A presentation about treatment options for infertility by Dr. Arlene Morales of Fertility Specialists Medical Group. (FSMG) This presentation includes statics, procedure explanations, images, and related data. http://ivfspecialists.com/

1. Fertility Diagnosis &
Treatment Options
Arlene J. Morales, MD, FACOG
Fertility Specialists Medical Group
AJM 4/2011

2. Diagnosis of Infertility
 “unprotected coitus of 1 year
duration”
 “active” versus no contraception
exposure
 Age:
 < 35 years 1 year
 35-39 years 6 months
 > 40 years 3 months
AJM 4/2011

3. Time Required for Conception:
An Inefficient Process
100
Time of Exposure % Pregnant 93
85
80 75
1 month 22%
60
3 months 57% 50
6 months 72% 40 36
1 year 85%
20 20
2 years 93%
9 13
5
0
1 2 3 6 12 24
Cumulative Pregnancy Rates (<35 yrs) 40 yrs
AJM 4/2011

4. Fertility Decreases with Age
100
90
80
70
60
50
40
30
20
10
0
25
35
45
Age (Years)
25 30 35 40 45
% Pregnant at 1 85 85
year
Monthly 22 22 15 5 1
pregnancy rate
AJM 4/2011

5. AJM 4/2011

6. Etiologies of Infertility
Tubal Factors:30-40% Male Factors: 30-40% Anovulation: 10-15%
Uterine Factors: 20% Cervical Factor:5-10%
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7. Uterine Diagnostic
Studies
Sonohysterogram (SHG or SIS) Hysterosalpingogram (HSG)
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8. The forgotten uterus
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9. Examples of Pelvic Disease
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10. Uterine Cavity
Abnormalities
Normal Polyp
Myoma Scarring Congenital
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11. Uterine Fibroids: Submucosal
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12. AJM 4/2011

13. Severe Tubal Factor
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14. Other Conditions
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15. Hormones
 Aging
 Cycle Day 3 FSH, Estradiol x 2 cycles
 AMH – Anti-Mullerian Hormone
 Hormonal Mileu
 TSH, Prolactin
 PCOS (FSH, LH, Fasting
Insulin/Glucose)
• Androgens (testosterone, 17OHP, DHEAS)
AJM 4/2011

16. Reproductive Aging
AGE=Quality ; AMH,AF,D3=Quantity
600
500 Hutterites
400 Burgeoisie 17th
Burgeoisie 16th
300 French Village
Iranian Village
200 USA 1955
100 USA 1981
0
20-24 25-29 30-34 35-39 40-44 45-49
AJM 4/2011

17. Etiologies of Male
Infertility
 Leading cause is varicocele
AJM 4/2011

18. A.R.T. Laboratory
Andrology
 Basic Semen Parameters (W.H.O.
Standards)
 Days Abstinence 2-5 days
 Sperm Count  20 M/ml
 Sperm Motility  50%
 Sperm Morphology  30% (W.H.O.)
 14 % (Strict: Krueger’s)
 Sperm Volume 2-5 ml
AJM 4/2011

19. Indications for Genetic
Diagnosis
 ICSI
 Severe Oligospermia
 Sperm concentration < 5 mil/cc
 Chromosomal testing
 Cystic fibrosis testing
AJM 4/2011

20. MESA
Electroejaculation
TESA
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21. Sterilization
 Tubal Ligation Reversal
 Pro’s & Con’s
 Vasectomy Reversal
 Pro’s & Con’s
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22. Recurrent Pregnancy Loss
 Definition
 1st & 2nd Trimester
 Prognosis
 Workup
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23. Traditional Algorithm
Detailed History and Physical Exam
Ovulation Cavity and Tubal Status Semen Analysis
Ovulation Induction
Timing of Intercourse
Ovulation Induction
Intrauterine Insemination
IVF
IVF Directly
AJM 4/2011

24. Traditional Therapy
 Ovulation Induction (OI)
 Clomiphene Citrate (1-3-5 eggs)
• 2 to 3 visits over 2 weeks
 Gonadotropins (5-8-10 eggs)
• 5 to 7 visits over 2 weeks
 Intrauterine Insemination (IUI)
AJM 4/2011

25. Intrauterine Inseminations
10 to 14 days
http://www.fertilityplus.org/faq/tomcat.jpg
http://www.universityfertilityassociates.com/images/art_08.jpg http://www.follistim.com/Authfiles/Images/349_91850.gif
AJM 4/2011

26. Efficacy of Clomid/IUI
CLOMID - 3 trials cross-over placebo trials
 UK: 118 patients with Unexplained (100 mg)
 Cumulative preg rate was 22.3% vs 14.6% (3 cycles)
 USA: 67 patients with Unexplained (50 mg)
 Monthly fecundity of 9.5% (148 cycles) vs 3.3% (150
cycles)
 Canada: 148 couples with Unexplained (100 mg)
 Cumulative preg rates was 13.2% vs 5.6%
AJM 4/2011

27. Efficacy of Gonadotropin and IUI for
Infertility
 Guzick and National Cooperative
Reproductive Medicine Network N Engl J Med 1999;340:177-83
 Couples: no identifiable etiology & motile
sperm
 4 cycles of treatment
COH & IUI IUI alone COH & ICI ICI alone
n=231/618 n=234/717 n=234/637 n=233/706
Cummulative 33 % 18 % 19 %
Per Cycle 10 %
15 % 5% 4% 2%
AJM 4/2011

28. IVF
Completed Check-list
Including Sonohysterogram and Mock-Transfer
Medication Protocol
Prep “stuff” 2-4 weeks
Medication Class
Your Stimulation Cycle
Retrieval (2 to 4 weeks)
Treatment 4 to 5 weeks
Embryo Transfer (3 to 6 days later)
Pregnancy Test (7 to 10 days later)
Prenatal care Follow-up
AJM 4/2011

29. Egg Collection Area
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30. Transvaginal Aspiration Oocytes
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31. Oocyte Aspiration
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32. Embryo Culture Area
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33. Embryologist at Work
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34. AJM 4/2011

35. Oocytes
MATURE
IMMATURE
STRIPPED
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36. AJM 4/2011

37. Insemination Methods
 Conventional Insemination
 10-30,000 motile sperm
 1-4 eggs in a 50 l drop of media
 Incubate overnight
 Check for fertilization
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38. Fertilized Egg From IVF
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39. AJM 4/2011

40. ART Lab Techniques: ICSI
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41. ICSI (cont)
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42. Embryo Development (D2-D4)
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43. Blastocyst Development
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44. Holding pipette AJM 4/2011
Hatching pipette

45. Assisted Hatching
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46. Preimplantation Genetic
Diagnosis (PGD)
 Consists of taking a single cell (biopsy) from
each embryo, followed by genetic analysis to
determine the normalcy of the embryo.
 Subsequent replacement to the patient of those
embryos classified by genetic diagnosis as
normal.
 Three PGD methods of analysis
 FISH (Fluorescent In Situ Hybridization)
 PCR (Polymerase Chain Recation)
 Whole Genomic
AJM 4/2011

47. Preimplantation Genetic Diagnosis
 Fluorescent In Situ Hybridization (FISH)
 Detects chromosomal abnormalities
• Chromosomal Aneuploidy (Missing Chromosomes)
 13, 16,18, 21, 22, X, Y
• Chromosome Translocation
 . Polymerase Chain Reaction
 Detects single gene defects
 Tay-Sachs Disease, Sickle-Cell Anemia
AJM 4/2011

48. Preimplantation Genetic
Diagnosis
AJM 4/2011

49. Preimplantation Genetic Diagnosis
 Advanced
maternal aged
• Increasing maternal
age is associated
with increased
aneuploid embryos
 Family history of
translocations
 Recurrent
Pregnancy Loss
(RPL)
AJM 4/2011

50. Extra chromosome 13 in an embryo
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51. Inefficient Process
 High incidence of failed conception in-vivo and in-vitro
 A lot attributed to differential embryo viability
15% of embryos < 50% reach
arrest by day-3 the blast stage
? Aneuploidy
AJM 4/2011

52. Catheter Placement
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53. We’ve come along way
 In 1978, Louise Brown born through IVF
 Since then, techniques have improved to
break the barriers of infertility
AJM 4/2011

54. Single Intrauterine Pregnancy
AJM 4/2011

55. Embryo Transfer and Multiple
Gestation
 Multifetal pregnancies constitute an
iatrogenic complication of assisted
reproduction
80
70
60 singletons
50 twins
40 triplets
30 quadruplets
20
10
0
World ASRM
Collaborative
Report AJM 4/2011

56. AJM 4/2011

57. Multiple Gestation; How do we
avoid?
 Judicious use of ovulation induction
 Limiting the number of embryos transferred
 How many is too many ?
 Improving cryopreservation & thawing
techniques
 Improving the quality selection criteria of the
embryos
 Improving the culture systems
AJM 4/2011

58. Multiple Gestation; How do
we avoid?
Day 3 embryo Day 5 or 6 embryo “ hatching blastocyst”
•Allow for screening of potential aneuploidy
•May improve the implantation rate
•Reduce the number of transferred embryos
AJM 4/2011

59. Inefficient Process
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60. ASRM Guidelines
VS <35 years old
35-37 yrs old
38-40 years old
Over 40 years
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61. Other Methods of Reproduction
 Donor Oocytes
 Gestational Carriers
 Gestational Surrogate
 Donor Gametes (both oocytes and sperm)
 Frozen Embryo Transfer of donated embryos
AJM 4/2011

62. Reproductive Aging
60
50
40 Donor Eggs
30
20 Own Eggs
10
0
27 31 35 39 43 47
AJM 4/2011

63. What is a good ART program?
High Quality Laboratory High Quality Clinical Care
Comprehensive Services Patient Choice
Excellent Documentation Research
Professional management Cost-effective care
Psychological Support Ethical Care
AJM 4/2011

64. Preconception Readiness
 Genetic Risk
 Cystic Fibrosis (ACOG Recommendation)
 African-American
• Sickle Cell Anemia
 Ashkanazi Jewish
• 9 disease screen
 Mediterrean/Asian
• Thalassemia
 Immunity
 Varicella
 Rubella
 Blood Type
 Prenatal Vitamins (Folic Acid)
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65. Advances in Assisted
Reproduction
ICSI IUI
Ovulation Induction
IVF
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Luteal Phase Support

66. AJM 4/2011

67. AJM 4/2011

68. Pronuclei
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69. AJM 4/2011

70. AJM 4/2011

71. Day 2 (post retrieval)
Cells or
blastomeres
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72. Day 3 (post retrieval)
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73. Day 4 (post retrieval)
Morula
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74. Day 5-6 (post retrieval)
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75. Blastocysts
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76. Day 5-6 (post retrieval)
Hatched blastocyst
Zona pellucida
Inner cell mass (fetus)
AJM 4/2011