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Fertility Diagnosis & Treatment Options

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Fertility Diagnosis & Treatment Options
Arlene J. Morales, MD, FACOG Fertility Specialists Medical Group

AJM 4/2011

Diagnosis of Infertility
 “unprotected coitus of 1 year

duration”  “active” versus no contraception exposure  Age:
  

< 35 years 35-39 years > 40 years
AJM 4/2011

1 year 6 months 3 months

Time Required for Conception: An Inefficient Process
Time of Exposure 1 month 3 months 6 months 1 year 2 years % Pregnant 22% 57% 72% 85% 93%

100 80 60 40 20 20 5 0 1 36 9 2 13 3 6 12 50 75 85

93

24

Cumulative Pregnancy Rates (<35 yrs) 40 yrs

AJM 4/2011

Fertility Decreases with Age
100 90 80 70 60 50 40 30 20 10 0

25

35
30 85 22 15 35

Age (Years)
25 % Pregnant at 1 year Monthly pregnancy rate 85 22 40 45

45
5

1

AJM 4/2011

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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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Uterine Diagnostic Studies

Sonohysterogram (SHG or SIS)
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Hysterosalpingogram (HSG)

The forgotten uterus

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Examples of Pelvic Disease

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Uterine Cavity Abnormalities

Normal

Polyp

Myoma

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Scarring

Congenital

Uterine Fibroids: Submucosal

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Severe Tubal Factor

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Other Conditions

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Hormones
 Aging
 

Cycle Day 3 FSH, Estradiol x 2 cycles AMH – Anti-Mullerian Hormone TSH, Prolactin PCOS (FSH, LH, Fasting Insulin/Glucose)
• Androgens (testosterone, 17OHP, DHEAS)

 Hormonal Mileu
 

AJM 4/2011

Reproductive Aging
AGE=Quality ; AMH,AF,D3=Quantity
600 500 400 300 200 100 0 20-24 25-29 30-34 35-39 40-44 45-49
AJM 4/2011

Hutterites Burgeoisie 17th Burgeoisie 16th French Village Iranian Village USA 1955 USA 1981



Leading cause is varicocele

Etiologies of Male Infertility

AJM 4/2011

A.R.T. Laboratory Andrology
 Basic Semen Parameters (W.H.O.

Standards)
   

Days Abstinence Sperm Count Sperm Motility Sperm Morphology Sperm Volume



2-5 days  20 M/ml  50%  30% (W.H.O.)  14 % (Strict: Krueger’s) 2-5 ml

AJM 4/2011

Indications for Genetic Diagnosis
ICSI  Severe Oligospermia



Sperm concentration < 5 mil/cc

Chromosomal testing  Cystic fibrosis testing

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MESA Electroejaculation

TESA
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Sterilization
 Tubal Ligation Reversal


Pro’s & Con’s

 Vasectomy Reversal


Pro’s & Con’s

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Recurrent Pregnancy Loss
 Definition  1st

& 2nd Trimester

 Prognosis  Workup

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Traditional Algorithm
Detailed History and Physical Exam Ovulation Cavity and Tubal Status Ovulation Induction Timing of Intercourse Ovulation Induction Intrauterine Insemination IVF
IVF Directly

Semen Analysis

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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

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

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) Monthly fecundity of 9.5% (148 cycles) vs 3.3% (150 cycles) Cumulative preg rates was 13.2% vs 5.6%
AJM 4/2011

USA: 67 patients with Unexplained (50 mg)




Canada: 148 couples with Unexplained (100 mg)


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
IUI alone n=234/717 18 % 5%
AJM 4/2011

COH & IUI n=231/618
Cummulative 33 % Per Cycle

COH & ICI n=234/637

ICI alone n=233/706

15 %

19 % 4%

10 % 2%

IVF
Completed Check-list
Including Sonohysterogram and Mock-Transfer

Medication Protocol
Prep “stuff” 2-4 weeks

Medication Class

Treatment 4 to 5 weeks

Your Stimulation Cycle Retrieval (2 to 4 weeks)

Embryo Transfer (3 to 6 days later)

Pregnancy Test (7 to 10 days later) Prenatal care
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Follow-up

Egg Collection Area

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Transvaginal Aspiration Oocytes

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Oocyte Aspiration

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Embryo Culture Area

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Embryologist at Work

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Oocytes
MATURE

IMMATURE STRIPPED
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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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Fertilized Egg From IVF

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ART Lab Techniques: ICSI

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ICSI (cont)

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Embryo Development (D2-D4)

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Blastocyst Development

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Holding pipette

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Hatching pipette

Assisted Hatching

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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

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

Preimplantation Genetic Diagnosis

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Preimplantation Genetic Diagnosis
Advanced maternal aged
• Increasing maternal age is associated with increased aneuploid embryos






Family history of translocations Recurrent Pregnancy Loss (RPL)
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Extra chromosome 13 in an embryo
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Inefficient Process
 

High incidence of failed conception in-vivo and in-vitro A lot attributed to differential embryo viability

15% of embryos arrest by day-3 ? Aneuploidy
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< 50% reach the blast stage

Catheter Placement

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We’ve come along way
 In 1978, Louise Brown born through IVF  Since then, techniques have improved to

break the barriers of infertility

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Single Intrauterine Pregnancy

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Embryo Transfer and Multiple Gestation
 Multifetal pregnancies constitute an

iatrogenic complication of assisted reproduction
80 70 60 50 40 30 20 10 0 World Collaborative Report ASRM
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singletons twins triplets quadruplets

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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
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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
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Inefficient Process

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ASRM Guidelines
VS <35 years old

35-37 yrs old

38-40 years old

Over 40 years

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Other Methods of Reproduction
 Donor Oocytes  Gestational Carriers  Gestational Surrogate  Donor Gametes (both oocytes and sperm)  Frozen Embryo Transfer of donated embryos

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Reproductive Aging
60 50 40 30 20 10 0 27 31 35 39 43 47
Own Eggs Donor Eggs

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

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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) AJM 4/2011

Advances in Assisted Reproduction
ICSI IUI

Ovulation Induction

IVF

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Luteal Phase Support

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Pronuclei

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Day 2 (post retrieval)

Cells or blastomeres

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Day 3 (post retrieval)

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Day 4 (post retrieval)

Morula

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Day 5-6 (post retrieval)

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Blastocysts

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Day 5-6 (post retrieval)
Hatched blastocyst

Zona pellucida

Inner cell mass (fetus)
AJM 4/2011

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