fertility seminar
DESCRIPTION
A presentation on fertility rates with statics, treatment options, and relevant data.TRANSCRIPT
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Fertility Diagnosis & Fertility Diagnosis & Treatment OptionsTreatment Options
Arlene J. Morales, MD, FACOGArlene J. Morales, MD, FACOGFertility Specialists Medical GroupFertility Specialists Medical Group
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Diagnosis of InfertilityDiagnosis of Infertility
““unprotected coitus of 1 year unprotected coitus of 1 year durationduration””
““activeactive”” versus no contraception versus no contraception exposureexposure
Age:Age:
< 35 years< 35 years 1 year1 year
3535--39 years39 years 6 months6 months
> 40 years> 40 years 3 months3 months
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Time Required for Conception: Time Required for Conception: An Inefficient ProcessAn Inefficient Process
Time of ExposureTime of Exposure % Pregnant% Pregnant
1 month1 month 22%22%3 months3 months 57%57%6 months6 months 72%72%1 year1 year 85%85%2 years2 years 93%93% 20
5
36
9
50
13
7585
93
0
20
40
60
80
100
1 2 3 6 12 24
Cumulative Pregnancy Rates (<35 yrs) 40 yrs
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Fertility Decreases with AgeFertility Decreases with Age
25 35 45
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100
Age (Years)
% Pregnant at 1year
85 85
Monthlypregnancy rate
22 22 15 5 1
25 30 35 40 45
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Etiologies of InfertilityEtiologies of Infertility
Cervical Factor:5-10%
Anovulation: 10-15%
Uterine Factors: 20%
Tubal Factors:30-40% Male Factors: 30-40%
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Uterine Diagnostic Uterine Diagnostic StudiesStudies
Sonohysterogram (SHG or SIS) Hysterosalpingogram (HSG)
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The forgotten uterusThe forgotten uterus
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Examples of Pelvic Disease Examples of Pelvic Disease
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Uterine Cavity Uterine Cavity AbnormalitiesAbnormalities
Normal Polyp
Myoma Scarring Congenital
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Uterine Fibroids: SubmucosalUterine Fibroids: Submucosal
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Severe Tubal Factor Severe Tubal Factor
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Other Conditions Other Conditions
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HormonesHormones
AgingAging
Cycle Day 3 FSH, Cycle Day 3 FSH, EstradiolEstradiol x 2 cyclesx 2 cycles
AMH AMH –– AntiAnti--MullerianMullerian HormoneHormone
Hormonal Hormonal MileuMileu
TSH, TSH, ProlactinProlactin
PCOS (FSH, LH, Fasting PCOS (FSH, LH, Fasting Insulin/Glucose)Insulin/Glucose)•• Androgens (testosterone, 17OHP, DHEAS)Androgens (testosterone, 17OHP, DHEAS)
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Reproductive AgingReproductive Aging AGE=Quality ; AMH,AF,D3=QuantityAGE=Quality ; AMH,AF,D3=Quantity
0
100
200
300
400
500
600
20-24 25-29 30-34 35-39 40-44 45-49
HutteritesBurgeoisie 17thBurgeoisie 16thFrench VillageIranian VillageUSA 1955USA 1981
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Etiologies of Male Etiologies of Male InfertilityInfertility
Leading cause is Leading cause is varicocelevaricocele
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A.R.T. LaboratoryA.R.T. Laboratory AndrologyAndrology
Basic Semen Parameters (W.H.O. Basic Semen Parameters (W.H.O. Standards)Standards)
Days AbstinenceDays Abstinence 22--5 days5 days
Sperm CountSperm Count
20 M/ml20 M/ml
Sperm MotilitySperm Motility
50%50%
Sperm MorphologySperm Morphology
30% (W.H.O.)30% (W.H.O.)
14 % (Strict: Krueger14 % (Strict: Krueger’’s)s)
Sperm VolumeSperm Volume 22--5 ml5 ml
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Indications for Genetic Indications for Genetic DiagnosisDiagnosis
ICSIICSI Severe Severe OligospermiaOligospermia
Sperm concentration < 5 mil/ccSperm concentration < 5 mil/cc Chromosomal testingChromosomal testing Cystic fibrosis testingCystic fibrosis testing
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MESAMESA
ElectroejaculationElectroejaculation
TESATESA
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SterilizationSterilization
Tubal Ligation ReversalTubal Ligation Reversal
ProPro’’s & Cons & Con’’ss
Vasectomy ReversalVasectomy Reversal
ProPro’’s & Cons & Con’’ss
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Recurrent Pregnancy LossRecurrent Pregnancy Loss
DefinitionDefinition
11stst & 2& 2ndnd TrimesterTrimester
Prognosis Prognosis
WorkupWorkup
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Traditional AlgorithmTraditional Algorithm
Ovulation
IVF
Ovulation InductionIntrauterine Insemination
Ovulation InductionTiming of Intercourse
Cavity and Tubal Status Semen Analysis
Detailed History and Physical Exam
IVFDirectly
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Traditional TherapyTraditional Therapy
Ovulation Induction (OI)Ovulation Induction (OI)
ClomipheneClomiphene Citrate (1Citrate (1--33--5 eggs)5 eggs)•• 2 to 3 visits over 2 weeks2 to 3 visits over 2 weeks
GonadotropinsGonadotropins (5(5--88--10 eggs)10 eggs)•• 5 to 7 visits over 2 weeks5 to 7 visits over 2 weeks
Intrauterine Insemination (IUI)Intrauterine Insemination (IUI)
AJM 4/2011AJM 4/2011http://www.universityfertilityassociates.com/images/art_08.jpg http://www.follistim.com/Authfiles/Images/349_91850.gif
http://www.fertilityplus.org/faq/tomcat.jpg
Intrauterine InseminationsIntrauterine Inseminations 10 to 14 days10 to 14 days
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Efficacy of Efficacy of ClomidClomid/IUI/IUI
CLOMID CLOMID -- 3 trials cross3 trials cross--over placebo trialsover placebo trials
UK: 118 patients with Unexplained (100 mg)UK: 118 patients with Unexplained (100 mg)
Cumulative Cumulative pregpreg rate was 22.3% rate was 22.3% vsvs 14.6% (3 cycles)14.6% (3 cycles)
USA: 67 patients with Unexplained (50 mg)USA: 67 patients with Unexplained (50 mg)
Monthly fecundity of 9.5% (148 cycles) Monthly fecundity of 9.5% (148 cycles) vsvs 3.3% (150 3.3% (150 cycles)cycles)
Canada: 148 couples with Unexplained (100 mg)Canada: 148 couples with Unexplained (100 mg)
Cumulative Cumulative pregpreg rates was 13.2% rates was 13.2% vsvs 5.6%5.6%
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Efficacy of Efficacy of GonadotropinGonadotropin and IUI for and IUI for InfertilityInfertility
GuzickGuzick and National Cooperative and National Cooperative Reproductive Medicine Network N Reproductive Medicine Network N EnglEngl J Med 1999;340:177J Med 1999;340:177--8383
Couples: no identifiable etiology & motile Couples: no identifiable etiology & motile spermsperm
4 cycles of treatment4 cycles of treatmentCOH & IUI
n=231/618IUI alonen=234/717
COH & ICIn=234/637
ICI alonen=233/706
33 %15 %
18 %5 %
19 %4 %
10 %2 %
CummulativePer Cycle
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Completed Check-listIncluding Sonohysterogram and Mock-Transfer
Medication Protocol
Medication Class
Your Stimulation CycleRetrieval (2 to 4 weeks)
Embryo Transfer (3 to 6 days later)
Pregnancy Test (7 to 10 days later)
Prenatal care Follow-up
Prep “stuff”
2-4 weeks
Treatment 4 to 5 weeks
IVF
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Egg Collection AreaEgg Collection Area
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TransvaginalTransvaginal Aspiration OocytesAspiration Oocytes
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OocyteOocyte Aspiration Aspiration
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Embryo Culture AreaEmbryo Culture Area
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Embryologist at WorkEmbryologist at Work
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OocytesOocytes
MATURE
IMMATURE
STRIPPED
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Insemination MethodsInsemination Methods
Conventional InseminationConventional Insemination
1010--30,000 motile sperm30,000 motile sperm
11--4 eggs in a 50 4 eggs in a 50 l drop of medial drop of media
Incubate overnightIncubate overnight
Check for fertilizationCheck for fertilization
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Fertilized Egg From IVFFertilized Egg From IVF
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ART Lab Techniques: ICSIART Lab Techniques: ICSI
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ICSI (cont)ICSI (cont)
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Embryo Development (D2Embryo Development (D2--D4)D4)
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BlastocystBlastocyst DevelopmentDevelopment
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Assisted Hatching Assisted Hatching
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PreimplantationPreimplantation Genetic Genetic Diagnosis (PGD)Diagnosis (PGD)
Consists of taking a single cell (biopsy) from Consists of taking a single cell (biopsy) from each embryo, followed by genetic analysis to each embryo, followed by genetic analysis to determine the normalcy of the embryo.determine the normalcy of the embryo.
Subsequent replacement to the patient of those Subsequent replacement to the patient of those embryos classified by genetic diagnosis as embryos classified by genetic diagnosis as normal.normal.
Three PGD methods of analysisThree PGD methods of analysis
FISH (FISH (FFluorescent luorescent IIn n SSituitu HHybridization)ybridization)
PCR (PCR (PPolymerase olymerase CChain hain RRecationecation))
Whole Genomic Whole Genomic
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PPreimplantation reimplantation GGenetic enetic DDiagnosisiagnosis
Fluorescent Fluorescent In SituIn Situ Hybridization (FISH)Hybridization (FISH)
Detects chromosomal abnormalitiesDetects chromosomal abnormalities•• Chromosomal Chromosomal AneuploidyAneuploidy (Missing Chromosomes)(Missing Chromosomes)
13, 16,18, 21, 22, X, Y13, 16,18, 21, 22, X, Y•• Chromosome TranslocationChromosome Translocation
. . Polymerase Chain ReactionPolymerase Chain Reaction
Detects single gene defectsDetects single gene defects
TayTay--Sachs Disease, SickleSachs Disease, Sickle--Cell AnemiaCell Anemia
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PreimplantationPreimplantation Genetic Genetic DiagnosisDiagnosis
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PPreimplantation reimplantation GGenetic enetic DDiagnosisiagnosis
Advanced Advanced maternal agedmaternal aged
•• Increasing maternal Increasing maternal age is associated age is associated with increased with increased aneuploid embryosaneuploid embryos
Family history of Family history of translocationstranslocations
Recurrent Recurrent Pregnancy Loss Pregnancy Loss (RPL)(RPL)
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Inefficient ProcessInefficient Process
High incidence of failed conception inHigh incidence of failed conception in--vivo and invivo and in--vitrovitro
A lot attributed to differential embryo viabilityA lot attributed to differential embryo viability
15% of embryosarrest by day-3? Aneuploidy
< 50% reach the blast stage
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Catheter PlacementCatheter Placement
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WeWe’’ve come along wayve come along way
In 1978, Louise Brown born through IVFIn 1978, Louise Brown born through IVF
Since then, techniques have improved to Since then, techniques have improved to break the barriers of infertilitybreak the barriers of infertility
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Single Intrauterine Pregnancy
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Embryo Transfer and Multiple Embryo Transfer and Multiple GestationGestation
MultifetalMultifetal pregnancies constitute an pregnancies constitute an iatrogenic complication of assisted iatrogenic complication of assisted reproduction reproduction
01020304050607080
WorldCollaborative
Report
ASRM
singletonstwinstripletsquadruplets
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Multiple Gestation; How do we Multiple Gestation; How do we avoid?avoid?
Judicious use of ovulation inductionJudicious use of ovulation induction
Limiting the number of embryos transferredLimiting the number of embryos transferred
How many is too many ?How many is too many ?
Improving cryopreservation & thawing Improving cryopreservation & thawing techniquestechniques
Improving the quality selection criteria of the Improving the quality selection criteria of the embryos embryos
Improving the culture systemsImproving the culture systems
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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
Multiple Gestation; How do Multiple Gestation; How do we avoid?we avoid?
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Inefficient ProcessInefficient Process
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ASRM GuidelinesASRM Guidelines
<35 years old
38-40 years old
Over 40 years
35-37 yrs old
VS
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Other Methods of ReproductionOther Methods of Reproduction
Donor OocytesDonor Oocytes
Gestational CarriersGestational Carriers
Gestational SurrogateGestational Surrogate
Donor Gametes (both oocytes and sperm)Donor Gametes (both oocytes and sperm)
Frozen Embryo Transfer of donated embryosFrozen Embryo Transfer of donated embryos
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Reproductive AgingReproductive Aging
0
10
20
30
40
50
60
27 31 35 39 43 47
Donor Eggs
Own Eggs
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What is a good ART program?What is a good ART program?High Quality Laboratory
High Quality Clinical Care
Comprehensive Services
Patient ChoiceExcellent Documentation
Research
Professional management
Cost-effective carePsychological Support
Ethical Care
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Preconception ReadinessPreconception Readiness
Genetic RiskGenetic Risk
Cystic Fibrosis (ACOG Recommendation)Cystic Fibrosis (ACOG Recommendation)
AfricanAfrican--AmericanAmerican•• Sickle Cell AnemiaSickle Cell Anemia
AshkanaziAshkanazi JewishJewish•• 9 disease screen 9 disease screen
MediterreanMediterrean/Asian/Asian•• ThalassemiaThalassemia
ImmunityImmunity
VaricellaVaricella
RubellaRubella
Blood TypeBlood Type
Prenatal Vitamins (Folic Acid)Prenatal Vitamins (Folic Acid)
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Ovulation Induction
Luteal Phase Support
IUI
IVF
ICSI
Advances in Assisted Advances in Assisted ReproductionReproduction
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Pronuclei
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Day 2 (post retrieval)Day 2 (post retrieval)
Cells or blastomeres
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Day 3 (post retrieval)Day 3 (post retrieval)
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Day 4 (post retrieval)Day 4 (post retrieval)
Morula
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Day 5Day 5--6 (post retrieval)6 (post retrieval)
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BlastocystsBlastocysts
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Day 5Day 5--6 (post retrieval)6 (post retrieval)
Hatched blastocyst
Zona pellucida
Inner cell mass (fetus)