Fertility Diagnosis Fertility Diagnosis and Therapy 2008and Therapy 2008

Gad Lavy, M.D.Gad Lavy, M.D.New England Fertility InstituteNew England Fertility Institute

Lifeline CryogenicsLifeline Cryogenics

The New Technology and the The New Technology and the Aging OvaryAging Ovary

Improvement in diagnosis and therapyImprovement in diagnosis and therapy Aging and its impact on fertilityAging and its impact on fertility The Approach to the “older infertile couple”The Approach to the “older infertile couple”

More aggressive diagnostic and therapeutic More aggressive diagnostic and therapeutic approachapproach

ART ART IVFIVF PGDPGD Egg donationEgg donation Freezing of embryos, eggs and ovarian tissueFreezing of embryos, eggs and ovarian tissue

Team approach to fertility therapyTeam approach to fertility therapy

Infertility Dx and RxInfertility Dx and Rx

Success in Success in DiagnosisDiagnosis

Success in Success in TherapyTherapy

Improved SuccessImproved Success

Better Diagnostics: fewer cases of unexplained Better Diagnostics: fewer cases of unexplained infertility.infertility. PCOSPCOS Ovulatory dysfunctionOvulatory dysfunction ImagingImaging Endometrial functionEndometrial function

Better Therapy: Higher overall success.Better Therapy: Higher overall success. SurgerySurgery Ovulation inductionOvulation induction IVF and related proceduresIVF and related procedures

Aging PopulationAging Population

Age at marriageAge at marriage Age at first pregnancyAge at first pregnancy

Age and FertilityAge and Fertility

Age and IVF SuccessAge and IVF Success

IVF success: Effect of age and number of eggs

The aging Ovary (and testicle)The aging Ovary (and testicle)

Decreased Ovarian Reserve (DOR)Decreased Ovarian Reserve (DOR) Lower conception ratesLower conception rates Higher rates of pregnancy lossHigher rates of pregnancy loss Higher incidence of Congenital defectsHigher incidence of Congenital defects

Menopausal ovary

The Aging OvaryThe Aging Ovary

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Normal ovary

Fewer eggsDecreased egg quality

A Practical Approach to the A Practical Approach to the aging ovaryaging ovary

Aggressive Diagnosis Aggressive Diagnosis and therapyand therapy

Expand Treatment Expand Treatment optionsoptions

Diagnosis: The evaluation Diagnosis: The evaluation cyclecycle

Baseline hormonesBaseline hormones Ovulation profileOvulation profile Imaging: HSG, Sono-Imaging: HSG, Sono-

HSG, MRIHSG, MRI Semen AnalysisSemen Analysis Other: Genetic Other: Genetic

studies, immune studies, immune workup etcworkup etc

Therapy-The aging ovariesTherapy-The aging ovaries

IVFIVF Pre-implantation Genetics (PGD)Pre-implantation Genetics (PGD) Egg DonationEgg Donation Egg Freezing/Ovarian tissue freezingEgg Freezing/Ovarian tissue freezing

In Vitro Fertilization and In Vitro Fertilization and Embryo Transfer (IVF-ET)Embryo Transfer (IVF-ET)

IVFIVF

Intra-cytoplasmic Sperm injection (ICSI)Intra-cytoplasmic Sperm injection (ICSI) Assisted zona Hatching (AZH)Assisted zona Hatching (AZH) Day 4-5 transfer and improved culture Day 4-5 transfer and improved culture

mediamedia Cryopreservation of embryosCryopreservation of embryos

ICSIICSI• Poor sperm quality

• Zona Pellucida hardening

• Poor egg-sperm interaction

Assisted Zona Hatching Assisted Zona Hatching (AZH)(AZH)

Improved Implantation

Zona Hardening

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are needed to see this picture.

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are needed to see this picture.

Improvements in culture Improvements in culture conditions- Blastocyst transferconditions- Blastocyst transfer

PGDPGD

Micromanipulation: remove a single Micromanipulation: remove a single blastomere from an 8-cell embryo without blastomere from an 8-cell embryo without damaging the embryodamaging the embryo

Genetic testingGenetic testing FISHFISH PCRPCR

PGD: Fluorescent In Situ PGD: Fluorescent In Situ Hybridization (FISH)Hybridization (FISH)

PGD- IndicationsPGD- Indications Chromosomal Chromosomal

disordersdisorders Single gene defects Single gene defects

(CF, Thalassemia, (CF, Thalassemia, Sickle cell disease)Sickle cell disease)

Recurrent pregnancy Recurrent pregnancy lossloss

Repeat IVF failuresRepeat IVF failures Severe male factorSevere male factor

How is PGD performed?How is PGD performed?

Ovarian StimulationIVF

Blastomere Biopsy on Day 3

Genetic AnalysisTransfer of

Unaffected Embryo

OutcomeChromosomally Normal Baby

PDG- Clinical outcomesPDG- Clinical outcomes

Identify normal embryosIdentify normal embryos Fewer embryos to transferFewer embryos to transfer Know when not to transferKnow when not to transfer Reduce pregnancy loss and anomaliesReduce pregnancy loss and anomalies

Third Party ReproductionThird Party Reproduction

Egg donationEgg donation Embryo donationEmbryo donation Gestational surrogacyGestational surrogacy

Egg Donation: IndicationsEgg Donation: Indications

Ovarian Failure.Ovarian Failure. Poor egg quality.Poor egg quality. Recurrent IVF failure.Recurrent IVF failure. Recurrent pregnancy lossRecurrent pregnancy loss Genetic defects precluding normal pregnancy.Genetic defects precluding normal pregnancy.

The Egg Donation ProcessThe Egg Donation Process The process involves IVF.The process involves IVF. The resulting offspring will carry genetic The resulting offspring will carry genetic

material of the material of the donordonor and the and the male partnermale partner..

The Egg Donation ProcessThe Egg Donation Process

Donor and recipient cycles are Donor and recipient cycles are synchronizedsynchronized..

Eggs taken from the donor after Eggs taken from the donor after ovarian ovarian stimulationstimulation..

Eggs are fertilized with Eggs are fertilized with recipient partner’s recipient partner’s spermsperm..

Embryos transferred to the uterus of a Embryos transferred to the uterus of a hormonally primed recipienthormonally primed recipient..

Egg Donation: The ProcessEgg Donation: The Process

DonorDonor Synchronize cycle with Synchronize cycle with

recipientrecipient Ovarian stimulationOvarian stimulation Egg retrievalEgg retrieval

RecipientRecipient Synchronize cycle with Synchronize cycle with

donordonor Preparation of the Preparation of the

uterusuterus FertilizationFertilization Embryo transferEmbryo transfer

Egg Donation: The donorsEgg Donation: The donors Donor recruitment: Who are the donors?Donor recruitment: Who are the donors? Donor Screening: How are they tested?Donor Screening: How are they tested? Donor matching: How do I pick a donor?Donor matching: How do I pick a donor?

Egg Donation: The recipient Egg Donation: The recipient couplecouple

Medical ScreeningMedical Screening The Mock cycleThe Mock cycle

Psychological issuesPsychological issues Legal IssuesLegal Issues Ethical concernsEthical concerns: Disclosure : Disclosure

Cryopreservation of embryos, Cryopreservation of embryos, eggs and ovarian tissueeggs and ovarian tissue

IVF and Cryopreservation of IVF and Cryopreservation of EmbryosEmbryos

AdvantagesAdvantages:: Well established Well established

method. method. High success.High success.

DisadvantagesDisadvantages:: More difficult for More difficult for

unmarried women.unmarried women. Limited number of Limited number of

embryosembryos Delay in cancer therapy Delay in cancer therapy

due to the IVF process.due to the IVF process. Contraindication to Contraindication to

ovarian stimulation in ovarian stimulation in Estrogen sensitive Estrogen sensitive tumors.tumors.

Egg FreezingEgg Freezing-Applications-Applications

Ovarian malignanciesOvarian malignancies Ovarian surgeryOvarian surgery AgingAging Egg banksEgg banks

Egg FreezingEgg Freezing

AdvantagesAdvantages No need for ovarian No need for ovarian

stimulationstimulation No need for No need for

fertilizationfertilization Enables preservation Enables preservation

of eggs prior to of eggs prior to surgery chemo or surgery chemo or agingaging

DisadvantagesDisadvantages Lower survivalLower survival Possible damage to Possible damage to

mitotic spindlemitotic spindle Still experimentalStill experimental

Egg Freezing At NEFIEgg Freezing At NEFI

Technique: Technique: New Advancements in New Advancements in cryopreservation.cryopreservation.

CandidatesCandidates Cancer and chemoCancer and chemo Egg bankEgg bank Preservation of reproductive potentialPreservation of reproductive potential

Age <38Age <38 FSH <12FSH <12

Good Survival/fertilization and embryo Good Survival/fertilization and embryo developmentdevelopment

Ready to launchReady to launch

SummarySummary

Technology is developing rapidlyTechnology is developing rapidly Ovarian aging is a major factorOvarian aging is a major factor ART is limited but can offer help for the ART is limited but can offer help for the

aging ovary.aging ovary.

HoweverHowever

Don’t Delay.Don’t Delay. Discuss all options early.Discuss all options early. Consult or refer if needed.Consult or refer if needed.

CT State Mandate for Fertility CT State Mandate for Fertility TherapyTherapy

BenefitsBenefits DiagnosticsDiagnostics Ovulation therapy/inseminations X3 Ovulation therapy/inseminations X3 IVFx1IVFx1

LimitationLimitation Age <40Age <40 Look Back: Look Back: Time with current carrier: at least one yearTime with current carrier: at least one year Excludes self insurers, religious organizations etc.Excludes self insurers, religious organizations etc.

Return to referring MDReturn to referring MDDelay in referralDelay in referral

Return to referring MDReturn to referring MDLength of clomid therapy by PMDLength of clomid therapy by PMD

Results (IV)

55%

53%

25%

0%

10%

20%

30%

40%

50%

60%

No CC 1-4 CC cycles >4 CC cycles

128/232 37/69 2/8

% of patients whoreturned to ROB

A Team ApproachA Team Approach

The primary caregiverThe primary caregiver The infertility specialistThe infertility specialist

PhysicianPhysician Nurse/midwife/NPNurse/midwife/NP LaboratoryLaboratory Emotional counseling and supportEmotional counseling and support

We would like to We would like to thank our sponsor:thank our sponsor:

OrganonOrganon

Thank you for coming.Thank you for coming.

Gad Lavy, M.D. F.A.C.O.G.Gad Lavy, M.D. F.A.C.O.G.

New England Fertility InstituteNew England Fertility Institute

Lifeline CryogenicsLifeline Cryogenics