hormonal profile
Raised FSH indicates
progressive decline
Azoospermia or severe
oligozoospermia
<5000000/ml
Repeat test as soon as
possible.
Severe Oligozoospermia
Hormonal profile
Genetic Testing
Azoospermia

25. 3/21/20 ELBOHOTY 25
Approach to
diagnose
Azoospermia
<1cc, acidic> 1cc, alkaline
History & Exam
Testicular
Small < 4 cm & soft Testis
Obstruction of
vas or epididymis
Low
High or normal
FSH
NO
Ejaculatory duct obstruction
Confirm by:Transrectal US
CBAVD
Cystic fibrosis
mutation analysis
YES
Palpable vas deferens
Karyotype
Y Microdeletion assessment
Not due to prior Chemo,
orchitis, etc
Prolactin
NormalHigh
Equivocal
FSH
High normal
Testicular biopsy
Semen volume-PH

26. Diagnostic Testicular
biopsy
3/21/20
ELBOHOTY 26
It is performed in men with azoospermia, normal
testicular volume and normal reproductive
hormones to differentiate between obstructive
and non-obstructive azoospermia.
Cryopreservation of testicular tissue for future
ICSI should be done, if spermatozoa are
available.

27. Indications of endocrine testing:
• Sperm count less than 10 mil/ml.
• Impaired sexual function
• Clinical suspicion of endocrine problem.
Clinical condition FSH LH Testosterone Prolactin
Normal/obstruction Normal
Hypogonadotrophic Low Low Low Normal
Prolactinoma Low Low Low High
Testesterone
therapy
Low Low High Normal
Testicular failure High/normal High/normal Low/normal Normal
3/21/20 ELBOHOTY 27

28. Management
3/21/20 28
ELBOHOTY

29. It is highly
variable and
depends on
the
3/21/20 ELBOHOTY 29
Cause
Severity of semen
abnormality
Wife (age or any cause of
subfertility)

30. Male Fertility preservation by offering sperm
cryopreservation :
Men and adolescent boys who are
preparing for medical treatment for
cancer
Severe Oligospermic males with
raised FSH & LH suggests
progressive decline in sperm
concentration
3/21/20 ELBOHOTY 30

31. Management according to the cause
3/21/20 ELBOHOTY 31
TreatmentDiagnosisClassification
Medical
IUI
History/Examination
Ejaculatory
Treatment of the cause.
HCG + Gonadotrophins
Low FSH, LH
Exclude 2ry causes: prolactin, MRI brain
Hypothalamic
pituitary failure
Mild cases: expectant x Medical
treatment??, IUI, IVF, ICSI
Severe cases: ICSI , Sperm retrieval + ICSI
History- Exam
High or normal FSH, LH
Karyoptyping- Y chromosome
microdeletion
Testicular
Surgical correction
Sperm retrieval + ICSI
History
Examination
US?
Obstruction

32. Management of Erectile & ejaculatory dysfunction
• Life style + Sildenafil citrate 25-100mg ~30 minutes prior to sexual activity
Erectile dysfunction
• Topical anaesthetic creams or SSRIs.
Premature ejaculation:
• Imipramine 25-75 3 times/day
• Collection of sperms by Alkalization of urine then IUI
Retrograde ejaculation
• Vibrostimulation and electro-ejaculation are effective methods of sperm retrieval.
In men with spinal cord injury:
IUI
3/21/20 32ELBOHOTY

33. Management according to Semen Analysis
Abnormalities
Mild to moderate
Life style
Medical treatment
Varicocelectomy
IUI
IVF-ICSI
Severe
ICSI
Azospermia
Obstructive
• Surgical correction
• Sperm retrieval +ICSI
NOB
• Medical
• Sperm retrieval +ICSI
3/21/20 ELBOHOTY 33

34. Mild to moderate semen analysis abnormalities
Life style modification
Medical treatments have a limited role in idiopathic male infertility:
• Antiestrogens, gonadotrophin therapy
• Antioxidants (Vitamin C 500mg, Vitamin E 400 mg, Zinc 25 mg, Selenium 26 mcg,…..)
Varicocelectomy can be indicated in:
• Clinically palpable varicocele clearly associated with
• Infertility with abnormal semen analysis or abnormal DNA fragmentation test
• Adolescents with progressive failure of testicular development documented by serial clinical examination.
• Time to improvement in semen parameters is approximately 3 to 6 months.
IUI
IVF-ICSI3/21/20 ELBOHOTY 34

35. IUI
• Indications in male infertility:
• Sexual dysfunction.
• Mild abnormalities in semen analysis
• Semen characters (different from one clinic to
another):
• Total motile sperm count in the native
sperm sample > 10 millions
• Motility > 30 %
• Abnormal forms: not more than 96 %
• Post wash
• TMSC >5 million/ml.
• Best pregnancy rates with >10
million/ml
3/21/20 ELBOHOTY 35

36. 3/21/20
ELBOHOTY
36
Azoospermia
Low volume<1cc, acidicVolume> 1cc, alkaline
History & Exam
Testicular
Small &soft Testis
Obstruction of vas
or epididymis
Normal hormones
Low
High or normal
FSH
NO
Transrectal US
For suspected ejaculatory duct
obstruction
Cystic fibrosis
mutation analysis
YES
Palpable vas deferens
Karyotype
Y Microdeletion assessment
Not due to prior Chemo, orchitis, etc
Prolactin
NormalHigh
Transurethral laser
excision
Sperm retrieval+ ICSI
MicroTESE + ICSI if Appropriate
Microsurgical
correction
Manage
Hyperprolactinemia
Gonadotrophins if Appropriate

37. Obstructive
azospermia
Potentially
treatable+
surgical expertise
Microsurgical
reconstruction
Reversal of
vasectomy
Sperm Retrieval
+ICSI
3/21/20 ELBOHOTY 37

38. Management of Hypogonadotrophic Hypogonadism
3/21/20 38
If It is not effective: Increase HMG or FSH dosage to 150 IU for another 6 months.
Follow up:
Monitor testosterone levels monthly Sperm counts after normalization of testosterone level
HCG 1,000 to 2,000 IU 3/week +/- FSH 75 IU 3/ week for 6 months
Identifying the cause, exclude hyperprolactinemia, Stop anabolic
steroids
ELBOHOTY

39. NOA with
testicular
failure
MicroTESE
+ ICSI if
Appropriate3/21/20 ELBOHOTY 39

40. Indications of IVF-ICSI in male infertility
•Azospermia (NOB or OB)
•Severe abnormalities in semen analysis
•Mild abnormalities in semen analysis
with no pregnancy > 2 years
•Associated Female infertility indication
3/21/20 40
ELBOHOTY

41. Sperm retrieval
For Obstructive and Non obstructive
azoospermia
Some cases with high DFT or cryptospermia !
3/21/20 ELBOHOTY 41

42. Chance of retrieving sperm by etiology or previous biopsy:
3/21/20 ELBOHOTY 42
Obstruction: 100%
Y Microdeletion type c: 70 %
Cryptorchidism: 60 % (worse if late orchidopexy)
Kleinfelters, postgonadotoxic therapy, testicular tumour: 50%
High FSH/small testes: 25%
Y Microdeletion type A or B: 0 %
Previous bispsy:
• Maturation arrest: 40-70%
• Sertoli cell only syndrome: 20-40%

43. Sperm retrieval
in OB
epididymal
sperm aspiration
PESA MESA
Failed
epididymal
sperm aspiration
TESA TESE
3/21/20 ELBOHOTY 43

44. Sperm
retrieval in
NOB
TESA
10-30%
TESE
17-45%
Micro TESE
35-77%
3/21/20 ELBOHOTY 44

45. Conclusions &
Recommendations
3/21/20 ELBOHOTY 45

46. •Male infertility is a common problem that requires
individualized assessment & care.
•Semen analysis remains the main initial investigation that
guides further assessment for infertile couple.
•Medical treatment of male subfertility is only proved to be
useful for cases of hypogonadotrophic hypogonadism.
•Varicocele is only diagnosed clinically and treatment
should be selected.
•IVF-ICSI is the revolutionary treatment in severe cases of
male infertility and should not be delayed if it is indicated.
3/21/20 ELBOHOTY 46

47. References
3/21/20 ELBOHOTY 47

48. • United Kingdom National External Quality Assessment Service (UK NEQAS). Reproductive Science Semen Analysis [http://www.ukneqas.
org.uk/content/PageServer.asp?S=784492418&C=1252&Type=N&A ID=16&SID=3].
• Royal College of Obstetricians and Gynaecologists. Perinatal Risks Associated with IVF. Scientific Impact Paper No 8. London: RCOG; 2007.
Oates RD, Lamb DJ. Genetic aspects of infertility. In: Lipshultz LI, Howards SS, Neiderberger CS, editors. Infertility in the Male. 4th ed. Cambridge: Cambridge University Press, 2009. p. 251–76.
• Honig S, Lamont J, Oates RD. Ultrasonographic renal and seminal vesicle abnormalities in patients with congenital absence of the vas deferens. J Urol 1991;145:453.
Cerilli LA, Kuang W, Rogers D. A practical approach to testicular biopsy interpretation for male infertility. Arch Pathol Lab Med 2010;134:1197–204.
• Aitken RJ. Sperm function tests and fertility. Int J Androl 2006;29:69– 75.
Barratt CL, Aitken RJ, Bjo€rndahl L, Carrell DT, de Boer P, Kvist U, et al. Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications-a position report. Hum
Reprod 2010;25:824–38.
• Simon L, Brunborg G, Stevenson M, Lutton D, McManus J, Lewis SE. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod 2010;25:1594–608. Lewis SE,
Simon L. Clinical implications of sperm DNA damage. Hum Fertil (Camb) 2010;13:201–7.
• Belker AM, Thomas AJ, Fuchs EF, Konnak JW, Sharlip ID. Results of 1,469 microsurgical vasectomy reversals by the vasovasostomy study Group. J Urol 1991;145:505–11.
Nicopoullos JD, Gilling-Smith C, Almeida PA, Norman-Taylor J, Grace I, Ramsay JW. Use of surgical sperm retrieval in azoospermic men: a meta-analysis. Fertil Steril 2004;82:691–701.
• Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur Urol 2011;59:455–
61.
Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, Salonia A, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol
2011;60:796– 808.
• Tanrikut C, McQuaid JW, Goldstein M. The impact of varicocele and varicocele repair on serum testosterone. Curr Opin Obstet Gynecol 2011;23:227–31.
European Society of Human Reproduction and Embryology. ART Fact Sheet [http://www.eshre.eu/ESHRE/English/Guidelines-Legal/ART-fact- sheet/page.aspx/1061].
• Bhattacharya S, Harrild K, Mollison J, Wordsworth S, Tay C, Harrold A, et al. Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for
unexplained infertility: pragmatic randomised controlled trial. BMJ 2008;337:a716.
• Steures P, van der Steeg JW, Hompes PG, Bossuyt PM, van der Veen F, Habbema JD, et al. Intra-uterine insemination with controlled ovarian hyperstimulation compared to an expectant
management in couples with unexplained subfertility and an intermediate prognosis: a randomised study. Ned Tijdschr Geneeskd 2008;152:1525–31.
• Lazendorf SE, Malony MK, Veek LL, Slusser J, Hodgen GD, Rosenwaks Z. A preclinical evaluation of pronuclear formation by microinjection of human spermatozoa into human oocytes. Fertil
Steril 1988;49:835– 42.
• de Mouzon J, Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V. European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology
(ESHRE). Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. Hum Reprod 2010;25:1851–62.
3/21/20 ELBOHOTY 48

49. • Agarwal A, Deepinder F, Sharma RK, Ranga G, Li J. Effect of cell phone usage on semen analysis in men attending
infertility clinic: an observational study. Fertil Steril 2008;89:124–8.
• Erogul O, Oztas E, Yildirum I, Kir T, Aydur E, Komesli G, et al. Effects of electromagnetic radiation from a cellular
phone on human sperm motility: an in vitro study. Arch Med Res 2006;37:840–3.
• Wdowiak A, Wdowiak L, Wiktor H. Evaluation of the effect of using mobile phones on male fertility. Ann Agric
Environ Med 2007;14:169–72.
• Mieusset R, Bujan L. Testicular heating and its possible contributions to male infertility: a review. Int J Androl
1995;18:169–84.
• Tiemessen CH, Evers JL, Bots RS. Tight-fitting underwear and sperm quality. Lancet 1996;347:1844–5.
• Munkelwitz R, Gilbert BR. Are boxer shorts really better? A critical analysis of the role of underwear type in male
subfertility. J Urol 1998;160:1329–33.
• Sigman M, Lipshultz LI, Howards SS. Office evaluation of the subfertile male. In: Lipshultz LI, Howards SS,
Neiderberger CS, editors. Infertility in the Male. 4th ed. Cambridge: Cambridge University Press; 2009. p. 153–76.
• Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization
reference values for human semen characteristics. Hum Reprod Update 2010;16:231–45.
3/21/20 ELBOHOTY 49

50. • Nielsen J and Wohlert M. Chromosome abnormalities found among 34,910
newborn children: results from a 13-year incidence study in Arhus, Denmark.
Hum Genet 1991:87: 81-83.
• Dul EC, van Ravenswaaij-Arts CMA, Groen H, van EchtenArends J and Land JA.
Who should be screened for chromosomal abnormalities before ICSI treatment?
Hum Reprod 2010;25:2673-2677.
• NVOG (Dutch Society of Obstetrics and Gynaecology). Guideline: Assessment and
treatment for male subfertility, 1999. NVOG-richtlijn 17:1-5. Available on (in
Dutch): http://nvogdocumenten.nl/uploaded/docs/17_onder_behan_manne
sub.pdf
3/21/20 ELBOHOTY 50

51. THANK YOU
3/21/20
ELBOHOTY 51