>>> WELCOME TO INNOVATIONS IN

REPRODUCTIVE TECHNOLOGY.

THIS IS OUR WOMEN'S HEALTH

SEMINAR FOR WOMEN'S HEALTH WEEK.

WE HAVE A WONDERFUL PROGRAM

BRAND FOR YOU.

WE HAVE TWO REPRESENTATIVES FROM

OUR COMMITTEE.

WHO WILL BE DOING INTRODUCTIONS.

KAREN PARKER.

KAREN IS THE ACTIVE CHIEF OF

SCIENCE AND PLANNING AND THE

WOMEN'S HEALTH OFFICER AT THE

NATIONAL CANCER INSTITUTE AND

TAMARA IS AT THE OFFICE OF

SPECIAL POPULATIONS AND RESEARCH

TRAINING AT NIAID IN THE WOMEN'S

HEALTH PROGRAM MANAGER THERE.

SO THANK YOU TO BOTH OF AND YOU

TO THE ENTIRE SEMINAR SERIES

COMMITTEE AS WELL AS JOYCE, THE

DIRECTOR OF PROGRAMS AND

MANAGEMENT AND ORWH FOR HELPING

TO PUT TOGETHER THIS WONDERFUL

PROGRAM.

I'D ALSO LIKE TO IDENTIFY OUR

COMMUNICATIONS TEAM, HEIDI,

BRETT ASK HERE IN THE AUDIENCE

AND FOR HER WONDERFUL POSTER

WORK AND FOR THE REST OF ORWH

STAFF FOR HELPING TO PUT THIS

TOGETHER.

AT THIS POINT, I'D LIKE TO ASK

KAREN TO COME UP TO DOT

INTRODUCTION FOR OUR FIRST

SPEAKER, NATIONAL WOMEN'S HEALTH

WEEK IS A SPECIAL TIME WHERE WE

ATTEND TO SOME OF THE HEALTH

CONCERNS OF WOMENY AND WE ARE

DELIGHTED TO FOCUS ON

REPRODUCTIVE TECHNOLOGIES THIS

YEAR.

AN ISSUE OF IMPORTANCE TO MANY

AND YOU'LL BE PARTICULARLY

EXCITED ABOUT THE RANGE OF

TOPICS RELATED TO REPRODUCTIVE

TECHNOLOGIES WE ARE ABLE TO

BRING TO YOU TODAY.

KAREN?

>> THE SEMINAR SERIES COMMITTEE

IS PARTICULARLY PLEASED THAT THE

SEMINAR IS BEING HOSTED DURING

NATIONAL WOMEN'S HEALTH WEEK AND

WE ARE VERY, VERY EXCITED ABOUT

THIS TOPIC.

IT'S VERY TIMELY AND WE HAVE A

WONDERFUL PANEL OF SPEAKERS.

OUR FIRST SPEAKER IS

DR. ALAN -- ALAN DECHERNEY.

FULL BIOS ARE IN THE PROGRAM.

HE'LL BE TALKING ABOUT ETHICAL

ISSUES IN EMERGING TECHNOLOGIES

AND REPRODUCTIVE MEDICINE AND HE

IS HERE AT NIH.

HE WORKS IN THE PROGRAM AND

REPRODUCTIVE AND ADULT

ENDOCRINOLOGY AT THE EUNICE

KENNEDY SHRIVER NATIONAL

INSTITUTE AND HUMAN DEVELOPMENT.

DR. ALAN DECHERNEY.

[ APPLAUSE ]

>> SO THIS IS DR. EDWARDS.

HE'S THE FOUNDER OF IBF.

IN 2010, HE GOT THE NOBEL PRIZE.

NOW HE DIDN'T GET THE NOBEL FOR

30 OR ALMOST 40 YEARS.

TWO REASONS.

ONE, HE WAS THE SOCIALIST.

MORE IMPORTANT REASON HE DIDN'T

GET THE NOBEL PRIZE UNTIL 40

YEARS AFTER HIS DISCOVER

SEBECAUSE, SUPPOSEDLY HE DIDN'T

DO IT IN ETHICAL FASHION.

HE STARTED DOING IVF IN HUMANS

WITH VERY LITTLE IN THE WAY OF

ANIMAL WORK.

BUT NEVERTHELESS, IT WORKED OUT.

THERE ARE PROBABLY 6 MILLION

BABIES IN THE WORLD AS A RESULT

OF IN-VITRO FERTILIZATION, AND

THE LARGE MAJORITY ARE HEALTHY

ADULTS, NOW.

SOME OF THEM.

AND 20 YEARS AGO, THE AMERICAN

SOCIETY FOR REPRODUCTIVE

MEDICINE, CDC AND CONGRESS

ACTIVATED A REGISTRY.

SO 95% OF CLINICS IN AMERICA,

WHICH THERE ARE ABOUT ALMOST 400

NOW, REGISTER THEIR RESULTS EACH

YEAR.

THIS IS A CONFUSING SLIDE.

IT'S NOT MEANT TO SHOW ANYTHING

OTHER THAN THE IN FACT THAT WE

DO HAVE A REGISTRY AND WE DO

REGISTER SUCCESS RATES AND

EMBRYO NUMBER, OVULATION

INDUCTION FOR PATIENTS TO

REVIEW.

AND THIS IS AVAILABLE ON THE WEB

AT THE CDC SITE.

SO WE'LL TALK ABOUT THE ETHICAL

ISSUES.

IT'S A LIMITED TIME SO WE CAN'T

TALK A LOT ABOUT MANY OF THE

ISSUES.

THIS IS A HIGHLY-INTERESTING

AREA AS FAR AS ETHICS ARE

CONCERNED.

THE MAJOR REASON IS THAT

EVERYBODY IS KIND OF

PARTICIPATES IN REPRODUCTION AT

SOME POINT, EVEN IF YOU'RE HERE,

YOU'RE THE RESULT OF

REPRODUCTION ESTIMATE POINT IN

YOUR LIFE.

SO, A DAY OR WEEK DOESN'T GO BY

THAT THERE IS NOT SOMETHING IN

THE NEWSPAPER THAT DOESN'T

REPRESENT SOMETHING IN REGARDS

TO THE ETHICAL OR LEGAL ISSUES

SURROUNDING THESE TECHNOLOGIES.

WE'LL TALK ABOUT SEX SELECTION

AND POST MORTEM REPRODUCTION,

FREEZING EGGS AND DISEASE PER

PETTATION AND SINGLE WOMEN.

SO FIRST LET'S LOOK AT THE HOT

PART NOW IN REPRODUCTIVE

TECHNOLOGIES, CHROMOSOMAL,LOR

GENETIC ANALYSIS.

THE ULTIMATE GOAL WOULD BE TO

LOOK AT OR BIOPSY EMBRYOS AND

LOOK AT EVERY EMBRYO BEFORE THEY

WERE REPLACED AND DO A GENETIC

PROFILE ON THOSE EMBRYOS SO YOU

WOULD FINISH YOUR CHILD HAS A

20% CHANCE OF DEVELOPING STAGE 2

DIABETES WHEN IT REACHES

ADULTHOOD.

SO THAT IS ALL HYPOTHETICAL.

WHAT IS PRACTICAL TODAY IS THERE

ARE PROBABLE BE400 DISEASE THAT

IS CAN BE IDENTIFIED AND CAN BE

ELIMINATED BY NOT PLACING THOSE

EMBRYOS BACK.

THAT SOUNDS LIKE A SIMPLE ISSUE

AND IF THE PATIENT HAS AN

EMBRYO, OR WILL HAVE A FATAL

DISEASE AT THE YOUNG STAGE OF

THAT PERSON'S LIFE, THAT SOUNDS

EASY.

BUT THIS IS EXTREMELY

CONTROVERSIAL.

A NUMBER OF YEARS AGO, I SPOKE

TO THE SMALL PEOPLE OF AMERICA,

THE LAY SOCIETY MADE UP OF

MIDGEITS AND DWARFS AND DWARFS,

COULD BE ELIMINATED IN ONE

GENERATION.

IT'S A SINGLE AUTOSOMAL

DOMINANCE.

THEY WERE UPSET BECAUSE THEY

DIDN'T THINK IT WAS A DISEASE.

THEY HAD A NORMAL LIFE.

THEY WORKED, THEY GOT MARRIED

AND THEY HAD CHILDREN.

SO THIS ENTERS INTO AN AREA OF

ETHICAL CONTROVERSY AS TO HOW

FAR WE GO AS FAR AS THIS IS

CONCERNED.

I THEN IS HARD TO READ.

IT'S JUST TO SHOW THERE ARE MANY

GENES INVOLVED IN MANY OF THESE

DISEASES.

NOW THAT WE DO GENETIC PROFILING

ON EMBRYOS, A LOT OF TIMES WE

FIND THINGS WE DON'T KNOW WHAT

THEY MEAN.

A BIG DELETION IN ONE OF THE

GENES.

OR AN OVEREXPRESSION OF SOME OF

THE GENES.

WHAT DO YOU TELL THE PARENT IN

WE DON'T KNOW THE OUTCOME OF

THAT GENE OR THAT CHANGE IN THE

GENETIC MAKEUP, BUT ETHICALLY,

YOU MUST TELL THE PARENTS THAT

THIS IS TRULY THE CASE.

I WANT TO GO BACK.

CAN I GO BACK?

CAN YOU TAKE ME BACK ONE?

GREAT.

SO I WANT TO GIVE YOU A COUPLE

OF SCENARIOS AND I WANT YOU TO

RANK THEM IN YOUR MIND AS FAR AS

HOW ACCEPTABLE THIS IS TO THE

PUBLIC.

ONE, DIAGNOSE A DISEASE THAT IS

FATAL.

MUSCULAR DYSTROPHY IS THE MOST

COMMON EXAMPLE.

NUMBER 2, YOU HAVE A CHILD WITH

FRAN CONIES ANEMIA.

SO YOU GET PREGNANT AGAIN AND

YOU MAKE SURE THAT CHILD, THE

NEXT CHILD, DOESN'T HAVE THAT

BYING THE EMBRYO AND WHEN THAT

CHILD IS BORN, YOU CAN USE THE

BONE MARROW OF THAT CHILD IN

ORDER TO TREAT THE EXISTING

SIBLING AND THEREFORE ELIMINATE

THE DISEASE.

THE NEXT SOMETHING LIKE BRCA1

WHERE IT'S NOT TERRIBLY OR NOT

FATAL, NECESSARILY.

AND IT HAS A LOW PENETRANTS AS

FAR AS DEVELOPING DISEASE IS

CONCERNED.

THE NEXT IS SEX SELECTION AND

THE LAST WOULD BE TRAIT

SELECTION, BLUE EYES, GOOD

ATHLETIC ABILITY.

JUST STUDY WAS DONE AND

PUBLISHED IN JAMA BY HUDSON WHO

WORKS HERE, AND YOU CAN SEE I

PETEY MUCH GAVE IN THE ORDER OF

THAT THEY ARE ACCEPTABLE.

CERTAINLY A SERIOUS DISEASE IS

HIGHLY ACCEPTABLE.

HAVING A CHILD, NOT HAVE THE

CHILD, YOU ALSO KEEP THE CHILD

AND LOVE THAT SECOND CHILD, JUST

LIKE THE FIRST CHILD, SOMEWHAT

QUESTIONABLE IN BCCA1 AND 21.

WHEN WE COME TO SEX SELECTION

AND TRAIT SELECTION THIS BECOMES

MUCH MORE CONTROVERSIAL.

WHEN YOU POLL A POPULATION, AT

LEAST THE UNITED STATES, YOU CAN

SEE THAT THE MAJORITY WOULD

PREFER WHEN CHOOSING A BOY OR

GIRL WOULD CHOOSE TO HAVE A

MALE.

MOST PEOPLE DO NOT CARE,

OBVIOUSLY BUT THE TRUTH IS WHEN

PEOPLE WANT TO HAVE SEX

SELECTION, THEY ARE -- THEIR

INTEREST DISAPPEARS.

WE SEE A NUMBER OF PARENTS WHEN

THEY FIND OUT IT'S EXPENSIVE,

THEY DON'T PURSUE THAT.

SO ALTHOUGH IS IT AN INTERESTING

ETHICAL ISSUE TO DISCUSS, IT'S

NOT A REAL PRACTICAL ONE THAT WE

TOLERATE.

THE OTHER THING IS TRUSTING

PEOPLE AS FAR AS GENETIC CENTRAL

CONCERNED.

WE'RE BUILDING DIAGNOSIS ON

THESE EMBRYOS.

WHAT ABOUT SHARING THIS

INFORMATION?

OBVIOUSLY PEOPLE TRUST

PHYSICIANS AND RESEARCH BUT THEY

DON'T WANT THIS INFORMATION TO

BE PUBLIC.

SO ANOTHER ETHICAL ISSUE IS TO

MAKE SURE THAT THIS INFORMATION

THAT WE GLEAN FROM THESE EMBRYO

THAT IS WE BIOPSY AS FAR AS

THEIR GENETIC MATERIAL IS

CONCERNED IS KEPT SOMEWHAT

PRIVATE.

NOW THE NEXT ETHICAL ISSUE, AND

A VERY CURRENT ONE AND HOTLY

DEBATED ONE, IS THE ISSUE OF

SINGLE EMBRYO TRANSFERS.

WHEN WE STARTED, YOU CAN SEE THE

TWINNING RATE AND THE TWINNING

RATE COMING DOWN.

BUT WHEN WE STARTED, YEARS AGO,

30 YEARS AGO, SUCCESS RATES WERE

VERY LOW.

AND THE ONLY WAY TO INCREASE

SUCCESS RATES WERE TO PUT A

LARGE NUMBER OF EMBRYOS BACK.

BUT AS WE GOT BETTER, THE

LABORATORY GOT BETTER.

OVULATION INDUCTION GOT BETTER,

PATIENT SELECTION GOT BETTER AS

WELL, THEN WE WERE ABLE TO PUT

FEWER EM BRIEOYS BACK AND

THEREFORE ACHIEVE THE SAME

SUCCESS RATE.

AND WHAT THIS GRAPH SIMPLY SHOWS

IS THAT IT PLOTS THE NUMBER OF

EMBRYOS YOU PUT BACK AGAINST AGE

AND THE MORE YOU PUT BACK,

LIKELY AS THE PATIENT TO GET

PREGNANT AND ALSO THE RISK OF

MULTIPLE GESTATION.

SO NOW, THE GOAL ACTUALLY

SOCIETY, DOCTORS, HAVE ONE GOAL,

AND PATIENTS HAVE A DIFFERENT

GOAL.

OUR ROLE IS SINGLE EMBRYO

TRANSFER BECAUSE WE DON'T WANT

TO CREATE TWINS OR TRIPLETS.

IT'S JUST CERTAINLY YOU'LL SEE

IN A MINUTE, TRIPLETS ARE A REAL

PROBLEM.

ON THE OTHER HAND, THIS IS

EXPENSIVE.

THE PATIENTS IS A LOT OF MONEY

INVESTED IN THIS.

AND FOR THAT REASON, THEY WOULD

LIKE TO HAVE THE HIGHEST SUCCESS

RATE POSSIBLE.

SO, THE DIALOGUE THEN IS BETWEEN

A SINGLE EMBRYO TRANSFER AND A

TWO EMBRYO TRANSFER OR A 3

EMBRYO TRANSFER.

NOW, WE DON'T ACTUALLY KNOW

WHICH IS THE BEST EMBRYO F WE

COULD PICK THE BEST, THAT WOULD

MAKE IT VERY SIMPLE.

WE HAVE SOME TOOLS THAT WE'LL

DISCUSS BUT WE DON'T KNOW REALLY

WHICH IS THE BEST EMBRYO TO

PLACE BACK IN THE UTERUS WITH

ANY FINITE DISTINCTION AT THIS

POINTER.

NOW PATIENTS WANT TWINS BECAUSE

IT'S INSTANT FAMILY, THEY WAITED

A LONG TIME.

THEY HAD A LOT OF MONEY INVESTED

AND THEY ARE HAPPY WITH THAT

RESULT.

NOW, WE HAD SOME IMPACT, IT JUST

LOOKS AT TWO TRIPLETS, TWINS AND

SINGLETONS.

YOU CAN SEE THAT IS GONE UP TO

5-12% IN THIS STUDY THAT WAS TWO

YEARS -- ACTUALLY FOUR YEARS OLD

NOW.

TWO EMBRYO TRANSFERS HAVE GONE

WAY AND YOU WANT NUMBER OF 3

EMBRYO TRANSFERS HAVE GONE WAY

WAY DOWN.

THIS IS A DRAMATIC IMPACT IN

THAT TRIP LETS ARE RARE NOW OR

GREATER THAN TRIP LETS.

BUT TWINS STILL ARE ABOUT 20% OF

PREGNANCIES RESULTING FROM

IN-VITRO FERTILIZATION.

NOW, ONE WAY TO COMPENSATE FOR

THIS IS TO DO A BLAST TRANSFER,

WHICH MEANS LETTING THE EMBRYO

GROW IN A DISH FOR FIVE DAYS

INSTEAD OF THREE.

THE ADVANTAGE OF THAT IS

OBVIOUS.

IF IT MAKES IT TO FIVE, IT'S A

HEALTHIER EMBRYO AND THEREFORE

WE KNOW THESE ARE HEALTHY.

THIS IS A STUDY WE WERE ABLE TO

DO.

WALTER REED CENTER, WE DO OUR

IVF.

AND THE PROBLEM OF COURSE WITH

TRIPLETS, EVEN THOUGH WE COUNCIL

PATIENTS, THE PREMATURITY AND

RATE IS EXTREMELY HIGH.

HYPERTENSION IN THE MOTHER AND

GESTATIONAL DIABETES ARE

EXTREMELY HIGH.

THESE PATIENTS, THE UTERUS IS

MARKEDLY DISSENDED SO HEMORRHAGE

IS A PROBLEM.

THEY USUALLY DELIVERED BY

C-SECTION AND THE OFFICIAL

BURDEN OF HAVING TRIPLETS IS

TREMENDOUS TO THE COUPLE

THEMSELVES AND ALSO TO SOCIETY.

THE AVERAGE SINGLETON COSTS

SOCIETY THROUGH THE FIRST MONTH

OF LIFE, ABOUT $10,000.

TWINS ABOUT $50,000 AND EACH OF

THE TRIPLETS COSTS ABOUT

$100,000 UNTIL THEY GET OUT OF

THE HOSPITAL OF BEING SO

PREMATURE AND FOR THE NICU FOR

THAT LENGTH OF TIME AND THEN

TRIPLETS MOSTLY ASSOCIATED WITH

PREMATURITY AND IS RESPIRATORY

DISTRESS, INTRACRANIAL

HEMORRHAGE, NEUROLOGIC DAMAGE

AND OF COURSE THESE CHILDREN

HAVE DISABILITIES.

SO TRIPLETS ARE SOMETHING TO BE

AVOIDED AND THAT'S WHY SINGLE

EMBRYO TRANSFERS, I THINK, IS

THE WAY OF THE FUTURE AND THAT

WOULD BE GENETICS, IT WILL BE

HELPFUL IN A MOMENT YOU'LL SEE.

BUT PATIENTS ON THE OTHER HAND,

IF THIS WAS A STUDY DONE IN

IOWA, WHERE THEY POLLED PATIENTS

AND YOU CAN SEE A FAIR NUMBER

WERE NOT SUPPORTIVE.

SOME WERE SUPPORTIVE BUT ONLY

THE 24.5%, THE REDDISH PIECE OF

PIE IN THIS GRAPH, WERE

SUPPORTIVE AND UNDERWENT EMBRYO

TRANSFER.

IF YOU LOOK ACROSS THE COUNTRY

AND POLL DIFFERENT GROUPS, MOST

GROUPS DON'T DO ANYWHERE 20% AS

FAR AS SINGLE EMBRYO TRANSFERS

AND MOST PEOPLE HAVE THE

PATIENTS SIGN UP FOR IT WHEN

THEY BEGIN THEIR CYCLE.

IF YOU LOOK AT TOTAL OR IF YOU

LET THE PREGNANCY GO OR THE

EMBRYO GO TO FIVE DAYS TO A

BLAST, AND YOU DO TOTAL

CHROMOSOMAL ABNORMALITY

ASSESSMENT, YOU CAN SEE HERE

THAT PATIENTS DO VERY WELL BY

SELECTING EMBRYO THAT IS ARE

CHROMOSOMALLY NORMALLY AS FAR AS

FATALITIES OR ANPLOYEDY IS

CONCERNED.

SO, THE FUTSURTHAT A SINGLE

EMBRYO TRANSFER WILL GET BETTER.

IT WILL BE ABLE TO SEE HOW THIS

EVOLVES FROM AN ETHICAL

STANDPOINT WHETHER PATIENTS WILL

ACCEPT THIS OR NOT AND WHETHER

THIS CONCEPT OF TWINS, BEING AN

INSTANT CURE FOR SERIOUS

PROBLEM, WILL TAKE HOLD AND

THEN -- NOW THE THIRD ETHICAL

ISSUE IS THE OUTCOME OF THESE

INFANTS.

ARE WE DOING QUOTE, BAD THINGS

AS FAR AS THESE INFANTS ARE

CONCERNED?

WELL, THERE WERE TWO STUD THESE

CAME OUT THAT WERE IMPORTANT.

THIS STUDY SHOWED THAT ALL

PATIENTS, ALL IN FERTILITY

PATIENTS, WHETHER THEY HAD ART

OR WHETHER THEY WERE TREATED

WITH SOMETHING ELSE, HAD A RISK

OF LOW GESTATIONAL WEIGHT AT THE

TIME OF DELIVERY AND OTHER

THINGS ASSOCIATED WITH THIS HAVE

ALSO BEEN LOOKED AT.

SO IT'S NOT NECESSARILY THE IVF

THAT IS IMPORTANT.

IT'S THE FACT THAT THESE

PATIENTS ARE INFERTEL TO START

WITH.

AND THEN THERE WAS A STUDY IN

THE NEW ENGLAND JOURNAL SIX

YEARS AGO THAT SHOWED THE

CONGENITAL ANOMALY RATE WAS

DOUBLED IN THIS GROUP THAT HAD

ART AND IXI, WHERE THE SPERM IS

INJECTED DIRECTLY INTO THE EGG

ITSELF.

THEY SAID IT WAS DOUBLED.

OF COURSE IF WENT FROM 4% TO 8%.

SO MOST PATIENTS ALTHOUGH THEY

ARE INFORMED, THEIR DESIRE TO

HAVE A CHILD OUT WEIGHS THE

PERCEPTION OF THAT RISK.

SO, THERE ARE RISKS IN THIS

ASSOCIATED WITH THE PREGNANCY.

THE INFERTILITY ITSELF IS A

PROBLEM.

BUT WHAT WE ARE REALLY

INTERESTED IN IS ART, DOES

GROWING THAT EMBRYO IN A PEE

TREE DISH FOR A PERIOD OF TIME,

IS THAT IMPLYING THAT THIS WILL

BE IMPACT SOME ABNORMALITY FOR

THESE OFFSPRING?

IS THERE SOME EVIDENCE THAT IS

VER ANECDOTAL.

THESE ARE IN PRINTING DEFECTS

WHERE BECK WIDTH AND WEED MAN

SYNDROME AS FAR AS CHROMOSOMAL

CONTENT CONCERNED, AND THIS IS A

CHROMOSOMAL MANIFESTATION THAT

CAN BE PERHAPS CENTERED WITH THE

CULTURE

MEDIA -- ASSOCIATED -- MIGHT BE

SOMEWHAT INCREASED IN THESE

PATIENTS.

UNFORTUNATELY, THESE STUDIES

COME FROM A GROUP OF INTERESTED

PEOPLE AND THEY ARE NOT

LONGITUDINAL STUDIES.

THAT BRINGS US TO A PAREN THAT

IS IN THIS WEEK'S NEW ENGLAND

JOURNAL, JUST ILLUSTRATING HOW

CURRENT THIS IS.

ANOTHER PAPER SHOWING THAT THE

CONGENITAL ANOMALY RATE OR

DEFECT RATE, GOES FROM 4% TO 8%.

SO IT'S PRETTY MUCH

CORROBORATING THE FIGURES AND

PERHAPS THERE IS A STORY HERE.

THIS IS ALWAYS -- THIS IS FROM

AUSTRALIA WHERE THEY HAVE GOOD

ARE REGISTRIES AS WELL.

THE CRITICISM IS ALWAYS THAT

IT'S NOT A GIANT DIFFERENCE.

IT'S HARD TO TELL WHETHER THERE

IS A REAL DIFFERENCE HERE.

BUT NEVERTHELESS, IT'S AN

OBSERVED AND PUBLISHED

DIFFERENCE SO IT'S SOMETHING WE

MUST COUNCIL OUR PATIENTS WITH

AND MUST PAY ATTENTION TO OVER

THE LONG HAUL.

NOW, THE NEXT IS FROZEN EGGS.

FROZEN EGGS ARE EXTREMELY

IMPORTANT.

THEY ALLOW US TO SAVE EGGS IN

PATIENTS THAT ARE BROUGHT ON TO

GO ON TO CANCER THERAPY FOR THAT

MATTER.

THIS IS A CONTROVERSIAL AREA.

SHOULD A WOMAN AT 24 HAVE HER

EGGS FROZEN SO THEN WHEN SHE IS

50 AND WANTS TO HAVE A CHILD,

SHE WILL HAVE THESE 24-YEAR-OLD

EGGS TO TRANSFER?

SO, BECAUSE I KNOW THAT YOU'RE

WELL AWARE OF THE FACT THAT AS A

WOMAN GETS OLDER, HER EGGS AGE

AS WELL.

YOU CAN SEE THE SO-CALLED

BIOLOGICAL CLOCK STARTING TO

TICK IN THIS BLUE AREA AND NOT

ONLY DOES HE THE PREGNANCY RATE

GO DOWN, BUT THE SPONTANEOUS

ABORTION RATE GOES UP AFTER A

WOMAN REACHES THE AGE OF 40.

SO, IS THIS SOMETHING THAT WE

SHOULD PAY ATTENTION TO?

IS THIS IMPORTANT?

IT'S EXPENSIVE.

IS THIS SOMETHING THAT SOCIETY

SHOULD SUPPORT?

INTEREST CONJUNCTION WITH THIS

IS IVF FOR SINGLE WOMEN.

WE HAVE DONE SINGLE WOMEN

INSEMINATIONS FOR MANY YEARS.

IT'S WORKED OUT QUITE WELL, AT

FLEET MY ADVANTAGE POINT.

BUT YET, ALL OF THE THINGS WE

TALKED ABOUT SO FAR, SINGLE

WOMEN INSEMINATION OR IVF FOR

SINGLE SWIM A

HIGHLY-CONTROVERSIAL AREA AND

MOST MEMBERS OF SOCIETY THINK

THIS IS SOMETHING THAT WE

SHOULDN'T DO.

THAT CONCEPTION SHOULD BE PART

OF THE USUAL NUCLEAR FAMILY.

NOW IT'S NOT ALWAYS PERFECT.

THIS IS ROBERT GRAHAM.

HE HAD A SPERM BANK THAT HE

WOULD ONLY ACCEPT THE SPERM FROM

NOBEL PRIZE WINNERS.

AND THE RECIPIENTS OF THE SPERM

HAD TO SHOW THAT THEY WERE

MEMBERS OF MENSA, THAT THEIR IQ

WAS OVER 140.

SO IT WAS KIND OF AUREUS.

OBVIOUSLY IT DIDN'T LAST VERY

LONG.

HE ONLY HAD SPERM FROM TWO NOBEL

PRIZE WINNERS AND HE KIND OF

LOWERED HIS STANDARDS AS FAR AS

WHO WERE THE SPERM DONATES.

SO OBVIOUSLY YOU'LL HEAR THINGS

PEEROTODICALLY PEOPLE BREAK THE

SYSTEM BUT BASICALLY THE SYSTEM

IS PRETTY FOOLPROOF.

THE LATEST, THE OCTO-MOM IN

CALIFORNIA.

SO, THE BOTTOM LINE OF COURSE IS

MONEY.

THIS IS EXTREMELY EXPENSIVE.

IT COSTS ANYWHERE FROM 10-20,000

DOLLARS A CYCLE FOR IVF AND YOU

CAN SEE WHY PATIENTS ARE INTENSE

IN ACHIEVING A PREGNANCY AT THAT

RATE AND OF COURSE, THE GENETIC

TESTING ADDS ANOTHER 3-5000

DOLLARS TO THE ULTIMATE COST.

AND THE QUESTION THEN IS:

[ READING ]

IS THIS SOMETHING THAT SOCIETY

SHOULD PAY FOR?

SHOULD INSURANCE COMPANIES PAY

FOR IT?

IT'S MANDATED IN 13 STATES THAT

PAY VARIOUS AMOUNTS, SOMETIMES

LIMIT THE AMOUNT OF PSYCHEELS

AND SOMETIMES LIMITS THE NUMBER

OF DOLLARS BUT SOME FEEL THIS

SHOULDN'T BE PAID FOR AT ALL

BECAUSE IT IS AN ECONOMIC DRAIN

ON SOCIETY THAT IS NOT

JUSTIFIED.

AND OF COURSE, THE PATIENTS HAVE

A DIFFERENT CONCEPTION.

BAD PUN.

I HAVE TICKETS FOR THE LION KING

IN FIVE YEARS SO I WANT TO

CONCEIVE NEXT MONTH.

SO THEIR CONCEPT A LITTLE BIT

DIFFERENT THAN WHAT OUR CONCEPT

IS.

SO I'LL STOP AND THANK YOU.

[ APPLAUSE ]

QUESTIONS?

[ OFF MIC ]

>> I DON'T KNOW.

SAY THE QUESTION AND I'LL REPEAT

IT.

>> [ OFF MIC ]

>> THE QUESTION IS IF YOU USE

DONOR - SIGHTS IN THESE PATIENTS

DO THEY HAVE THE SAME EFFECT AS

THE RECENT NEW ENGLAND JOURNAL

PAPER THAT SHOWS THE CONGENITAL

ANOMALY RATE WAS DOUBLED.

4-8% IS NOT REALLY DOUBLING.

IT'S DOUBLING THE NUMBER, NOT

THE INCIDENCE.

BUT THE ANSWER IS, NO.

THE ANSWER IS, IT'S CORRECTED IN

THOSE PATIENTS.

DONOR PATIENTS THAT ARE DONORS

DO NOT HAVE A PROBLEM.

SO YES, THE IMPLICATION IS THAT

THESE ARE, THAT IT'S INHERENT IN

THE EGG OR THE MEN ARE OLDER AS

WELL TOO.

SO IT COULD BE FROM THE SPERM.

THERE ARE VERY LITTLE STUDIES

THAT LOOK AT OLDER WOMEN AND

YOUNGER MEN, THAT JUST DOESN'T

SEEM TO HAPPEN ENOUGH FOR US TO

STUDY THAT POPULATION.

SO WE CAN'T ANSWER THAT QUESTION

AT LEAST NOW FROM AN

EPIDEMIOLOGIC STANDPOINT LOOKING

AT PATIENT POPULATIONS.

[ APPLAUSE ]

>> THANK YOU DR. ALAN DECHERNEY

NEXT WE HAVE DOCTOR CLARISA.

A PROFESSOR IN OBSTETRICS AND

GYNECOLOGY AT THE PEN FERTILITY

CARE.

SHE WILL BE DISCUSSING EMERGING

TECHNOLOGY IN ONCOFERTILITY.

>> THANK YOU VERY MUCH FOR

INVITING ME TO BE HERE TODAY.

I APPRECIATE THE OPPORTUNITY TO

PRESENT THIS TOPIC DEAR TO MY

HEART AND REPRESENT THE WORK

THAT I HAVE BEEN DOING.

SO, AS MANY OF YOU KNOW, A

BETTER DIAGNOSTIC METHOD AND

STRATEGIES FOR TREATMENT IN

CANCER PATIENTS HAVE BASICALLY

ALLOWED MORE AND MORE CANCER

PATIENTS TO SURVIVE AND LIVE

PRODUCTIVE LIVES.

IN PARTICULAR, OVER 130,000

REPRODUCTIVE AGED PATIENTS ARE

DIAGNOSED WITH CANCER ANNUALLY

AND APPROXIMATELY 77% OF THOSE

WERE DIAGNOSED DURING THEIR

REPRODUCTIVE YEARS, ACTUALLY

LIVE AT LEAST 5 YEARS.

SHOW HAS CHANGED THE LANDSCAPE A

LITTLE BIT IN ONCOLOGY IN THAT

ONCOLOGISTS ARE NOT ONLY

FOCUSING ON TREATING CANCER AND

CURING CANCER BUT ALSO FOCUSING

ON LONG TERM QUALITY OF LIFE AND

SURVIVORSHIP ISSUES IN THIS

POPULATION.

UNFORTUNATELY, BECAUSE MORE AND

MORE INDIVIDUALS ARE DELAYING

CHILD BEARING, MANY INDIVIDUALS

DIAGNOSED WITH CANCER DURING THE

REPRODUCTIVE YEARS HAVE NOT YET

COMPLETED THEIR FAMILIES.

AND SO, THIS HAS BECOME A MAJOR

QUALITY OF LIFE ISSUE IN THIS

POPULATION.

THANKFULLY, TECHNIQUES HAVE

IMPROVED TO PRESERVE FERTILITY

NEINDIVIDUALS WITH DIAGNOSIS OF

CANCER.

ALLOWING MORE AND MORE CANCER

SURVIVORS TO HAVE BIOLOGICAL

CHILDREN.

AND ACTUALLY, THE ENTHUSIASM AND

GROWTH OF THIS AREA FERTILITY

PRESERVATION IN CANCER PATIENTS

HAS REALLY LED TO AN ENTIRELY

NEW DISCIPLINE CALLED

ONCOFERTILITY, WHICH HAS BEEN

THE MERGING OF THE FIELDS OF

ONCOLOGY AND REPRODUCTIVE

MEDICINE.

SO TODAY I'M GOING TALK A LITTLE

BIT ABOUT EMERGING TECHNOLOGIES

IN FERTILITY PRESERVATION.

AND I'M GOING TO FOCUS ON THE

THEE MAIL JUST IN THE INTEREST

OF TIME.

AND SO YOU HEAR THIS SLIDE JUST

SHOWS A OVERVIEW OF THE

TECHNOLOGIES THAT ARE CURRENTLY

AVAILABLE IN REPRODUCTIVE

MEDICINE.

SO ONE OPTION THAT FEMALES HAVE

IS GOING THROUGH THE PROCESS OF

OVARIAN STIMULATION, AND HAVING

MATURE - SITES RETRIEVED FERT

LIED WITH SPERM FROM A PARTNER

OR SPERM DONOR AND BASICALLYCRYO

PRESERVING EMBRYOS.

ANOTHER OPTION THAT IS MORE

ATTRACTIVE FOR WOMEN WITHOUT A

SEXUAL PARTNER WITH WHOM THEY

WANT TO HAVE A FAMILY IN THE

FUTURE IS GOING THROUGH THE SAME

PROCESS BUTCRYO PRESERVING

MATURE EGGS.

THIS IS ALLOWING WOMEN TO HAVE

REPRODUCTIVE AUTONOMY AND ALLOWS

THEM TO HAVE A BABY WITH

WHOMEVER THEY WANT IN THE

FUTURE.

ANOTHER TECHNIQUE IS TO

BASICALLY COLLECT IMMATURE EGGS

FROM THE OVARIES AND THEN PUT

THEM THROUGH A PROCESS OF

IN-VITRO MATURATION AND THEN

FREEZE EITHER MATURE - SITES OR

FERTILIZE THEM AND THEN FREEZE

EMBRYOS THAT THE TIME AND

THENCRYO PRESERVE OVARIAN

TISSUE.

SO THIS HAS BEEN AROUND FOR A

LONG TIME.

IT'S IMPORTANT TO RECOGNIZE THE

FIRST HUMAN LIVE BIRTH WAS

REPORT FRIDAY EGG FREEZING IN

1986.

JUST TWO YEARS AFTER THE FIRST

LIVE BIRTH FROM EMBRYO FREEZING.

IT'S BEEN VERY, VERY SLOW TO

TAKE OFF.

AND WHY IS THAT?

BASICALLY BECAUSE THE EARLIER

RESULTS WERE DISAPPOINTING WHEN

WE COMPARED THEM TO EMBRYO

FREEZING.

THE SEGA LARGE AS WELL A HIGH

WATER CONTENT SO WHEN YOU FREEZE

WATER, ICE CRYSTALS FORM, THE

CELL EXPANDS, THE CELL RUPTURES

AND THAT VERY DELICATE MYOTICS

SPINDLE CAN BECOME DISRUPTED.

THIS SAY REAL CHALLENGE FOR

OOCYTE PRESERVATION.

THERE HAVE BEEN DRAMATIC

IMPROVEMENTS IN THE TECHNIQUE

OVER THE PAST 5-10 YEARS AND THE

BIGGEST CHANGE HAS REALLY BEEN

THE MOVE FROM USING A

SLOW-FREEZE TECHNIQUE TO

VENTRIFICATION.

VITRIFICATION ESSENTIALLY

INVOLVES PLACING THE - SITES IN

VERY SMALL VOLUMES AND VERY

CONCENTRATEDCRYO PROTECT

OPPORTUNITIES DEHYDRATE THESE

CELLS AND PLUNGE THEM INTO LICK

WIT NITROGEN WHICH PREVENTS ICE

CRYSTAL FORMATION AND ALLOWS THE

OOCYTE TO MAINTAIN ITS

INTEGRITY.

AND MULTIPLE STUDIES HAVE BEEN

PUBLISHED SHOWING THAT SUCCESS

RATES HAVE IMPROVED.

AND MOST OF THESE STUDIES USE

TECHNIQUES LIKE VITRIFICATION.

I THINK THE MOST IMPORTANT STUD

THEY IS RECENTLY COME OUT IN THE

PAST FEW YEARS WAS BY ANNA AND

PUBLISHED IN HUMAN REPRODUCTION

IN 2000 10 AND IF YOU HAVEN'T

SEEN THIS PAPER, SHOULD YOU LOOK

AT IT.

BASICALLY THIS WAS A RANDOMIZED

CONTROL TRIAL OF ALMOST 600

DONOR EGG CYCLES LOOKING AT

USING EITHER VITRIFIED OR FRESH

OOCYTES AND BASICALLY, IN THESE

YOUNG PATIENTS, THEY FOUND THAT

SURVIVAL OF OCYTES WAS EXCELLENT

OVER 90% SURVIVED AND

FERTILIZATION RATES,

IMPLANTATION SEPARATES CLINICAL

PREGNANCY RATES FOR TRANSFER

WERE NO DIFFERENT WHEN THEY USED

VITRIFIED AND WARMED VERSUS

FRESH EGGS.

AND SO THIS IS REALLY A LANDMARK

STUDY.

OVERALL, THE CLINICAL PREGNANCY

RATES PERO SITE WERE ABOUT 4.5%.

WHICH IS SIMILAR TO OTHER

STUDIES IN THE AREA.

THEY HAVE CONSIDEREDO SITECRYO

PRESERVATION EXPERIMENTAL AND

STATES THIS SHOULD ONLY BE

PERFORMED UNDER AN

INVESTIGATIONALAL PROTOCOL UNDER

AN IRB.

AND REALLY THIS IS KIND OF WHAT

WAS MENTIONED EARLIER.

THAT THE BIGGEST AREA OF

CONTROVERSY HAS NOT BEEN IN THE

CANCER POPULATION BUT HAS BEEN

IN THE AREA OF ELECTIVE EGG

FREEZING IN ORDER TO DELAY CHILD

BEARING.

AS MORE DATA COMES OUT, I

SUSPECT THEY WILL RECONSIDER THE

EXPERIMENTAL DESIGNATION.

WORN OF THE MAJOR PROBLEMS WITH

FREEZING MATURE EGGS OR EMBRYOS

FOR THAT MATTER IS THE FACT THAT

WOMEN HAVE TO GO THROUGH THE

PROCESS OF OVARIAN STIMULATION

WHICH FIRST OF ALL IS ONLY

POSSIBLE IN A POST-PUBITAL

FEMALE AND THEN ESSENTIALLY

INVOLVES A PROCESS OF OVARIAN

STIMULATION WITH INJECT TABLES

WHICH REQUIRES CLOSE MONITORING.

THIS HAS THE POTENTIAL TO DELAY

CHANCER THERAPY FOR 2-4 WEEKS

AND CAN BE ASSOCIATED WITH

HIGHEST JEN LEVELS WHICH MAY BE

A CONCERN IN THE SETTING OF

ESTROGEN-SENSITIVE CANCERS LIKE

ENDOMETRIAL OR BREAST CANCER.

AN ALTERNATIVE APPROACH HAS BEEN

SUGGESTED BY SEVERAL

INVESTIGATORS, IVF WHERE YOU

BASICALLY AS OPERATE EGGS FROM

THE OVARIES, USUALLY

TRANSVAGINALY WITH VERY LIMITED

STIMULATION OR NO STIMULATION AT

ALL.

THIS HAS CONSISTENTLY SHOWN TO

HAVE LOWER SUCCESS RATES THAN

WHEN YOU TAKE MATURE OOCYTES AND

FREEZE THEM.

IN ADDITION, DEPENDING ON THE

PROTOCOL USED, IT MAY ONLY SHAVE

OFF A FEW DAYS OR A WEEK FROM

THE STIMULATION PROCESS AND IN

MY EXPERIENCE, IF A PATIENT WITH

CANCER CAN WAIT FIVE DAYS TO

UNDERGO STIMULATION, THEY CAN

WAIT A COUPLE OF WEEKS.

THAT'S PART OF THE REASON WHY

THIS TECHNIQUE HASN'T TAKEN OFF.

ANOTHER STRATEGY THAT GAINED A

LOT OF ATTENTION IS OVARIAN

TISSUE BANKING.

THE BENEFIT OF THIS TECHNIQUE IS

THAT THEORETICALLY, IT

REPRESENTS A WAY TO CRYOPRESERVE

THOUSANDS OFO SITES AT ONE TIME

AND DOESN'T REQUIRE STIMULATION

OF ANY SORT.

SO MINIMAL DELAY IN TREATMENT.

NO PARTNERS ARE NEEDED.

THE TISSUE HAS TO BE REMOVED

SURGICALLY.

A OVARY CAN BE REMOVED AND

ESSENTIALLY AFTER LATER ON AFTER

CANCER HAS BEEN CURED,

TRANSPLANTATION MAY BE POSSIBLE

OR THE TISSUE COULD BE GROWN AND

MATURE OCYTES, THEORETICALLY

COULD BE ISOLATED TO USE IN IN

VITRO MATURATION.

THIS SAY PICTURE OF A PATIENT OF

MINE WHO UNDERWENT OVARIAN

TISSUE CRYOPRESERVATION.

SHE WAS 18 WITH A SARCOMA

PLANNING ON GETTING HIGH DOSE

ALKYLATING AGING THERAPY AND YOU

CAN SEE LAPAROSCOPIC REMOVAL OF

THE CORTICAL TISSUE FROM THE

OVARY.

ALL THE EGGS RESIDE IN THE

CORTEX OR IN THE OUTSIDE OF THE

OVARY.

SO YOU HAVE TO TAKE A PIECE OR

SHAVE OFF THAT CORTICAL TISSUE

IS TYPICALLY THE TECHNIQUE THAT

IS USED.

THE CORE TEXT THEN DIVIDED INTO

SMALL FRAGMENTS PLACED

CRYOPROTECTANT AND FROZEN.

TO TRANSPLANT THE TISSUE, DO YOU

ANOTHER SURGICAL PROCEDURE WHERE

YOU TAKE THE CORTICAL TISSUE OFF

THE OVARY WHICH PRESUMABLY IS OR

HAS NO EGGS THAT THE POINT AFTER

TREATMENT, AND THEN THE

FRAGMENTS OF TISSUE GET PLACED

ON THE OVARY.

YOU PUT AN ABSORBABLE MESH OVER

THE TOP WHICH HOLDS THE PIECES

IN PLACE AND SO FAR, THERE HAVE

BEEN AT LEAST 16 LIVE BIRTHS

REPORTED THROUGH TRANSPLANTATION

OF PREVIOUSLY CRYOPRESERVED

TISSUE.

I HEARD THAT THE NUMBER WAS UP

TO 22 BUT AGAIN THIS IS WHAT I

FOUND IN TERMS OF PUBLISHED

REPORTS.

A VARIETY OF DIFFERENT DIAGNOSIS

ARE REPRESENTED AS YOU CAN SEE,

AND ALL THE INDIVIDUALS WHO

CRYOPRESERVE TISSUE WERE ADULTS

AT THE TIME THE TISSUE WAS

ACQUIRED.

PREGNANCIES HAVE BEEN REPORTED

TO OCCUR WITHOUT ASSISTANCE AND

SOME PREGNANCY OCCURRED AFTER

IVF.

AND THE IMPORTANT THING TO

RECOGNIZE IS IS THERE NO WAY TO

REALLY PROVE THAT THE EGG CAME

FROM THE TRANSPLANTED TISSUE OR

IF IT CAME FROM TISSUE THAT WAS

EXISTING IN THE WOMAN'S OVEREES

ALREADY.

AND IT'S REALLY NOT CLEAR WHAT

THE EFFICIENCY OF THIS PROCESS

IS BECAUSE NOBODY KNOWS HOW MANY

TRANSPLANTS HAVE BEEN PERFORMED.

ONE OF THE BIGGEST YOUR HONOR

ABOUT OVARIAN TISSUE

TRANSPLANTATION IS THE POTENTIAL

TO TRANSPLANT BACK CANCER CELLS

INTO A WOMAN'S BODY AND ONE OF

THE BIGGEST CANCER THAT WE WORRY

ABOUT IS LOU KEIM YEAH, LIQUID

TUMORS WHERE LOU KEIMIC CELLS

COULD BE PRESENT WHEN THE OVARY

IS REMOVED.

THE OTHER GROUP THAT CONCERNS

SUSPATIENTS WITH OVARIAN AND

PATIENTS WITH BRCA MUTATIONS.

UNFORTUNATELY, THIS IS A VERY

COMPLICATED PROCESS AND WHILE IT

HAS BEEN SUCCESSFUL IN A MOUSE

MODEL, IT HAS NOT BEEN

SUCCESSFUL YET IN A PRIMATE OR

HUMAN.

AND A ROAD MAP GRANT FUNDED BITE

NIH WAS IN THIS AREA OF

INVESTIGATION AND SO A LOT OF

WORK HAS BEEN DONE LOOKING AT

HOW OR WHETHER IT IS POSSIBLE

AND MOVING THIS TECHNOLOGY

FORWARD.

BUT STILL MUCH WORK NEEDS TO BE

DONE.

RECENTLY, JOHN TILLY PUBLISHED A

PAPER SUGGESTING THAT THERE ARE

OVARIAN GERM CELLS WITHIN THE

OVARIES AND POTENTIALLY THAT

THESE GERM CELLS MAY ACTUALLY

GROW BETTER IN CULTURE THAN

REGULAR FOLLICLES.

SO IT MIGHT BE POSSIBLE TO

ISOLATE THESE GERM CELLS AND

GROW THEM AND THIS COULD

REPRESENT OR BE A MAJOR

BREAKTHROUGH IN THIS FIELD.

SO, I HAVE DISCUSSED SOME OF THE

FERTILITY PRESERVATION OPTIONS

AVAILABLE TO FEMALES.

HOWEVER, AND WHILE THEY HAVE

IMPROVED, THERE ARE A LOT OF

PROBLEMS WITH THESE TECHNOLOGIES

AT THIS POINT.

THEY GENERALLY DELAY CANCER

THERAPY FROM DAYS TO WEEKS.

SOME OF THEM ARE VERY COSTLY.

ALL OF THEM ESSENTIALLY INVOLVE

SOME KIND OF INVASIVE PROCEDURES

MANY ARE EXPERIMENTAL, AS I

MENTIONED.

THERE IS SIGNIFICANT ETHICAL

QUESTIONS, PARTICULARLY IN

APPLYING THESE PRESERVATION

TECHNIQUES IN CHILDREN.

AND THE REALITY IS THAT MOST OF

THE PATIENTS WHO PURSUE

FERTILITY PRESERVATION ARE

OLDER, WEALTHIER AND HAVE EARLY

STAGE DISEASE.

BUT THE QUESTION THAT I HAVE IS

REALLY, WHO SHOULD WE BE

TARGETING FOR FERTILITY

PRESERVATION?

WHILE STUDIES SUGGEST THAT SOME

CANCER TREATMENTS MAY BE MORE

RISKY THAN OTHERS, OFTEN

TREATMENT, THE REPRODUCTIVE

EFFECTS ARE UNPREDICTABLE.

SO WE NEED FIGURE OUT WHAT

FACTORS DETERMINE THE DEGREE AND

RANGE OF OVARIAN DYSFUNCTION IN

THESE YOUNG PATIENTS.

SO I CAN CONDUCT AN

OBSERVATIONAL LONGITUDINAL STUDY

OF OVARIAN RESERVE IN FEMALES

11-35 YEARS OF AGE WITH A NEW

DIAGNOSIS OF CANCER WHO ARE

PLANNING ON RECEIVING

CHEMOTHERAPY.

THIS IS JUST AN EXAMPLE OF WHAT

HAPPENS TO THESE MEASURES OF

OVARIAN RESERVE OVER THE COURSE

OF TREATMENT.

AND THESE ARE DATA FROM A

17-YEAR-OLD PATIENT WHO WAS

PARTICIPATING IN THE STUDY WITH

HODGKIN'S LYMPHOMA WHO RECEIVED

ABVD.

NOT A VERY TOXIC THERAPY.

YOU CAN SEE THAT DIRECT MEASURES

OF OVARIAN RESERVE LIKE

ANTIMALIGN HORMONE AND ARREST

DIAL, PLUMMET DURING TREATMENT

AND INDIRECT MEASURES LIKE

FOLLICLE STIMULATING HORMONE

INCREASES IN RESPONSE TO THE

FOLLICULAR DESTRUCTION OCCURRING

WITH CANCER THERAPIES.

WE ARE LOOKING FOR RECOVER IN

OVARIAN RESERVE OVER TIME.

WE HAVE FOUND A COUPLE OF TIMES.

ONE THE PRE-TREATMENT OF LEVELS

APPEAR TO BE IMPORTANT

PREDICTORS OF WHAT HAPPENS

DURING AND AFTER THERAPY.

AND PATIENTS WHO START OUT WITH

AMH LEVELS ABOVE TWO, GENERALLY

HAVE A MUCH FASTER RECOVERY IN

OVARIAN RESERVE COMPARED TO ONES

WHO START OUT LESS THAN TWO.

AND WE ALSO FOUND THAT THOSE

PATIENTS WHO RECEIVEDAL CALADING

AGING TREATMENT HAVE A SLOWER

RECOVERY IN THEIR A MH LEVELS

POST TREATMENT COMPARED TO THOSE

WHO DID NOT RECEIVE ALKYLATERS.

SURVIVORS HAVE ABNORMAL MEASURES

OF RESERVE.

SOCIETY LEVELS NEVER MAKE IT

BACK UP TO THEIR PRETREATMENT

BASELINE LEVELS.

WE THEN BECAUSE WE HAVE ALSO

BEEN FOLLOWING SURVIVORS REMOTE

FROM THERAPY TO SEE HOW THEIR

OVARIAN RESERVE LOOKS OVER TIME.

AND SO, WE HAVE COMPARED OVARIAN

RESERVE IN A GROUP OF CANCER

SURVIVORS IN THEIR MID 20s AND

TO SIMILAR AGE CONTROL PATIENTS

AND WE HAVE FOUND THAT OVERALL,

MEASURES OF OVARIAN RESERVE ARE

IMPAIRED IN THIS POPULATION WITH

ELEVATED LEVELS OF FOLLICLE

STIMULATING HORMONE AND LOWER

LEVELS OF ANTIMALIGN HORMONE AND

FOLLICLE COUNTS.

EVEN WHEN WE RESTRICT THE

ANALYSIS TO INDIVIDUALS WHO ARE

HAVING ONLY REGULAR MENSTRUAL

CYCLES, NO CLINICAL EVIDENCE OF

OVARIAN DYSFUNCTION, WE FIND

THESE MEASURES OF RESERVE ARE

STILL IMPAIRED.

OVARIAN RESERVE DOES APPEAR TO

DEPEND ON THE TREATMENT THAT WAS

RECEIVED.

SO INDIVIDUALS WHO WERE EXPOSED

TO PELVIC RADIATION HAD IMPAIRED

MEASURES OF OVARIAN RESERVE AND

REDUCED UTERINE VOLUME OVERALL

COMPARED TO THE CONTROL

POPULATION.

ANDAL CALADING AGENT EXPOSURE

APPEARED TO BE ASSOCIATED WITH A

DEGREES OVARIAN RESERVE.

SO YOU CAN KIND OF SUMMARIZE THE

ACCUMULATIVE ALKYLATING AGENT

EXPOSURE BY COMING UP WITH THIS

SCORE AND FOR EACH UNIT

INCREASINGAL CALATER SCORE, AMH

DROPPED AND FSH LEVELS

INCREASED.

IT APPEARS THAT MEASURES OF

OVARIAN RESERVE REFLECT THE

TOXICITY OF THESE AGENTS AND

ULTIMATELY, THESE MEASURES MAY

BE HELPFUL IN DEVELOPING NOVEL

THERAPEUTICS THAT TO PROVIDE

EQUALLY EFFECTIVE CANCER

THERAPIES THAT MIGHT HAVE LESS

OF A RISK, REPRODUCTIVE RISK

ASSOCIATED WITH THEM.

WHAT ARE THESE MEASURES TELLING

US?

I'M INTERESTED FIND OUT WHETHER

THESE MEASURES REALLY GIVE US

INFORMATION ABOUT WHETHER

INDIVIDUALS WILL BE ABLE TO GET

PREGNANT OR WHETHER THEY WILL

GIVE US A LOOK OR HELP US

PREDICT WHEN THESE PATIENTS WILL

GO THROUGH MENOPAUSE AND WHAT

THEIR REPRODUCTIVE WINDOW WILL

LOOK LIKE.

AND SO, I KNOW THIS IS DIFFICULT

TO SEE, BUT WE HAD THE

OPPORTUNITY TO COMPARE MEASURES

OF OVARIAN RESERVE IN OUR

POPULATION TO THE PATIENTS WHO

ARE AGING NATURALLY CLOSE TO THE

MENOPAUSAL TRANSITION AND WE

HAVE BASICALLY FOUND THAT WHEN

WE DIVIDE CANCER SURVIVORS INTO

TWO GROUPS, A LOW-RISK GROUP A

HIGH-RISK GROUP BASED ON

PREVIOUS TREATMENT, WE FIND AMH

LEVELS IN THAT HIGH-RISK GROUP

IN THESE SURVIVORS WHO ARE STILL

IN THEIR MID 20s, LOOK VERY

SIMILAR TO NATURALLY AGING WOMEN

WITHOUT A HISTORY OF CANS WHO

ARE ARE IN THEIR EARLY 40s.

SO DOES THAT MEAN THAT THESE

20-YEAR-OLDS HAVE THE

REPRODUCTIVE FUNCTION OF A

40-YEAR-OLD?

THAT'S SOMETHING WE ARE LOOKING

AT.

WE HAVE ALSO BEEN FOLLOWING

THESE PATIENTS OVER TIME FOR UP

TO FIVE YEARS IN SOME CASES.

AND WHEN WE LOOK AT SURVIVORS

AND CONTROLS WHO HAVE HAD

INTERCOURSE DURING THE COURSE OF

THE STUDY AND ARE AT RISK FOR

PREGNANCY, WE FIND PREGNANCY

RATES AMONG THE TWO GROUPS ARE

NOT DIFFERENT.

THEN WHEN WE LOOK AT RESERVE

AMONG THE SURVIVORS IT IS

IMPAIRED IN THE SURVIVORS WHO

CONCEDE CEIVED COMPARED TO THE

CONTROLS WHO CONCEIVED.

SOME OF THE SURVIVORS ACTUALLY

NEEDED HELP THROUGH FERTILITY

TREATMENTS TO CONCEIVE.

SO WHILE THIS INFORMATION IS

PRELIMINARY, I THINK IT DOES

SUGGEST THAT OVARIAN RESERVE

MEASURES MAY ACTUALLY REFLECT

QUANTITY RATHER THAN EQUALITY IN

THIS YOUNG COHORT OF SURVIVORS.

ULTIMATELY, I THINK MEASURES OF

OVARIAN RESERVE MAY BE MORE HELP

ENVELOPE PREDICTING THE TIME TO

MENOPAUSE IN THESE SURVIVORS

GIVING US A LOOK AT THEIR

REPRODUCTIVE WINDOW.

WE HAVE SHOWN THAT AMS A GOOD

PREDICTOR OF TIME TO MENOPAUSE

IN LATE REPRODUCTIVE AGED WOMEN.

AND CLEARLY, WE NEED A LOT MORE

DATA IN ORDER TO ANSWER SOME OF

THESE QUESTIONS.

AND IN ORDER TO DO THAT, IT

WOULD BE IDEAL TO COME UP WITH A

LESS INVASIVE TEST OF OVARIAN

RESERVE WHERE WOMEN DID NOT HAVE

TO COME TO THE OFFICE AND GET

TRANSVAGINAL ULTRASOUNDS AND

BLOOD LEVELS IN ORDER TO ASSESS

THEIR OVARIAN RESERVE.

SO I HAVE BEEN WORKING WITH TOM

AT NORTHWESTERN UNIVERSITY, AND

WE HAVE VALIDATED A AMH ASSAY IN

A FINGER PRICK BLOT SPOT THAT

PATIENTS CAN DO AT HOME AND WE

HAVE FOUND THAT LEVELS OF AMH IN

THE SERUM AND LEVELS IN THE

DRIED BLOOD SPOT CORRELATE QUITE

WELL IN THIS COHORT OF 106

REPREDICTIVE-AGED WOMEN.

SO THING IS AN EXCITING AREA OF

INVESTIGATION.

SO, IN THE FUTURE, I THINK

ULTIMATELY WE NEED TO DEVELOP

LESSGON ADDIC TOXIC THERAPIES

FOR CANCER AND HOPEFULLY THESE

MEASURES WILL BE HELP NATURAL

ALLOWING US TO DO THAT.

WE NEED TO COME UP WITH BETTER

ONESES FOR FERTILITY

PRESERVATION MORE EFFECTIVE AND

SAFE AND COST LES MONEY.

AND ULTIMATELY, I THINK

UNDERSTANDING THE REPRODUCTIVE

WINDOW AND FERTILITY RATES AFTER

CANCER OPTIONED BEFORE THERAPY

AND COUNSELING THEM ABOUT

FERTILITY AFTER TREATMENT IS

FINISHED AND ALSO ABOUT THE USE

OF CONTRACEPTION, WHICH IS

CRITICAL IN THIS POPULATION.

SO I'D LIKE TO ACKNOWLEDGE MY

FUNDING AND THANK YOU VERY MUCH.

[ APPLAUSE ]

ANY QUESTIONS?

>> I HAVE ONE AGAIN.

>> OKAY.

>> SO, DID YOU LOOK AT THE

PEOPLE WHO GOT PREGNANT AND

CORRELATE WHETHER THEIR AMH

LEVELS WERE HIGHER PRETREATMENT

OR IF THEY JUST HAD A LARGER

REBOUND POST TREATMENT?

THERE WAS ANY CORRELATION

BETWEEN THOSE WHO ACHIEVED

PREGNANCY AND BOTH THE

REBOUNDING AFTER TREATMENT OF

THE AMH --

>> SO, UNFORTUNATELY, BECAUSE

GRANTS ARE TYPICALLY ONLY FIVE

YEARS, WE HAVE TWO COHORT

STUDIES GOING.

ONE FOR NEW DIAGNOSIS PATIENTS,

AND ONE FOR SURVIVORS BECAUSE

REALLY YOU WHAT NEED TO DO IS

TAKE THESE WOMEN BEFORE

TREATMENT AND FOLLOW THEM FOR 20

YEARS.

BUT THAT'S REALLY NOT SOMETHING

THAT WE CAN DO.

SO WE HAVE SHORT-TERM DATA ON

THE ACUTE CHANGES.

THOSE PEOPLE WE DON'T WANT THEM

TO GET PREGNANT BECAUSE THEY ARE

OUT FROM THEIR CANCER TREATMENT.

THEN WE HAVE SURVIVORS WITH MORE

STABLE MEASURES WE ARE LOOKING

AT CHANGES OVER TIME AND

FIGURING OUT WHO IS GETTING

PREGNANT AND WHO IS NOT.

BUT WE DON'T HAVE THOSE PEOPLE'S

PRETREATMENT VALUES IS THE

PROBLEM.

THANK YOU VERY MUCH.

[ APPLAUSE ]

>> THANK YOU.

THAT WAS OUTSTANDING.

OKAY, SO, I'M GOING TO INTRODUCE

DR. ALICIA ARMSTRONG.

SHE IS THE ASSOCIATE FELLOWSHIP

DIRECTOR OF REPRODUCTIVE

ENDOCRINOLOGY AND INFERTILITIY

AND REPRODUCTIVE BIOLOGY

MEDICINE BRANCH AT THE NATIONAL

INSTITUTES OF CHILD HEALTH AND

HUMAN DEVELOPMENT.

SHE IS GOING TO GIVE A TALK

ENTITLED, HEALTH DISPARITIES AND

FEES EMERGING TECHNOLOGY IN

REPRODUCTIVE MEDICINE.

DR. ARMSTRONG.

[ APPLAUSE ]

>> THANK YOU FOR THE OPPORTUNITY

TO SPEAK TO YOU TODAY.

THE COMMENTS ARE GOING TO BE

ABOUT ART, IVF IN TERMS OF

REPRODUCTIVE TECHNOLOGIES.

I'M GOING TO START BY TALKING

ABOUT THE EVIDENCE FOR DISPARITY

IN HEALTH CARE IN GENERAL, TALK

ABOUT SOME POSSIBLE ETIOLOGIES,

LOOK AT THE RESEARCH IN

DISPARITIES IN TERMS OF ACCESS,

EXAMINE HEALTH LEDGEIVATION AND

STRATEGIES FOR INCREASING

ACCESS.

SO THERE IS EVIDENCE FOR

DISPARITY BY GENDER, RACE AND

SOCIOECONOMIC STATUS AND A LOT

OF THAT INFORMATION COMES FROM

THE INSTITUTE OF MEDICINE

STUDIES, WHICH I'M GOING TALK

ABOUT A LITTLE LATER IN THIS

PRESENTATION.

WHETHER IT'S GENDER, RACE OR

ECONOMICS.

THE DISADVANTAGE RECEIVE

DISPARATE TREATMENT AND ONE OF

THE TRAGIC EXAMPLES OF THAT IS

DURING KATRINA.

AND 30% OF THE NEW ORLEANS

RESIDENTS WERE LIVING IN POVERTY

AND TENS OF THOUSANDS HAD NO

TRANSPORTATION.

SO THEIR ACCESS TO HEALTH CARE

AND OTHER RESOURCES WERE NEEDED

DURING THAT TRAGEDY WAS IMPACTED

BY SOCIOECONOMIC STATUS.

SO THE INSTITUTE OF MEDICINE

REPORT PROVIDES A LOT OF

INFORMATION ABOUT PROBLEMS WITH

ACCESS.

AND THEY HAVE A WIDE RANGE OF

DISEASE AREAS IN TERMS OF

CLINICAL SERVICES, THERE WERE A

RANGE OF CLINICAL SETTINGS IN

TERMS OF URBAN AREAS, INPATIENT

TREATMENT AND OUTPATIENT

TREATMENT AND DISPARENTS WERE

ASSOCIATED WITH HIGHER

MORTALITIES AMONG MINORITIES.

SO WHAT IS THE EVIDENCE THAT

PHYSICIAN BIASES AND STEREOTYPES

MAY INFLUENCE THE CLINICAL

ENCOUNTER?

WELL, DR.S IN 2000

REPORT -- DOCTORS ARE MORE LIKE

3 ASCRIBE NEGATIVE RACIALLY

STEREOTYPES THEIR MINORITY

PATIENTS REGARDLESS OF

EDUCATION, INCOME AND

PERSONALITY CHARACTERISTICS.

IN AN OLDIER STUDY, THE

PHYSICIANS WERE MORE LIKELY TO

MAKE NEGATIVE COMMENTS WHEN

DISCUSSING MINORITY PATIENT

CASES.

SOME OF THE BARRIERS THEY FOUND

IN THE INSTITUTE OF MEDICINE

REPORT WERE THAT THERE WERE

CULTURAL LINGUISTIC BARRIERS AND

LACK EVER STABLE RELATIONSHIP

WITH PRIMARY CARE PROVIDERS WAS

A FACTOR AND THAT MANY MEMBERS

OF GROUPS THAT ARE ECONOMICALLY

DISADVANTAGED USE ACUTE-CARE

FACILITIES LIKE THE EMERGENCY

ROOM AS THEIR PRIMARY CARE

PROVIDERS.

THERE WERE FINANCIAL INCENTIVES

TO LIMIT SERVICES AND I'LL TALK

ABOUT THAT WHEN I TALK ABOUT

INSURANCE COVERAGE FOR IVF, THAT

MAY DISPROPORTIONATELY AND

NEGATIVELY EFFECT MINORITIES.

IT WAS ALSO FRAGMENTATION OF

HEALTH CARE FINANCING AND

DELIVERY.

NOW MOVING ON TO TALKS

SPECIFICALLY ABOUT THE

DISPARITIES AND INFERTILITY,

THIS IS A 2000 PUBLICATION WHICH

LOOKED AT AFRICAN AMERICAN WOMEN

AND CAUCASIAN WOMEN.

AND THERE WERE DISPARITIES BOTH

IN THE CAUSES OF INFERTILITY AND

DISPARITIES IN THE OUTCOMES.

AND AFRICAN AMERICAN PATIENTS AS

A GROUP HAD A MORE THAN 2 1/2

FOLD DECREASE ODDS OF PREGNANCY.

MOST OF THE LARGER STUDIES IN

THE LITERATURE COME FROM THE

SOCIETY OF ASSISTED REPRODUCTIVE

TECHNOLOGY DATABASE.

AND THEY HAVE VERY LARGE

COHORTS.

ALL OF THOSE STUDIES HAVE

DEMONSTRATED A SIGNIFICANT

REDUCTION ANYWHERE FROM 25-38%,

IN AFRICAN AMERICAN LIVE BIRTH

RATES AFTER IVF WHEN COMPARED TO

CAUCASIAN COHORTS.

WE BECAME INTERESTED IN THE

QUESTION OF, IF YOU INCREASE

FEES CARE, DOES THE UTILIZATION

OF IN INFERTILITY TREATMENT

SPECIFICALLY IVF, DIFFER, AND

DOT OUTCOMES CHANGE?

AND BECAUSE AS DR. ALAN

DECHERNEY MENTIONED, OUR IVF

SERVICES ARE ACROSS THE STREET

AT WALTER REED, AND BECAUSE

PATIENTS ARE DOD BENEFICIARIES,

THE CYCLE COSTS ARE LESS THAN IN

THE PRIVATE SECTOR BECAUSE THEY

ARE NOT PAYING PHYSICIAN FEES

AND OTHER ASPECTS OF THE CYCLE

COSTS.

SO THIS WAS A RETROSPECTIVE

STUDY LOOKING AT CLOSE TO 3000

CYCLES OVER A FIVE-YEAR PERIOD

AND PATIENTS, ONE OF THE THINGS

THAT IS ALSO UNIQUE ABOUT OUR

SYSTEM IS PATIENTS SELF IDENTIFY

THEIR RACIAL AND ETHNIC GROUPS.

AND WE HAVE A HIGH RATE OF

HAVING THAT INFORMATION WHEREAS

IN MANY OF THE SART TRIALS, AS

MUCH AS THIRDY% OF THE TIMES,

THEY DIDN'T HAVE IDENTIFICATION

OF RACE OR ETHNICITY.

 -- 30% OF THE

TIME -- MINORITIES ARE

OVERREPRESENTED IN THE MILITARY

POPULATION COMPARED TO THE U.S.

POPULATION N AFRICAN AMERICAN

WOMEN, WE FOUND THAT WHEN ACCESS

TO IVF WAS INCREASED,

UTILIZATION INCREASED.

BUT THEIR OUTCOMES WERE WORSE.

WE SAW DIFFERENT RESULTS IN THE

HISPANIC POPULATION IN THAT

THERE WAS NO INCREASE IN

UTILIZATION AND THEY HAD SIMILAR

OUTCOMES TO CAUCASIAN WOMEN.

SO IF YOU LOOK HERE AT THE FIRST

COLUMN, THIS IS THE RACIAL

DEMOGRAPHICS FOR THE USA

OVERALL, THIS IS FOR IVF

POPULATIONS AND YOU CAN SEE

HERE, FOR INSTANCE, HISPANIC

WOMEN, ALTHOUGH THEY ARE ABOUT

13% OF THE U.S. POPULATION, LESS

THAN 6% OF WOMEN UNDERGOING IVF.

AND IN THE DEPARTMENT OF DEFENSE

POPULATION, THEY ARE 9% BUT EVEN

IN ENHANCED ACCESS TO CARE

ENVIRONMENT THEY WERE ONLY 4% OF

THE IVF PATIENTS WHEREAS

AFRICAN-AMERICAN WOMEN INCREASED

TO 17% OF THE IVF PATIENTS WHEN

ACCESS TO CARE WAS INCREASED.

WHEN WE LOOKED AT THE OUTCOMES,

THIS IS CONSISTENT WITH THE SART

DATA IN THAT AMONG AFRICAN

AMERICAN WOMEN, THE SPONTANEOUS

ABORTION RATE WAS HIGHER AND

ALSO THE LIVE BIRTHRATE WAS

HIGHER AND ALTHOUGH IT DIDN'T

ACHIEVE STATISTICAL SIGNIFICANTS

IN OUR GROUP AND THE SART

STUDIES, WHICH HAD A LARGER

COHORT, IT DID OR WAS

STATISTICALLY SIGNIFICANT.

AND IN A REPORT FROM REUTERS,

BASED ON THIS ARTICLE, THEY

CONCLUDED THAT AFRICAN AMERICAN

WOMEN ARE MORE LIKELY TO USE

ASSISTED REPRODUCTIVE

TECHNOLOGIES ONCE YOU DECREASE

THE ECONOMIC BARRIERS, HOWEVER,

THEIR OUTCOMES WERE STILL WORSE.

IN OUR PARTICULAR STUDY, WE HAD

INFORMATION ABOUT FIBROIDS AND

WE FOUND AN ASSOCIATION WITH

THAT AND WE THINK AT LEAST SOME

OF THE DIFFERENCE IN PREGNANCY

OUTCOMES CAN BE ATTRIBUTED TO

FIBROIDS.

SO I'D LIKE TO MOVE ON TO

TALKING A LITTLE MORE ABOUT

ETIOLOGIES IN TERMS OF THINGS

THAT ARE BARRIERS TO ACCESSING

REPRODUCTIVE TECHNOLOGIES,

SPECIFICALLY IVF.

AND THE BIGGEST FACTOR IS

SOCIOECONOMIC STATUS IN TERMS OF

INCOME.

THIS IS VERY EXPENSIVE THERAPY.

AND ALSO EDUCATION.

THERE ARE ALSO CULTURAL ISSUES

IN TERMS OF GENERAL MISTRUST OF

THE HEALTH CARE SYSTEM AND

RELIGIOUS BELIEFS ETHICAL ISSUE

THAT IS MAY PREVENT PATIENTS

FROM SEEKING REPRODUCTIVE

TECHNOLOGIES.

IN TERMS OF FEES CARE, RACE, IN

SOME INSTANCES, MAY BE A

SURROGATE FOR SOCIOECONOMIC

STATUS IN THAT SOME ETHNIC AND

RACIAL GROUPS MAY BE

OVERREPRESENTED IN ECONOMICALLY

DISADVANTAGED POPULATIONS.

IN THIS PARTICULAR STUDY WHICH

WAS LOOKING AT BREAST CANCER, IN

AFRICAN AMERICAN WOMEN, WHEN

THEY RECEIVED THE SAME TREATMENT

AND HAVE THE SAME PROGNOSTIC

VARIABLES, THE OUTCOMES WERE

SIMILAR.

SO IN SOME STUD HIGHS CONTROL

FOR SOCIOECONOMIC STATUS, THE

DIFFERENCE IN RACIAL OUTCOMES

GOES AWAY.

IN OTHER STUDIES, THEY FOUND

THAT DESPITE SOCIOECONOMIC

STATUS, THAT CERTAIN ETHNIC

GROUPS OFTEN PRESENT WITH MORE

ADVANCED DISEASE AND HAVE WORST

OUTCOMES WHEN YOU CONTROL FOR

SOCIOECONOMIC STATUS.

MOVING ON TO TALK SPECIFICALLY

ABOUT ACCESS TO CARE IN TERMS OF

INFERTILITY TREATMENT.

IN THE NATIONAL SURVEY OF FAMILY

GROWTH, ACCESS TO CARE WAS

IMPACTED BY INCOME AND

SPECIFICALLY WHERE INCOME WAS

LESS THAN 150% OF POVERTY LEVEL,

THOSE WOMEN WERE LIKELY

TO -- LESS LIKELY TO ACCESS

INFERTILITY SERVICES.

IF THEY LESS THAN A HIGH SCHOOL

EDUCATION, THEY WERE LESS LIKELY

TO ACCESS SERVICES.

CULTURAL BELIEFS CAN ALSO PLAY A

ROLE, PARTICULARLY IN TERMS OF

IVF SERVICES.

AND THIS WAS A STUDY WHERE THEY

LOOKED AT ETHNICITY NEEDS AND

DECISION-MAKING.

THEY LOOKED AT DECISION-MAKING

AMONG DIFFERENT ETHNIC GROUPS

AND LOOKED AT THINGS,

HYSTERECTOMY, THEY LOOKED AT

BELIEFS REGARDING PHYSIOLOGIC

FUNCTIONS SUCH AS MENSTRUATION,

USE OF CONTRACEPTION, NUMBER OF

DIFFERENT THERAPIES.

IN EVER CAN AMERICAN AND

NON-HISPANIC WOMEN, EXPRESSED

MOST DISTRUST OF PHYSICIANS, ALL

THE GROUPS THOUGHT THAT DOCTORS

DON'T TAKE ENOUGH TIME TO

EXPLAIN ISSUES AND ALL THE

GROUPS INDICATED THAT THEY WOULD

SEEK ADDITIONAL OPINIONS IF THEY

COULD AFFORD IT.

ALL THE ATTITUDES TOWARDS

PHYSICIANS WERE NEGATIVE IN THE

VARIOUS DIFFERENT GROUPS EXCEPT

AMONG HISPANIC WOMEN.

THERE WAS AN ASSOCIATION TOWARDS

MENSTRUATION AND THEIR

WILLINGNESS TO USE CONTRACEPTIVE

METHODS AND FAMILY SIZE.

SO WOMEN THAT DID NOT HAVE A

NEGATIVE ATTITUDE TOWARDS

MENSTRUATION WERE MORE LIKELY TO

USE MODERN METHODS AND THEY WERE

MORE LIKE 3 HAVE SMALLER FAMILY

CISE.

I THINK THERE HAS POTENTIAL TO

HAVE VERY SIGNIFICANT IMPACT IN

TERMS OF ACCESS TO REPRODUCTIVE

TECHNOLOGIES.

SO CURRENTLY, WITH THE MINIMUM

BENEFITS PACKAGE HAS NOT BEEN

ESTABLISHED UNDER THE PATIENT

PROTECTION AND AFFORDABLE HEALTH

CARE ACT.

IF THERE IS A FEDERAL MANDATE

WHICH INCLUDES ART, IVF, THIS

WOULD MARKEDLY INCREASE IVF

ACCESS.

IN RECENT LITERATURE THAT IS

LOOKED AT THE IMPACT OF

INSURANCE ON ACCESSING

REPRODUCTIVE TECHNOLOGIES, THREE

TYPES OF INSURANCE WERE

IDENTIFIED.

UNIVERSAL INSURANCE COVERS ART.

RESTRICTED WHERE SOME SPECIFIC

TYPES OF INSURERS MUST COVER

ART.

AND OTHERS, WHERE INFERTILITY

TREATMENT BUT NOT SPECIFICALLY

IVF COVERED.

AND THEY FOUND IN STATES THAT

HAD MANDATED HEALTH CARE, THAT

THERE ARE MANY MORE WOMEN WHO

WILL UTILIZE IVF SERVICES.

WHAT ARE SOME OF THE STRATEGIES

THAT CAN BE ADOPTED TO INCREASE

THE ACCESS OF ALL WOMEN TO

REPRODUCTIVE TECHNOLOGIES?

WELL, ONE OF THE BIGGEST ISSUES

IS INSURANCE STATUS.

SO AGAIN, ECONOMICS.

SO, IN THE IOM REPORT, IT WAS

THE MOST IMPORTANT PREDICTOR OF

THE QUALITY OF HEALTH CARE

ACROSS ALL RACIAL AND ETHNIC

GROUPS.

SO THIS IS WHERE A LOT OF THE

EMPHASIS WILL NEED TO BE IN

TERMS OF MAKING THIS PARTICULAR

TECHNOLOGY MORE ACCESSIBLE.

ONE OF THE THINGS THAT CAN BE

DONE TO REACH GROUPS THAT HAVE

ACCESS TO IVF AND OTHER

REPRODUCTIVE TECHNOLOGIES IN LOW

NUMBERS, IS TO HAVE

MULTICULTURAL OUTREACH PROGRAMS

AND SCREENING PROGRAMS WHICH

WILL EDUCATE PATIENTS ABOUT THIS

OPPORTUNITY AND MULTILINGUAL

OUTREACH PROGRAMS, WHICH WILL

ALSO INCREASE THE ACCESS OF

WOMEN WHO ARE NOT NATIVE ENGLISH

SPEAKERS.

ALSO COLLABORATIONS WITH

COMMUNITY AND LAY HEALTH

EDUCATORS, CHURCHES, ADVANCED

PRACTICE NURSES AND PELVIC

HEALTH PROGRAMS.

THE NIH GUIDELINES HAVE BEEN

ADOPTED TO INCLUDE MINORITIES

AND SOME POPULATIONS THAT

HAVEN'T BEEN PREVIOUSLY

REPRESENTED IN CLINICAL STUDIES.

SO STUDIES OF THIS NATURE IN

TERMS OF ACCESS THAT ARE SPONSE

OARED BY THE NIH, HOPEFULLY WILL

INCLUDE REPRESENTATION FROM MANY

DIVERSE POPULATIONS SO THAT

THESE FINDINGS CAN BE APPLICABLE

TO THE GENERAL POPULATION.

SO I WANTED TO ALSO MENTION HERE

ONE OF THE STRATEGIES THAT WE

HAVE IMPLEMENTED IN TERMS OF THE

AMERICAN SOCIETY FOR

REPRODUCTIVE MEDICINE, WHICH IS

AN INTERNATIONAL GROUP FOCUSED

ON REPRODUCTIVE HEALTH.

WE HAVE AN ASRM SPECIAL INTEREST

GROUP IN HEALTH DISPARITIES.

THE PURPOSE OF THIS GROUP IS TO

IDENTIFY DISPARITIES OF ACCESS

AND OUTCOMES AND TO IDENTIFY

STRATEGIES TO ADDRESS THESE

DISPARITIES.

THERE ARE ALSO RECOMMENDATIONS

FROM THE INSTITUTE OF MEDICINE

REPORT WHICH MAKES SUGGESTIONS

IN TERMS OF THINGS THAT CAN BE

DONE IN TERMS OF POLICY CHANGES

THAT WILL INCREASE ACCESS TO

HEALTH CARE WHICH OBVIOUSLY CAN

BE APPLIED TO INCREASING ACCESS

TO REPRODUCTIVE TECHNOLOGIES.

AND SOME OF THOSE THINGS INCLUDE

IMPROVING THE RESOURCES TO THE

DHHS, INCREASING THE NUMBER OF

REPRESENTATION OF HEALTH CARE

PROVIDERS AND ALSO EXPANSION OF

HEALTH CARE COVERAGE S TWO OF

THE STRATEGIES CURRENTLY THAT

DIRECTLY ADDRESS ACCESS TO

REPRODUCTIVE TECHNOLOGIES, ART,

ARE PREDICTING THE EXISTING

STATEMENT STATE MANDATES AND

SUPPORTING ADDITIONAL MANDATES.

FURTHER RESEARCH IS NEEDED

FURTHER LOOKING AT ETHICAL

ISSUES, CULTURAL ISSUES AND

OTHER BARRIERS ELIMINATING

DISPARITIES IN ACCESS AND THERE

IS RECENTLY BEEN A NEW

INSTITUTE, WHICH WILL FOCUS ON

SOME OF THE PUBLIC HEALTH

ASPECTS OF REACHING

UNDERREPRESENTED POPULATION

GROUPS, WHICH PERHAPS CAN

SUPPORT SOME OF THE RESEARCH IN

THIS AREA.

AND SO, THAT ENDS MY COMMENTS.

AND I'M HAPPY TO TAKE ANY

QUESTIONS.

[ APPLAUSE ]

[ OFF MIC ]

>> ONE OF THE THINGS THAT

HAPPENED IN RESIDENCY EDUCATION

IS NOW CULTURAL COMPETENCE IS

ONE OF THE CORE COMPETENCIES.

SO, IT HAS TO BE TAUGHT.

SO ALL RESIDENTS IN TRAINING GET

SOME EXPOSE TOWER THAT.

IT'S ALSO SORT OF INTERESTING

WITH CERTAIN POPULATION THAT IS

ARE LARGELY, FOR INSTANCE,

CATHOLIC, THAT YOU WOULD THINK

RELIGION EFFECTS, AS YOU SAW

HERE, WE HAD HISPANIC WOMEN,

EVEN WHEN YOU DECREASED THE

CYCLE COST, DIDN'T ACCESS ART

SERVICES AT THE SAME RATE.

AND ACTUALLY, IF LOOK AT HOW

CATHOLIC WOMEN ACCESS CONTRA

ACCEPTION AND THERE ARE SOME

RELIGIOUS AND ETHICAL OBJECTIONS

TO THAT -- CONTRACEPTION -- IT'S

COMPARABLE TO NON-CATHOLICS.

SO IT'S MORE COMPLEX THAN A

SPECIFIC RELIGION OR CULTURE BUT

YOU'RE POINT IS WELL TAKEN IN

THAT WE DO HAVE A OBLIGATION TO

EDUCATE HEALTH CARE PROVIDERS

ABOUT ISSUES OF CULTURAL

COMPETENCE AND THAT IS SOMETHING

THAT IS A REQUIREMENT IN

RESIDENCY TRAINING CURRENTLY.

THANK YOU.

>> THANK YOU.

OUR NEXT SPEAKER IS GUSTAVO

DONCEL, SCIENTIFIC DIRECTOR OF

CONRAD, A U.S. PROGRAM FOCUSED

ON DEVELOPING NEW TECHNOLOGIES

IN HIV, AIDS, PREVENTION AND

CONTRACEPTION AND HE IS ALSO A

PROFESSOR OF OBSTETRICS AND

GYNECOLOGY AT EASTERN VIRGINIA

MEDICAL SCHOOL.

>> GOOD AFTERNOON.

AND THANK YOU TAMARA AND THE

ORGANIZING COMMITTEE FOR HAVING

INVITED ME TO GIVE THIS TALK.

IT IS A VERY IMPORTANT TOP NICK

GENERAL AND A VERY TIMELY ONE IN

THIS WEEK, IN PARTICULAR.

I GUESS WE ARE GOING TO SWITCH

FROM TRYING TO ENHANCE FERTILITY

AND GO OR PREVENT PROBLEMS

RELATED TO FERTILITY, TO THE IN

THE LAST TWO TALKS, TRYING TO

PREVENT PREGNANCY.

OR ENABLE WOMEN TO PLAN THEIR

FAMILIES.

SO I'LL PROVIDE AN OVERVIEW ON

EFFORTS THAT ARE UNDERWAY TRYING

TO DEVELOP MULTIPURPOSE

PREVENTION TECHNOLOGIES THAT

ENABLE WOMEN TO PLAN THEIR

FAMILIES AND AT THE SAME TIME,

BE PROTECTED AGAINST SEXUALLY

TRANSMITTED INFECTIONS.

NOW TWO WORDS ABOUT THE PROGRAM.

I WORK AND I HAVE BEEN WORKING

WITH FOR THE LAST 22 YEARS, WE

ARE ESTABLISHED AS A COOPERATIVE

AGREEMENT BETWEEN THE U.S.

AGENCY FOR INTERNATIONAL

DEVELOPMENT AND THE EASTERN

VIRGINIA MEDICAL SCHOOL.

OUR SUBMISSION TO IMPROVE GLOBAL

REPRODUCTIVE HEALTH BY

PREVENTING TRANSMISSION OF HIV

AIDS, OTHER SEXUALLY TRANSMITTED

INFECTIONS AND UNINTENDED

PREGNANCIES.

WE DO SO BY FOCUSING ON THE

DEVELOPMENT OF NEW, SAFE AND

EFFECTIVE MICROBICIDES, THAT ARE

TOPICAL AGENTS THAT PREVENT OR

DESIGNED TO PREVENT STI,

SEXUALLY TRANSMITTED INFECTIONS.

CONT SEPTEMBER AND I WAS

MULTIPURPOSE PREVENTION

TECHNOLOGIES.

OUR FUNDING COMES OUR MAIN

FUNDING COMES FROM USAID, THE

BMGF, NIH IN PARTICULAR, NIAID

AND NICHD, ANDING OTHER

ORGANIZATIONS SUCH AS CDC AND

SMALLER FOUNDATIONS.

THE MAIN FEATURES OF OUR

PROGRAMS ARE FOCUSED ON

DEVELOPMENT AND R&D.

WE HAVE EXTENSIVE NETWORK OF

COLLABORATORS AND PROVEN RECORD

ON MOVING COMPOUNDS FROM BENCH

TO CLINIC AND CONTRACEPTIVE ON

STI OR HIV PREVENTION.

MULTIPURPOSE PREVENTION

TECHNOLOGIES IN SEXUAL AND

REPRODUCTIVE HEALTH, THERE ARE

PRODUCTS THAT ARE ASSIGNED TO

ADDRESS MORE THAN ONE INDICATION

IN REPRODUCTIVE HEALTH AND THOSE

ARE FAMILY PLANNING, EXAMPLES OF

THEM ARE, FAMILY PLANNING,

PREVENTION OF STs AND

IMPROVEMENT OF MATERNALO-FETAL

HEALTH.

THE RATIONAL IS THAT BY

COMBINING INDICATIONS IN ONE

PRODUCT, WE WILL INCREASE USE,

CONVENIENCE, ACCEPTANCE AND

EFFECTIVENESS OF THE PRODUCT AND

WHILE DECREASING THEIR COST,

DEMAND ON RESOURCES AND

ENVIRONMENTAL IMPACT.

THE INDICATIONS EXAMPLES OF

INDICATIONS OF THESE MPTs,

MULTIPURPOSE PREVENTION

TECHNOLOGIES ARE, CONCEPTION AND

HIV, PREVENTION OF HIV AND OTHER

STIs SUCH AS HERPES AND PAP

LEEM VIRUS.

PREVENTION OF TWO OR

MORE -- PAPILLOMA -- TWO OR MORE

STIs, HSV AND HPV, AND

CONTRACEPTION AND OR STI WITH

PREVENTION OF IMPROVEMENT OF

MATERNAL FETAL HEALTH.

THE STRATEGIES FOR PRODUCT

DEVELOPMENT IN THESE AREAS ARE

TO RESPOND TO THESE INDICATIONS

ARE THE COMBINATION OF TWO OR

MORE DRUGS WITH DIFFERENT

MECHANISMS OF ACTION.

ONE DRUG WITH DUAL ACTIVITY.

THE COMBINATION OF DRUGS AND

DEVICES, DEVICES ALONE, AND LAST

BUT NOT LEAST, THE USE OF

BIOLOGICS LIKE VACCINES AND

ANTIBIOTICS AND PROBIOTICS.

THE DOSAGE IN THE ADMINISTRATION

FORMS ARE ESSENTIALLY SYSTEMIC

AND TOPICAL.

SYSTEMIC ARE ORAL FORMS LIKE

PILLS, INJECTABLES AND

IMPLANTABLES AND TOPICALS, AND

WE HAVE BEEN CONCENTRATING

MOSTLY ON TOPICAL APPLICATION,

LOCAL APPLICATION.

THE FORMS ARE GELS, CREAMS,

TABLETS, FILMS AND RINGS.

TODAY, I'M GOING CONCENTRATE ON

CONTRACEPTION AND HIV BECAUSE OF

TIME CONSTRAINTS.

AND WHY DID WE CHOOSE

CONTRACEPTION AND HIV

PREVENTION?

THESE STATISTICS I THINK SPEAK

BY THEMSELVES AND THIS IS

REGARDING THE NUMBER OF PEOPLE

LEAVING -- LIVING WITH HIV/AIDS

CLONALLY AND WE

HAVE -- GLOBALLY -- WE HAVE

NUMBERS FROM THE U.N. AIDS

RECORD IN 200010, 34 MILLION

PEOPLE INFECTED.

2.7 MILLION NEW INFECTIONS IN

THAT YEAR AND ABOUT TWO MILLION

DEATHS ASSOCIATED THROUGH HIV

INFECTION AND AIDS.

THE HARDEST-HIT AREA BY FAR IS

SUB SAHARAN AFRICA WITH 23

MILLION PEOPLE INFECTED.

THE EPIDEMIC IS FEMININEIDES AND

THERE ARE AREAS, 60% OF THE NEW

INFECTIONS ARE IN WOMEN AND

THERE ARE AREAS OF THIS

PERCENTAGE UP TO 70% OF THE NEW

INFECTIONS WE HAVE FIGURES HERE

IF LATINAMERICAN SOUTHEAST ASIA.

SEXUAL TRANSMISSION ACCOUNTS FOR

60-90% OF THE NEW INFECTIONS

GLOBALLY.

THE U.S., THIS IS CLEARLY MUCH

LESS.

GLOBALLY, THIS IS THE, WHAT WE

NEED TO CONCENTRATE OUR EFFORTS

ON.

CONCERNING GLOBAL POPULATION

NOW, THE SITUATION HAS GOTTEN

BETTER.

WE ARE 7 BILLION PEOPLE HEADING

TOWARDS 9-10 BILLION.

AND ALTHOUGH THE BIRTHRATE HAS

DECREASED OVERALL, THE

POPULATION IS GROWING FASTEST

WHERE THE NEEDS IN THE REGIONS

THAT HAVE THE GREATEST NEEDS.

AND FOR INSTANCE THE 49

LEAST-DEVELOPED COUNTRIES WILL

TRIPLE IN SIZE BY 2050.

SEW GERMANY AND FRANCE WILL NOT

HAVE THAT ISSUE AND PERHAPS THE

U.S. WILL IS NOT THAT ISSUE

EITHER, MANY COUNTRIES WILL

SUFFER FROM OVERPOPULATION.

IN MANY OF THESE COUNTRIES,

WHERE POPULATION IS NOT PROPERLY

UNDER CONTROL, THE AIDS PANDEMIC

IS ALSO A MAJOR HEALTH ISSUE.

AND THE AIDS PANDEMIC IS CLEARLY

INTRICATELY INTERTWINED WITH

OVERALL POPULATION, POVERTY,

MALL NUTRITION AND GENDER AND

INEQUALITY.

THAT LEADS TO LACK OF

HIGHLY-EFFECTIVE CONTRACEPTION

BY ACCESS OR BY CHOICE.

IT LEADS TO HALF OF THE

PREGNANCIES WORLDWIDE

UNINTENDED.

IT LEADS TO ABOUT 40 MILLION

ABORTIONS AND THE CONSEQUENCES

OF UNSAFE ABORTIONS IN THOUSANDS

OF MATERNAL DEATHS AND MILLIONS

OF WOMEN WITH DISABILITIES.

THIS IS VERY CLEAR THAT A

WOMAN -- THAT IS EXPOSED TO

UNWANTED PREGNANCY IS DOING SO

BECAUSE OF UNPROTECTED

INTERCOURSE AND UNPROTECTED

INTERCOURSE ALSO LEADS TO

STIs, IN PARTICULAR, HIV.

SO THERE IS NO WOMAN WANTS TO BE

INFECTED.

AND THE SAME WOMEN AT TIMES,

DON'T WANT TO HAVE OR BECOME

PREGNANT.

AND THEREFORE, THERE IS A NICHE

FOR THE DEVELOPMENT OF

MULTIPURPOSE PREVENTION

TECHNOLOGIES THAT WILL ADDRESS

BOTH INDICATIONS.

THERE ARE SOME EXISTING MPTs

LIKE THE MALE FEMALE CONDOMS,

BUT FOR DIFFERENT REASONS,

MOSTLY BEHAVIORAL, THE UPTAKE OF

THESE TECHNOLOGIES IS NOT GREAT.

SO UNDERDEVELOPMENT.

WE HAVE BEEN WORKING ON DRUGS,

DEVICES AND COMBINATIONS.

THE MAIN PRODUCT DEVELOPMENT AND

STRATEGIES RELY ON PHYSICAL

BARRIERS LIKE CONDOMS, DIAPHRAMS

AND CERVICAL CAPS AND THE NEW

DEVELOPMENTS IN THESE AREAS.

TWO OR MORE DRUGS WITH DIFFERENT

TARGETS AND MECHANISMS OF

ACTION.

THIS SEEMS TO BE THE MOST

ADVANCED INNOVATION AT THIS

MOMENT.

AND THE EXAMPLES HERE ARE THE

COMBINATION OF HIGHLY-POTENT

CONTRACEPTIVE AND

ANTIRETROVIRALS THAT ARE ON THE

MARKET TO TREAT PEOPLE INFECTED

WITH HIV AND IT'S IN CLINICAL

TESTING AS A PREVENTIVE FOR HIV.

SO THE COMBINATION OF THESE IN A

RING, THE COMBINATION OF THESE

IN MID 150, ANOTHER ARV IN

DEVELOPMENT.

THE COMBINATION OF THE P RING IN

A CONTRACEPTIVE AND THE

COMBINATION OF MIV150 AND ZINC

ASITATE REPRESENTS A VERY GOOD

PIPELINE IN THIS AREA AND THE

DEVELOPERS ARE CONRAD AND THE

POPULATION COUNCIL AND THE IPM,

INTERNATIONAL PARTNERSHIPS FOR

MICROBICIDES.

ONE DRUG WITH DUAL ACTIVITY,

THIS IS AN AREA THAT HAD A LOT

OF ACTIVITY IN THE PAST.

THE FIRST DUAL PRODUCTION

TECHNOLOGY THAT WAS TESTED FOR

PREVENTION OF HIV WAS NONOXYNOEL

9.

IT'S A SPERMICIDE ON THE MARKET.

AT THAT POINT, IT IS IN-VITRO,

IT SHOWED VERY GOOD ACTIVITY

AGAINST HIV AND OTHER VIRUSES

AND STI PATHOGENS.

HOWEVER, WHEN IT WAS TESTED,

CLINICALLY, IN A PHASE III

TRIAL, FAILED TO

PREDICT -- PROTECT WOMEN AND THE

WORST CASE SCENARIO, WOMEN WHO

USE IT VERY FREQUENTLY HAD

ENHANCED OR INCREASE IN RISK OF

HIV ACQUISITION.

I'M GOING REFOREIT FOR A

MOMENT -- REFER TO IT LATER AND

EXPLAIN WHY THIS MIGHT HAVE

HAPPENED.

THERE ARE A SLEW OF OTHER DRUGS

WITH DUAL ACTIVITY AND THE

LATEST ONE, 10 OVVEER IS ONE

THAT SURPRISED US ALL BY SHOWING

NOT ONLY HIV OR HIV ACTIVITY AND

ANTIHSV ACTIVITY AND PROTECTED

WOMEN FROM ACQUIRING HERPES.

DRUG DEVICE COMBINATIONS IS

ANOTHER POSSIBILITY IN THIS

PRODUCT DEVELOPMENT INNOVATIVE

PATHWAY FOR MULTIPURPOSE

PREVENTION TECHNOLOGIES.

WE ARE WORKING ON A COMBINATION

OF SILCS, A DIAPHRAM WITH THE

GEL AND FINALLY, BIOLOGICS, THE

USE OF VACCINES AND ANTIBODY IN

ENGINEERED BACTERIA.

THERE IS NEW RECENTLY FUNDED

PROGRAM, PROJECTS BY NIH IN

THESE AREAS.

SO, IT'S VERY IMPORTANT WHEN YOU

DEVELOP THIS PRODUCT THAT YOU

BEAR IN MIND THAT HIV PENETRATES

THROUGH WOMEN THROUGH THE

CERVICAL VAGINAL MUCOSA.

THAT'S A VAGINAL MUCOSA

REPRESENTS A FORM IDABLE BARRIER

FOR THE VIRUS.

IF WE DISRUPT THAT BARRIER, WE

ARE LIKELY TO DIMINISH THE

DEFENSIVE, NATURAL AND INNATE

DEFENSIVE CAPACITY OF THE

MUCOSA.

ASSOCIATED VIRUSES DO PENETRATE

THROUGH THE EP THILLIUM, THE

VAGINAL EP THILLIUM, BUT THEY DO

SO WITH GREAT DIFFICULTY.

HOWEVER, IF YOU HAD BREACH LIKE

REPRESENTED IN THIS CARTOON,

THEN THE ACCESS OF THOSE

VARYIENCE TO THE TARGET SELLS IN

THE EPITHELIUM IS MUCH EASIER.

THE VIRUS USES A SUB-CLINICAL

INFLAMMATORY REACTION IN ORDER

TO EXPAND THE INITIAL FOUNDER

POPULATION IN AND DISSEMINATE

SYSTEMICALLY.

IF YOU INDUCE INFLAMMATORY

REACTION FOR THE VIRUS, THEN YOU

ARE ENHANCING ITS POSSIBILITY TO

DISSEMINATE.

THIS IS SOME DATA FROM OUR LAB.

MICROARRAY ANALYSIS, GENE

EXPRESSION ANALYSIS OF HUMAN

CERVICAL VAGINAL CELLS THAT HAVE

BEEN INCUBATED WITH A SERIES OF

CLASSICAL PRO-INFLAMMATORY

COMPOUNDS, LIGANDS AND TNF ALPHA

AND POWERFUL CYTOKINES.

THIS IS THE COMPARISON WITH THE

NONINFLAMMATORY CONTROLS.

SO THERE IS NO MODULATION OF THE

PRO-INFLAMMATORY GENES BY THE

CONTROLS.

GREAT UP REGULATION OF THESE

GENES BY THE COMPASS AND IT IS

ACTUALLY INDISTINGUISHABLE FROM

THE PRO-INFLAMMATORY COMPOUNDS.

AS I SAID, CREATING INFLAMMATORY

RESPONSE AND PROBABLY WHAT LED

TO THE INCREASED TRANSMISSION.

HERE IS DATA TAKING COX 2, I

BELIEVE FAMILIAR TO ALL OF YOU,

IT'S A KEY INFLAMMATORY ENZYME

AND IT PRODUCES PROSPECT

LANDINGS, SYNTHETIC PATHWAY

ACROSS THE LANDINGS:; AND THIS
IS

20 TIMES UP REGULATED BY

MICROARRAY AND QPCR AND A NICE

PICTURE OF CELLS LIGHTENING UP

WHEN THEY ARE INCUBATED WITH

THIS.

THIS IS SOMETHING THAT TOLD US

AND CERTAINLY INDICATED TO THE

FIELD THAT SAFETY OF ANYTHING

THAT YOU ARE DEVELOPING, BE THAT

A CONTRACEPTIVE ALONE, VAGINAL

PRODUCT TO TREAT MANY CAUSES, OR

A PREVENTIVE HIV, YOU MUST HAVE

IN MIND THE DAMAGE THAT YOU

MIGHT DO TO THE MUCOSA.

ESPECIALLY IF THAT PRODUCT IS TO

BE USED IN AREAS WHERE THERE IS

HIGH INCIDENCE AND PREVALENCE OF

HIV.

TWO NEW INNOVATIVE TECHNOLOGIES

THAT ADDRESS THE ISSUE OF

CONTRACEPTION AND HIV ARE

DEPICTED HERE.

AND LET'S TALK ABOUT THE RING.

THE ISSUE IS THAT AS I SAID, THE

RING THAWER DEVELOPING CONTAIN

10 OVVEER AND -- WHY CHOOSE 10

OVVEER?

IT'S THE ONLY MICROBICIDE WITH A

PROOF OF CONCEPT IN ANIMALS AND

HUMANS.

AT THE VADA IS BEING RECK

BLENDED FOR APPROVAL BY AN

ADVISORY COMMITTEE TO THE FDA TO

BE USED AS A PREVENTIVE DRUG IN

HIV AND IN CERTAIN POPULATIONS

OF PATIENTS.

NOW LNG IS AN EXCELLENT

CONTRACEPTIVE WITH EXCELLENT

TRACK RECORD OF SAFETY AND

EFFICACY.

THE RING IS A CONCEPT GOING

DEVELOPED AND THE FEES BUILT IS

BEING DEVELOPED IN THE 80s BY

THE W.H.O. WITH A CLINICAL

TRIAL.

WHY THE RING?

THE RING IS A MAJOR ADVANTAGE BY

PROVIDING CONTROLLED RELEASE

OVER AN EXTENDED PERIOD WITH A

SINGLE APPLICATION.

MANY PROBLEMS RELATED TO PILL

TAKING IN THIS AREA IN THE AREA

OF PREVENTATIVE HIV OR

PREVENTION FOR STIs AND HIV IS

COMPLIANCE.

AND PROBABLY COMPLIANCE IN THE

FUTURE WITH USE AND REGIMEN.

SO, WE -- A RING WILL PROVIDE A

CONTROLLED RELEASE, SINGLE

APPLICATION.

IT WILL PROVIDE BETTER

PROTECTION, LOWER DRUG EXPOSURE,

HIGHER SAFETY MARGINS AND

DISCRETE USE AND LOWER COST.

SO, JUST TO POINT AGAIN ABOUT

TENOFIVIRE FOR THOSE WHO ARE NOT

FAMILIAR.

YOU SEEN THE GEL, AND THEY

STUDIED THEM 50% PROTECTION AT

12 MONTHS AND THEN AT 30 MONTHS,

A 39% OF PROTECTION WITH INTENT

TO TREAT.

IF YOU DO SUBGROUP ANALYSIS, THE

PROTECTION INCREASES UP TO 54%.

NOW, VERY INTERESTINGLY,

TENOFOVIR, WHICH IS AGAIN AN

ANTIRETROVIRAL, INTERFERES WITH

THE HIV LIFE CYCLE ALSO

PREVENTED ANY CHANCE OF PRIMARY

INFECTION AND THIS TECHNOLOGY

WITH DUAL PROTECTION IN ITSELF.

THE RING THEN CONTAINS -- HERE

THE CHALLENGE TO MATERIALIZE

THIS INNOVATION WAS TO PUT

TOGETHER TENOFOVIR, A

HYDROPHILIC MOLECULE, WITH LNG,

A STARED MOLECULE AND BOTH DON'T

WANT TO GO TOGETHER.

AND THE RINGS THAT ARE AVAILABLE

ON THE MARKET LIKE NUVA RING,

THEY CONTAIN POLYMERS THAT DO

NOT RELEASE TENOFOVIR.

SO WE HAVE TO DEAL WITH THE

ISSUES OF PUT THESE TWO TOGETHER

IN TWO SEGMENTS THAT WOULD

ENABLE US TO CONTROL RELEASE OF

BOTH DRUGS.

AND WE SUCCEEDED TO DO SO IN

THIS AS IN-VITRO RELEASE OF

TENOFOVIR AND LNG

CONSUBSTANTIALLY FOR 90 DAYS.

ANOTHER POINT OF OUR TARGET

PROFILE.

IT HAD TO BE NOT LESS THAN THREE

MONTHS.

AND HERE THERE ARE TWO DOSES OF

LNG BECAUSE WE WANTED TO CHECK

BOTH.

HERE IS DATA IN ANIMAL MODELS

THAT INDICATE WE ACHIEVED THE

TARGET CONCENTRATIONS IN

TISSUES.

FOR BOTH.

THE IMPORTANT POINT IS THAT THIS

IS VERY GOOD STEADY STATE

RELEASE AND ACCUMULATION WHICH

HAS BEEN PROVEN IN HUMANS TO BE

PROTECTIVE OF HIV INFECTION.

SOWER FINALIZING SAFETY PKPN

ANIMAL MODELS AND WITH THE

CLINICAL PART, WITH THE FIRST IN

CLASS STUDY WITH PKPD AND THOSE

FINDING SLATED FOR NEXT YEAR IN

THE GINGOF NEXT YEAR.

SO IN SUMMARY, THERE IS URGENT

NEED TO DEVELOP MPTs, TO

PROVIDE WOMEN WITH SAFE,

EFFECTIVE AND AFFORDABLE

PRODUCTS OF ADDRESSING MULTIPLE

NEEDS SUCH AS FAMILY PLANNING

AND PREVENTION OF STIs IN

PARTICULAR HIV.

PRODUCT DEVELOPMENT STRATEGIES

TO IMPROVED PHYSICAL BARRIERS,

DRUG-DEVICE COMBINATIONS,

DRUG-DRUG COMBINATIONS AND

DUAL-ACTIVITY COMPOUNDS AND BY

LOGICS.

CONRAD LEAD MPTs ARE THE

TENOFOVIR AND LNG RELEASING RING

AND NEW DIAPHRAM, THE SILCS

DIAPHRAM IS A CARRIER FOR

TENOFOVIR YELL THEY HAVEN'T HAD

TIME TO DISCUSS THIS INNOVATION

 --

GEL.

THE DEVELOPMENT OF THESE

TECHNOLOGIES IS NOT WITHOUT

CHALLENGES.

IT REQUIRES BROADER MORE AMPLE

TESTING SINCE YOU ARE ADDRESSING

TWO INDICATIONS.

IT REQUIRES CLEARLY WIDER

EXPERTISE IN THE PRODUCT

DEVELOPING GROUP.

IT FACES UNCHARTED REGULATORY

PATHWAYS.

AND FOR THE TIME BEING IT FACES

THE PROBLEM OF BEING

UNDERFUNDED.

THE IMPACT OF PROVIDING WOMEN

WITH MULTIINDICATION PRODUCTS,

IS THE SYNERGISTIC REDUCTION OF

SEXUALLY TRANSMITTED INFECTIONS

AND UNPLANNED PREGNANCIES IN

WOMEN FROM LOW-INCOME COUNTRIES

WHERE THESE PROBLEMS HAVE THE

HIGHEST INCIDENCE.

I WANT TO FINISH WITH

ACKNOWLEDGING THE COLLABORATORS

IN THE PROGRAM.

OUTSIDE OF THE PROGRAM, THE

FUNDING AGENCIES, AND THANK YOU

VERY MUCH AND I'M OPEN FOR

QUESTIONS.

[ APPLAUSE ]

YES, CLARISA?

[ OFF MIC ]

>> THAT IS A VERY GOOD QUESTION.

SHE IS ASKING ABOUT PROGESTIN

ONLY CONTRACEPTIVES HAULS A

ISSUE OF BLEEDING,

INTRAMENSTRUAL BLEEDING.

AND SO, I DON'T HAVE THE TIME TO

EXPLAIN ALL THE DETAILS BUT WE

ARE USING VERY LOW DOSES,

MICRODOSES, 20 MICOGRAMS PER DAY

TYPE OF RELEASE.

AND WE ALSO TESTING, PUSHING THE

ENVELOPE AND GOING DOWN IN THAT

DOSE WITH THE ASSUMPTION THAT WE

WILL BE ABLE TO PREVENT

FERTILIZATION WHILE LOCAL

EFFECTS WITHOUT INHIBITING

OVULATION GIVEN THE PLASMA

LEVELS ARE VERY LOW.

SO IT'S A BOLD, RISKY

PROPOSITION BUT THAT'S WHY WE

HAVE THE PHASE I STUDY.

THANK YOU.

[ APPLAUSE ]

>> THANK YOU DR. GUSTAVO DONCEL.

OUR LAST SPEAKER AND TOPIC FOR

TODAY IS DR. REGINE SITRUK-WARE,

REPRODUCTIVE ENDOCRINOLOGIST AND

A DISTINGUISHED SCIENTIST AT THE

POPULATION COUNCIL.

AND HER TALK IS ENTITLED, NEW

TECHNOLOGIES IN CONTRACEPTION

RESEARCH.

[ APPLAUSE ]

>> THANK YOU VERY MUCH FOR YOUR

INVITATION.

I'M VERY HONORED.

ALSO THIS OTHER ASPECT OF

REPRODUCTION AND CONTROL OF

FERTILITY, AS GUSTAVO HAS DONE

BEFORE ME, WHAT IS IMPORTANT TO

NOTE IS THAT IN SOME SOCIETIES

WHERE PEOPLE ARE PREPARED TO PAY

A LARGE PRICE TO GET A CHILD,

AND I CAN UNDERSTAND THAT VERY

WELL, MANY SOCIETIES ARE NOT

PREPARED TO ENDORSE THE COST OF

CONTRACEPTION THAT MAY PREVENT

LIVES.

AND WOMEN ARE DYING OF REPEATED

PREGNANCY OR OF UNSAFE ABORTION

IN MANY COUNTRIES.

SO I THINK IT'S URGENT AND

IMPORTANT TO FIND METHODS THAT

WILL ADDRESS THESE UNMET NEEDS.

HAVE YOU SEEN I MODIFIED

SLIGHTLY THE TITLE OF MY TALK ON

EMERGING SCIENCE AND TECHNOLOGY

FOR CONTRACEPTION, TO MATCH THE

EMERGING SCIENCE IN FERTILITY

SO, FOR THE FUTURE, AS I SAID,

WE WANT TO WORK ON DIFFERENT

BARRIERS AND SEVERAL

ORGANIZATIONS ARE WORKING ALSO

IN THIS AREAS TO MEET THE UNMET

NEEDS.

AND THE TARGETS WHICH HAVE BEEN

IDENTIFIED IS PEOPLE AND THEIR

NEEDS.

THEY WANT TO HAVE BIRTH SPACING

AND WE NEED BETTER BIRTH SPACING

THAT ONLY RELYING ON LACTATION

AS IN SOME COUNTRIES.

WE NEED MID-ACTING METHODS, YOU

KNOW THAT LONG-ACTING METHODS

ARE VERY EFFECTIVE AND SAFE.

BUT THE NEEDS TO HELP PROVIDERS

TO INSERT AN IUD OR IMPLANT, AND

THE METHODS THAT ARE NOW BEING

DEVELOPED, SEMI-LONG ACTING,

VAGINAL RINGS AND I COME BACK ON

THAT, OR INJECTABLES AND NEED

HAVE USER CONTROL METHODDED THAT

DO NOT REQUIRE THE TRAINING OF

HEALTH PROVIDER AND IN FACT,

IMPROVING ACCESS.

SO, WHAT WE KNOW ALSO IS THAT

MANY WOMEN PREFER TO HAVE METHOD

THAT I USED PRIVATELY THAT NO

ONE WOULD KNOW IN THEIR

ENVIRONMENT THEY ARE USING AND

WE HAVE STARTED WORKING ON

TRANSDERMAL GELS AND IN THE

INITIAL STUDIES THE WOMEN WERE

VERY PLEASED WITH THIS CONCEPT

AS NO ONE WOULD NOTICE THAT THEY

HAD USED CONTRACEPTION.

WE DEFINITELY NEED TO ADDRESS

THE NEED OF ADOLESCENCE AND THE

YOUNGER POPULATION.

AND IT'S VERY DIFFICULT TO FIND

METHOD THAT FOR WHICH THERE WILL

BE COMPLIANT AND SOME OF THIS

YOUNG POPULATION HAVE OCCASIONAL

INTERCOURSE ONLIY AND WE WERE

TRYING TO DEVELOP CONTRACEPTION

ON DEMAND.

THE DUAL PRO SECTION A MAJOR

NEED AND DR. DORSAL ADDRESS

TODAY VERY WELL.

I WILL ADDRESS THE METHODS FOR

MEN AS WE CAN FIND HERE A GENDER

INIQUITY AS MEN ARE NOT REALLY

TAKEN CARE OF IN THE FIELD OF

CONTRACEPTION RESEARCH.

SO, IN ORDER TO HAVE BETTER

SEMILONG-ACTING METHOD AND USER

CONTROL METHOD AS I SAID, THE

CONTRACEPTIVE RINGS ARE A NEW

FIELD OF RESEARCH AND THEY ARE

MANY RINGS WHICH ARE BEING

DEVELOPED BY DIFFERENT

ORGANIZATIONS AND ALSO RINGS ARE

USED FOR DELIVERING OTHER

TREATMENT THAT CONTRACEPTIVES IN

WOMEN BECAUSE THE ADVANTAGE OF

THIS METHOD OF DELIVERY IS THAT

THE VAGINA ABSORBS VERY WELL

SMALL MOLECULES AND YOU CAN GIVE

MUCH LOWER DOSES BECAUSE OF

INCREASED AVAILABILITY FROM THIS

ADMINISTRATION IN THE VAGINA.

SO, WE HAVE DEVELOPED A ONE-YEAR

VAGINAL RING.

SO YOU KNOW THE NEW RING ON THE

MARKET IS ONE MONTH AND THE

WOMAN NEEDS A PRESCRIPTION TO

RENEW EVERY MONTH HER

CONTRACEPTION.

AND THE ADVANTAGE OF HAVING A

RING THAT IS EFFECTIVE FOR

THIRTEEN CYCLES AND THE WOMEN

WOULDN'T NEED TO GET REPEATED

PRESCRIPTIONS AND SHE WILL HAVE

HER METHOD FOR ONE YEAR, HAS

BEEN SEEN AS A BIG ADVANTAGE.

AND THIS PROGRAM HAS BEEN

SUPPORTED BY USAID AND BY NICHD

AND THE WORLD HEALTH

ORGANIZATION WHO SUPPORTED THE

LARGE PHASE III TRIALS AFTER A

LONG DEVELOPMENT OF THE NESTA

RONE, WHICH WAS THE NEW CHEMICAL

ENTITY IN THIS RING COMBINED

WITH THIN ESTRADIOL.

AND THIS RING IS USED ON 13

CYCLES BUT ON THE SAME BASIS AS

NUVA RING, AS 3 WEEKS ON

FOLLOWED BY ONE WEEK OFF AND

DURING THAT WEEK OFF, WE USUALLY

HAVE A WITHDRAWAL BLEED AND THE

WOMEN HAD VERY SATISFACTORY

BLEEDING PATTERN, VERY

PREDICTABLE REGULAR BLEEDING

PATTERN.

AND ANOTHER RING WHICH IS ON THE

MARKET IN LATIN AMERICA AND HAS

BEEN DEVELOPED BY THE COUNCIL IS

NOW BEING STUDIED IN OTHER

COUNTRIES WHERE LACTATION IS

POPULAR.

THE REASON IS THAT PROGESTERONE,

THE NATURAL HORMONE, WOULD NOT

BE SUFFICIENT TO BLOCK OVULATION

IN WOMEN WHO ARE NOT BREAST

FEEDING BUT WHEN WOMEN ARE

BREAST FEEDING, THEY ARE STILL

AT RISK OF HAVING A PREGNANCY

BECAUSE OF THE FOLLICLE GROWING

AFTER A FEW MONTHS AND WHEN THEY

ARE NOT BREAST FEEDING MORE THAN

SIX TIMES A DAY, PROGESTERONE

WOULD ACT ON CONTINUOUS RELEASE

FROM THE VAGINAL RING AND THIS

HAS BEEN SHOWN TO BE VERY

EFFECTIVE, AS EFFECTIVE AS AN

IDUD.

AND THE FACT IT IS UZI

CONTROLLED CAN BE USED FOR THREE

MONTHS, RENEWED FOR FOUR TIMES

FOR WOMEN WHO WILL BE BREAST

FEEDING FOR ONE YEAR.

IT IS ALSO VERY IMPORTANT IN

COUNTRIES WHERE BREAST FEEDING

IS SO NECESSARY FOR THE INFANT

AND IS NECESSARY FOR THE HEALTH

OF THE WOMAN TO SPACE BIRTH AND

OF THE INFANT TO GET BREAST

FEEDING.

WE HAVE ALSO CONSIDERED THIS

MODE OF DELIVERY FOR

PROGESTERONE RECEPTOR MODULATORS

AND COMPOUNDS LIKE CDB2914 WHICH

IS NOW NAMED -- ASITATE.

SHOWN TO BE VERY WELL DELIVERED

BY VAGINAL RING AND CAN BE

CONTRACEPTION WITHOUT ESTROGEN

AND THEREFORE, HAVE LES RISK

WITHOUT ESTRADIOL.

AND THIS MODE OF CONTRA

ACCEPTION WOULD INDUCE AMEN ARIA

WHICH IS ANOTHER ASPECT WOMEN

MAY PREFER.

I WOULDN'T OF COURSE SPEAK ABOUT

THE DUAL-PROTECTION RING AS

GUSTAVO HAS DONE IT VERY WELL.

WE HAVE ALSO IDENTIFIED THE NEED

FOR ADDING HEALTH BENEFIT, OTHER

MEDICAL BENEFITS TO THE

CONTRACEPTIVE ACTION.

AND THIS IS IN ORDER TO MOTIVATE

PEOPLE TO USE CONTRACEPTION.

AND THE DIFFERENT MOLECULES THAT

HAVE BEEN STUDIED SO FAR WHERE

WE IDENTIFIED HUGE POTENTIAL

BENEFIT, IS THESE PROGESTERONE

RECEPTOR MODULATOR, WHICH NOT

ONLY HAS AN ANTIOV LATORY EFFECT

BUT HAS NO STIM LA TOIREY EFFECT

ON BREAST CELLS AS PROGESTERONE

DOES.

SO, IT'S A POTENTIAL ADVANTAGE

FOR LONG-TERM USE OF

CONTRACEPTION IF THE BREAST

WOULD BE PROTECTED.

BUT OF COURSE, THIS NEEDS LARGE

STUDY TO BE DEMONSTRATED BUT

THERE IS POTENTIAL BENEFIT THAT

IS WORTH RESEARCHING.

WE ALSO HAVE FOUND THAT NESTER

OWN, VERY CLOSE TO PROGESTERONE,

IS EVEN MORE ACTIVE THAN

PROGESTERONE TO STIMULATE MILE

IN REPAIR IN IN-VITRO AND

IN-VIVO MODELS AND FOR WOMEN WHO

HAVE MS AND NEED A CONTRACEPTION

IN THE POSTPARTUM PHASE, THAT

WOULD BE A REAL MEDICAL

ADVANTAGE.

WE FOUND ALSO IN COLLABORATION

WITH ROBERTA IN L.A., THAT IT

STIMULATES NEURO-REGENERATION.

IT STIMULATES THE STEM CELLS OF

THE HYPOCAMPAL CELLS AND

THEREFORE IT WOULD PROTECT THE

BRAIN AGAINST DEGENERATION AND

FOR LONG-TERM CONTRACEPTION,

IT'S VERY IMPORTANT TO STUDY

THEIR EFFECT ON THE NEURONAL

CELLS.

IMMENSED METHODS TO BE USED

PRIVATELY AND THE GEL.

THE PATCH IS NOT REALLY

INVISIBLE.

IT IS REALLY VISIBLE.

THE PATCH HAS BEEN USED BUT WAS

VERY POPULAR BECAUSE IT'S A

SEVEN-DAY PATCH.

YOU HAVE TO THINK OF YOUR

CONTRACEPTION ONLY ONCE A WEEK

AND THERE ARE THREE OTHER

TRANSDERMAL SYSTEMS IN

DEVELOPMENT.

STILL WITH ESTRADIOL BUT WITH

OTHER PROGESTINS, SUCH AS LNG,

WHICH ARE SLIGHTLY MOREAND

ROWGENIC THAN THE ORTHOEFRA

PATCH AND COUNTER ACT THE

ESTRADIOL ACTION.

ANOTHER PRODUCT WHICH IS ALSO

DEVELOPED AT NICHD IS THE LEVEL

OF LNG ONLY LOW DOSE PATCH AS

THE PROGESTIN-OWN ONLY PILLS.

HERE YOU HAVE A PATCH SO YOU

DON'T NEED TO THINK EVERY DAY.

YOU HAVE A STEADY STATE AND NO

PROBLEM OF COMPLIANCE AND BETTER

EFFICACY.

THE PROGRAM WE HAVE DEVELOPED

USING THE PROGESTIN NESTER OWN I

JUST DESCRIBED BUT COMBINED WITH

ESTRADIOL AND NOTETHINAL DIAL.

THE FACT IT IS A ACTIVE ANTIAF

LATORY AMOUNT, MEANS YOU DON'T

NEED TO COMPLIMENT THE REACTION.

AND ESTRODIAL IS JUST A BACKUP

THERAPY AND SAFER THAN THIS.

AND IT WAS CLEARLY SHOWN IN

POSTMENOPAUSAL WOMEN THAT USING

TRANSDERMAL ESTRADIOL RATHER

THAN ORAL ESTRADIOL LEADS TO A

VERY MUCH DECREASED RISK.

SO THE CONCEPT WE DEVELOPED WAS

TO USE TRANSDERMAL APPLICATION

AND HERE YOU SEE THE SMALL

DEVICE THAT THAT WILL DELIVER A

PUMP THAT WILL DELIVER A DOSE

FOR EVERY DAY USE.

AND THIS WOULD BE FOR THE WOMAN

TO KEEP IN HER BATHROOM AND THEN

WHEN SHE LEAVES FOR THE WEEKEND,

SHE MAY HAVE A LITTLE SACH A IN

HER PURSE AND THAT IS HER

SATURDAY, SUNDAY DOSING.

AND THE OTHER SYSTEM WHICH IS

ALSO FOR TRANSDERMAL SUES A

METRO DOSE TRANSDERMAL SYSTEM.

THAT AGAIN IS A VERY WELL

MEASURED DELIVERY BY THIS LITTLE

DEVICE THAT CONTAINS, IN FACT,

IN THIS BODY OF THE DEVICE,

THERE IS A SMALL CANISTER THAT

CONTAINS A SOLUTION AND THE

SOLUTION, OF COURSE, CONTAINING

TWO STEROIDS, PRO GEST IN AND

ESTROGEN, WOULD BE APPLIED ON

THE IN AND DELIVER FILM WHICH IS

INVISIBLE.

AND THIS DEVELOPMENT HAS BEEN

MADE BY SMALL COMPANY IN

AUSTRALIA AND WE HAVE WORKED

WITH THEM TO DELIVER NESTER OWN,

WHICH IS THE PROGEST IN THAT WE

HAVE FOUND SAFE AND EFFECTIVE

AND ONE OF THE MOST ACTIVE OF

AGENTS.

WE NEED TO REACH 250 TO BLOCK

OVPOLICE STATION WE SHOWED AFTER

DOSING FOR FIVE DAYS WITH THIS

DELIVERY

SYSTEM -- OVULATION -- WE COULD

REACH HIGHER AND STABLE.

THE VAGINAL GEL WAS ANOTHER

METHOD THAT WE TRIED TO DEVELOP

FOR PRECOIDAL CONTRACEPTION ON

DEMAND.

AND THE INITIAL GOAL WAS TO USE

THE VAGINAL GEL AND WE HAD THE

VAGINAL GEL WHICH WAS

MICROBICIDE.

WE KNEW IT WAS WELL ABSORBED

FROM THE VAGINA.

WE KNOW FROM THE LITERATURE AND

ALL THE INFORMATION ON

CONTRACEPTION, LEVON GUEST REL,

WHAT ARE THE DOSES TO BLOCK

OVULATION AND THE GOAL WAS TO

USE THE GEL BEFORE INTERCOURSE.

WHEN IT WAS ADMINISTERED FROM

THE VAGINIA ACCORDING TO THE

DIAMETER OF THE TOL KEEL AT THE

TIME THE WOMEN RECEIVED THE

TREATMENT, EITHER VAGINAL IN THE

GREEN BARS OR ORAL IN THE YELLOW

GOLDEN BAR, YOU SEE EVEN IN MORE

THAN 18 MILLIMETERS, VERY CLOSE

TO OVULATION, A MUCH HIGHER

PERCENTAGE OF SUPPRESSION OF

OVULATION.

AND THIS DUE TO THE REATTENTION

OF THE GEL ON THE VAGINAL WALLS

WHICH WAS LONGER THAN THE PIQUE

REACHED BY THE ORAL TABLETS AND

EVEN HERE, WE USED HALF DOSE AS

COMPARED TO THE ORAL TAP LETS.

SO THIS IS A PROMISING METHOD

AND WE ARE TRYING TO CONTINUE

THE DEVELOPMENT OF THIS VECTOR.

ANOTHER GROUP WE SHOULD CONSIDER

EACH IF WE ARE HERE FOR THE

WOMEN'S HEALTH, FOR THE SAKE OF

WOMEN'S HEALTH, MEN SHOULD TAKE

CONTRA ACCEPTION.

MANY WOMEN CANNOT USE

CONTRACEPTIVES AND WE NEED SOME

SOME SITUATIONS, TO HAVE AN

ALTERNATIVE POSSIBILITY.

AND WE HAVE SEEN THAT THE

INDUSTRY WITHDREW FROM THIS

FIELD WITH THE BELIEF THAT MEN

WILL NOT USE CONTRACEPTION,

AUGUST THOUGH TWO LARGE SURVEYS

INDICATED, MADE IT MORE THAN

9000 MEN IN FOUR CONTINENTS,

THAT IN FACT 55% OF MEN TED IT

WOULD BE A GOOD IDEA AND THEY

WOULD BE READY TO USE IT IF IT

WAS AVAILABLE.

THERE WERE -- THEY WERE ALSO

FAVORING DIFFERENT METHOD, A

PILL WOULD BE THE FIRST BUT

IMPLANTS WERE ALSO MENTIONED AND

WE HAVE DEVELOPED FURTHER

IMPLANTS THAT DELIVER MENT  --

[ INDISCERNIBLE ]

WHICH IS A TISSUE SELECTIVE

ANDROGEN WITH NO EFFECT ON PRO

STATE.

AND THIS IS THE MAJOR PROBLEM

WITH INJECTION -- PROSTATE  --

AND INVESTIGATE LONG-TERM SOME

QUESTION OPEN ABOUT THE ROLE OF

ANDROGEN ON THE PROSTATE, THE

FACT THAT THIS COMPOUND DOES NOT

CONVERT INTO

DEHYDROTESTOSTERONE, IT IS AN

ADVANTAGE FOR PROSTATE.

SO FAR, WE DEMONSTRATED 85%

EFFICACY ON SPERM SUPPRESSION

BUT IT SEEMS THAT WE NEED TO

COMBINE THE ANDROGEN WITH

PROGESTIN FOR INCREASING THIS

EFFICACY RATE.

NOW, VERY BRIEFLY, THERE ARE NEW

TECHNOLOGIES AND NEW NONHORMONAL

TARGETS FOR CONTRACEPTION AND

FOR MALE AND FEMALE

CONTRACEPTION.

AND WORK IS BEING DONE TO LIMIT

THE MOTILITIY OF THE SPERM,

PREVENT THE ACTIVITY OF THE

SPERM AND THE ENTRY INTO THE

ZONA PELIS TA OF THE OV UM.

THIS IS LINKED TO THE PAST

DECADE WORK AND WHAT IS CALLED

THE "OHMIC" REVOLUTION IN

GENEMIC AND APPROPRIATE OHMIC T

DEALS WITH GENES SPECIFIC IN THE

REPRODUCTIVE

TARGETS -- PROTEOMICS AND -- AND

COFACTORS THAT WOULD BE SPECIFIC

TO THE SPERM OR TO THE OV UM

THAT COULD BE TARGETED BY SMALL

MOLECULES, SMALL DRUGS THAT

WOULD OPPOSE THEIR ACTION AND

THIS WOULD LEAD TO NON-HORMONAL

METHOD OF COPT ACCEPTION WITHOUT

INTERFERENCE WITH THE HORMONES

CYCLE -- CONTRACEPTION -- OR THE

HORMONAL SECRETION IN MEN.

SEVERAL PROMISING LEADS HAVE

BEEN IDENTIFIED FOR MEN BUT THEY

ARE THE STAGE OF THE VERY EARLY

PRECLINICAL WORK BUT IN ALL OF

THE MODELS, IT HAS BEEN SHOWN

THAT THESE ANTAGONISTS CAN

PREVENT SPERM MATURATION OR

ACTIVATION OR MOTILITY.

AND IN WOMEN, THERE ARE SOME

OTHER TARGETS, I JUST MENTIONED

THIS ONE FROMMORGON, OUR

COLLEAGUES WHO WORK ON THE

CUMULUS OOCYTE EXPANSION WHICH

LEADS TO THE FOLLICLE RUPTURE.

THEY IDENTIFIED PROSTAGLANDIN E2

INDUCED IN THIS PHENOMENON AND

THEY WORKED WITH ANTAGONISTS

BLOCK THE RECEPTOR OF PGE2 TO

BLOCK THIS OOCYTE EXPANSION.

AND OTHER INHIBITORS AND

INHIBITORS OF MMP CAN BLOCK THE

FOLLICLE RUPTURE AND MAINTAIN A

LAWSUIT NEEDS FOLLICLE WITH PRO

GEST RIN SECRETION AND NORMAL

ENVIRONMENTS.

AS YOU KNOW, THE NICHD

UNDERTAKEN LAST YEAR A SERIES OF

WORKSHOPS AND THE GOAL WAS THE

VISION FOR THE NEXT DECADE AND

THE SCIENTIFIC OPPORTUNITIES IN

VARIOUS AREAS SUPPORTED BY

NICHD, INCLUDING REPRODUCTION,

AND IN THESE SUBSECTION ON

CONTRA ACCEPTION RESEARCH, IT

WAS IDENTIFIED THAT ONE OF THE

MAJOR OPPORTUNITIES AND NEED WAS

TO UNDERSTAND THE RISK FACTORS

FOR UNINTENDED PREGNANCY.

AND OF COURSE, WE NEED TO KNOW

WHY THE WOMEN WOULD NOT TAKE THE

CONTRACEPTION AND WOULD NOT HAVE

BEHAVIOR THAT LEADS TO

NONCOMPLIANCE.

AND IMPROVE EXISTING

CONTRACEPTIVE METHODS AND STILL

CONTINUE TO RESEARCH AND DEVELOP

NEW METHODS WITH ADDED BENEFITS

AS I MENTIONED EARLIER.

AND I WANT TO THANK ALL OF THE

SPONSORS AND DO NORS WHO

SUPPORTED THE WORK OF THE

CONSOLATION OVER THE YEARS.

THANK YOU FOR YOUR ATTENTION.

[ APPLAUSE ]

QUESTIONS?

YES?

[ OFF MIC ]

>> COULD BE USED AFTER

INTERCOURSE.

WHEN WE DEVELOPED IT WITH A

MICROBICIDE TO PREVENT

TRANSMISSION OF HIV, WE SAID WE

BETTER ADMINISTER IT BEFORE.

NOW OF COURSE IF YOU DO NOT HAVE

THE MICROBICIDE, WE DON'T NEED.

WE CAN HAVE IT JUST FOR THE THE

HORMONE TO BLOCK AND POSTPONE

OVULATION, ANY TIME AROUND THE

OVULATION.

>> [ OFF MIC ]

>> AND I THINK SOME

ANTIRETROVIRAL AGENT MAY BE

ACTIVE AFTER THE INTERCOURSE AND

MAYBE TWO OR THREE DAYS.

THE PROBLEM IS REAL TOW

DETERMINE WHEN THEY WILL BE

ACTIVE AND HAVE THIS POSSIBILITY

OF BEFORE OR AFTER.

THANK YOU.

>> [ OFF MIC ]

>> THE QUESTION WAS ABOUT THE

POSSIBILITY.

WE NEED A REVERSIBLE METHOD FOR

MEN AND IN THE HORMONAL

CONTRACEPTION, ALL THE STUD

THESE HAVE BEEN CONDUCTED SHOW

COMPLETE RETURN TO FERTILITY.

AND THAT IS REALLY CLEAR.

WE DO NOT KNOW YET WITH THE NEW

NONHORMONAL METHOD AND THAT IS

WHY IT'S FAR AWAY IN THE HORIZON

WE WOULD HAVE SUCH METHODS.

THANK YOU.

[ APPLAUSE ]

>> SO I WANT TO THANK OUR

AMAZING SPEAKERS.

REALLY FANTASTIC TOPICS.

I THINK THE AUDIENCE JOINS ME IN

OUR IMPRESSION OF THIS

INCREDIBLE SCIENCE, FOCUSED ON

REPRODUCTIVE TECHNOLOGIES.

NATIONAL WOMEN'S HEALTH WEEK

GIVES US ONE WEEK TO REALLY

FOCUS ON WOMEN'S HEALTH.

BUT THAT IS NOT BECAUSE WE DON'T

WANT TO FOCUS ON THAT FOR THE

REST OF THE YEAR.

SO I WANTED TO HIGHLIGHT THIS

WEEK SOME AREAS THAT ARE

CRITICALLY IMPORTANT TO WOMEN,

REPRODUCTIVE ISSUES.

WE HEARD ABOUT ONCOFERTILITY,

MULTIPURPOSE TECHNOLOGIES, WE

HEARD ABOUT THE POTENTIAL FOR

ANTIHIV AND ANTIRETROVIRAL

TREATMENTS BEFORE AND AFTER, WE

HEARD ABOUT CHALLENGING ETHICAL

ISSUES AND RELATED TO ASSISTIVE

REPRODUCTIVE TECHNOLOGY SPEC

THIS NEW GENERATION THAT HAS

DIFFERENT ATTITUDES ABOUT SOME

OF THE THINGS THAT HAVE BEEN

PROPOSED IN THE PAST.

AND THEN WE HEARD ABOUT

CHALLENGES RELATED TO

DISPARITIES AND REPRODUCTIVE

TECHNOLOGIES AND ASSISTED

REPRODUCTION.

SO I THINK WE HEARD FROM MANY

DIFFERENT PERSPECTIVES AND I

WANT TO AGAIN THANK OUR SPEAKERS

AND THE ORGANIZERS FOR THIS

INCREDIBLY EXCITING CONFERENCE.

PLEASE JOIN ME IN ANKING OUR

SPEAKERS ONCE AGAIN.

[ APPLAUSE ]