1. Infertility
Lectures 3
N.Petrenko, MD, PhD

2. Infertility Primary infertility Secondary infertility
a couple that has never conceived
Secondary infertility
infertility that occurs after previous pregnancy regardless of outcome

3. Requirements for Conception
normally developed reproductive tract in both the male and female partner
normal functioning of an intact hypothalamic-pituitary-gonadal axis supports gametogenesis (the formation of sperm and ova).
timing of intercourse
Unblocked tubes that allow sperm to reach the egg
The sperms ability to penetrate and fertilize the egg
Implantation of the embryo into the hormone-prepared endometrium
Finally a healthy pregnancy

4. Infertility. Statistic
A female factor (ovulatory dysfunction, pelvic factor) is in approximately 50%
A male factor (sperm and semen abnormalities) is in approximately 35%
Unexplained factors and causes (e.g., coital techniques) related to both partners are in approximately 15%

5. Causes for infertility

6. Cause of Female Infertility
CONGENITAL OR DEVELOPMENTAL FACTORS
Abnormal external genitals
Absence of internal reproductive structures
HORMONAL FACTORS
Anovulation-primary
Pituitary or hypothalamic hormone disorder Adrenal gland disorder
Congenital adrenal hyperplasia
Anovulation-secondary
Disruption of hypothalamic-pituitary-ovarian axis Early menopause
Amenorrhea after discontinuing OCP Increased prolactin levels
TUBAL/PERITONEAL FACTORS
Absence of fimbriated end of tube Tubal motility reduced
Absence of a tube Inflammation within the tube Tubal adhesions
UTERINE FACTORS
Developmental anomalies
Endometrial and myometrial tumors
Asherman syndrome (uterine adhesions or scar tissue)

7. Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS

8. Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS

9. Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS

10. Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS

11. Cause of Female Infertility TUBAL/PERITONEAL FACTORS
Chlamidial infection
Pelvic infections (ruptures appendix, STIs)

12. Cause of Female Infertility UTERINE FACTORS
Uterine fibroids

13. Cause of Female Infertility UTERINE FACTORS
Endometrial tumor

14. Cause of Female Infertility UTERINE FACTORS
Asherman syndrome

15. Cause of Female Infertility VAGINAL-CERVICAL FACTORS
Vaginal-cervical infection
Sperm antibody

16. Cause of Male Infertility
STRUCTURAL OR HORMONAL DISORDERS
Undescended testes Hypospadias Testicular damage
Varicocele Low testosterone levels caused by mumps
OTHER FACTORS
Endocrine disorders Genetic disorders Psychologic disorders
Sexually transmitted infections Exposure of scrotum to high temperatures
Exposure to workplace hazards such as radiation or toxic substances
SUBSTANCE ABUSE
Changes in sperm (Smoking, heroin, marijuana, amyl nitrate, butyl ni­trate, ethyl chloride, methaqualone, Monoamine oxidase)
Decrease in sperm (Hypopituitarism, Debilitating or chronic disease, Trauma, Gonadotropic inadequacy, Decrease in libido
Heroin, methadone, selective serotonin reuptake in­hibitors, and barbiturates)
Impotence (Alcohol, Antihypertensive medications)
OBSTRUCTIVE LESIONS OF THE EPIDIDYMIS AND VAS DEFERENS
NUTRITIONAL DEFICIENCIES

17. Cause of Male Infertility STRUCTURAL OR HORMONAL DISORDERS

18. Evaluation of the Infertile couple
History and Physical exam
Semen analysis
Thyroid and prolactin evaluation
Determination of ovulation
Basal body temperature record
Serum progesterone
Ovarian reserve testing
Hysterosalpingogram

19. Assessment of woman 1.Age
2. Duration of infertility (length of contraceptive and noncontraceptive exposure)
3. Obstetric
A. number of pregnancies, miscaridges and abortion
B. Length of time required to initiate each pregnancy
C. Complication of pregnancy
D. Duration of lactation
4. Gynecologic: detailed menstrual history
5. Previous tests and therapy of infertility
6. Medical: general (chronic&hereditary disease), medication, family problem, sexual development, galactorrhea
7. Surgical: abdominal or pelvic surgery

20. Cause
1. Follicular development, ovulation, and luteal development are supportive of pregnancy:
a. Basal body temperature (presumptive evidence of ovulatory cycles) is biphasic, with temperature elevation that persists for 12 to 14 days before menstruation
b. Cervical mucus characteristics change appropriately during phases of menstrual cycle
c. Laparoscopic visualization of pelvic organs verifies follicular and luteal development
2. The luteal phase is supportive of pregnancy:
a. Levels of plasma progesterone are adequate
b. Findings from endometrial biopsy samples are consistent with day of cycle
3. Cervical factors are receptive to sperm during expected time of ovulation:
a. Cervical os is open
b. Cervical mucus is clear, watery, abundant, and slippery and demonstrates good spinnbarkeit and arborization (fern pattern)
c. Cervical examination does not reveal lesions or infections
d. Postcoital test findings are satisfactory (adequate number of live, motile, normal sperm present in cervical mucus)
e. No immunity to sperm demonstrated

21. Cause 4. The uterus and uterine tubes are supportive of pregnancy:
a. Uterine and tubal patency are documented by Spillage of dye into peritoneal cavity
Outlines of uterine and tubal cavities of adequate size and shape, with no abnormalities
b. Laparoscopic examination verifies normal development of internal genitals and absence of adhesions, infections, endometriosis, and other lesions
5. The male partner's reproductive structures are normal:
a. No evidence of developmental anomalies of penis, testicular atrophy, or varicocele (varicose veins on the spermatic vein in the groin)
b. No evidence of infection in prostate, seminal vesicles, and urethra
c. Testes are more than 4 cm in largest diameter
6. Semen is supportive of pregnancy:
a. Sperm (number per milliliter) are adequate in ejaculate
b. Most sperm show normal morphology
c. Most sperm are motile, forward moving
d. No autoimmunity exists
e. Seminal fluid is normal

22. Abnormalities of Spermatogenesis

23. Normal Sperm made in seminiferous tubules Travel to epididymis to
mature

24. Normal Sperm exit through vas deferens
Semen produced in prostate gland, seminal glands, cowpers glands
Sperm only 5% of ejaculation
Sperm can live 5-7 days

25. Semen Analysis (SA) Obtained by masturbation
Provides immediate information
Quantity
Quality
Density of the sperm
Morphology
Motility
Abstain from coitus 2 to 3 days
Collect all the ejaculate
Analyze within 1 hour
A normal semen analysis excludes
male factor 90% of the time

26. Normal Values for SA
Volume Sperm Concentration Motility Viscosity Morphology pH WBC
2.0 ml or more
20 million/ml or more
50% forward progression
25% rapid progression
Liquification in min
30% or more normal forms
Fewer than 1 million/ml

27. Causes for Abnormal SA Abnormal Count No sperm Few sperm
Klinefelter’s syndrome
Sertoli only syndrome
Ductal obstruction
Hypogonadotropic-hypogonadism
Few sperm
Genetic disorder
Endocrinopathies
Varicocele
Exogenous (e.g., Heat)

28. Continues: causes for abnormal SA
Abnormal Morphology
Varicocele
Stress
Infection (mumps)
Abnormal Motility
Immunologic factors
Infection
Defect in sperm structure
Poor liquefaction
Abnormal Volume
No ejaculate
Ductal obstruction
Retrograde ejaculation
Ejaculatory failure
Hypogonadism
Low Volume
Obstruction of ducts
Absence of vas deferens
Absence of seminal vesicle
Partial retrograde ejaculation
Infection

29. Causes for male infertility
42% varicocele
repair if there is a low count or decreased motility
22% idiopathic
14% obstruction
20% other (genetic
abnormalities)

30. Abnormal Semen Analysis
Azoospermia
Klinefelter’s (1 in 500)
Hypogonadotropic-hypogonadism
Ductal obstruction (absence of the Vas deferens)
Oligospermia
Anatomic defects
Endocrinopathies
Genetic factors
Exogenous (e.g. heat)
Abnormal volume
Retrograde ejaculation
Infection
Ejaculatory failure

31. Evaluation of Abnormal SA
Repeat semen analysis in 30 days
Physical examination
Testicular size
Varicocele
Laboratory tests
Testosterone level
FSH (spermatogenesis- Sertoli cells)
LH (testosterone- Leydig cells)
Referral to urology

32. Evaluation of Ovulation

33. Female Reproductive System
Ovaries
Two organs that produce eggs
Size of almond
30,000-40,000 eggs
Eggs can live for hours

34. Menstruation Ovulation occurs 13-14 times per year
Menstrual cycles on average are Q 28 days with ovulation around day 14
Luteal phase
dominated by the secretion of progesterone
released by the corpus luteum
Progesterone causes
Thickening of the endocervical mucus
Increases the basal body temperature (0.6° F)
Involution of the corpus luteum causes a fall in progesterone and the onset of menses

36. Ovulation A history of regular menstruation suggests regular ovulation
The majority of ovulatory women experience
fullness of the breasts
decreased vaginal secretions
abdominal bloating
Absence of PMS symptoms may suggest anovulation
mild peripheral edema
slight weight gain
depression

38. Diagnostic studies to confirm Ovulation
Basal body temperature
Inexpensive
Accurate
Endometrial biopsy
Expensive
Static information
Serum progesterone
After ovulation rises
Can be measured
Urinary ovulation-detection kits
Measures changes in urinary LH
Predicts ovulation but does not confirm it

39. Basal Body Temperature
Excellent screening tool for ovulation
Biphasic shift occurs in 90% of ovulating women
Temperature
drops at the time of menses
rises two days after the lutenizing hormone (LH) surge
Ovum released one day prior to the first rise
Temperature elevation of more than 16 days suggests pregnancy

41. Serum Progesterone Progesterone starts rising with the LH surge
drawn between day 21-24
Mid-luteal phase
>10 ng/ml suggests ovulation

42. Salivary Estrogen: TCI Ovulation Tester- 92% accurate

43. Add Saliva Sample

46. Non-Ovulatory Saliva Pattern

47. High Estrogen/ Ovulatory Saliva Pattern

48. Anovulation

49. Anovulation Symptoms Evaluation*
Irregular menstrual cycles
Amenorrhea
Hirsuitism
Acne
Galactorrhea
Increased vaginal secretions
Follicle stimulating hormone
Lutenizing hormone
Thyroid stimulating hormone
Prolactin
Androstenedione
Total testosterone
Order the appropriate tests based on the clinical indications

50. Anatomic Disorders of the Female Genital Tract

51. Sperm transport, Fertilization, & Implantation
The female genital tract is not just a conduit
facilitates sperm transport
cervical mucus traps the coagulated ejaculate
the fallopian tube picks up the egg
Fertilization must occur in the proximal portion of the tube
the fertilized oocyte cleaves and forms a zygote
enters the endometrial cavity at 3 to 5 days
Implants into the secretory endometrium for growth and development

52. Fertilization

53. Implantation

55. Acquired Disorders Acute salpingitis Intrauterine scarring
Alters the functional integrity of the fallopian tube
N. gonorrhea and C. trachomatis
Intrauterine scarring
Can be caused by curettage
Endometriosis, scarring from surgery, tumors of the uterus and ovary
Fibroids, endometriomas
Trauma

56. Hysterosalpingogram
An X-ray that evaluates the internal female genital tract
architecture and integrity of the system
Performed between the 7th and 11th day of the cycle
Diagnostic accuracy of 70%

57. Hysterosalpingogram The endometrial cavity Fallopian tubes
Smooth
Symmetrical
Fallopian tubes
Proximal 2/3 slender
Ampulla is dilated
Dye should spill promptly

58. HSG: Tubal Infertility

59. Treatment of the Infertile Couple

60. Artificial Insemination
Sperm donation or sperm aspiration

61. In Vitro Fertilization

63. Emotional Impact
Infertility places a great emotional burden on the infertile couple.
The quest for having a child becomes the driving force of the couples relationship.
The mental anguish that arises from infertility is nearly as incapacitating as the pain of other diseases.
It is important to address
the emotional needs
of these patients.

65. Thank You
for attention!