power point presentation on infertility for undergraduates and postgraduates

1. Infertility
DR KAVERI
Associate Professor
DEPT OF OBGY
GIMS

2. DEFINITION
• After one year of frequent, unprotected
sexual intercourse there is no conception or
maintenance of pregnancy
• INCIDENCE : 15 – 30% couples

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. • FECUNDABILITY : probability that a cycle
will result in pregnancy.
• FECUNDITY : probability that a cycle will
result in a live birth.
• In a normal fertile couple - 20% to 30%

5. Types of Infertility
• PRIMARY INFERTILITY: Patients who
have never conceived
• SECONDARY INFERTILITY : Previous
pregnancies but failure to conceive
subsequently

6. ETIOLOGY
• Male factors: 30%
• Female: 45%
• Tubal: 20%
• Ovulatory disorders: 25%
• Uterine: 10%
• Endometriosis: 5%
• Unexplained:25%
• Combined male and female: 40%

7. SPERMATOGENESIS
• 74 days from spermatocyte stage
• Transport 12-21 days

8. HORMONE REGULATION

9. Causes of Male Infertility
• 1. IDIOPATHIC (40-50%)
• 2. HYPOTHALAMIC & PITUITARY
DISORDERS (1-2%) Pre – Testicular
• 3. PRIMARY GONADAL DISORDERS (30-40%)
Testicular
• 4. SPERM TRANSPORT DISORDERS (10-
20%) Post - Testicular

10. PRE – TESTICULAR CAUSES
Hypothalamic & pituitary disorders (1-2%)
CONGENITAL
• Idiopathic isolated
gonadotropin
deficiency(M/C)
• Kallmann syndrome
• Single gene mutations
• Multiorgan genetic
disorders:
PraderWilli syndrome
Laurence Moon Beidl
syndrome.
ACQUIRED
• • Hth & pit tumors
• • Infilterative diseases
• • Hyperprolactinemia
• • Drugs
• • Critical illness
• • Chronic systemic illness
• • Infections
• • Obesity

11. TESTICULAR CAUSES
Primary gonadal disorders (30-40%)
• CONGENITAL
• Klinefelter syndrome
• Y chromosome deletions
• Single gene mutations
• Cryptorchidism
• Varicoceles
• Androgen insensitivity
syndromes
• 5 alpha reductase
deficiency
• ACQUIRED
• Infection(mumps orchitis)
• Drugs
• Radiation
• Gonadotoxins
• Chronic illness
• Hyperthermia
• Immunologic disorders
• Trauma
• Torsion
• Castration

12. Post Testicular causes
SPERM TRANSPORT DISORDERS (10-20%)
• • Epididymal obstruction or dysfunction
• • Hypospadias
• • CBAVD
• • Infections
• • Vasectomy, herniorraphy
• • Kartagener syndrome
• • Young syndrome
• • Ejaculatory dysfunction

13. MALE INFERTILITY EVALUATION
• ●History
• ●Examination
• ●Investigation
• 1. Conventional Semen analyses
• 2. Specialized Semen analysis
• 3. Endocrine testing
• 4. Genetic tests

14. HISTORY
Focuses on causes of infertility.
• Personal:
Age, occupation, special habits
• Present:
Type of infertility, duration
• Sexual:
Frequency, erection, ejaculation, dysparunia,
habits, libido.

15. History
Past:
• Medical:
Chronic medical illness
Infections: mumps orchitis, sinopulmonary symptoms,
STI, and GUI (prostatitis)
• Surgical:
inguinal and scrotal areas such as vasectomy,
orchiectomy, and herniorrhaphy
• Trauma
• Developmental:
testicular descent, pubertal development, loss of body
hair, or decrease in shaving frequency

16. History
• Drugs and environmental exposures
alcohol, radiation therapy, anabolic steroids,
cytotoxic chemotherapy, drugs that cause
hyperprolactinemia, exposure to toxic
chemicals.
• School performance : determine if he has a
history of learning disabilities

17. Examination
• General physical examination : general built ,
nutrition, skin & hair, sec sexual characteristics,
habitus & breast development.
• Examination of penis, location of urethral
meatus
• Palpation of testes & size
• Presence & consistency of vas & epididymis
• Digital rectal Examination

18. Semen analysis
A. Macroscopic
• 1. Delayed liquefaction
• 2. Increased viscosity
• 3. Semen volume
• 4. pH
B. Microscopy
• 1. Agglutination
• 2. Concentration
• 3. Motility
• 4. Morphology
• 5. Round cells
• 6. Leukocytes

19. Normal Semen Analysis Results
(WHO)
• Volume >2ml
• pH 7-8
• Concentration >20 x 106/ml
• Motility >50% forward & >25% with
rapid linear progress
• Morphology > 15% normal
• Alive > 50%
• Antisperm antibodies Negative
• WCC < 1x106

20. • II. SPECIALIZED SEMEN ANALYSIS
Not routinely performed
used to determine the cause of male infertility
• 1. Sperm autoantibodies
• 2. Semen Fructose
• 3. Semen culture
• 4. Sperm function tests
CASA
SDNAF

21. Investigations
• III. ENDOCRINE
TESTS
1. Testosterone
2. LH and FSH
3. Prolactin
• IV. GENETIC TESTS
1. Karyotyping
2. Y chromosome
microdeletions
3. Cystic fibrosis
conductance regulator
(CFTR) gene mutation

22. Semen Analysis

23. Abnormalities of Semen Analysis
• Azoospermia : Complete absence of sperm
on std microscopic examination in
ejaculate.
• Oligospermia : sperm density < 20
million/ml.

24. • Asthenospermia : Poor sperm motility.
• Teratospermia : > 70% abnormal
morphology.
• Necrospermia : dead sperm.
• Leucocytospermia > 1million leucocytes/ml

25. Urologic evaluation
• Physical examination
• TRUS (transrectal usg for duct obstruction)
• Transscrotal Usg
• Renal Scan
• Testis Biopsy in azoospermic men
• Vasogram

26. MEDICAL 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.
Hypogonadotropin hypogonadism unrelated to
cause- Portable programmable pulsatile infusion
pump s/c

27. Eugonadotropin Hypogonadism
• Severe oligospermia
• Low Sr. testosterone
• T/t by aromatase inhibitor (Testolactone 50-
100 mg BD or Anastrazole 1 mg OD)

28. Hypergonadotropic Hypogonadism
• Insemination with donor sperm
• IVF with ICSI with preliminary genetic
evaluation
Erectile dysfunction :Sildenafil- 25-100mg
1hr before intercourse

29. Retrograde Ejaculation-
• Sympathomimetics, pseudoephidrine, ephedrine
• IVF & IUI & ICSI
Leucocytospermia-
• Antibiotics (doxycycline, erythromycin,
cotrimoxazole
Idiopathic Male Infertility-
• Androgen therapy
• Exogenous FSH
• Clomiphene citrate (25 mg)/Tamoxifen (20 mg)

30. SURGICAL TREATMENT
1. Vasovasostomy & vasoepididymostomy- In
vasectomized men
2. Transurethral resection of the ejaculatory ducts- in
men with Ejaculatory duct obstruction.
3. Varicocele repair- In men with varicoceles.
4. Orchipexy – In cryptorchidism
5. Vibratory stimulation & Electroejaculation – In
neurological dysfunctions

31. 3-Reproductive Technique (ART)
• I- Intrauterine Insemination (IUI)
• II- IVF/ICSI

32. ARTIFICIAL INSEMINATION
• Indications :
• Oligospermia,
• Asthenospermia,
• Premature or retrograde ejaculation,
• Sperm autoantibodies & cervical factors,
• Unexplained infertility
• Sex selection in genetic & chromosomal anomalies
• Hypospadias
• HIV positive

33. Types:
• 1. IUI
• 2. Intracervical
• 3. Pericervical & Vaginal
• 4. DIPI (Direct intraperitoneal insemination

34. Implementation and
Collaborative Care
• Sperm Washing for Intrauterine
Insemination (IUI)
– Ejaculate is centrifuged to concentrate sperm,
which are then rinsed with saline to remove the
seminal fluid
– Sperm are again centrifuged, and then used for
either IVF or Intrauterine artificial insemination

35. IUI

36. Implementation and
Collaborative Care
• Intrauterine Insemination (a form of
artificial insemination)
– Sperm are collected within 3 hours of colitus
and are inserted via a catheter into the uterus
– Donor sperm may be used
– Identify of the sperm donor is kept confidential

37. Donor Sperm
INDICATIONS :
• 1. Azoospermia
• 2. Immunological factors not correctable
• 3. Genetic disease in husband

38. Female infertility
• ovulatory dysfunction
• tubal and peritoneal factors
• cervical factors
• Uterine factors
• others
• unexplained infertility

40. Ovarian disorders
Ovulatory disorders:
Infrequent ovulation (oligoovulation)
or
absent ovulation (anovulation)
Oocyte aging:
Ovarian cysts:

43. PCOS
Rotterdam Criteria (2 out of 3)
Menstrual irregularity due to
anovulation or oligo-ovulation
Evidence of clinical or biochemical
hyperandrogenism
Polycystic ovaries by US
• presence of 12 or more follicles in each ovary
measuring 2 to 9 mm in diameter and/or increased
ovarian volume.

44. Ovarian failure
Causes
• 1. Idiopathic.
• 2. Genetic.
• 3. Autoimmune
• 3. Viral/bacterial infection
• 4. Pelvic surgery, chemotherapy
• 5. Galactosemia

45. Tubal factors
• Tubal disease and pelvic adhesions prevent
normal transport of the oocyte and sperm
through the fallopian tube.
• PID
• Severe endometriosis
• Previous surgery or non-tubal infection (eg,
appendicitis, inflammatory bowel disease),
• Pelvic TB

47. Endometriosis

48. Uterine factors
Impaired implantation, either mechanical or
due to reduced endometrial receptivity, are the
basis of uterine causes of infertility.
Uterine leiomyomata:A meta-analysis showed
that only leiomyomata with a submucosal or
intracavitary component were associated with
lower pregnancy and implantation rates.

49. Uterine anomalies; Uterine abnormalities are
thought to cause infertility by interfering with
normal implantation. Müllerian anomalies are a
significant cause of (RPL), with the septate
uterus associated with the poorest reproductive
outcome .
Other structural abnormalities
endometrial polyps
synechiae from prior pregnancy related
curettage.

50. CERVICAL FACTORS
Normal midcycle cervical mucus
facilitates the transport of sperm.
Congenital malformations and trauma
to the cervix (including surgery) may result in
stenosis and inability of the cervix to produce
normal mucus, thereby impairing fertility.

51. UNEXPLAINED
Unexplained infertility is the diagnosis
given to couples after a thorough evaluation
has not revealed a cause.
Many cases of unexplained infertility may
be due to small contributions from multiple
factors.

52. History-General
• Both couples should be present
• Age
• Previous pregnancies by each partner
• Duration of infertility
• Sexual history
Frequency and timing of intercourse
Use of lubricants
Impotence, dyspareunia
• Contraceptive history

53. History-Female
• Previous female pelvic surgery
• PID
• Appendicitis
• IUD use
• Ectopic pregnancy history
• Endometriosis
• Leiomyoma

54. History
• Irregular menses, amenorrhea, detailed
menstrual history
• Molimina
• Vasomotor symptoms
• Changes of hair growth, breast discharge
• Stress
• Weight changes
• Exercise-drug –radiation -chemotherapy
• Cervical and uterine surgery

55. Physical Exam-Female
• Thyroid exam
• BMI
• Hair distribution
• Galactorrhea
• Scar in the abdomen
• Pelvic masses
• Uterosacral nodularity
• Abdominopelvic tenderness
• Uterine enlargement
• Uterine mobility
• Cervical abnormalities
• Abnormal vaginal discharge

56. Investigations
Assessment of ovulation
• Basal body temperature
• Urine LH kits
• Mid luteal serum progesterone
• Routine hormonal profile: FSH, LH,Prolactin,TSH
• Endometrial biopsy
• Serial pelvic Ultrasonography

58. • Evidence of ovulation:
1. Menstrual history of regular cycles.
2. Serum progesterone in the mid-luteal phase of
their cycle (day 21 of a 28-day cycle) even if they
have regular menstrual cycles.
3. Serum gonadotrophins ( FSH & LH) on Day2-3
especially in irregular periods.
No role for basal body temperature

59. Ovarian reserve tests
More important in >35 years old, suspected ovarian
failure and to detect response to ovulation induction.
• 1. Total antral follicle count.
• 2. AMH of less than or equal to 5.4 pmol/l for a
low response and greater than or equal to 25 pmol/l
for a high response
• 3. FSH greater than 8.9 IU/l for a low response
and less than 4 IU/l for a high response.

60. Ovarian Reserve Tests

61. Investigations of tubal factor
• Hysterosalpingography (HSG)
• Hysterosalpingo-contrast
sonography(HyCoSy)
• Laparoscopy with chromotubation
• Hydrolaparoscopy.
• Fluoroscopic/hysteroscopic- selective tubal
cannulation.
• Falloposcopy

62. Diagnostic Studies –
Female
• Hysterosalpingogram (HSG)
– Detects uterine anomalies (septate, unicornate,
bicornate)
– Detects Tubal anomalies or blockage
– Iodine-based radio-opaque dye is instilled
through a catheter into the uterus and tubes to
outline these structures and x-rays are taken to
document findings

63. Tubal Patency Tests

64. HSG

65. Diagnostic Studies –
Female
• Laparoscopy
– General or epidual anesthesia
– Abdomen is insufflated with carbon dioxide
– One or more trochars are inserted into the
peritoneum near the umbilicus & symphysis
pubis
– Laparoscope visualizes structures in the pelvis
– Can perform certain surgical procedures

68. Assessment of the uterine cavity
Modalities to assess the uterine cavity include
• Saline Infusion Sono-hysterography (SIS)
• Three dimensional sonography
• Hysterosalpingography (HSG)
• Hysteroscopy

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

72. Treatment of female infertility
General advice
• 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

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

74. Mangement of Anovulation

75. Management of Hypothalamic
pituitary failure
Amenorrhea or severe oligomenorrhea
FSH & LH: low
Prolactin: normal
• 1. Reverse the life style factors:
• Increase wt if BMI <19
• Moderating exercise if high levels of exercise.
• Treat stress
• 2. Gonadotrphins with LH activity or Pulsatile
GnRH (pump)

76. Management of PCOS
Weight reduction
Drugs
• Clomiphene citrate
• Gonadotrophin releasing hormone
• Gonadotrophin
• Others: insulin sensitising agents (metformin)
• Letrozole
Surgery
• ovarian drilling

77. Clomiphene Citrate (cc)
• 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 50 mg in each cycle,
until a maximum of 150mg per day.
• 5) If no response to the maximum dose, further increase
is not effective

78. 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

79. Insulin sensitizing drug

80. Management of Resistant PCOS

81. Management of Tubal Factors
Tubal surgery
• microsurgical technique
• laparotomy or laparoscopy
• adhesiolysis, re-anastomosis,
salpingostomy
• In vitro fertilization and embryo transfer
(IVF-ET)

82. Management of Uterine Factors
Myomectomy indications

83. Management of Uterine Factors
• Septate uterus
Not increased among women with infertility
compared with other women (2–3%).
More common: RM or PTL.
• Hysteroscopic metroplasty:

84. Management of Uterine Factors
Intrauterine adhesions with amenorrhoea
• hysteroscopic adhesiolysis

85. Management of unexplained
infertility

86. Assisted Reproductive
Technologies (ART)
• IVF-in vitro fertilization and embryo
transfer
• GIFT-gamete intrafallopian tube transfer
• ZIFT-zygote intrafallopian tube transfer
• ICSI - Intracytoplasmic sperm injection

87. INVITRO FERTILIZATION
(IVF)
Indications
• - Severe tubal damage/ blockage.
• - Bilateral salpingectomy.
• - Endometriosis.
• - Mild male infertility.
• - Unexplained infertility.
• - Immunologic infertility..
• Success rate: About 20-30%

88. Basic Steps in IVF
• Ovary stimulation
• Egg retrieval
• Sperm retrieval-wash sperm
• Fertilization
• Embryo transfer
• Progesterone

89. Drugs used for ovary stimulation
• Clomiphene (clomid)-anti-estrogen
• hMG (pergonal)-menopausal gonadotropin (FSH
and LH)
• FSH-(metrodin)
• GnRH
• GnRH agonists (lupron)-FSH/LH first promoted,
then inhibited hCG-acts like LH

90. Egg retrieval

91. Sperm Retrieval Techniques
• MESA – microsurgical epididymal sperm
aspiration.
• PESA – percutaneous epididymal sperm
aspiration.
• TESE – testicular sperm extraction.

92. • Gametes mixed for GIFT

93. GIFT

94. GIFT

95. ZIFT

96. ZIFT

97. Intracytoplasmic sperm injection
ICSI

98. ICSI

99. ICSI
• Indication : (Male factors)
• - Oligozoospermia.
• - Asthenospermia.
• - Teratozoospermia.
• - Antisperm Ab.
• - Fertilization failure after conventional IVF.
• - Ejaculatory disorder

100. IVF Side Effects
• Cysts on the ovaries
• Multiple births
• Ovarian Hyperstimulation
• Risk of ovarian cancer

101. Alternatives to Childbirth
• Adoption
• Surrogate mothers
• Frozen embryos
• Egg donors
• Frozen eggs
• Cloning