Infertility affects approximately 15% of couples globally and can have various medical and social causes. It is defined as the inability to conceive after 12 months of regular unprotected intercourse. Evaluation of both partners is important, as factors may relate to either the female or male. Testing includes semen analysis, evidence of ovulation, and assessing fallopian tube patency. Treatment options depend on identified factors but may include ovulation induction, intrauterine insemination, assisted reproductive technologies like in vitro fertilization, and surgical procedures in some male cases.

1. Infertility

2. • Significant social and medical problem affecting couples worldwide
• Average incidence of infertility is about 15% globally
• Some causes can be detected and treated.
• Unexplained infertility constitutes about 10% of all cases
• Definition: Inability to conceive after 12 months of having sexual
intercourse with average frequency (2 to 3 times per week),
without the use of any form of birth control.
(In advanced maternal age duration is set to 6 months)

3. Types of infertility:
• Primary infertility
- Couple has never produced a pregnancy
• Secondary infertility
- Woman has previously been pregnant, regardless of the
outcome and now is unable to conceive

4. Conception and fertility
• The chances of conceiving in any given menstrual cycle is less
than 20%
• Main events necessary for pregnancy to occur are:
- ovulation
- fertilization
- implantation
• Any condition that interferes with these events may result in
infertility

5. Factors Affecting Fertility:
• Frequency of Intercourse:
Coital frequency is positively correlated with pregnancy rates

6. • Timing of Intercourse
Intercourse just before ovulation maximizes the chance of pregnancy
• Sperm survives as long as 5 days in the female genital tract.
• Ovum life expectancy is about 1 day if not fertilized
• Sperm should be available in the female genital tract at or
shortly before ovulation

7. STIs and Other Infections
• Gonorrhea and chlamydia can cause:
 in women: pelvic inflammatory disease (major cause of
tubal infertility) and cervicitis
 in men: urethritis, epididymitis, accessory gland infection
Mumps, leading to orchitis, may cause secondary
testicular atrophy
Other infections that may affect fertility include
tuberculosis, toxoplasmosis, malaria, schistosomiasis
and leprosy

8. • Age of the woman
After 40 the fertility rate decreases by 50% while the risk
of miscarriage increases
• Age of the man
Increased age affects coital frequency and sexual function
• Nutrition
For women, weight 10% to15% below normal or obesity
may lead to less frequent ovulation and reduced fertility

9. • Factors that can contribute to fertility problems
include:
toxic agents, such as lead, toxic fumes and pesticides
 smoking and alcohol
All these factors may cause:
in women: reduced conceptions and increased
risk of fetal wastage
 in men: reduced sex drive and sperm count

10. Female and male factors
Infertility may be a result of one or more male or female factors
Female and male factors are equally responsible for
infertility (30% to 40 % each)
In 20% of cases there is a combination of both factors
Evaluating both partners is essential

11. Requirements for Female Fertility
• Vagina capable of receiving sperm
• Normal cervical mucus to allow sperm passage
• Ovulatory cycles
• Patent fallopian tubes
• Uterus capable of developing and sustaining pregnancy
• Adequate hormonal status to maintain pregnancy
• Adequate sexual drive and function
• Normal immunologic responses to accommodate sperm and
conceptus
• Adequate nutritional and health status to maintain nutrition and
oxygenation of placenta and fetus

12. Requirements for male fertility
• Normal spermatogenesis in order to fertilize
egg:  sperm count
 motility
 biological structure and function
• Normal ductal system to carry sperm from the
testicles to the penis
• Ability to transmit sperm to vagina achieved through
 adequate sexual drive
 ability to maintain erection
 ability to achieve normal ejaculation
placement of ejaculate in vaginal vault

13. Causes of female infertility
• Local factors in the uterus and cervix
 - may interfere with implantation and woman’s ability
to carry pregnancy to term
• Luteal phase defect
 - results in low production of
progesterone
 may lead to early miscarriage
• Production of anti-sperm antibodies
- can interfere with fertilization

14. • Pelvic inflammatory disease (PID) leading to blocked
or damaged fallopian tubes:
 - may interfere with fertilization and transport of egg
• Ovarian dysfunction resulting in absent or diminished
egg production

15. Causes of male infertility
Conditions that affect quality or quantity of sperm
may lead to infertility
These conditions include:
 - varicocele
 - primary testicular failure
 - accessory gland infection
 - idiopathic low sperm motility

16. Basic workup for infertility
Evaluating both partners is essential
- Detailed history and physical examination
- Semen analysis
- Evidence of ovulation
- Evidence of fallopian tubes patency

17. Fertility evaluation procedure
• Couple should be informed about:
- different causes of infertility
- tests and procedures required to make a diagnosis
- various therapeutic options
• Couple’s interview is conducted together as well as separately
to obtain confidential information

18. General and Sexual History
• General history
occupation and background use of tobacco, alcohol and
drugs
 history of abdominal surgery and earlier diseases/infections
• Sexual history
sexual disturbances or dysfunction such as vaginismus,
dyspareunia or erectile dysfunction
sexually transmitted infections

19. Obstetric and gynecological history
• Reproductive history
• Gynecological history
• Age of menarche
• Menstrual periods, duration and intervals
• Previous contraceptive use
• Previous testing and treatment for infertility

21. Evidence of ovulation
• Urine test
measures the LH in urine to detect if and when ovulation occurs
• Basal body temperature chart
temperature is measured every morning, before woman
get out of bed, elevation in TEMP indicates ovulation
• Progesterone test
progesterone level in blood is measured on days 21 or 22 of cycle
• Endometrial biopsy
done during premenstrual phase detects if endometrium
undergoes expected changes

22. Other tests (female)
• Hysterosalpingogram (HSG)
to determine whether fallopian tubes are blocked
• Laparoscopy
to evaluate for pelvic disease, such as endometriosis, and
check patency of fallopian tubes
• Hysteroscopy
to evaluate condition of uterine cavity (polyps, fibroids)

23. Evaluation of male partner
• Semen analysis
- Volume (1.5 cc to 5.0 cc)
- Number of sperm present (> 20 million/ml)
- Sperm motility (> 60%) and forward progression
(more than 2 on scale 1 to 4)
- Morphology (> 60% normal forms)
- Presence of any infection

24. • Other tests
- Urine analysis: to rule out infection
- Endocrine tests: to measure concentrations of
hormones testosterone, FSH and LH
- Anti-sperm antibodies
- Sperm penetration assay: to establish ability of
sperm to penetrate egg
- Postcoital test (low validity): to establish ability of
sperm to penetrate cervical mucus

25. Treatment possibilities
• Female infertility

26. • Induction of ovulation:
Involves the use of medication to stimulate development of
one or more mature follicles
Success rates vary considerably and depend on:
- age of the woman
- the type of medication used
- whether there are other infertility factors present
in the couple and other reasons

27. • Ovulation induction agents:

28. Clomiphene:
• Chemically stimulates pituitary gland to produce
hormones that trigger ovulation process
• Usual dosage: 50 mg/day for 5 days
• Numerous side effects
• May not be appropriate for patients with:
▪ Large fibroid tumors
▪ Ovarian cysts
▪ Liver problems

29. • Intrauterine insemination:
A fertility procedure in which sperm are washed,
concentrated and injected directly into a woman’s
uterus
Increases the number of sperm in the fallopian tubes
Not recommended in cases of tubal blockage, poor egg
quality, ovarian failure and severe male factor infertility
Most successful when coupled with drugs inducing
ovulation (success rates of 5% to 20% per cycle)

30. • Assisted reproductive technology (ART)
Noncoital methods of conception
Includes all fertility treatments in which both eggs
and sperm are manipulated
Types of ART include:
- In Vitro Fertilization (IVF)
- Zygote Intrafallopian Transfer (ZIFT)
- Gamete Intrafallopian Transfer (GIFT)

31. • In vitro fertilization:
Involves retrieving eggs and sperm from female
and male partners and placing them in a lab dish to
enhance fertilization
Fertilized eggs are transferred several days later
into the uterus
Ovarian stimulation drugs are used prior to procedure in order
to retrieve several eggs and maximize chances for successful
fertilization
Success rates are about 20% per egg retrieval

32. • Gamete intrafallopian transfer (GIFT):
GIFT is a procedure that involves:
 - ovarian stimulation
 - retrieval of eggs
 - placing a mixture of sperm and eggs directly into
the woman’s fallopian tube
GIFT does not allow visual confirmation of fertilization
Success rates per egg retrieval are about 28%

33. • Zygote intrafallopian transfer (ZIFT):
ZIFT, also called tubal embryo transfer, is another variation
of IVF
As with IVF, the actual fertilization takes place in a lab dish
Fertilized eggs are placed directly into a fallopian tube
Success rate is about 29% per egg retrieval

34. • Treatment possibilities male infertility:
- Surgical treatment in some cases (varicocele)
- Intrauterine insemination can be performed either
with patient’s or donor sperm
- ART procedures:
GIFT
IVF
ICSI

35. • Intracytoplasmic sperm injection (ICSI):
Involves injection of single sperm into the egg
The woman is administered fertility drugs prior to
the procedure to aid in the production of multiple eggs
Only active undamaged sperm are selected for
injection
Eggs are observed to see if fertilization takes place
average fertilization rate is 65%
Implantation into the uterus takes place within 72 hours after
ICSI
Success rates range from 15% to 35% per egg

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

38. Genetic counseling and Prenatal detection of
birth defects

39. Genetic counseling

43. Prenatal diagnosis
Defined as the detection of abnormalities in the fetus, before birth

44. The purpose of prenatal diagnosis is not simply to detect
abnormalities in fetal life and allow termination.It rather
have following goals :
Provide a range of informed choice to the couples at
risk of having a child with abnormality.
Provide reassurance & remove anxiety, especially
among high risk groups.
Allow couples at high risk to know that the presence or
absence of the disorder can be confirmed by testing.
Allow the couples the option of appropriate
management (
psychological, pregnancy/delivery, postnatal)
To enable prenatal treatment of the fetus.

45. INDICATIONS OF PRENATAL DIAGNOSIS
1. Advanced maternal age.
2. Previous child with a chromosomal abnormality.
3. Family history of a chromosomal abnormality.
4. Family history of a single gene disorder.
5. Family history Neural Tube Defect.
6. Family history of other congenital structural
abnormality.
7. Abnormalities identified in pregnancy.
8. Other risk factors(consanguinity,poor obs.
History,maternal history)

46. METHODS OF PRENATAL DIAGNOSIS
NON INVASIVE
TECHNIQUES
Fetal visualization
Maternal serum screening
Separation of fetal cells
from the mother's blood
INVASIVE TECHNIQUES
Fetal visualization
Fetal tissue sampling
Cytogenetics
Molecular genetics

47. NON INVASIVE TECHNIQUES
FETAL VISUALISATION
1. ULTRASONOGRAPHY
2. FETAL ECHOCARDIOGRAPHY
3. MAGNETIC RESONANCE IMAGING (MRI)

48. FETAL VISUALISATION
1. ULTRASONOGRAPHY :
-It is a noninvasive procedure for imaging fetal anatomy & is
harmless to both the fetus and the mother
.
-The developing embryo can first be visualized at about 6
weeks gestation. Recognition of the major internal organs &
extremities to determine if any are abnormal can best be
accomplished between 16 to 20 weeks gestation.
- Thus USG is used in the 2nd trimester to identify major fetal
structural anomalies & fetal anatomical markers.
-Ultrasound also is used to guide invasive sampling, such as
amniocentesis, CVS, cordocentesis, & various fetal biopsies

49. US markers of fetal congenital abnormalities or genetic syndromes
found in first trimester scanning [at 11-13weeks' gestation]

50. 2D US

51. 2D US

52. 2D US

53. 2D US

54. 2D US

55. 3D & 4D US
• In recent years three-dimensional ultrasound (3D) &
four-dimensional ultrasound (4D) have started to
play an increasing role in prenatal diagnosis. They
can be applied in assessing facial features, central
nervous system abnormalities and skeletal defects

56. FETAL VISUALISATION
2. FETAL ECHOCARDIOGRAPHY
-Fetal echocardiography is capable of diagnosing most significant
congenital heart lesions as early as 17-19 wk of gestation.
-When this technique is used with duplex or color flow Doppler,
it can identify a number of major structural cardiac defects &
rhythm.
-Fetal echocardiography is recommended in cases where cardiac
defects are suspected.

57. FETAL VISUALISATION
3. MAGNETIC RESONANCE IMAGING (MRI)
• MRI is used in combination with ultrasound, usually
at or after 18 weeks‘ gestation. MRI provides a tool
for examination of fetuses with large or complex
anomalies, and visualization of the abnormality in
relation to the entire body of the fetus. Apparently
MRI is a risk-free method

58. for pregnancy complications.
MATERNAL SERUM SCREENING
 Levels of MSAFP ( alpha Feto protein ), human chorionic
gonadotrophin (HCG) & unconjugated oestriol (UE3) are
measured between 15 & 18 weeks gestation.
 These substances are of fetal origin & cross from the amniotic
fluid into maternal circulation via the placenta.
 Low maternal serum AFP
, low UE3 and/or elevated HCG levels
are associated with increased risks of fetal Down syndrome,
 whereas low levels of all three substances suggests increased
risks for trisomy 18 or triploidy.
 High levels of AFP are associated with increased risk of neural
tube & abdominal wall defects;
 while high levels of HCG can be associated with increased risk

59. Separation of fetal cells from the mother's blood
 A technique currently being developed for clinical use
involves isolating fetal cells from maternal blood to analyse
fetal chromosomes and/or DNA. Ordinarily, only a very
small number of fetal cells enter the maternal circulation;
but once they enter,can be readily identified, they will be
accessible for analysis by a variety of techniques, without
the risks of complications or miscarriage associated with
invasive procedures (CVS & amniocentesis).
 These cells can be collected safely from approximately 10 -
18 weeks' gestation onward.

60. INVASIVE TECHNIQUES
Fetal visualization
Fetal tissue sampling
Cytogenetics
Molecular genetics

61. Fetal visualization
-Embryoscopy
 Embryoscopy is performed in the first trimester
.

62. Fetal visualization
-Fetoscopy

63. Fetal Tissue Sampling
 Amniocentesis
 Chorionic villus sampling (CVS)
 Percutaneous umbilical blood sampling (PUBS)
 Percutaneous skin biopsy
 Other organ biopsies, including muscle & liver
biopsy
6
3

64.  Amniocentesis :
 Amniocentesis is an invasive, well-established, safe,
reliable, & accurate procedure & can be performed at 10-
14 weeks of gestation (early amniocentesis) but usually
done at 16-18 weeks of gestation.
 Although early amniocentesis is ass. with a pregnancy loss
rate of 1 – 2 % & an increased incidence of clubfoot.
 It is performed under ultrasound guidance.
 A 22-gauge needle is passed through the mother's lower
abdomen into the amniotic cavity inside the uterus, & 10-
20 mL of amniotic fluid ( that is replaced by fetus within
24hrs ) that contains cells from amnion, fetal skin, fetal
lungs, and urinary tract epithelium are collected.

65.  Amniocentesis :

66.  Amniocentesis :
1. The Cells are grown in culture for chromosomal,
biochemical, & molecular biologic analyses.
2. The Supernatant amniotic fluid is used for the
measurement of substances such as AFP
,
AChE,bilirubin & pulmonary surfactant
3. In the third trimester of pregnancy, the amniotic fluid
can be analyzed for determination of fetal lung
maturity.
 The results of cytogenetic and biochemical studies on
amniotic cell cultures are more than 90% accurate.
 Risks with amniocentesis are rare but include 0.5-1.0%
fetal loss and maternal Rh sensitization.

67.  Percutaneous umbilical blood sampling (PUBS)
(cordocentesis)
Performed to
obtain fetal blood
for testing.
Done between 18
and 24 weeks of
gestation

68. Cytogenetic Investigations
 Chromosome Analysis ( Karyotype Analysis )
 Fluorescence in situ Hybridization (FISH)

69.  Chromosome Analysis :
 Chromosome analysis is a technique used to identify
aneuploidy, microdeletions, microduplications & major
structural aberrations.
 The most common method of detecting aneuploidy is
karyotype analysis, wherein metaphase cells are examined
microscopically & the number of chromosomes counted.
 Typically 10–15 cells are analysed to rule aneuploidy in or
out.

70. • Chromosome Analysis ( Karyotype Analysis )
Normal Karyotype Down Syndrome Karyotpe

71.  Fluorescence in situ Hybridization (FISH) :
 FISH analysis for common aneuploidies (involving chromosomes 13,
18, 21, X and Y) is often performed by simultaneously applying
specific multicoloured centromeric probes. In fetal trisomies, three
probes are present for a specific chromosome, while monosomies
show only one.
(a) A nucleus has been hybridized with probes for chromosomes 18 (aqua), X (green) and one Y(red).
(b) A nucleus has been hybridized with probes for chromosomes 13 (green) and 21(red)

72.  Fluorescence in situ Hybridization (FISH) :

73. Thank you