1. DR MOHD NASIR BIN TAK ABDULLAH
REPRODUCTIVE UNIT
DEPARTMENT OF OBSTETRICS & GYNAECOLOGY
HOSPITAL SULTANAH NUR ZAHIRAH
KUALA TERENGGANU
INFERTILITYINFERTILITY

2. Grading of evidence
 (A) Systematic review and meta-analysis of randomised
controlled trials or at least one randomised controlled trial
 (B) At least one well-designed controlled study without
randomisation or at least one other type of well-designed quasi-
experimental study.
 (C) Well-designed non-experimental descriptive studies, such as
comparative studies, correlation studies or case studies or
extrapolated recommendation from either A or B
 (D)Expert committee reports or opinions and/or clinical
experience of respected authorities or extrapolated
recommendation from either grade A,BorC.
 Good practice point (GPP) :- The view of the guide line
development group

3. Subfertility
Inability to conceive after one year of regular
unprotected intercourse in the absence of known
reproductive pathology.
Peak monthly pregnancy rate ~ 30%
 cumulative rate in 1 year ~ 85%
 cumulative rate in 2 years ~ 95%

4. After 2 years of unexplained infertility,
the pregnancy rate is 1.1% per month
Crosignani 1991
(18026 patient-cycles)

5. Incidence
10 – 15% of couples affected

6. Causes of subfertility
Multiple factors are common
Female factors (2/3)
ovulatory
tubal
endometriosis
others

7. Causes of subfertility
Male factors (1/3)
 Subnormal semen due to production defects e.g. idiopathic,
endocrine, trauma, genetic
 No sperm due to obstructive defects e.g. absent vas, vasectomy
 Coital
Unexplained
 Ovulation, patent tubes and normal semen

9. The causes of infertility among Malaysian couples,
based on the study done in HUSM, include:
 ovulatory dysfunction (46%)
 unexplained infertility (22%)
 mixed factors (13%)
 male infertility (6%)
 tubal factor (5%)
 cervical factor (3%)
 others (5%)

10. Five important causes
1. Ovulatory dysfunction
2. Tubal problems
3. Endometriosis
4. Male factors
5. Unexplained

11. History
Age
Menstrual cycle
 regularity
History of PID or pelvic
surgery
Previous investigations
and treatment
Age / occupation
Past health
Coital history
Smoking/alcoholic

12. People who are concerned about their fertility should be informed
that female fertility declines with age, but that the effect of age on
male fertility is less clear. (C)

13. In women both active and passive
smoking will affect fertility.
(B)
In men smoking reduced semen
quality but the impact of this on male
infertility is uncertain (GPP)
SMOKING

14. History of present complaint
Type of infertility
Duration of infertility
• Sexual history
 Libdo, Impotance
Frequency of intercourse
• Medical History
Recent febrile illness
 Mumps Orchitis
Venereal disease
Renal failure
Secondary Infertility is
not congenital
Reflects testosterone level
Depresses
spermatogenesis
Testicular damage
Obstruction
Testicular failure
History Items Relevance in
Oligo/Azoospermia

15. History Items Relevance Oligo/Azoospermia
Medical History
Liver failure
Chemotherapy/radiotherapy
Multiple Sclerosis
Diebetes Mellitus
Spinal Cord injury
Surgical History
Orchidopexy
Vasectomy
Inguinal Hernia Repair
Pelvic/Scrotal Injury/ Urethral
Surgery
Prostatectomy
Hormonal abnormality
Testicular damage
Ejaculatory dysfunction
Ejaculatory dysfunction
Ejaculatory dysfunction
Indicative of previous
maldecent/torsion
Obstruction
Obstruction
Ejaculatory
dysfunction/obstruction
Ejaculatory dysfunction

16. History Items Relevance in Oligo/Azoospermia
Testicular History
Maldecent, Torsion, trauma
Drug History
Cimetidine, Spironolactone
Anabolic steroids, GnrH agonist
Chemotherapy
Occupational & recreational
exposure
Pesticides,herbicides, X- Ray
Excess heat
Radiation
Alcohol/ drug abuse
Systems review
Headache/ visual disturbance
Anosmia
Galactorrhoea
Testicular Damage
Anti-androgen
Inhibit pituitary gonadotrophin secretion
Testicular damage
Testicular damage
Testicular damage
Testicular damage
Testicular damage
Pituitary tumours
Kallmans,s syndrome
Hyperprolactinaemia

18. Physical examination
Body weight
Vaginal examination
 uterine size
 mobility
 adnexal mass
? Necessary
Testicular size
Vas and epididymis
Varicocele

19. Body weight
•Women with BMI>29 are likely to take
longer to conceive and losing weight is
likely to increase their chance of
conception (B).
•Participating in a group program
involving exercise and dietary advice
leads to more pregnancies than weight
loss advice alone. (A)
•Men who have a body mass index of
more than 29 should be informed that
they are likely to have reduced fertility.
(B)

20. Women who have a body mass index of more than 29 and who are
not ovulating should be informed that losing weight is likely to
increase their chance of conception. (B)
Women who have a body mass index of less than 19 and who have
irregular menstruation or are not menstruating should be advised
that increasing body weight is likely to improve their chance of
conception. (B)

21. TESTICULAR PROBLEM
High testesVaricocoele
Inguinal hernia Testicular injury

22. INFANTILE “TINY” PENIS

23. Basic Investigations

24. Semen analysis

25. Semen analysis
Produced by masturbation after 2-7 days of
sexual abstinence
Do not use lubrication
2 to 3 samples required; additional if
abnormal
Protect against extreme temperatures (<20
C / >40 C)
Analysis within one hour of collection
(WHO Manual)

26. Semen Analysis
Semen Analysis (WHO 2000)
- Volume – 2 ml or more
- Liquifaction time - within 60 min
- pH - 7.2 or more
- Concentration/ml – 20 mil/ml or more
- Motility – 50% grade a and b
- Total count – 40 mil per ejaculate or more
- Morphology – 15%
- WBC/Pus cells - < 1 mil/ml
- Vitality – 75% or more

27. Semen analysis
WHO criteria (2010):
 volume: >=1.5 ml
 concentration: >=15 million / ml
 motility: >=32% progressive motility
 normal forms: >=4% (strict criteria)
Low predictive values

29. Semen analysis
If the result of the first semen analysis is abnormal, a
repeat confirmatory test should be offered. (B)
Repeat confirmatory tests should ideally be
undertaken 3 months after the initial analysis to allow
time for the cycle of spermatozoa formation to be
completed. However, if a gross spermatozoa
deficiency (azoospermia or severe oligozoospermia)
has been detected the repeat test should be
undertaken as soon as possible. (GPP)

30. Investigations--
a. Ovulation
 Mid-luteal progesterone (eg D21- 28 day Cyc.)
 Irregular cycles
FSH & LH (D2),prolactin, thyroxine,
Ultrasound--ovarian morphology (PCO)
 Regular cycles
prolactin or thyroxine not indicated

31. Assessment of Ovulation
Women with fertility problems should
be asked about the frequency and regularity of
menstrual cycles.
Women with regular monthly menstrual cycles are
likely to be ovulating. (Grade B)
The use of basal body temperature charts to confirm
ovulation does not reliably predict ovulation and is
not recommended. (Grade B)

32. -
λ Measure 7 days before expected period
λ Interpret after next LMP known
<16 nmol/L
-ovulation induction
>16 but <30 nmol/L
-repeated
>30 nmol/L
-ovulation
If corrected timed,
interpret as below
Serum progesterone

33. Pelvic ultrasound

34. Transvaginal scanning

35. Ultrasound assessment: international
consensus definitions
1. ≥12 follicles of 2-9 mm in diameter
in at least one ovary or
2. Increased ovarian volume (>10
cm3
)
(Balen et al., 2003)

36. Revised PCOS diagnostic criteria
Two out of three:
1. Oligo- and/or anovulation
2. Clinical and/or biochemical signs of
hyperandrogenism and exclusion of other
aetiologies (congenital adrenal hyperplasias,
androgen-secreting tumours, Cushing’s
syndrome)
3. Polycystic ovaries on scanning
(PCOS consensus workshop group, Rotterdam, May 2003)

37. Investigations--
b. Tubal patency

38. Tubal patency tests
1. HSG
2. Laparoscopy and dye
3. Hysterosalpingo-contrast-sonography (HyCoSy)-
USS, no radiation
4. Salpingoscopy or falloposcopy

40. Hydrosalpinx

41. Hysterosalpingogram
False positive because of spasm in proximal ends
Peritubal adhesion not detected
4-5% pelvic inflammatory disease after
hysterosalpingogram

42. Assessment of tubal factor
The results of semen analysis and assessment of ovulation
should be known before a test for tubal patency is performed.
Women who are not known to have co-morbidities
(such as pelvic inflammatory disease, previous
ectopic pregnancy or endometriosis) should be
offered HSG to screen for tubal occlusion because
this is a reliable test for ruling out tubal occlusion,
and it is less invasive and makes more efficient use
of resources than laparoscopy. (Grade B)

43. Laparoscopy-
diagnostic / therapeutic

44. Tubal pathology detected at laparoscopy has a
stronger effect on future fertility than that detected at
HSG. (B)
Women who are thought to have
comorbidities should be offered
laparoscopy and dye so that tubal
and other pelvic pathology can be
assessed at the same time. (B)

45. Investigations NOT indicated in
clinical practice
Serum antisperm antibody
Postcoital test
Sperm function test
Endometrial biopsy
Hysteroscopy
Ultrasound of endometrium

46. Endometrial biopsy

47. Hysteroscopy

48. Ultrasound of endometrium

49. Treatment

50. General advice (Female)
folic acid whilst trying to conceive and during the
first 12 wks of pregnancy to prevent neural tube
defects
Reduce body weight in obese women
Stop smoking
Avoid excessive alcohol

51. Good health
Free from illness eg thyroid, blood pressure,
diabetes
Avoid food fads
Balanced diet
Folic Acid
Supplements

52. General advice (Male)
Stop smoking
Avoid excessive alcohol
Men with poor quality sperm advised to
 wear loose fitting underwear and trousers and
 avoid occupational or social situations that might cause
testicular hyperthermia

53. Causes of subfertility
Ovulatory
Tubal factors
Male factors
Unexplained/min. endometriosis

54. Ovulation induction
Development of a single follicle

55. Ovulation Induction
FSH & Prolactin
Prolactin Normal FSH FSH
Hyperprolactinaemia
-Bromocriptine
-Cabergoline
PCOS/Hypothalamic
-Optimize weight
-Drugs
-Surgery
Ovarian failure
-Donor eggs
USS

56. Ovulation induction
Weight reduction
Drugs
 Clomiphene citrate
 Gonadotrophin releasing hormone
 Gonadotrophin
 Others: insulin sensitising agents (metformin),
 letrozole
Surgery
 ovarian drilling

57. Mx
1) Starting dose is 50 mg daily for 5 days, can be
started b/t day 2- 6 of menses,
2) Check for ovulation
3) If there is ovulation, continue the same dose for 3-6
cycles, either with timed coitus or with IUI.
4) No response, increase dose by 5o mg in each cycle,
until a maximum of 150mg per day.
5) If no response to the maximum dose, further
increase is not effective and therefore not
advisable.

58. Mx
Gonadotrophin therapy
In women with PCOD
Aim:
 Ripen follicles with repeated doses of FSH
 Stimulate ovulation with injection of LH or hCG
Drugs in use:
 HMG– 75 iu FSH, 25-75 iu LH
 Urofollitrophin—75 iu FSH n almost no LH
 Recombinant FSH—75 iu FSH
 hCG—1000-5000 iu hCG

59. Anovulatory women with polycystic ovary syndrome
who have not responded to clomifene citrate and who
have a body mass index of >25 should be offered
metformin combined with clomifene citrate because this
increases ovulation and pregnancy rates. (A)
Metformin

60. Women with polycystic ovary syndrome who have
not responded to clomifene citrate should be offered
laparoscopic ovarian drilling because it is as effective as
gonadotrophin treatment and is not associated with an
increased risk of multiple pregnancy.
Ovarian Drilling

61. Causes of subfertility
Ovulatory
Tubal factors
Male factors
Unexplained/min. endometriosis

62. Tubal factors
Tubal surgery
 microsurgical technique
 laparotomy or laparoscopy
 adhesiolysis, re-anastomosis, salpingostomy
 results
In vitro fertilization and embryo transfer (IVF-ET)

63. Mx
Tubal surgery

64. Male Factor

65. Treatment
1-Medical -Empirical - unexplained male subfertility
Treatment Concensus
Studies with pregnancy as an outcome
HMG/FSH
Androgens
Anti-estrogens
Dopamine agonists
Glucocorticoids
Kalikrein
Aromatase inhibitors
Antioxidants
Mast cell blocker (Tranilast)
Studies with sperm parameters
GnRH
Growth Hormone
Tribestan (herbal)
No benefit
No benefit
No benefit
No benefit
No benefit
No benefit
No benefit. (only one RCT)
Potential benefit, but needs further
evaluation
as an outcome
No benefit
No benefit

66. Antibiotics
In the absence of any clinical symptoms, the role
antibiotics therapy still uncertain according to
prospective studies and small RCT.
2- Surgery
Obstructive Azoospermia

67. 2- Surgery
Obstructive Azoospermia
- appropriate expertise is available, should offered
surgical correction of epididymal blockage to improve
fertility,
- surgical correction should be considered as an
alternative to surgical sperm recovery and in vitro
fertilization
Varicoceles
- varicocele correction does not improve pregnancy
rates

68. 3-Reproductive Technique (ART)
I- Intrauterine Insemination (IUI)
 IUI is not beneficial unless a total motile sperm
count above 10 mil.
 at least three and a maximum of six IUI cycles
can be proposed depending on the women’s age
II- IVF/ICSI
 if no pregnancy after IUI
 Total sperm count< 10 mil
 + TESA/PESA – if Azoospermia

69. PERCUTANEOUS EPIDIDYMAL
SPERM ASPIRATION (PESA)

71. ♦Ejaculatory failure - Hypospadius-
Vaginismus-
Impotence- retrograde ej.
♦Cervical factor - mucus hostility-poor
mucus
♦Male subfertility - Mild, moderate
♦Immunological - Male sperm a.bs-
female antisperm
a.b
♦Unexplained Infertility
INDICATIONS FOR IUI

72. ♦Endometriosis (mild).
♦Ovulatory.
INDICATIONS
FOR IUI

73. For IUI, sperm are first washed and placed into a sterile
medium. The sperm are then concentrated in a small
volume of medium and are injected directly into the
uterus.

74. Outcomes of Treatment
Unexplained Infertility
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4 5 6
months/treatment cycles
%pregnant
IUI
HMG
HMG+IUI
IVF

75. Success Rate of IUI
♦ Published Rates: Low as 5% to as high as
70%
♦ Usual acceptable clinical pregnancy rate for
all aetiologies is 10-20%
♦ When combined with COH in unexplained
infertility , cumulative pregnancy rates may
approach those of IVF.

76. ASSISTED REPRODUCTIVE
TECHNIQUE (ART)
A) INVITRO FERTILIZATION (IVF).
B) INTRA CYTOPLASMIC INJECTION
(ICSI).

77. (A) INVITRO FERTILIZATION (IVF)
Indication:Indication:
- Severe tubal damage/ blockage.
- Bilateral salpingectomy.
- Endometriosis.
- Mild male infertility.
- Unexplained infertility.
- Immunologic infertility..
Successful rate:Successful rate: About 20-30%%.
Cost per attempt:Cost per attempt: RM 3,000-4,000 (HSNZ)
ASSISTED REPRODUCTIVE TECHNIQUE
(ART)

78. (B) Intracytoplasmic Sperm Injection (ICSI)
Indication : (Male factors)Indication : (Male factors)
- Oligozoospermia.
- Asthenospermia.
- Teratozoospermia.
- Antisperm Ab.
- Fertilization failure after
conventional
IVF.
- Ejaculatory disorder.

79. (C) Intracytoplasmic Sperm Injection
(ICSI)

80. World HSNZ
1st
Test Tube
Baby
1978-UK 31 Aug 2010
1st
Test Tube
Baby Twin
1982-UK 28 Dec 2010
1 st Frozen
Embryo Birth
1983-US 8 Feb 2012
1st
ICSI Baby
Birth
1992-UK 31 Aug 2010
1st
TESA/PESA
Baby Birth
1993 27 Oct 2012
Fertility Milestone – World Vs HSNZ

81. World HSNZ
1st
Test Tube
baby Triplets
Birth
17 June 2013
1st
TESA/PESA +
ICSI twin baby
birth
27 Oct 2012
Fertility Milestone – World Vs HSNZ

82. THANK YOU