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Pre‐PregnancyTune‐Up:PredictingSuccessandAvoidingLiability

February9,2017

G.WrightBates,Jr.,M.D.ProfessorandDirector

ReproductiveEndocrinologyandInfertility

Participantwillbeableto:

• Describepre‐pregnancycounselingandlifestylemodification

Objectives

• Describeoptimizationofnaturalfertility• Describethehistoryandagebasedevaluation• Describeappropriategeneticscreeningpriortopregnancy

• Provideoverviewoffertilitytreatmentoptions

Ihavenorelevantfinancialinterest

Disclosure

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Patient‐CenteredFamilyPlanningCare

Am J Obstet Gynecol Feb 2017

4. Do you like the children that you have?

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Pre‐conceptionRiskStratification

Borowski, etal, Fertil Steril 2015 104(1):28‐31

Pre‐conceptionRiskStratification

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LifestyleandReproductiveHealth

ASRM Practice Committee, 2016

Marijuana

Testosterone supp

TobaccoandFertility

• Increasedriskofmiscarriageandectopic

• Hastensmenopause 30

40

50

nonsmoker

%

• Damagessperm• REDUCEDchanceofsuccesswithIVF

(regardlessofwhosmokesinthehousehold)

0

10

20

SuccessfulPregnancy

FemaleSmokes

MaleSmokes

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Obesity and Birth Defects

ACOG Obesity in Pregnancy, April 2016Stothard, KJ, et al., JAMA 2009. 301:636‐50

“Getting Pregnant” Diet“Getting Pregnant” Diet

Avoid raw meat, fish, etc.

Carefully wash vegetables and fruits

Limit process meats, fish,

soft cheeses

Limit refined sugars

Avoid Alcohol once pregnant

Limit Caffeine

OB,obesityandlitigation

Walkingthefinelinebetweenfrankcounselingofriskanddiscriminationbecauseofdisability

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Lifestyle Modification

Recommend losing 7% of body weight with

• Increase exercise to 150 minutes of moderate activity such as brisk walking

R d l i i t k b 500 1000 k l/d• Reduce caloric intake by 500 – 1000 kcal/day

(composition of diet may not be crucial)

• Multi-disciplinary approach with support structure (UAB’s PCOS Eat Right Clinic)

Obesity and Reproduction: A Committee Opinion. Fertil Steril 2015. 104(5)1116‐26

PCOSandExercise

• Aerobic Exercise• 30 minutes 3 – 4 x week (100 – 200 kcal)• 40% improvement in insulin sensitivity lasting 48 hours

• 3 month exercise regimen Defronzo RA, Diabetes 1997:36,1379Segar KR J Appl Physiol 1991; 71;2502g

• (92 min / week)• 5% reduction in BMI and improved glucose

dynamics• 60% had return of menstrual cycle

Segar KR, J Appl Physiol 1991; 71;2502

Vigorito C, et al, JCEM (online) February 2007

Realities

• Only 20% of patients lose 10% of body weight

• 60 – 86% of lost weight regained at 3 yearsg g y

• 75 – 121% of lost weight regained at 5 years

Obesity and Reproduction: A Committee Opinion. Fertil Steril 2015. 104(5)1116‐26

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StarbucksBaby??

StarbucksBaby??

KEEP IT SHORT (<180)T ll 280Tall up to 280 mgGrande up to 375 mgVenti up to 475 mg

• Age

• SexualActivity• Coital Practices

OptimizingNaturalFertility

• CoitalPractices• Frequency• Lubricants

• TimingorFertilityWindow

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AgeandFertility

ASRM, 2013

TimingofIntercourseProbabilityofConception

221 patients, a total of 625 normal menstrual cycles221 patients, a total of 625 normal menstrual cycles

--6 6 --5 5 --4 4 --3 3 --2 2 --1 0 +11 0 +1DaysDays

Wilcox AJ, et al. N Engl J Med 1995;333:517

Dunson DB, et al, Hum Reprod 2002;1399

DayofConception

ASRM, 2013

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MythsofMaleReproduction

• MoreSexisbetter……(abstinenceinterval)

• Boxersversusbrief• Hottub/Baths

(temperature matters??)(temperaturematters??)• Considermale“pre‐natalvitamins”• AvoidcommonTOXINS:

tobacco,THC,Testosterone

• Iamfine…Ihavekids,agreatlibido,noED,etc…soIamFERTILE

• HealthandAgedoesn’tmatter

CoitalFrequencyandConceptionCoitalFrequencyandConception

•• 221healthy“fertile”221healthy“fertile”couplescouples

•• Attempted DailyAttempted Daily 25

30

35

40

AttemptedDailyAttemptedDailyIntercourse:Intercourse:•• IncreasedstressIncreasedstress•• DecreasedsexualDecreasedsexualesteemesteem

•• DecreasedsatisfactionDecreasedsatisfaction•• DecreasedfrequencyDecreasedfrequency

0

5

10

15

20

25

Fecundity

Daily

QOD

Q 3 day

J Endo Invest, 2003

AbstinenceIntervalandAbstinenceIntervalandIUIPregnancyRateIUIPregnancyRate

•• RetrospectivestudyRetrospectivestudyof929cyclesof929cycles

•• AbstinencepositivelyAbstinencepositivelycorrelatedwithcountcorrelatedwithcount

10

12

14

16

andnegativelywithandnegativelywithmotilitymotility

0

2

4

6

8

10

Abstience Interval

0-3

4-10 days

>10

Jurema MW, Fertil Steril 2005;84:678

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• Nopositionorpractice(restingsupine)increasesfecundity

• Organismdecreasestransittime

CoitalCoitalPracticesPracticesandandConceptionConception

• Lubricantsmustbechosencarefully• MostBadforsperm• Pre‐Seed®orConceivEase®

• Universalscreeningnotrecommend• Screenwithriskfactors:

• Familyorpersonalhistoryofthyroiddisease• SymptomsorSignsofhypothyroidismT 1 Di b t

Pre‐pregnancyThyroidScreening

• Type1Diabetes• Infertility(ifirregularcyclesandprolactin)• Historyofmiscarriageorpretermdelivery• Historyofautoimmuneconditions• Historyofupperbodyradiation

ASRM Practice Committee, 2016ACOG Committee Opinion, 2007

• PCOS• FamilyHistory• AfricanAmerican,Latino/HispanicorAmericanIndian

• History of Gestational Diabetes or baby greater

Pre‐PregnancyScreening:GlucoseIntolerance

• HistoryofGestationalDiabetesorbabygreaterthan9pounds

• Hypertension• Hyperlipidemia• PhysicalInactivity• MetabolicPhenotype?

Endocrine Society, Screening for Type 2 Diabetes, Hormone.org

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• Infertilityandolderthan35,amenorrhea,?menopausalsymptoms

• AMH• BasalFSHANDEstradiol

Pre‐pregnancyScreening:OvarianReserve

• BasalAntralfolliclecount(ovarianvolume)

• CCCT• Inhibin• Responsetomedication

ScreenforFragileX• Withprematureovarianfailure(POI)ORelevatedFSHbefore40screenforFragileX

• UnexplainedMR,autismordevelopmentaldelays

• Ethnicity??andfamilyhistorybasedscreening

RecommendedScreening:GeneticsorCarrierStatus

y y y g• Only27‐33%correctlyidentifiedtheirethnicity• AfricanAmerican:SickleCell• OFFERtoALLethnicgroups:CysticFibrosis• Greek,Italian,SouthernAsians:Thalassemia• EasternEuropeansJews,(FrenchCanadians):Tay Sachs,Canavan,CF,Familialdysautonomia

• Offercarrierstatusscreening(geneticcounselors)

OfferGeneticCounselingand/screeningifpersonalorfamilyhistoryof:

RecommendedScreening:GeneticsorCarrierStatus

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• $600KfailuretoscreenAfricanAmericanforSC• $1millionforThalassemia“didnottakefamilyhistory”

• $1.25millionfailuretoscreenAshkenaziJewishf il f C Di

FailuretoScreenAwards

familyforCanavanDisease• $1.2milliondidnottestforFragileXwithfamilyhistoryofmentalretardationandautism

• $14millionclaimbyCFcarrierforwrongfullife–DefenseVerdict(patientgivenapamphlet)

SystematicApproach

TreatmentApproachesTreatmentApproaches

TimingTiming LifestylemodificationLifestylemodification CCorCCorLetrozoleLetrozole

3cyclewithOPKandTI3cyclewithOPKandTI3withultrasoundmonitoringandIUI3withultrasoundmonitoringandIUIggIUIearlierinunexplainedorIUIearlierinunexplainedormildmalefactormildmalefactor

•• ConsiderConsideradjuctiveadjuctive therapytherapy•• MetforminMetformin•• DexamethasoneDexamethasone

Gonadotropins/IUIGonadotropins/IUIOvarianDrillingOvarianDrillingIVFIVF

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Conclusions:

Allcounseling,evaluationsandtreatmentshouldbeAGE sensitiveandtailoredtotheindividualpatient’scircumstances

• DietandLifestyleModification

• Pre‐conceptualcounselingandrisk• Assessmentiscrucial

• Systematicgenetic screening