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2. Evaluate different treatments of varicocele
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Panel Discussion Problems of MALE INFERTILITY & Management of Oligo Astheno Teratospermia (OAT) , Dr.Sharda Jan, Dr. Jyoti Agarewal , Dr. Jyoti Bhaskar, Dr. Abhishek parihar
1. Panel Discussion
Problems of MALE INFERTILITY &
Management of
Oligo Astheno Teratospermia
(OAT)
Dr. Sharda Jain
Dr. Abhishek Parihar
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar
2. MODERATOR
Brig. R.K. Sharma
Dr. Sharda Jain
PANELIST
• Dr Shilpi Tiwari ,(Urologist)
• Dr Aruna Saxena , ( IVF Expert )
• Dr Anita Sabharwal, (Gynaecologist)
• Dr Sangeeta jain, ( IVF Expert )
• Dr Shweta Lochan, ( IVF Expert )
• Dr Abhishek S Parihar ( IVF Expert )
3. Causes of infertility
Male factor
Female factor
Combined
Unexplained
40%
40%
10%
10%
•Life style
4. MALE INFERTILITY
Male factor is solely responsible in about 20%
of infertility couples & contributing in
another 30 to 40% of infertility
Human Reproduction 1991,6,811
Another study suggested
spermatozoal defect accounting for 30-50%
cases of infertility
Hull MG et al BMJ 1992,306,465
6. Causes of Male Infertility 15% 5%
50%
30%
Disorders of Spermatogenesis Obstruction of VAS
Disorders Sperm Motility Physiological
7. WHAT IS RECENT WHOCRITERIA FOR
SEMEN ANALYSIS AND ITS LIMITATIONS??
8. Normal Values of Semen Variables:
WHO Guidelines
1999 2010
Volume 2.0 mL or more 1.5 ml (1.4–1.7);
pH 7.2 to 8.0
Sperm concentration 20 million or more 15 million per ml (12–16);
Total sperm count : 40 million or more 39 million per ejaculate (33–46);
Motility : 50% or more with forward
progression or 25% or more with
rapid progression
progressive motility, 32% (31–34);
total (progressive + non-progressive)
motility, 40% (38–42
Morphology 30% or more with normal forms 4.0% (3.0–4.0).
White blood cells Less than 1 million
Immunobead MAR<50% bound/adherent 8
9. VARIABILITY IN SEMEN
PARAMETERS is universal
• Day to Day variation
– More than 50 % variation in two analyses
• 2 semen reports at two different times
• 2 evaluation are recommended to
establish profile of seminal parameters.
• Period of Abstinence
– Counts increase with days of Abstinence
– Quality declines with more than 7 days of
Abstinence
9
10. CAUTION
• Semen analysis is guide to fertility
but not absolute proof of fertility of
an individual.
• Pregnancy is the only irrefutable
proof of the sperm's capability to
fertilize.
10
11. ROUTINE SEMEN ANALYSIS
Provides useful information
concerning sperm production by the
testis, sperm motility and viability,
the patency of the male genital
tract, the secretions of the
accessory organs, as well as
ejaculation and emission
12. ROUTINE SEMEN ANALYSIS
It is not a test of fertility, and it
provides no insights into the
functional potential of the
spermatozoon to fertilize an ovum
or to undergo the subsequent
maturation processes that are
required to achieve fertilization
23. Male WORK-UP
• History & examination
• Andrological diagnostic methods used in
the clinical setting
• “basic" semen analysis
• ? analysis of sperm
function/biochemical tests (second tier
level)
24. HISTORY
• Age
Volume
Decreases by 3-30% from age 30 to 50
Concentration
No change
Motility
Decrease 3-37% from age 30 to 50
Morphology
Decrease 4-22% from age 30 to 50
Pregnancy rates
Confounded by age but a trend for a 38%
decrease from age 30 to 50
Kidd et al. Fertil Steril 2001
25. • ETHNIC ORIGIN
• MARRIED LIFE (together since / cohabit)
• TRYING SINCE
• PREVIOUS MARRIAGE
• PRIMARY / SECONDARY
• COITAL FREQUENCY& SEXUAL DYSFUNCTION
(use of spermicidal agents)
• RESULT OF ANY PREVIOUS EVALUATION OR
TREATMENT FOR INFERTILITY
Sperm Viability by Staining
26. • OCCUPATION
• WEIGHT (OBESITY)
• HABITS smoking, alcohol, drug abuse.
• H/O EXPOSURE TO ENVIRONMENTAL TOXINS
27. MEDICAL HISTORY
• 1. DIABETES MELLITUS
• 2. HTN
• 3. PITUITARY DYSFUNCTION
• 4. TUBERCULOSIS
• 5. INFL. BOWEL DIS
• 6. THYROID DISORDER
• 7. HYPERPROLCATINEMIA
• 8.RESPIRATORY DIS (chronic RTI / Bronchiectasis)
• 9. PARASITIC DISORDER
• 10. CYSTIC FIBROSIS
• 11. A recent history of fever is important since
semen quality can be suppressed for up to 3
months after fever or illness
28. H/O INFECTIONS / PAST H/O
• UTI
• STI
• MUMPS
• TUBERCULOSIS
• LEPROSY
A
B
A Eosin – nigrosin stained smear showing
sperm with defective mid – piece
B Sperm with abnormalities
29. HISTORY OF MEDICATIONS & ALLERGIES
A) IMPAIRED SPERMATOGENESIS
Sulfasalazine, Mtx, Nitrofurautoin, CT
B) PITUITARY SUPPRESSION-Testosterone
injections, GnRH analogues
C) ANTIANDROGENS- cimetidine, spironolactone
D) EJACULATION FAILURE- alpha blockers,
antidepressants, phenothiazines
E) ERECTILE DYSFUNCTION- beta blockers, thiazides,
metoclopramide
F) DRUGS OF MISUSE- cannabis, heroin, cocaine
31. FAMILY HISTORY OF INFERTILITY
• GENETIC CAUSE (CF)
Personal history
- Sauna / steam / tight underwear
- Stress / irregular diet / Cig. > 10 per day /
excess alcohol
- Marijuana / recreational drugs
32. Examination
• General examination
Built
Weight (Obesity)
*Abnormalities of the secondary sex
characteristics
May indicate whether there is a
congenital endocrine disorder - eunuchoid
appearance associated with Klinefelter's
syndrome.
33. Examination
Gynaecomastia is suggestive of either an
estrogen/androgen imbalance or an excess of
Prolactin.
Situs inversus raises the possibility of
Kartagener's syndrome associated with
immotile cilia and thus immotile sperm.
34. LOCAL EXAMINATION
Penis –
look for hypospadias
Scrotum –
Hypo – Osmotic swelling test (400x)
examine with the patient standing in a warm
room to allow for relaxation of the cremaster
muscle.
Testes –
determine consistency and rule out the
presence of an intratesticular mass.
The dimensions of the testes should be
measured, using calipers, an orchidometer, or
sonography ( Takihara et al, 1983 ).
35. Testes –
Decreased testicular size, whether unilateral or
bilateral, correlates with impaired spermatogenesis
( Lipshultz and Corriere, 1977 ).
Epididymis –
Careful palpation of the head, body, and tail.
- possibility of epididymal obstruction suggested by
the presence of induration or cystic dilation of the
epididymis.
Vas Deferens –
To rule out CBAVD
36. INVESTIGATIONS
• BLOOD TESTS
Complete blood count
Tests for sexually transmitted disease
PCR for tuberculosis in Semen
Kidney function tests SGOT /SGPT / Glycoselated HB/ FBS
Tests for antisperm antibodies. ( Not of much significance as
Treatment with IUI can bypass the effect of antisperm
antibodies )
37. Normal semen parameters (WHO 2010)
PARAMETERS
LOWER REFERENCE
LIMIT
SEMEN VOLUME (ml) 1.5(1.4 - 1.7)
TOTAL SPERM NO. 39 (33 - 46)
SPERM CONC. 15 (12 - 16)
TOTAL MOTILTY
(PR+NP)
40 ( 38 - 42)
PROGRESSIVE
MOTILITY (PR%)
32 (31 - 34)
NORMAL FORMS (%) 4(3 - 4)
38. Hormone Assays
Fewer than 10% cases of male infertility are caused by
primary endocrine defects
Serum FSH and LH
Useful for assessing testicular function
If testicular failure is the cause of azoospermia or severe
oligospermia, it is reflected by a raised FSH levels
In a patient with azoospermia or severe oligospermia,
biopsy is indicated.
The anti-estrogen receptor clomiphene, often used for
male infertility can also raise FSH levels.
39. Testosterone
Indicates whether testes are normally functioning or
not
Low in cases of hormone related hypogonadism and
abnormal Leydig's cell function in testes.
Most infertile men have normal testosterone levels as
physiological component of hormone production
separate from the site of production of sperms.
40. Serum Prolactin
Measurement is must in infertile men with c/o sexual
dysfunction and show any signs of pituitary disease.
Causes of high Prolactin levels in blood –
• Drugs – metoclopromide, chlorpromazine,
antidepressants
• Hypothyroid state
• Prolactinoma
41. Ultrasound and Color Doppler USG (CDU)
Routinely used to evaluate testes and ductal system.
TRUS with CDU is specially useful in patients with
obstructive azoospermia, when a block at the level of
ejaculatory duct or seminal vesicle is suspected.
TRUS enables an accurate diagnosis of congenital and
acquired anomalies of lower Urogenital tract.
CDU is singularly the most important tool to detect sub
clinical varicocele.
42. Testicular Biopsy
Performed mainly to differentiate primary testicular
failure from obstructive ductal lesions in
azoospermic patients.
As the testicular tissues are being examined directly, it
remains the gold standard for judging testicular
function.
If there are indications of ductal obstruction or
testicular failure, both testes should be biopsied as
both have different degrees of dysfunction.
The argument in favor of unilateral biopsy is that the
opposite testes is completely untouched to obviate
adhesions or fibrosis.
Can be performed by open method using window
technique or by FNAC.
43. Vasography
invasive technique requires exploration of vas in
scrotum.
Mainly indicated in men with azoospermia with
testicular biopsy showing normal spermatogenesis.
CDU has now replaced it as the primary imaging
technique for imaging distal ductal system.
Chromosome studies
Considered in patients with severe oligospermia or
azoospermia to look for autosomal and sex
chromosomal abnormalities.
About 13% cases of non-obstructive azoospermia are
caused by deletion of azoospermia factor ( AZF ).
44. Magnetic resonance imaging
Gold standard for diagnosis of cryptorchidism
Using endo-rectal coil, MRI provides intricate detailed
information of distal ductal system – seminal vesicles,
ejaculatory ducts, pelvic and inguinal parts of Vas.
Radionuclide scanning
Presently scinti-graphy is reserved for situations, when CDU
for patients with low velocity and low volume testicular
flow show unsatisfactory sensitivity.
Hypo – osmotic swelling test (200X)
45. Treatment of Male Infertility
• Life style
• Medical-pharmacological interventions
• Urological procedures,
• IUI
• IVF, ICSI, IMSI
Sperm Viability Uptake of the
sperm, indicating nonviability
48. What are the
surgical (Urological)
treatment options?
49. • correction of varicocele, epididymo-and vaso-vasostomy,
and modern approaches for
ejaculatory disorders.
• Varicocele is most controversial area in
infertility
50. Varicocele
in adolescent with varicocele – testicular growth is
impaired & varicoceles are associated with smaller
ipsilateral testes
DIAGNOSIS
It should be diagnosed clinically
Scrotal doppler are not recommended for evaluation
& diagnosis of su-clinical varicocele since there are no
control study demonstrating improved P.R. after
treatment of sub – clinical varicocele
51. Varicocele & color Doppler
• Accuracy of color doppler ultrasound is only
60%
• Imaging studies should not be used to search
for varicocele in man with normal physical
examination
52. Varicocele Surgery
Should be offered in case of “clinical varicocele ,
oligospermia ,duration of infertility at least 2
years and otherwise unexplained infertility “
Guidelines on male infertility ,EAU 2012 grade B
53. Varicocele surgery
Varicocele repair in adolescent with grade – II & III
varicocele with testicular growth retardation is
recommended.
The present of varicocele is NOT an indication for
varicocele repair
As majority of man with varicocele are fertile
Only infertile man with abnormal semen analysis is an
indication for varicocele repair
54. Surgical treatment
• Preferred Approach – micro surgical
technique & a subinguinal approach
• Conventional inguinal operations are
associated with HYDROCELE formation in 7-8
% cases
• Improvement in semen Parameters is seen in
70% cases
56. THE IMPACT OF THE TOTAL MOTILE SPERM COUNT
Total motile sperm count
Pregnant group 38.7 x 106
Non pregnant group 28.6 x 106
Significance was reached when the total
motile sperm count exceeded 5 x 106.
The impact of the total motile sperm count on the success of intrauterine insemination with
husband's spermatozoa. Huang HY, et al. J Assist Reprod Genet 13: 1, 56-63, Jan, 1996
57. THE IMPACT OF THE TOTAL MOTILE SPERM
COUNT
An average total motile sperm count of 10x106
may be a useful threshold value for decisions
about treating a couple with IUI or IVF.
Makler Chamber Charged with
sperm at 200x magnification
Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine
insemination and in vitro fertilization. Van Voorhis BJ, et al. Fertil Steril 2001 Apr;75(4):661-8
58. SPERM QUALITY NECESSARY FOR SUCCESSFUL
INTRAUTERINE INSEMINATION
• Initial sperm motility 30%
• The total motile sperm count 5 X 106.
• When initial values are lower, IUI has little
chance of success
Comparison of the sperm quality necessary for successful intrauterine insemination with World
Health Organization threshold values for normal sperm. Dickey RP, et al. Fertil Steril 1999
Apr;71(4):684-9
59. IMPACT OF SPERM MORPHOLOGY
Patients with more than 60% normal
sperm morphology (NSM) had higher
pregnancy rate than those with less than
60% NSM (24.3% vs. 7.7%, P=0.0052).
Intrauterine insemination: pregnancy rate and its associated factors in a university hospital
in Iran Zahra Rezaie, et al. Middle East Fertility Society Journal,Vol. 11, No. 1, 2006, pp.59-63
60. ADVANCED SEMEN ANALYSIS - HIGHLY
PREDICTIVE OF IUI SUCCESS
• The number of motile normal sperm
available for insemination
• 24-hour survival rate.
Advanced semen analysis: a simple screening test to predict intrauterine insemination
success. Branigan EF, et al. Fertil Steril 1999 Mar;71(3):547-51
61. Male infertility & IUI
Male age - < 35 yrs
> 45 yrs
>10 million prewash count
5-10 million Post Wash Count
Normal morphology – 04% (Krugers)
DNA fragmentation - 30 %
Sperm survival (24 hours) - ↑ 80%
63. Oligo/asthenospermia -?IUI
Intrauterine insemination with or without
ovarian stimulation is an effective treatment
where the man has abnormalities of semen
quality, (A)
NICE Guidelines : Grade B Recommendation 2004
National guideline clearinghouse grade B 2009
Cohlen et al., January 1999 (Cochrane Review). In: The
Cochrane Library, Issue 2 2002. Oxford: Update Software.
65. COH AND IUI
• Ovarian stimulation is the fundamental tool
of subfertility treatment
• Different options pose challenges
• Choice depends on doctors expertise and
patients condition, choice
• Increases the pregnancy rate
• Judicious monitoring to avoid complications
66. RISK FACTORS FOR POOR OUTCOME WITH
IUI
• Advanced female age
• Poor postwash sperm motility
• History of corrective pelvic surgery
Poor postwash sperm motility in combination with
either of these other two risk factors resulted in no
successful pregnancies
The effect of patient and semen characteristics on live birth
rates following intrauterine insemination : A Retrospective
study HENDIN B. N.et al. Journal of assisted reproduction
and genetics ; 2000, vol. 17, no5, pp. 245-252
69. Intracytoplasmic sperm
injection (ICSI) is indicated in
• Severe deficits in semen quality
• Obstructive azoospermia
• Non obstructive azoospermia
• Previous IVF cycle with failed or very poor
fertilisation.
RCOG 2012
72. • 47 XXY (klinefelter’s syndrome) - =10% of men with
azoospermia
• Chromosomal translocations and deletions may be
found which may be hereditary and can cause
habitual abortions and congenital malformations in
the child
• Deletions in azoospermic factor region (AZF) of Y
chromosome -5% incidence in pts with azoospermia
or OAT
• CBAVD - 85% cases – cystic fibrosis gene positive
73. Recently new devices to achieve high
magnification levels (6600x) have been
proposed in order to detect subtle ultra-structural
alterations that would be
impossible to identify with conventional
methods.
In the routine ICSI procedure, sperm cells
are selected from the sperm pool under a
regular microscope that magnifies 200-400x
Important – as fertility disorder and possibly the corresponding genetic defect may be transferred to the offspring . most common abnormality – 47 XXY (klinefelter’s syndrome) - =10% of men with azoospermia
Chromosomal translocations and deletions may be found which may be hereditary and can cause habitual abortions and congenital malformations in the child
Deletions in azoospermic factor region (AZF) of Y chromosome can occur (around 5% incidence in pts with azoospermia or OAT)than the defect would be passed on to the sons who would than be infertile
CBAVD - 85% cases – cystic fibrosis gene positive
Since it’s introduction, ICSI has consented the selection of a good looking spermatozoon under a magnification of maximum 400 times.
This limit was recently overcome by the introduction of new devices that have been proposed in order to detect subtle ultra-structural alterations undetectable with conventional methods.