Educational Materials

2. Infertility- definition
 Inability of a couple to conceive after
one year of regular, unprotected
sexual intercourse

3. Infertility- Incidence
 Infertility affects 10-15 % of couples
 In normal young couples- Fecundity
25% conceive after one month
70% conceive after six months
90% conceive by one year

4. Infertility- Risk factors
 Risk factors
Women’s age- ↑age → ↓fecundity
Others:
Smoking, illicit drugs, occupational
and environmental exposures

5. Infertility- Types
 Primary infertility
Infertility without previous pregnancy
 Secondary infertility
- Infertility following a previous pregnancy
- 2 years after a previous pregnancy without
contraception including lactation.

6. 35%
50%
5%
10%
Male
Combined
Unexplained
Female
Infertility- Causes

7. Infertility- Causes
1.Male factors (35%)
2. Female factors (50%)
• Ovulation (20%)
• Tubal & peritoneal factor (20%)
• Uterine & Cervical factor (10%)

8. Infertility- Causes
3. Unexplained infertility (10-15%)
4.Combined factors (5%)
Male & female factors
Sexual disorders
Immunological factors

9. Role of female in fertility
 Ovulation and functioning CL
 Transport of ovum from ovarian surface to
the tube- normal peritoneum & Fimbria
 Transport of the ovum and the zygot
through the tube to the uterus
 Implantation of the blastocyst in the uterus
 Transport of sperms through cervix & vagina
Female causes

10. Ovulatory disorders
 According to WHO classification
- Group 1:Hypothalamic
pituitary failure
- Group II: Hypothalamic-
pituitary dysfunction
- Group III- Ovarian failure
- Hyperprolactinemic
Pituitary
Ovary
GnRH
+
+
+
--
-- --
High
E2
LH
FSH
Hypothalamus
Low
P4
Low
E2
+
--
Ovary
pituitary
ovary

11.  WHO type I- hypothalamic-pituitary
failure
Criteria
Hypogonadotrophic hypogonadism
 ↓ FSH, LH, E
Normal prolactin level
Presents with amenorrhea
Progesterone challenge test is –ve
Ovulatory disorders

12.  WHO type I- hypothalamic-pituitary
failure
Causes
- Anorexia nervosa
- Exercise-related
- Post-pill amenorrhea
- Pituitary infarction (Sheehan's syndrome)
- Kallman’s syndrome
- Hypothyroidism -Idiopathic

13.  WHO type II- Hypothalamic pituitary
dysfunction
Criteria
Most common
 imbalanced Gn H (High LH/FSH ratio- >2)
 Normal estrogen or hyperestrogenemia
 Chronic anovulation
 oligomenorrhia
Causes- Polycystic ovarian syndrome (PCOS)

14.  WHO type III- ovarian failure
Criteria
 Hypergonadotrophic hypogonadism
 ↑ FSH, LH, ↓ E
Causes
Premature and age-related ovarian failure
Resistant ovarian syndrome
Turner syndrome (XO)

15.  Symptoms suggestive of ovulation
Regular cycle
Spasmodic dysmenorrhea
Premenstrual tension syndrome
Mid-cycle pain (mettelschmerz pain)
Mid-cycle discharge & spotting
Diagnosis of ovulatory disorders

16. symptoms suggestive ovulatory factor
 Irregular period
 Headache, visual changes, galactorrhea-
hyperprolactinemia (pituitary tumor)
 Palpitation, heat/cold intolerance-thyroid
dysfunction
 Hirsutism-hyperandrogenemia
Diagnosis of ovulatory disorders

17. Symptoms suggestive ovulatory factor
Excessive exercise- hypothalamic-pit
failure
Advanced age, hot flushes, vaginal
dryness-peri-menopause, menopause, POF
Ovulatory disorders- cont.

18. Examination suggestive ovulatory factors
PCOS- Obesity, hirsutism may be detected
Breast examination- galactorrhea
Signs of - Hypo or hyperthyroidism
- Turner syndrome
Underweight- hypothalamic factors
Diagnosis of ovulatory disorders

19. Detection of ovulation
 Special tests
1. Basal body temperature (BBT)
Ovulation
Sudden thermal
shift for 10 days
Anovulation
No thermal shift
LPD
Thermal shift
<10 d
pregnancy

20. 2. Serial cervical mucous
study
 Profuse with +ve ferning &
+ve spinnbarkeit tests
 Tests turns –ve in 2nd half
of the cycle
Detection of ovulation

21. 3. Serial TVS
(folliculometry)
 To detect pre-ovulatory
mature follicle
(Graffian follicle 17-20mm)
Detection of ovulation

22. 4. Hormonal assay
 Serum progesterone at D21 of the cycle
Level > 10 ng/ml-ovulation
Level 3-10 ng/ml-LPD
Level < 3 ng/ml- anovulation
Detection of ovulation

23.  Serial LH in urine- to detect LH surge-36
hrs before ovulation
 S.prolactin, TFT
5. Serial vaginal smear
6. Endometrial biopsy
Detection of ovulation

24. Treatment of ovulatory disorders
 WHO type I
Gaining weight- BMI >20 kg/m2
Pulsatile administration of GnRH agonists
 WHO type II
Weight loss, exercise
Induction of ovulation

25. 1. Medical treatment
 Clomiphene Citrate
Non-steroidal drugs similar to estrogen
It blocks ER in the hypothalamus & pit.
Glands → ↑LH, FSH → follicle development
Given form D2-D6 of the cycle
Induction of ovulation

26.  Side effect
Anti E effect
Hot flushes, vaginal dryness, etc
Headache & blurred vision(retinal vein
thrombosis/sudden loss of vision: rare)
Thinning of the endometrium
Thickening of cervical mucous
induction of ovulation

27. Induction of ovulation
GIT upset, abdominal bloating
Breast discomfort
↑ risk of twins & abortion
Ovarian hyperstimulaiton syndrome
(OHSS)
 Ovulation is induced in 80% of cases
 Pregnancy rate is 35-40% ???????
 20-25% show no response- Resistant

28. Induction of ovulation
 Human menopausal gonadotrophin HMG
Prepared from urine of menopausal women
Used in combination with CC or alone
Dose: ampoule of 75 IU LH/ 75 IU FSH/ IM
Side effect
Expensive, painful
OHSS
Multiple pregnancy

29.  Purified urinary FSH
 Recombinant FSH
 GnRH analogue (agonist)
 Pit. suppression by Down-regulation of Gn
R → ↓ FSH, LH followed by OI using HMG
or FSH
Given as daily nasal spray or SC injections
Given in cases of resistant PCO, ART
Induction of ovulation

30.  Human chorionic gonadotrophin HCG
 Prepared from the urine of the pregnant
women
 10.000 IU/IM give to resemble LH peak
 Used after stimulation of follicular growth
by CC or HMG to induce ovum maturation
Induction of ovulation

31.  Others
Tamoxifen, non-steroidal aromatase inhibitor-
(letrozole)
Insulin sensitizer- Metformine (PCO)
 Bromocriptin, Cabergoline: hyperprolactinemia
Dexamethasone- PCO to ↓ adrenal androgens
Thyroxine- hypothyroidism
Induction of ovulation

32.  Ovarian wedge resection (laparoscopy)
Induction of ovulation
2. Surgical treatment

33.  Laparoscopic ovarian drilling in PCO
Induction of ovulation

34. Tubal & peritoneal factors
Most common cause of 2ry infertility
1. Infection
 Pelvic inflammatory disease (PID)
Gonococcal, chlamydia, TB
Block of the lumen of the fallopian tube
Peritubal adhesions-kinking of the tubes
 Previous pelvic peritonitis-ruptured appendix

35. 2. Surgery
 Previous pelvic operation
Previous ectopic pregnancy, C/S
Previous gynecological surgery
3. Cornual fibroid
4. Endometriosis
5. Congenital- hypoplasia, aplasia
6. Functional- tubal spasm
Tubal & peritoneal factors

36.  Diagnosis
 History
Pelvic pain- salpingitis, endometriosis
h/o pelvic or abdominal operation
h/o ectopic pregnancy or tubal surgery
 Examination
Tender adnexal mass- salpingitis
Limited mobility of uterus & ovaries
Enodmetriotic nodules in US ligament
Tubal & peritoneal factors

37.  Tests for tubal patency
Hysterosalpingography (HSG)
Saline infusion sonography (SIS)
Laparoscopy + hysteroscopy
Tubal & peritoneal factors

38. HSG

39. SIS

40. Laparoscopy

42.  Treatment
Tuboplasty??
Treatment of endometriosis
Hydrotubation- insufflations of the tubes
Assisted reproductive technique ART
Tubal factors

43. Uterine factors
 Causes
Congenital- aplasia, hypoplasia, septate,
bicurnuate uterus
Uterine surgery
Endometritis & Asherman’s syndrome
Endometrial polyp or fibroids
Prolapse & retroverted uterus
Refractory endometrium

44.  Diagnosis
History
h/o 1ry amenorrhea- congenital cause
Oligomenorrhea or recurrent abortion-
congenital cause
h/o repeated curettage or puerperial
sepsis- Asherman’s syndrome
Menorrhagia- uterine fibroids or polyp
Uterine factors

45.  Examination
Small or absent uterus
Failure to pass uterine sound
Symmetrical enlargement of the uterus
 Investigations
USS
HSG, SIS
Hysteroscopy, Endometrial biopsy
Uterine factors

46. Uterine factors
 Treatment
Lysis of adhesions, E therapy
Myomectomy, polypectomy
Correction of malformation- Metroplasty
Antibiotics for endometritis

47. Cervical factors
 Causes
Congenital stenosis
Trauma to the cervix
Conization or cauterization of the cx
Obstetric trauma
Chronic cervicitis-hostile cx mucus
Cervical fibroids-distortion of cx canal
Immunological- Antisperm antibodies

48.  Investigations
1. Quality of cervical mucous at ovulation
2. Post-coital test
3. Sperm penetrations test
4. Culture & sensitivity- infection
Cervical factors

49.  Treatment
Treatment of infections
Cervical dilatation, myomectomy
Antisperm antibodies - corticosteroids
- IUI
Cervical factors

50. Role of male in fertility
Spermatogenesis by testis is stimulated by
FSH from pituitary G
Transport of sperms from the testis to
exterior by epididimis, vas deference,
ejaculatory ducts through the prostate and
urethra
Deposition of sperm in the vagina via coitus
Male factors

51.  Causes
1. Defect in spermatogenesis
Congenital- undescended testis
Exposure to radiation, chemicals, smoking
Infection- Orchitis (mumps, TB)
Chromosomal- klinefelter’s syndrome (47
XXY)
Hormonal- hypothyroidism
- hyperprolactinemia
Immunological -Drugs
Male factors

52. 2. Bilateral obstruction of the vas deference
Congenital- CBAVD (cystic fibrosis)
Ligation during hernia repair
Infection- gonorrhea
3. Failure of deposition of sperm
Severe hypospadius
Impotence
Retrograde ejaculation
4. Idiopathic
Male factors

53.  Diagnosis
History
Age, occupation, Smoking
Past h/o infection, operation
Past medical history
Sexual history
Drug history
Male factors

54. General examination
 Klinefelter syndrome - tall
- Gynacomastia
- Small testis
 Endocrine abnormalities- hypothyroidism
Male factors

55. Local examination
Penile deformities
Testis- detect undescended or atrophic
testis
Varicocele
PR- detect prostate abnormalities
Male factors

56.  Investigation
Semen analysis
Doppler US- varicocele
Hormonal assay
FSH
Androgens, prolactin,
thryoid H.
Male factors

57. Male factors
Testicular biopsy
Chromosomal analysis
Immunological studies
Microbiology of the semen
 Investigation

58.  Semen analysis (WHO criteria)
Liquefies within 30 min of collection
Volume: 2-5 ml - pH: alkaline (≥7.2)
Count: ≥ 20 million/ml
Motility: ≥ 25% grade A (rapid progressive)
≥ 50% grade A+B
Normal forms: ≥ 30%
Viability: ≥ 75% viable
WBC: <1 million/ml
Male factors

59.  Azoospermia- (absence of sperms)
 Oligozoospermia- (sperm conc. <20 m/ml)
 Asthenozoospermia- impaired motility-
(Kartgener’s syndrome)
 Teratozospermia: > 70% abnormal sperm
morphology on microscopy
Male factors

60. Male factors
 Treatment
1. General measures
 Changes in lifestyle
Stopping smoking
Stopping or reducing alcohol consumption
Exercise, reduce wt
 Avoid tight underwear
 Avoid chemical and radiological exposure

61. 1. Medical:
Bromocriptin/Cabergoline
Thyroxin
Antibiotics
Multivitamins- Vit A, E, C, l-arginine, l-
carnitine, Co-enyme Q10
Clomiphene citrate or hMG, hCG
Male factors

62. 2. Surgical treatment
Varicocele ligations
Correct the obstruction to vas deference
3. Ejaculatory failure
4. ART (Assisted Reproductive Technique)
 using surgical sperm retrieval from testis or
epididymis
Male factors

63. Immunological factors
 Presence of Ag-Ab reaction
 In Male:
Antisperm Abs- serum, seminal fluid, sperm
Post-trauma, surgery-testis or duct sys,
infections.
 In female:
Auto Abs against CL, Ovum, Blastocyst
Cross Abs against sperm in Cx mucous

64. Immunological factors
 Diagnosis
Last and least to think about
Anti sperm Abs tests
Agglutination tests
Immobilization test
Immunoflorescent tests
Immunobeads tests
 Treatment
corticosteroids, ART

65.  Is diagnosed when routine investigation
including semen analysis, tubal evaluation,
tests of ovulation yield normal results.
 A period of 3 years is generally accepted
before active intervention is considered
Unexplained infertility

66. Unexplained infertility
 Treatment
Clomiphene citrate
IUI with or without superovulation
IVF

67. Assisted Reproductive Technology
ART

68. ART Treatments for Infertility
IVF with embryo transfer
Zygote intra-fallopian transfer (ZIFT)
Cryopreservation
Intra-cytoplasmic sperm injection (ICSI)
Gamete intra-fallopian transfer (GIFT)
Intrauterine insemination (IUI)

69. Intrauterine insemination
IUI

70. Intrauterine insemination
IUI
 Indications
Unexplained infertility
Mildly impaired semen analysis
Sexual dysfunction
Ovulatory disorders
Mild endometriosis

71.  Technique
Induction of ovulation- follicle of ≥18mm
HCG injections- final maturation of ovum
34-36 hrs later- processed semen is injected
into the uterine cavity using special catheter
Intrauterine insemination
IUI

72. IUI

73.  Indications
Severe tubal disease-blockage
Severe endometriosis
Moderate male factor
Unexplained infertility
Unsuccessful IUI
IVF with Embryo Transfer
IVF-ET

74. IVF with Embryo Transfer
IVF-ET
Controlled ovarian hyperstimulation (COH)
• Ovum aspiration (pickup) 34-36 hrs after
HCG injection
• Sperm preparation
• Combining sperm and ovum in a petri
dish with culture medium, incubated for
2–5 days

75. TVOR or ovum pickup

76. IVF with Embryo Transfer
IVF-ET
•If fertilization and cleavage occurs,
embryos are graded and the best chosen.
•ET- at 8-cell stage of Day 2 embryos
•ET- at blastocyst stage of D5 embryo

77. Indication:
 Severe male factor
 Poor or total non-fertilization from
previous IVF cycles
 PGD
Intra-cytoplasmic Sperm Injection
(ICSI)

78. Intra-cytoplasmic Sperm Injection
(ICSI)
 A single normal sperm is
injected directly into the
cytoplasm of the oocyte
under microscope
 Increases probability of
fertilization

79. ICSI microscope and micromanipulator

80. Sperm Oocyte
Pronuclear stage
(fertilization)
24 hrs after ovum pickup

81. 2-cell stage
End of 24hrs
4-cell stage
D2 embryo
8-cell stage
D3 embryo
Morula
Expanded
blastocyst
Hatched
blastocyst

82. Cryopreservation
Sperm or embryos are preserved by freezing
for replacement in subsequent cycles

83. Gamete Intra-fallopian Transfer
(GIFT)
Ovum retrieved via laparoscopy
Ovum and sperm placed in same catheter
Injected directly into the fallopian tube
via laparoscopy
Embryo travels through the fallopian
tube to the uterus for implantation

84. Zygote Intra-fallopian Transfer
(ZIFT)
Combines techniques used in IVF and GIFT
Ovum are placed in a petri dish with
sperm
If fertilization occurs, the zygote:
• Is injected into fallopian tube
• Travels through tube to uterus
• Implants in uterus

85. complications of ART
 OHSS
 Multiple pregnancy
 Ectopic pregnancy
 Complications of TVOR