1. Infertility and Family planning
Lecture
Petrenko N.V., MD, PhD,
assistant professor of obstetric and gynecology department № 2

2. Film fertilization

3. Requirements for Conception
Three general strategies:
Generation of ovum and sperm (spermatogenesis, ovulation);
Fertilization (union of gametes: sperm & ovum).
Implantation in the uterus.

4. Definition
Infertility - the inability to conceive following unprotected sexual intercourse during
1 year (age < 35)
6 months (age >35)
Primary infertility
Secondary infertility
Subfertility – reduced fertility decreased fertility or a decreased chance of getting pregnant, but not a complete inability to get pregnant.
Sterility – inability to conceive

5. Infertility Causes

6. Male infertility

7. Normal spermatogenesis
Sperm is constantly produced by the germinal epithelium of the testicle
Sperm generation time 73 days
Travel to epididymis to mature
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 7

9. Cause of Male Infertility
STRUCTURAL OR HORMONAL DISORDERS
Undescended testes
Hypospadias
Testicular damage caused
by mumps
Varicocele
Low testosterone levels

10. Cause of Male Infertility
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)

11. Cause of Male Infertility
OBSTRUCTIVE LESIONS OF THE EPIDIDYMIS AND VAS DEFERENS
NUTRITIONAL DEFICIENCIES
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

12. Assessment of Male Infertility
Laboratory data
Routine urinary test, Gonorrhea and Chlamidia tests, serologic test for syphilis
Complete semen analysis
Additional lab studies
Basic endocrine studies indicated in men with oligospermia or aspermia
FSH, LH, testosteron
T3, T4, TSH
Test for sperm antibodies
17-hydroxycorticoids and 17 ketosteroids
Buccal smear and chromosome studies (e.g. Klinefelter syndrome, XXY sex chromosomes
Testicular biopsy where correct interpretation is available, vasography
Ultarasonography

13. Assessment of Male Infertility
Physical examination
General
Complete physical examination, with special attention given to physical condition and fat and hair distribution
Genital tract
Assessment of penis and urethra, scrotal size, position, size, and consistency of testes, epididimides and vasa deferentia, prostate size and consistency
Careful search for varicocele with man in both supine and upright position

14. Semen Analysis (SA)
Obtained by masturbation after 2 to 5 days of abstinence from ejaculation
Volume
2.0 ml or more
Sperm Concentration
20 million/ml or more
Total sperm count
40 million/ml or more
Motility
50% forward progression
25% rapid progression
Viscosity
Liquefaction in min
Morphology
30% or more normal forms pH
WBC
Fewer than 1 million/ml 14

15. Semen Analysis. Azoospermia Oligozoospermia (No sperm in semen)
Klinefelter’s syndrome
Sertoli only syndrome
Ductal obstruction
Hypogonadotropic-
hypogonadism
Oligozoospermia
(Few sperm in semen)
Genetic disorder
Endocrinopathies
Varicocele
Exogenous (e.g., Heat)
Abnormal Volume
No ejaculate
Ductal obstruction
Retrograde ejaculation
Ejaculatory failure
Hypogonadism
Semen
Analysis.
Abnormal Morphology
Varicocele
Stress
Infection (mumps)
Asthenozoospermia
(Abnormal Motility)
Immunologic factors
Infection
Defect in sperm structure
Poor liquefaction
Varicocele
Low Volume
Obstruction of ducts
Absence of vas deferens
Absence of seminal vesicle
Partial retrograde ejaculation
Infection 15

16. Male Infertility If SA is abnormal: and referral to urologist or
lab test US
and referral to urologist or
sexopatologist

17. Female infertility

18. Female Reproductive System
Ovaries
Two organs that produce eggs
Eggs can live for hours
Uterine tubes
Two tubes allow union egg and sperm
Uterus
Pear shape organ that receive fertilized egg

19. Menstrual function

20. Cause of Female Infertility
Congenital or developmental factors
Hormonal factors
Tubal/Peritoneal factors
Uterine factors

21. Cause of Female Infertility 1
CONGENITAL OR DEVELOPMENTAL FACTORS
Abnormal external genitals
Absence of internal reproductive structures

22. Cause of Female Infertility 2
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

23. Cause of Female Infertility TUBAL/PERITONEAL FACTORS
Absence of fimbriated end of tube
Tubal motility reduced
Absence of a tube
Inflammation within the tube
Tubal adhesions

24. Cause of Female Infertility 3
UTERINE FACTORS
Developmental anomalies
Endometrial and myometrial tumors
Asherman syndrome (uterine adhesions or scar tissue)

25. Cause of Female Infertility Developmental anomalies of uterus

26. Cause of Female Infertility Developmental anomalies of uterus

27. Cause of Female Infertility Developmental anomalies of uterus

28. Cause of Female Infertility Developmental anomalies of uterus

29. Cause of Female Infertility Endometrial and myometrial tumors

30. Cause of Female Infertility Endometrial and myometrial tumors
Endometrial tumor

31. Cause of Female Infertility Asherman syndrome

32. Assessment of Female Infertility
Physical examination
General
Complete physical examination
Genital tract
State of hymen (full penetration)
Clitoris
Vaginal infection (trichomoniasis, candidiasis)
Cervical tears, polyps, infection, patency of os, accessibility to insemination
Uterus (size, position, mobility)
Adnexae (tumor, evidence of endometriosis)

33. Assessment of Female Infertility
Laboratory data
Chlamidia test and gonorrhea culture
For woman with irregular menstrual cycle or amonorrhea
Serum prolactin level with tomographic radiographs of skull
FSH,LH, serum progesteron and estrogen determanation, 17-ketosteroid assay test, 17-hydroxycorticosteroid test, glucose tolerance test
T3, T4, TSH
Endometrial biopsy US
Hysterosalpingography
Laparoscopy, hysteroscopy

34. Hysterosalpingography
An X-ray that evaluates the internal female genital tract uterine cavity and tubes after instillation of radiopaque contrast material through the cervix
Performed between the 7th and 11th day of the cycle
Diagnostic accuracy of 70% 34

35. Hysterosalpingography
It is possible to see abnormalities of uterus
Congenital defect, submucous myomas, endometrial polyps
Distortions of uterine cavity o uterine tubes can be a result of current or past PID
Scar tissue and adhesions from inflammatory process can immobilize the uterus and tubes, kink the tubes and surround the ovaries 35

36. Hysterosalpingography36

37. Detection of Ovulation
Basal body temperature
Cervical mucus characteristic
Endometrial biopsy US
Serum progesterone level
Urinary ovulation-detection kits

38. 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

39. Basal Body Temperature

40. Cervical mucus
requires that the woman recognize and interpret the cyclic changes in the amount and consistency of cervical mucus that characterize her own unique pattern of changes
Postmenstrual mucos: scant
Preovulational mucus: cloudy, yellow, or white, sticky
Ovulation mucus: clear, wet, sticky, slippery
Right before ovulation, the watery, thin, clear mucus becomes more abundantand thick. It can be stretched 5+ cm between the thumb and forefinger. This indicates the period of maximal fertility
Postovulation fertile mucus: thick, cloudy, sticky
Postovulation, postfertile mucus: scant

41. Cervical mucus Ovulation-Detection Method

42. Predictor test for ovulation
detects the sudden surge of luteinizing hormone (LH) that occurs approximately 12 to 24 hours before ovulation. Unlike BBT, the test is not affected by illness, emotional upset, or physical activity

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

44. Endometrial biopsy
Check endometrial response to progesteron and adequacy of luteal phase
Late (21-27 days) of menstrual cycle? 2-3 days before expected menses

45. Ultrasonography Collapse of follicle after ovulation
7, 14, 21 days of menstrual cycle

46. Laparoscopy Allow good visualization of internal pelvic structures
Small endoscope is inserted through small incision in the anterior abdominal wall
General anesthetic is usually given
Laparoscopy reveal endometriosis, pelvic adhesions, tubal occlusion, leyomiomas or polycyclic ovaries
Possible procedure
fulguration (destruction of tissue by means of elctricity) of small endometrial implants,
lysis of adhesions
tacking ovarian biopsies

47. Hysteroscopy
is the inspection of the uterine cavity by endoscopy with access through the cervix. It allows for the diagnosis of intrauterine pathology and serves as a method for surgical intervention

48. Postcoital test
PCT used to test for adequacy of coital technique, cervical mucus, sperm and degree of sperm penetration through cervical mucus
Test is performed within several hours after ejaculation of semen into vagina
A specimen of cervical mucus obtained from the cervical os and examined under a microscope
The quality of mucus and the number of forward-moving sperm are noted

49. ??? Unexplained infertility ???
10% of infertile couples will have a completely normal workup
Pregnancy rates in unexplained infertility
no treatment %
clomid and intrauterine
insemination 8.3%
gonadotropins and
intrauterine
insemination 17.1%
??? 49

50. Treatment

51. Inadequate Spermatogenesis
Eliminate alterations of thermoregulation
Clomiphene citrate is occasionally used for induction of spermatogenesis
20% success
In vitro fertilization may facilitate fertilization
Artificial insemination with donor sperm is often successful

52. Anovulation Clomiphene citrate Antiestrogen
Combines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedback
Increases FSH production
stimulates the ovary to make follicles
Given for 5 days in the early part of the cycle
Maximum dose is usually 150mg
50mg dose - 50% ovulate
100mg -25% more ovulate
150mg lower numbers of ovulation
7% risk of twins 0.3% triplets

53. Human menopausal gonadotropin
If no response with clomid then PERGONAL (FSH and LH in 1:1 ratio) can be administered intramuscularly
Adverse effects
Hyperstimulation of the ovaries
Multiple gestation
Fetal wastage

54. Purified FSH Metrodin has derect action on ovarian follicle Indication
Treastment of polycystic ovarian disease
Side effect
Ovarian enlargement, ovarian hyperstimulation, local irritation at injection site, multifetal gestations

55. Human chorionic gonadotropin
Profasi has direct action on ovarian follicle to stimulate meiosis and rupture of the follicle
Side effect
Local irritation at injection site

56. Danazol (Danocrine) Indication
Treatment of endometriosis
Combination of estrogen and androgen suppresses ovarian activity, eliminating stimulation to endometrial glands and stroma, with resultant shrinkageand disappearance
Side effect
Mild hirsutism, acne, edema and weight gain, increase liver enzyme levels

57. GnRH agonists(Synarel, Lupron,Zoladex)
Indication
Treatment of endometriosis, uterine fibroids
Desensitization and downward regulaion of GnRH receptors of pituitary. resulting in suppression of LH, FSH, and ovarian function
Side effect
Synarel, nasal irritation, nosebleeds;
Synarel and Lupron, hot flashes, vaginal dryness, myalgia and arthralgia, headaches, mild bone loss (usually reversible within mo after treatment)

58. Progesterone (progesterone inoil, Progestoral)
Indication
Treatment of luteal-phase inadequacy
Direct stimulation of endometrium
Side effect
Breast tenderness, local irritation, headaches

59. Anatomic Abnormalities
Surgical treatments
Lysis of adhesions
Septoplasty
Tuboplasty
Myomectomy
Surgery may be performed
laparoscopically
hysteroscopically

60. Immune infertility
Use of condom during genital intercourse for 6 to12 months
1/3 of couples conceive

61. ?
If the fallopian tubes are beyond repair one must consider reproductive alternatives

62. Intrauterine insemination (artificial insemination)
definition: sperm introduced into female reproductive tract by means other than coitus
sperm can come from donor / sperm bank or from husband
usually, several ejaculations are pooled
often used when male has low sperm count or antibodies present in ejaculate

63. In Vitro Fertilization – embrio transfer (IVF-ET)
1st performed in 1978 (Louise Joy Brown)
Sperm collected from ovary after hyperstimulation and combined with sperm in the lab (IVF)
Zygote placed back into the uterus (ET)
Indication:
Tubal disease or blockage;
Severe male infertility;
endometriosis;
unexplained infertility;
cervical factor;
immunologic infertility

64. In Vitro Fertilization

65. GIFT and ZIFT
GIFT = gamete intrafallopian transfer = ova are collected and together with sperm inserted into oviducts below point of blockage
ZIFT = zygote intrafallopian transfer = is like IVF, only zygotes (1 cell stage) are inserted below blockage in oviduct
Indication
Same as for IVF-ET, except there must be normal tubal anatomy, patency, and absence of previous tubal disease in at least one uterine tube

66. Intracytoplasmic sperm injection (ICSI)
Selection of one sperm cell that is injected directly into the egg to achieve fertilization. Used with IVF-ET.
Indication
Male partner is azoospermic or has a very low sperm count;
couple has a genetic defect;
male partner has antisperm antibodies

67. Gestational carrier (embryo host); surrogate mother
A couple undertakes an IVF cycle and theembryo(s) is transferred to another woman's uterus (the carrier) who has contracted with the couple to carry the baby to term. The carrier has no genetic investment in the child. Surrogate motherhood is a process by which a woman is inseminated with semen from the infertile woman's partner and then carries thebaby until birth.
Indication
Congenital absence or surgical removal of uterus;
a reproductively impaired uterus. myomas, uterine adhesions, or other congenital abnormalities;
a medical condition that might be life-threatening during pregnancy, such as diabetes, immunologic problems, or severe heart, kidney, or liver disease

68. Donor oocyte
Eggs are donated by an IVF procedure, and the donated eggs are inseminated. The embryos are transferred into the recipient's uterus, which is hormonally prepared with estrogen/progesterone therapy.
Indication
Early menopause; surgical removal of ovaries; congenitally absent ovaries; autosomal or sex-linked disorders; lack of fertilization in repeated IVF attempts because of subtle oocyte abnormalities or defects in oocyte/spermatozoa interaction

69. Donor embryo (embryoadoption)
A donated embryo is transferred to theuterus of an infertile woman at theappropriate time (normal or induced) ofthe menstrual cycle.
Indication
Infertility not resolved by less aggressive forms of therapy;
absence of ovaries;
male partner is azoospermic or is severely compromised

70. Thank You
for attention!