>> OKAY.
WE'LL GET STARTED.
WE HAVE A SOMEWHAT SMALLER BUT
HIGHLY SELECTIVE AUDIENCE THIS
AFTERNOON BUT I'M SURE NORMALLY
THERE ARE SOMEWHERE AROUND TWO
TO THREE HUNDRED PEOPLE ONLINE
WATCHING, AND THEN WHEN THIS IS
PUT ON THE NIH VIDEO ARCHIVE IT
GOES AROUND THE WORLD SO ALSO
EXCITING, A LOT OF PEOPLE ARE
WITH US FOR THIS.
FOR THOSE WHO WANT TO TAKE THE
FINAL EXAM I KEEP TELLING YOU
ABOUT, IT'S GOING TO BE
POST
IN
TWO OR THREE WEEKS.
THE FIRST QUESTION IS TO
IDENTIFY THE STRUCTURES, I'M NOT
GOING TO GIVE YOU THE ANSWER
AGAIN.
TODAY WE'RE VERY FORTUNATE TO
HAVE TWO FOLKS HERE WHO ARE
KNOWLEDGEABLE, FERTILITY AND
INFERTILITY.
I
WAS INTRIGUED WITH THE QUOTE,
NO SOCIETY WILL SURVIVE ARE A
SHORTAGE OF WOMEN.
DISEASE AND AFFLICTION, THAT'S
RESTRICTIVE TO THE FEMALE.
SO THE THOUGHTS THAT RUN THROUGH
MY HEAD WHEN PLANNING THIS, TO
SUMMARIZE HERE, MAYBE WE HOPE
THEY WILL PROVOKE YOUR QUESTIONS
AND WE'LL BE DISCUSSED TODAY.
SO WHAT ARE THE FACTS ABOUT MALE
AND FEMALE INFERTILITY?
SHOULD WE REALLY BELIEVE WHAT WE
READ IN NEWSPAPERS, A  COLUMNIST
WHO SEES MY WAY OF THINKING?
IS THE RISING INCIDENCE OF
INFERTILITY DUE TO AN AGING
POPULATION?
THAT APPEARS IN THIS DISCUSSION
OF FERTILITY.
WHAT ARE THE CAUSES OF
INFERTILITY AND HOW DO WE
DIAGNOSE IT, WHAT CAN WE DO
ABOUT IT, SORT OF LINKED IN WITH
THIS IS THOSE OF YOU WHO FOLLOW
"SCIENCE" AND "NATURE" TOO, SOME
COMMENTARIES THIS YEAR, HOW GOOD
IS IN VITRO FERTILIZATION, GOOD
MEANING THE OUTCOME, HOW
SUCCESSFUL.
ARE THERE DIFFERENCES, DOES IT
MATTER?
MAYBE THIS WILL COME UP TODAY.
WE HAD TALK ABOUT PERSONALIZED
MEDICINE, ARE THERE THOUGHTS AS
TO HOW THIS IS GOING TO
INFLUENCE THE FERTILITY PROBLEM?
ONE OF THE MORE CONTEMPORARY
THINGS, ARE WE ENTERING AN ERA
OF EMBRYO ENGINEERING, WHICH
BEARS ON FERTILITY ISSUES, THESE
ARE THOUGHTS THAT CAME TO MY
MIND, WE ENCOURAGE YOU TO ASK
QUESTIONS.
OUR FIRST SPEAKER TODAY RECEIVED
HER Ph.D. IN EPIDEMIOLOGY AT
THE STATE UNIVERSITY OF NEW YORK
AT BUFFALO, SHE WAS TRAINED AS A
NURSE AND ALSO IN SOCIOLOGY, HAS
BEEN HERE AT NIH SINCE 2000 AND
SHE IS THE DIRECTOR AND SENIOR
INVESTIGATOR IN THE DIVISION OF
EPIDEMIOLOGY, STATISTICS AND
PREVENTIVE RESEARCH IN CHILD
HEALTH AND DEVELOPMENT.
AND AS YOU'LL SEE FROM THE
WEBSITE WHERE WE CONDENSED A BIT
HER CV AND PUT IT UP THERE SO
YOU HAVE SOME REFERENCES, YOU
SEE THE WIDE RANGE OF ACTIVITIES
AND STUDIES THAT SHE'S BEEN
INVOLVED AND PRIMARILY FROM
EPIDEMIOLOGIC POINT OF VIEW, BUT
LOOKING AT SOME OF THE MAJOR
ISSUES WHICH DON'T NECESSARILY
APPEAR  TEST TUBE.
THE SECOND SPEAKER RECEIVED HIS
MEDICAL DEGREE AT TEMPLE
UNIVERSITY, HE'S BEEN THE
PROFESSOR AND CHAIRMAN OF
OBSTETRICS AND GYNECOLOGY AT
YALE AND TUFTS IN BOSTON, AND
THEN IN CALIFORNIA, AT UCLA.
AND THEN CAME HERE -- WHEN DID
YOU COME HERE?
PARDON?
SEVEN YEARS AGO.
AMONGST MANY ACCOMPLISHMENTS IS
THE EDITOR AND CHIEF OF THE
JOURNAL ON FERTILITY AND
STERILITY, MEMBER OF THE
INSTITUTE OF MEDICINE AT THE
NATIONAL ACADEMY, AND HAS WORKED
AND WRITTEN AND DISCUSSED
EXTENSIVELY PROBLEMS RELATED TO
FERTILITY AND ALL ASPECTS OF
CONCEPTION.
SO IT'S A PLEASURE.
OH, HIS
CURRENT TITLE AT NICHD,
WE'RE VERY GRATEFUL TO BOTH OF
YOU FOR BEING HERE AND I GUESS
YOU'RE GOING TO LEAD OFF.
>> RIGHT.
GOOD AFTERNOON.
I KNOW IT'S LATE IN THE DAY.
I THANK YOU FOR COMING OUT,
INFERTILITY AND FERTILITY IN
GENERAL TENDS TO ATTRACT A
SPARSE CROWD FOR REASONS I DON'T
KNOW BECAUSE IT'S SO IMPORTANT,
AND WITHOUT IT NONE OF US WOULD
BE HERE SO THANK YOU FOR COMING.
IN THINKING ABOUT THIS TALK
TODAY ALAN THOUGHT IT MIGHT BE
GREAT TO HEAR ABOUT INFERTILITY
FROM THE POPULATION PERSPECTIVE,
AND SO THAT'S WHAT I'M GOING TO
DO IS GIVE YOU AN OVERVIEW, WHAT
WE THINK WE KNOW TO PUT INTO
CONTEXT A LOT OF THE MYTHS ABOUT
WHAT WE THINK WE KNOW ABOUT
INFERTILITY AS A POPULATION
LEVEL, TO GIVE YOU A FRAMEWORK
TO THINK ABOUT IT CLINICALLY,
ONE OF THE MOST DISTURBING
FIGURES IS ABOUT HALF OF COUPLES
EXPERIENCE A PROBLEM ACTUALLY
COME IN AND SEEK CLINICAL CARE.
SO IF YOU'RE ONLY SEEING HALF OF
THE AFFECTED INDIVIDUALS, OUR
CLINICAL PERSPECTIVE MIGHT NOT
BE ACCURATE.
SO WHY DON'T PEOPLE COME IN AND
WHY IS IT HARD TO GET A HANDLE
ON INFERTILITY AT THE POPULATION
LEVEL?
SO I'M GOING TO TALK ABOUT THE
POPULATION PERSPECTIVES, GENERAL
INCIDENCE FIGURES, RISK FACTORS,
AND I WANT TO LEAVE YOU WITH A
SENSE INFERTILITY IS MORE
ABOUT -- MORE THAN JUST HAVING A
HARD TIME GETTING PREGNANT.
WE'RE NOW APPRECIATING IT MIGHT
BE AN EARLY SIGNAL ABOUT YOUR
HEALTH ACROSS THE LIFESPAN.
AND THEN ALAN IS GOING TO TALK
ABOUT INFERTILITY FROM THE
CLINICAL PERSPECTIVE THAT MIGHT
BE OF MORE INTEREST TO MOST OF
YOU AND HOPEFULLY GIVE YOU AN
OVERALL SENSE OF WHAT WE THINK
WE DO KNOW.
I WANT TO START BY SAYING THAT
FECUNDITY, COULD YOU IMPREGNATE
A WOMAN IF YOU WANTED TO OR HAD
THE OPPORTUNITY, AND COULD YOU
GET PREGNANT IF YOU WERE A
WOMAN, SO EVERYBODY THINKS ABOUT
FERTILITY ONLY PREGNANCY BUT
IT'S SO MUCH MORE.
THERE ARE VERY GOOD POPULATION
DATA FOR MOST OF THE DEVELOPED
WORLD, INCLUDING THE UNITED
STATES, TO SUGGEST THAT PUBERTY,
THE ONSET FOR GIRLS IS EARLIER
AND FASTER AND NOT SO MUCH FOR
BOYS.
IT HASN'T HAD SUCH A STEEP
DECLINE IN TERMS OF THE AGE OF
ONSET, AND THIS IS CONCERNING TO
A NUMBER OF PEOPLE, CONSIDERABLE
CONTROVERSY WHETHER SEMEN
QUALITY IS DECLINING ACROSS THE
GLOBE WITH A FLURRY OF LAY
ARTICLES PUBLISHED IN THE
1990s AND EARLY 2000s
TALKING ABOUT HOW TODAY'S MEN
ARE ONLY HALF THE MAN THEIR
FATHER WAS BECAUSE OF CURRENT
SEMEN QUALITY.
REALLY QUITE ALARMING DATA
SUGGESTING THAT DANISH MEMBER
HAVE PROBABLY SOME OF THE
POOREST SEMEN QUALITY IN THE
WORLD WHICH NOW MEANS THAT THEY
ENCOURAGE ALL MILITARY CON
SCRIPTS AS PART OF THEIR
BASELINE PHYSICAL EXAM TO DONATE
A SEMEN SAMPLE SO THE COUNTRY
CAN MONITOR THE QUALITY.
MEN IN NEW YORK CITY LOOK PRETTY
GOOD COMPARED TO THE REST OF THE
WORLD SO THERE YOU HAVE IT.
BUT FROM A CLINICAL PERSPECTIVE
WE'RE CONCERNED THE REPRODUCE
INTERVAL FOR WOMEN INCREASED
OVER TWO YEARS OVER TIME, THIS
STUDY, THE FIRST BULLET SUGGESTS
THAT FOR WOMEN BORN IN 1915
THROUGH 1919, THEY HAD ABOUT 36
YEARS OF BEING REPRODUCTIVE AGE,
FOR LATER BORN COHORTS TWO YEARS
LATER.
IN PART WE THINK BECAUSE OF
THEIR EARLIER AGE AT MENARCHE,
ALSO THE SLIGHTLY INCREASING AGE
AT MENOPAUSE, NATURAL, NOT
MEDICALLY OR SURGICALLY INDUCED
MEANING WOMEN ARE REPRODUCTIVELY
AGED FOR A LONGER PERIOD OF
TIME.
WHAT DOES THAT MEAN?
ISN'T THAT GOOD?
BECAUSE PEOPLE ARE STARTING
LATER.
SO I HAVE A WHOLE COLLECTION OF
CARTOONS ABOUT HOW THE MEDIA
PORTRAYS CONCERNS, THE POTOMAC
RIVER, THIS IS CLEARLY A
CONGRESS PERSON DRINKING WATER,
READING PROBABLY THE WASHINGTON
POST, SPITTING OUT HIS WATER
BECAUSE OF WHAT IS FOUND IN THE
WATER, FISH EGGS FOUND TO BE
MALE AND FEMALE WITH ENDOCRINE
DISRUPTING CHEMICALS.
ALSO LIFESTYLE, THIS IS HOW OUR
STUDY LOOKING AT BMI AND SEMEN
QUALITY THAT WE RECENTLY
COMPLETED WAS PORTRAYED IN THE
"NEW YORK TIMES," AND BY THE
WAY, INCREASING BMI IS NOT GOOD
FOR SEMEN QUALITY.
OF COURSE, MY PET PEEVE, I HAVE
TO BE CAREFUL, THIS IS PART OF
THE ARCHIVE, IS THAT WE
CONSTANTLY BLAME WOMEN FOR
STARTING LATER, AND WHY, YOU
KNOW, WOULDN'T YOU EXPECT MAYBE
TO EXPERIENCE MORE INFERTILITY
BECAUSE WE'RE STARTING OUR
FAMILIES MUCH LATER.
AND THIS IS VERY TRUE, THE
AVERAGE AGE AS FIRST PREGNANCY
IN MOST DEVELOPED COUNTRIES IS
NOW APPROACHING 29 TO 31 YEARS
DEPENDING ON THE COUNTRY.
TALKING ABOUT INFERTILITY WHICH
ONE OF THESE MEN, THIS IS ABOUT
THE RIGHT ESTIMATE, IS LIKELY TO
HAVE INFERTILITY?
THEY DON'T SEEM THICK.
THEY ALL SEEM DIFFERENT.
AND IF THESE SIX MEN CAME INTO
YOUR OFFICE AND YOU HAD A BET
WHICH ONE WOULD YOU BET?
HOW ABOUT THESE WOMEN?
THERE'S NOTHING UNIQUE, NOTHING
PHYSICALLY PRESENTING THAT WOULD
ALLOW YOU TO BE ABLE TO PICK
SOMEBODY OUT.
I LOVE THIS CARTOON, IF ONLY
COUPLES CAME DRESSED NEATLY TO
THEIR PHYSICIAN TO DISCUSS PLANS
FOR GETTING PREGNANT.
THE CDC HAS GUIDANCE FOR
PRE-CONCEPTION CARE AND MOST
PHYSICIANS SURVEYED UNDERSCORE
HOW IMPORTANT IT IS YET VERY
LITTLE PRE-CONCEPTION GUIDANCE
IS OFFERED, MOSTLY BECAUSE
PEOPLE SORT OF DECIDE I THINK
THEY ARE GOING TO START THEIR
FAMILIES OR TRY FOR THEIR
FAMILIES MAYBE AFTER A RAISE, A
PAPER PUBLISHED, YOU MADE
"SCIENCE," "CELL," "NATURE."
I'VE DONE TWO COHORTS AND THEY
DECIDE WHEN THE MOOD IS RIGHT
AND GO FOR IT.
WE ONLY HAVE A HANDFUL OF
PRE-CONCEPTION STUDIES ACROSS
THE GLOBE, I WANT TO
REMIND YOU
THIS IS 2015.
HOW DO YOU TELL YOUR COUPLES IT
SHOULD TAKE?
I HAVE NEVER GOTTEN AN EMPIRICAL
ANSWER.
YOU CAN'T GENERALIZE PEOPLE, IT
DEPENDS ON THE WOMAN, BLAH,
BLAH, BLAH.
I DON'T BLAME THE CLINICAL
COMMUNITY, TRUTH IS WE HAVE VERY
FEW DATA TO GET INFORMED ANSWER
TO THIS QUESTION, SO ON AVERAGE
MAYBE ABOUT A 20 TO 30%
PROBABILITY OF GETTING PREGNANT
IN AN EXPOSED MENSTRUAL CYCLE TO
INTERCOURSE, AND KEEP IN MIND
HUMANS ARE THE MOST INEFFICIENT
REPRODUCERS OF ALL SPECIES ON
THE PLANET.
WE DON'T GET IT RIGHT VERY
OFTEN.
AND WHEN WE TRYING TO WORK IN
THE POPULATION LEVEL WE HAVE ALL
KIND OF FAMILIES, ALL KINDS OF
PARTNERSHIPS SO THE TRADITIONAL
MODEL IS NULL AND VOID.
SO I JUST WANTED TO EMPHASIZE
AGAIN WHEN WE'RE TALKING ABOUT
FECUNDITY, WE'RE TALKING ABOUT
BIOLOGICAL CAPACITY FOR
REPRODUCTION IN MEN AND WOMEN.
FERTILITY IS A LIVE BIRTH,
WHETHER YOU FATHERED IT OR
DELIVERED IT, THE BEST BIOMARKER
WE HAVE.
SO THIS IS WHY IT'S SO HARD TO
UNDERSTAND INFERTILITY AT THE
POPULATION LEVEL, IF ONLY WE
COULD CATEGORIZE YOU AND YOU AND
YOU, INTO BEING FECUND, CAPABLE
OF DOING IT, INFECUND,
INCAPABLE, BECAUSE YOU WERE
STERILE FOR MEDICAL OR
CONTRACEPTIVE REASONS OR
IMPAIRED FECUNDITY.
WHEN YOU'RE TRYING TO PLAN A
STUDY, POPULATION BASED, HOW DO
YOU THINK YOU KNOW?
WE CAN'T LOOK AT PEOPLE ACROSS
THE ROOM, AHA, AND IF I SEE
YOU'RE PREGNANT WE CAN PLUG YOU
IN, BUT EVEN AMONG COUPLES WHO
HAVE IMPAIRED FECUNDITY, THEY
CAN BE CLINICALLY HELPED TO BE
FECUND AND FERTILE.
THIS EMPHASIZES THE POINT.
THREE COUPLES, ALL HAD A BIRTH,
THIS ONE CAME THROUGH THE
TRADITIONAL WAY, FECUND, BECAME
PREGNANT, THEY HAD THEIR BABY,
THEIR DELIVERY, RIGHT NEXT TO
THIS COUPLE THAT HAD A PREVIOUS
LOSS, THEY BECAME PREGNANT WITH
OR WITHOUT TREATMENT, CLINICAL
CARE, HAD THEIR BABY, THIS WITH
TREATMENT, THIS WITHOUT, THEY
RESOLVED INFERTILITY SOMEHOW
WITHOUT MEDICAL CARE.
THE OUTCOME IS THE SAME.
NOWADAYS WHEN WE'RE THINKING
ABOUT A LOT OF DIFFERENT
OUTCOMES, CHILD HEALTH OR EVEN
COUPLES HEALTH, JUST ASKING HOW
MANY CHILDREN THEY HAVE PROBABLY
NO LONGER TELLS THE PICTURE.
SO INFERTILITY, WHEN WE TRY TO
DEFINE IT, IT CAN BE FURTHER
BROKEN DOWN BY PRIMARY OR
SECONDARY WITH PRIMARY BEING
NEVER ABLE TO CONCEIVE, NEVER
BEEN PREGNANT, WHEREAS THE
SECONDARY HAD A PREVIOUS
PREGNANCY, REGARDLESS OF
OUTCOME, BUT TRYING TO ATTEMPT,
THEY CAN'T GET PREGNANT.
YOU PROBABLY ALL KNOW
INDIVIDUALS WHO HAVE FALLEN INTO
THOSE CATEGORIES, ONES WHO --
OOPS, SORRY.
COUPLES TRYING FOR YEARS FINALLY
GAVE UP, AND THEY HAD A BABY,
RIGHT?
THEY RESOLVED THEIR INFERTILITY.
WE KNOW VERY LITTLE ABOUT
COUPLES WHO RESOLVE THEIR
INFERTILITY IN A POPULATION
LEVEL.
HOWEVER, SCANDINAVIAN COUNTRIES
WITH LINKAGES, WE CAN LOOK AT
COUPLES WHO RESOLVE INFERTILITY
IN MONTHS 13 THROUGH 24 BECAUSE
OF THE RECEIPT OF FREE
INFERTILITY TREATMENT REQUIRES
TWO YEARS OF TRYING.
SO WE CAN LOOK AT WHO GETS
PREGNANT BETWEEN MONTH 13 AND 24
AND A SIZEABLE PERCENTAGE OF
COUPLES DO, THEY SORT OF OUTGROW
THEIR INFERTILITY, IF YOU WILL.
NOW, THIS SLIDE REALLY IRRITATES
ME BECAUSE IT SAYS HERE ARE THE
CLINICAL DIAGNOSTIC SUBTYPES OF
INFERTILITY, AND IN GENERAL THEY
SAY HALF IS ATTRIBUTED TO MALE,
HALF TO FEMALE, HALF TO THE
COUPLE, 10% TO THE COUPLE, 10%
TO UNKNOWN.
DID YOU HAVE A QUESTION?
OH, SORRY.
I HAVE YET TO ACTUALLY SEE ANY
EMPIRICAL EVIDENCE FROM A COHORT
STUDY OF TRIERS WHO ARE
CLINICALLY DIAGNOSED, SO THIS IS
OUR BEST GUESS, IN FACT THERE
ARE SOME VERY GOOD DATA THAT
SHOW THE MORE YOU UNDERGO
INVESTIGATION, THE MORE FACTORS
POP UP.
I'M THINKING ABOUT A STUDY DONE
IN THE MID-1990s AT THE
UNIVERSITY OF ROCHESTER WHERE
THEY SUBJECTED NORMAL FERTILE
COUPLES WHO HAD A BABY TO
STANDARD INFERTILITY DIAGNOSIS
AND FOUND A HIGH PERCENTAGE OF
BOTH MALES AND FEMALES OF THE
COUPLE WITH SO-CALLED
INDICATIONS OF INFERTILITY.
REALLY WHAT THIS UNDERSCORES IS
WE STILL DON'T UNDERSTAND
PHYSIOLOGIC VARIATIONS VERY WELL
WHEN IT COMES TO HUMAN FECUNDITY
BUT IT GIVES US SOMETHING WE CAN
TELL COUPLES, AND WHAT'S MOST
IMPORTANT IS THAT WE NOW
RECOGNIZE THAT INFERTILITY IS
COUPLE-BASED, IT IS NOT JUST
HER.
I MEAN, I CAN THINK ABOUT HOW MY
TWO AUNTS COULDN'T HAVE BABIES
BUT I NEVER HEARD ABOUT MY UNCLE
NOT BEING ABLE TO FATHER A
PREGNANCY.
SO WE CERTAINLY HAVE COME A LONG
WAY IN THIS REGARD.
SO POPULATION LEVEL, WE TRY TO
ASK PEOPLE ABOUT WHETHER WE'RE
DIRECTLY OBSERVING THEM OR
ASKING THEM TO RECALL HOW LONG
DID IT TAKE, TIME TO PREGNANCY,
AND SO USUALLY THERE'S SOME
PROMPTS GIVEN AND SIX MONTHS,
MOST COUPLES THAT ARE TRYING GET
PREGNANT WITHIN SIX MONTHS, OF
THESE FEW PRE-CONCEPTION STUDIES
THEY SAY THE SAME THING, THAT
ABOUT THE VAST MAJORITY GET
PREGNANT BY SIX MONTHS, AND BY
12 MONTHS OF TRY IN
PRE-CONCEPTION STUDIES 15 TO 20%
OF COUPLES WILL NOT BE PREGNANT
AT 12 MONTHS.
SO THE CUT-POINTS OF SIX MONTHS
AND TWELVE MONTHS FOR CONCEPTION
DELAYED INFERTILITY DO HAVE SOME
EMPIRICAL BASIS.
THIS SLIDE SHOWS THE CUMULATIVE
PROBABILITY OF PREGNANCY, THIS
IS FROM A STUDY WHERE WE
RECRUITED COUPLES AND THE POINT
IS AFTER 12 MONTHS OF INFERTILE
IT FLATTENS OUT, WE DIDN'T GO
THROUGH 24 MONTHS.
JUST BECAUSE YOU'RE NOT PREGNANT
AT 12 MONTHS DOESN'T MEAN YOU
WON'T GET PREGNANT EVEN ON YOUR
OWN.
BUT YOU CAN SEE STARTING FROM
ABOUT SIX MONTHS WHAT THE RAPID
INCREASE IS, AND THEN IT DOES
SLOW.
AND SO THIS HAS LED TO A
CLINICAL GUIDANCE FOR OLDER
WOMEN, IN PARTICULAR, 35 AND
ABOVE, IF YOU'RE NOT PREGNANT
WITHIN SIX MONTHS, IT'S PROBABLY
QUITE PLAUSIBLE AND EMPIRICALLY
SUPPORTED TO SEEK CARE FOR
DIAGNOSTIC EVALUATION.
I'M NOT GOING TO GO OVER ALL
THESE BUT LOOKING AT WHAT
ACCOUNTS FOR HOW LONG IT TAKES
YOU, BUT MY POINT HERE IS WHEN
WE DO STUDY MALES, WE USUALLY
SEE THE SAME ASSOCIATIONS THAT
WE SEE IN FEMALES BUT MOST OF
THEM ARE STILL FOCUSING ON
FEMALE.
I WANT TO POINT OUT THIS STUDY
BECAUSE THERE'S ALL KINDS OF
GUIDANCE, IF YOU'RE GOING TO GET
PREGNANT, DON'T, DON'T, DON'T DO
ALL THESE THINGS.
WE PRACTICE PRECAUTIONARY
PRINCIPLE, RIGHT?
AND IN SWEDEN WHERE THEY TAKE
BIRTH COHORTS FOR SEVERAL YEARS
AND LINK WOMEN WITH OTHER
PREGNANCY COHORTS AND DATA THAT
THEY HAVE, OF A WHOLE HOST OF
LIFESTYLE FACTORS THAT WERE
ASSESSED, AT BEST THEY COULD
ONLY EXPLAIN 14% OF THE
VARIATION IN COUPLES TIME TO
PREGNANCY AND THE ONLY FACTORS
WERE WHETHER OR NOT SHE USED
ORAL CONTRACEPTIVE BEFORE
ATTEMPTING PER MENSTRUAL
CYCLING, AGE AND PARITY.
ALL THIS GUIDANCE WE'RE TELLING
PEOPLE DON'T SMOKE, DON'T DRINK,
DON'T HAVE COFFEE, DON'T
EXERCISE TOO MUCH COULD NOT BE
RETAINED IN THE MODEL.
WE DON'T KNOW WHY IT TAKES SOME
COUPLES LONGER THAN OTHERS,
USUALLY.
NOW, RETROSPECTIVELY REPORTING
TIME TO PREGNANCY, HOW LONG IT
TOOK, THERE ARE ONLY TWO STUDIES
THAT TRIED TO ASSESS THE
VALIDITY, THESE ARE TWO
PRE-CONCEPTION STUDIES, WHETHER
OR NOT THE CYCLE WAS AT RISK,
DID THEY HAVE INTERVIEWS IN THE
FERTILE WINDOW, THEY INTERVIEWED
THE WOMEN A FEW YEARS LATER AND
ASKED HOW LONG.
WHAT WAS DISTURBING TO US, ONLY
17% OF WOMEN COULD SAY THE RIGHT
NUMBER OF TIMES.
THIS IS AMAZING BECAUSE THEY
WERE DOING DAILY REPORTING FOR A
YEAR IN JOURNALS AND ONLINE AND
THEY STILL COULDN'T REMEMBER,
BUT THE GOOD MUSE  -- NEWS IS BY
THREE MONTHS A HIGH PERCENT MORE
OR LESS AGREES.
I THINK IF WE'RE BASING IT ON
CONCEPTION DELAY OR INFERTILITY,
WHETHER THEY COME AND TELL TH
PHYSICIAN IT'S 13 MONTHS OR 33
MONTHS, IT DOESN'T MATTER, IT'S
STILL GETTING THEM IN THE RIGHT
CATEGORY OF WHETHER THEY ARE
FECUND OR EXPERIENCING
INFERTILITY.
WHAT ABOUT INCIDENCE?
IT'S UNKNOWN.
WE REALLY HAVE VERY POOR DATA
EXCEPT FOR THE HANDFUL OF
PRE-CONCEPTION STUDIES THAT HAVE
BEEN ABLE TO GET COUPLES TO DO
DAILY REPORTING ON MENSES, ON
SEXUAL INTERCOURSE AND TO HAVE A
BIOMARKER SO WE CAN IDENTIFY
WHEN PEAK OVULATION OCCURS.
IN THOSE VERY COUPLE OF STUDIES
THE INCIDENCE RANGED FROM 12 TO
18% WITH PRE-CONCEPTION
ENROLLMENT.
ACROSS THE GLOBE MY POINT -- I
THINK THE PERCENT THAT'S USUALLY
TALKED ABOUT IS ABOUT 15%, AND
THESE NUMBERS THAT ARE SHOWN
HERE IS REALLY TO EMPHASIZE THIS
IS NOT JUST A DEVELOPED WORLD
PROBLEM.
WE TEND TO THINK ABOUT THE
DEVELOPING WORLD OR SOCIAL,
ECONOMICALLY, THE LEAST
RESOURCEFUL COUNTRIES HAVING NO
PROBLEM AT ALL.
THEY HAVE TOO MANY KIDS IN FACT.
HOW OFTEN DO YOU HEAR THAT BIAS?
IN FACT, INFERTILITY IS A REAL
PROBLEM IN MANY PARTS OF THE
GLOBE AND IT HAS INCREDIBLE
ECONOMIC AND SOCIAL STIGMA AND
IMPLICATION PARTICULARLY FOR THE
FEMALE PARTNER.
SO THE W.H.O. IS VERY INTERESTED
IN INFERTILITY ACROSS THE GLOBE.
I WANT TO TELL YOU ABOUT THE
DELIGHT IN FINALLY HAVING ONE OF
MY LIFELONG PET PEEVES RESOLVED
BY A GREAT DOCTORAL STUDENT,
POSTDOC.
SO ONE OF THE SURVEYS WE DO IN
THIS COUNTRY, THE NATIONAL
SURVEY FOR FAMILY GROWTH DONE
PERIODICALLY AND THEY REPORT NOT
MUCH OF AN INFERTILITY PROBLEM
IN THE U.S., THAT IT'S ABOUT 7%.
AND ALL MY COLLEAGUES ACROSS THE
GLOBE SAY HOW CAN INFERTILITY BE
SO LOW IN THE UNITED STATES WHEN
IT'S TWICE THAT IN CANADA, AND
GIVEN HOW HIGH YOUR RATES OF IVF
ARE?
THAT MUST MEAN YOUR PHYSICIANS
ARE DOING IVF WITH FERTILE
PEOPLE BECAUSE THE NUMBERS DON'T
JIVE.
AND FROM THE TIME I WAS ON
FACULTY TEACHING, WE LOOKED AT
DATA, STUDENTS, TRYING TO FIGURE
OUT WHY OUR VALUES ARE SO LOW.
ALONG CAME A GREAT DANISH TEAM
LED BY A STATISTICIAN WHO
DEVELOPED THIS METHOD.
WHAT IT DOES IS REMOVES THE
BIASES AND ASSUMPTION ABOUT YOUR
BEHAVIOR, YOUR BEHAVIOR, YOUR
BEHAVIOR WHEN IT COMES TO
INTERCOURSE AND WHO IS AT RISK
FOR INTERCOURSE AND ASKED
COUPLES IF THEY ARE ON ANY
CONTRACEPTION AND HOW LONG THEY
HAVE BEEN WITHOUT CONTRACEPTION
AND IF THEY ARE SEXUALLY ACTIVE.
WE APPLIED THIS METHOD TO THIS
SAME DATA, 7%, WE APPLIED THIS
METHOD BASED ON FEMALES
REPORTING OF TIME, WE FOUND THAT
THE PREFERENCE OF INFERTILITY
WAS MORE LIKE 15% AND THEN
BELIEVE IT OR NOT WE REPLICATED
THE METHOD WITH A PRE-DOC, BASED
ON MALE REPORT AND FIND THAT
EVEN BASED ON MALE REPORTS, NOT
COUPLES, IT WAS 12%.
THE POINT ON THIS SLIDE IS THAT
THESE ARE CONFIDENCE INTERVALS
AROUND THE ESTIMATE AND YOU'LL
NOTICE THE FIGURE IS NOT EVEN IN
THE CONFIDENCE INTERVAL.
WE FOUND THE 7% FIGURE IS A
CONSTRUCT.
INDIVIDUALS ARE NEVER ASKED IF
THEY HAD INFERTILITY.
THEY ARE ASKED ABOUT DO THEY
HAVE A PARTNER, DO THEY HAVE A
REGULAR PARTNER, DO THEY LIVE
TOGETHER, DO THEY HAVE
INTERCOURSE, AND SO ON THE BASIS
OF ALL THESE ANSWERS YOU DERIVE
THIS CONSTRUCT, AND WE ACTUALLY
FELT IT WAS NOT IN KEEPING WITH
CONTEMPORARY POPULATIONS AND
BEHAVIORS OF CONTEMPORARY
POPULATIONS.
MY COLLEAGUES ACROSS THE GLOBE
THINK OKAY, U.S. HAS OUTGROWN
INFERTILITY PROBLEMS, YOU HAVE A
PROBLEM JUST LIKE US.
WE THINK THIS IS PROBABLY A MORE
REALISTIC PREVALENCE ESTIMATE
FOR THE U.S.
NOW, MOST OF THE LITERATURE
FOCUSES ON THE FEMALE.
THERE'S LOTS OF CONCERNS WHO IS
GOING TO PAY FOR THE OLD PEOPLE,
IF  WE DON'T KEEP THIS BIRTH
RATE
UP.
WHAT THIS SLIDE SHOWS IS JUST
LOOKING -- THESE ARE
COUPLE-BASED, WOMEN AGE 35, IF
HER MALE PARTNER IS THE SAME AGE
PREVALENCE OF INFERTILITY IS 18.
FOR THE SAME 35-YEAR-OLD FEMALE,
WITH A GUY FIVE YEARS OLDER,
PREVALENCE NEARLY DOUBLES.
HIS AGE MATTERS.
JUST SHOOK THE WORLD, OH MY
GOSH, HOW COULD THAT BE?
SO IN THE SAME DATA SET, THEY
ASK A SIMPLE QUESTION IS THERE A
LOW TECH SOLUTION TO
INFERTILITY?
WE LOOKED AT WHAT'S THE ONE
THING YOU NEED TO DO TO GET
PREGNANT IN THE TRADITIONAL
VENUE, THAT'S TO HAVE
INTERCOURSE, THERE'S A LOT OF
MYTHS YOU CAN'T HAVE TOO MUCH
BECAUSE IT WATERS DOWN SEMEN
QUALITY AND A HOST OF OTHER
THINGS.
WE TELL PEOPLE NOT TO DO SOME
THINGS THAT IS UNNECESSARY BUT
NOT SUFFICIENT CONDITION FOR
PREGNANCY.
SO IN THE SAME LARGE DATABASE,
WHAT YOU SAW FOR THE COUPLES
THAT WERE HAVING INTERCOURSE AT
LEAST TWICE WEEKLY, BY THE
FEMALE'S AGE, YES, PREVALENCE
DID GO UP WITH FEMALE'S AGE, BUT
RELATIVE TO THE COUPLES THAT
WERE ONLY HAVING INTERCOURSE
UNDERSTAND ONCE, IT WAS MUCH
LOWER.
SO THESE TWO SLIDES SUGGEST A
VERY LOW TECH, THAT'S GOING TO
BE A JOKE, PUBLIC HEALTH
SOLUTION.
HAVE MORE SEX WITH A YOUNGER
MALE PARTNER TO REDUCE
INFERTILITY.
THERE YOU HAVE IT.
[ LAUGHTER ]
YOU HAVE GUIDANCE.
BOTH OF THESE POINTS UNDERSCORE,
YOU CAN'T LOOK AT A COUPLE'S
INTENDED OUTCOME FROM ONLY ONE
PARTNER PERSPECTIVE.
ESPECIALLY AT THE POPULATION
LEVEL.
AND THIS IS JUST THE SAME SLIDE
AS THE SO-CALLED DETERMINANTS OF
TIME TO PREGNANCY FOR
INFERTILITY AND I'M PURPOSELY
STRESSING WHAT WE SEE IN
FEMALES, WHEN WE LOOK AT MALES.
THIS DELIGHTS ME, THE MALE
BIOLOGIC CLOCK.
MOST OF MY RESEARCH IS
CHEMICALS, LIFESTYLE, HUMAN
FECUNDITY AND FERTILITY, THEY
HAVE BEEN ALL OVER THIS FOR A
LONG TIME.
YES, THERE ARE LOTS OF MOVIE
STAR LEGEND WHO FATHERED BABIES
INTO THEIR EIGHTH AND NINTH
DECADES OF LIFE, I REMEMBER
HEARING ABOUT THEM AND SEEING
THE BIG PICTURES IN THE
MAGAZINES.
BUT THE TRUTH OF THE MATTER IS
THERE SEEMS TO BE A MALE
ANDROPAUSE LIKE A FEMALE
MENOPAUSE.
HOWEVER, IT DOESN'T RESULT IN
QUOTE/UNQUOTE STERILITY BUT A
FEW LONGITUDAL STUDIES SHOW
ANDROGEN PRODUCTION AND
SPERMATOGENESIS DOES DECLINE
OVER THE LIFESPAN, NOT WITH THE
SAME RATE AS FEMALES.
AGING OF TESTES AND ACCESSORY
GLANDS MAJOR LONGITUDAL STUDY,
1% REDUCTION IN BLOOD
TESTOSTERONE LEVEL STARTING AT
AGE 30.
BUT WHAT IS REALLY INTERESTING
AND CONCERNING IS THAT ADVANCING
PATERNAL AGE HAS BEEN ASSOCIATED
WITH A FEW OF THESE PREGNANCY
AND CHILD OUTCOMES, ALL OF THE
OUTCOMES THAT WE THINK ABOUT AS
BEING OLDER MATERNAL AGE, AND IN
GENERAL AT THE POPULATION LEVEL,
HE IS TWO YEARS OLDER THAN SHE.
SO THE QUESTION IS WHETHER OR
NOT WE'RE THINKING ABOUT MAYBE A
COMBINED PARENTAL AGE EFFECT
MORE SO THAN JUST OLDER MOTHERS
OR FATHERS.
SO DADS MATTER.
SO JUST BRIEFLY WHY FECUNDITY IS
MORE THAN JUST ABILITY TO GET
PREGNANT, A LOT OF THIS IS IS
COMING FROM THE ENVIRONMENTAL
SIDE, I HAVE TO SAY, BUT WE'RE
NOW APPRECIATING THAT YOUR
FECUNDITY AND FERTILITY STATUS
IS QUITE INFORMATIVE ABOUT YOUR
OWN HEALTH ACROSS THE LIFESPAN.
FOR EXAMPLE, MEN THAT ARE BORN
WITH GENITOURINARY MALFORMATIONS
ACROSS THE GLOBE ARE REPORTED TO
HAVE POOR SEMEN QUALITY, SO
THERE'S BEEN SEVERAL MORE OR
LET'S "HITS" IF YOU WILL, ALSO
WE KNOW MEN WITH GU MALFORMATION
ARE MORE AT RISK OF TESTES
CANCER, AND SEMEN QUALITY IS
SHOWN TO BE HIGHLY ASSOCIATED
WITH MORTALITY.
IN DENMARK, IN CALIFORNIA,
TEXAS, I DON'T KNOW IF YOU SELF
IDENTIFY WITH THOSE PLACES, AND
WHAT IS REALLY INTERESTING IN
THE U.S. DATA WHERE THEY ARE
EVALUATING THOUSANDS OF MEN
COMING FROM SEMEN ANALYSIS WHICH
MEANS AT LEAST HALF OF THEM LOOK
PERFECTLY FINE, STARTING 7 YEARS
FOLLOWING THAT ANALYSIS THEY
HAVE A MUCH HIGHER RATE OF
MORTALITY OF ALL CAUSES COMPARED
TO THE GUYS WHO ARE FINE.
AND THIS COLLABORATED A MAJOR
STUDY, EVEN LARGER, OF THOUSANDS
OF MEN IN DENMARK SUGGESTING
SEMEN QUALITY MAY GIVE YOU A
SENSE ABOUT WHAT'S COMING NEXT.
SO ON FEMALE THERE'S ACTUALLY
PEOPLE HAVE BEEN LOOKING AT IT
LONGER THAN IN MALES, PROBABLY
BECAUSE THEY GIVE BIRTH, BUT
COHORTS OF GIRLS WHO WERE BORN
GROWTH RESTRICTED, SO LESS THAN
THREE OR FIFTH PERCENTILE OF
BIRTH WEIGHT FOR GESTATIONAL AGE
ENTER PUBERTY EARLIER, COMPLETE
IT FASTER, EARLIER MENOPAUSE AND
MORE LIKELIHOOD WITH METABOLIC
SYNDROME, AFTER THE REPRODUCTIVE
YEARS.
AND WE KNOW THAT EARLIER
MENARCHE OR INCREASING LENGTH OF
REPRODUCTIVE WINDOW FOR WOMEN,
NOLO PARITY, POLY OVARIAN
SYNDROME, PRE-ECLAMPSIA ARE
ASSOCIATED WITH HIGHER RISK OF
CANCER, AND DIABETES ASSOCIATED
WITH CORONARY HEART DISEASE,
METABOLIC SYNDROME, STROKE, YOU
NAME IT.
ENDOMETRIOSIS IS ASSOCIATED WITH
NOT ONLY AUTOIMMUNE DISORDERS
BUT HIGH RISK OF SOME TYPES OF
OVARIAN CANCER AS WELL AS OTHER
REPRODUCTIVE SITE CANCERS, IN
SOME SCANDINAVIAN COUNTRIES, A
MARKER FOR TUMORIGENESIS IS
SOMETHING OF INTEREST.
SO I'M GOING TO JUST END ON
THESE LAST TWO SLIDES.
HAS ANYBODY EVER HEARD OF TDS?
DENMARK, NEIL SKAKEBAK,-A CLINIC
AT ONE OF THE MAJOR HOSPITALS IN
DENMARK AND HE'S BEEN VERY
CONCERNED ABOUT THE DECLINING
MALE FECUNDITY IN THE COUNTRY
AND PROPOSED A HYPOTHESIS CALLED
TESTICULAR DYSGENESIS SYNDROME.
EVERYBODY POOH-POOHED AND NO
EVERYBODY EMBRACING IT.
GENES AND ENVIRONMENT COME
TOGETHER AND AFFECT TESTICULAR
DEVELOPMENT AND THE CELLS WILL
GIVE YOU A HINT OF WHAT ENDPOINT
YOU CAN SEE, FROM THOSE RESULTS
FROM ANDROGEN INEFFICIENCILY
LIKE GENITOURINARY MALFORMATION,
AND IT CHANGED THE TOXICOLOGY
PARADIGM, THE DOSE MAKES THE
POISON, YOU LOOK A AND ONE
OUTCOME AND SO 
NOW
PEOPLE ARE LOOKING AT A SPECTRUM
OF REPRODUCTIVE OUTCOMES.
SO I WAS TRYING TO FIGURE OUT
WHY THE ANDROGENROLOGY WORLD WAS
SO FAR AHEAD OF THE GYNECOLOGY
WORLD BECAUSE THERE WAS NOBODY
TALKING ABOUT COULD THE SAME
SORT OF THING BE HAPPENING WITH
THE FEMALE GONAD, AND QUITE
FRANKLY THE MALE AND FEMALE GO
MADS AREN'T THAT DIFFERENT.
I HAD ANOTHER POST DOCK, WE WERE
KIND OF FRUSTRATED WE TRIED TO
SEE IF THERE WAS AN ODS, OVARIAN
DISGENESIS SYNDROME AND WE HAD
ENOUGH TO DO TO THINK ABOUT CDS
AND BASICALLY THE SAME THING,
THAT DEPENDING ON MODE OF
ACTION, YOU COULD HAVE A WHOLE
SPECTRUM OF END POINTS IN
FEMALES, TOO.
AND BASICALLY ALL ANYBODY'S
TRYING TO SAY, IS IN
REPRODUCTIVE HEALTH, IT MIGHT
GIVE US SIGNALS ABOUT WHAT'S
DOWN STREAM, UPSTREAM, DEPENDING
ON YOUR PERSPECTIVE.
WHAT ARE YOU LIKELY TO ENCOUNTER
IN YOUR LIFE.
ON THAT NOTE, THERE'S A GREAT
DEAL OF CONCERN ACROSS THE GLOBE
ON THE PART OF THEM BUT NOT ALL.
I SHARE THE CONCERN, I WILL JUST
SAY, THAT ARE HISTORICALLY,
RECORD LOW FERTILITY RATES MAY
NOT JUST SIMPLY BE COUPLED, SO
YOU KNOW FROM THE PREGNANCY TMAY
BE THAT OUR BASIC UNDERLYING
BIOLOGY AS SNPs.
AND THIS IS A CRITICAL TIPPING
POINT, THE WHOLE HYPOTHESIS 
GATEWAY TO THIS.
SO IT'S PROPOSE THAD MALE
REPRODUCTIVE HEALTH CAN BE THE
CANARY IN THE CASE FOR THE
POPULATION, IF WE KNOW WHAT'S
HAPPENING TO HIM, WE MIGHT HAVE
A SENSE OF WHAT'S HAPPENING AT
THE HEALTH POPULATION LEVEL AND
BECAUSE OF THE RAPID RATE OF
ONSET OF THE DECLINE OF COURSE,
THE COUPLE OF DECADES, PEOPLE
FEEL THAT IT'S MORE THAN JUST
GENES.
IT HAS TO BE CHANGES IN THE
ENVIRONMENT INSTEAD.
ON THAT NOTE, I WILL TALK ABOUT
THE CLINICAL PER
OH, OKAY.
>> --ESPECIALLY IN THE UNITED
STATES AND DIFFERENT
[INDISCERNIBLE]
>> RIGHT.
YES, PEOPLE ARE LOKING AT TIME
TO PREGNANCY, HOW LONG IT TAKES
TO GEEING PREGNANT IN RELATION
TO THE LENGTH OF GUESTATION AND
CARRY THE PREGNANCY AND BIRTH,
SIZE, EVEN SOME DATA ON BIRTH
DEFECTS.
AND IN GENERAL THE EVIDENCE
SUGGEST THAD LONGER IT TAKES,
THE HIGHER THE ODDS OF HAVING
EARLIER BABY, A LIGHTER BABY,
BIRTH DEFECTS, CERTAIN ONES, NOT
ALL SEEM TO BE ASSOCIATED AS
WELL SO PEOPLE ARE DEFINITELY
THINK BEING IT.
HAVEN'T HAD IT DIRECTLY LINKED
TO INFANT MORTALITY, ONLY IN
PRETERM DELIVERY.
>> GOOD TALK.
>> YOU MENTIONED THE FERTILITY
PROBLEMS ARE RELATED TO A COUPLE
FACTORS WHAT COULD THAT ENTAIL?
WITH ONE OR THE OTHER?
>> BOTH OF THEM HAVE SOMETHING
ONBOARD, THAT MIGHT MAKE IT
DIFFICULT FOR THEM TO BE
CONCEIVED, IT COULD BE QUALITY
AND SHE HAS ENDOMETRIOSIS AND
ONE OF THE THINGS THAT IS VERY
INTERESTING O ME IS THAT WE
REALLY HAVE VERY POOR DATA ON
THE ODDS OF GETTING PREGNANT.
IF SHE'S A LITTLE OFF, THE ODDS
IF HE'S A LILE OFF AND THE
ODDS IF THEY'RE BOTH A LITTLE
OFF.
WE JUST DON'T HAVE THOSE DATA
RIGHT NOW AND I DON'T
THINK--ALAN'S GOING ABOUT THIS
BUT EVEN WITH SEMEN QUALITY, WE
DO THE FANCY ANALYSIS, NOTHING
PREDIBLGHTS WHETHER THE COLE
CAN GET PREGNANT OR NOT.
AND THERE ARE AUTHORS RIGHT NOW
ARGUING WHY ARE WE DOG THIS
EITHER TO LOOK AT SPERMIA OR
OTHER UPDATES BECAUSE WE HAVEN'T
BEEN ABLE TO GET PREDICTION OUT
OF THE SEMEN ANALYSIS.
SO IT WOULD BE A COUPLE COME
NOTHING FOR EVALUATION, WHETHER
HE FOUND ONE OR MORE THINGS IN
EACH OF THEM.
>> WERE THERE ANY SORT OF LARGE
SCALE PERSPECTIVE STUDIES GOING
ON THAT ARE DESIGNED TO LOOK AT
BOTH THE BIOLOGICAL AND PERHAPS
FUNCTIONAL ASPECTS OF FERTILITY.
WELL WE FINISHED SOME A COUPLE
YEARS AGO WHERE WE FOLLOWED 500
THROUGH THE POPULATION, AND THEN
WE COULD ONLY FOLLOW THEM FOR A
FEW YEARS AND FROM PREGINANCE
TOW DELIVERY AND WE'VE BEEN
LOOKING AT CHEMICALS, THE
LIFESTYLE BECAUSE I LIKE TO HAVE
A HOPEFULNESS, AT LEAST ON SOME
OF THE ENVIRONMENTAL CHEMICALS,
YOU CAN'T DO MUCH ABOUT THEM.
THEY NEAR YOUR BODY, THEY HAVE
LONG HALF LIFE SO IT DOESN'T
SOUND VERY HOPEFUL SO WE'RE
LOOKING AT THE ROLE OF STRELSZ
ANDOXIDATIVE STRESS TO LOOK GET
A BETTER SENSE.
BUT I THINK IT'S EXCITING
BECAUSE THE NEW SCIENCE, NEW
STATISTICAL MODELS ARE CALLED
JOINT MODELS AND SO IF WE SEE
LIKE THE BMI EFFECT, THE SEMEN
QUALITY IN OUR STUDY, THE NEXT
QUESTION IS DOES IT IMPACT TIME
OF PREGNANCY OR PREGNANCY LOSS.
SO HE HAS POOR QUALITY SEMEN, SO
IT DOESN'T MEAN THE COUPLE WILL
TAKE LONGER AND ARE THEY AT
HIGHER RISK FOR PREGNANCY LOSS,
SO THE NEW MODELS, CAN  YOU CAN
MODEL
MORE THAN ONE END POINT.
YOU CAN MODEL YOUR CANCER
DIAGNOSIS AND HYPERTENSION AND
SOMETHING ELSE.
THIS IS REALLY EXCITING.
THIS IS HOW PEOPLE COME TO US.
>> ALAN ARE YOU GOING TO DISCUSS
SOMETHING ABOUT THE IMPACT OF
INDUSTRY, AGRICULTURE,
PHARMACEUTICAL, INDUSTRY IN
TERMS OF PATHS O GENESIS OF
FERTILITY AND THOSE THINGS
RELATED, IS THERE ANY CONCERTED
MOVEMENT, ORGANIZATIONALLY,
PROFESSIONALLY, FROM WHEREVER TO
DEAL WITH THIS, IT'S A GENERAL
PUBLIC AWARE.
>> HOW MANY OF YOU USE IS
SUNSCREEN IN THIS ROOM?
ONLY ONE?
>> SO WE'RE NOT GOING TO TALK
ABOUT THAT BUT IT IS AN EMERGING
COMPOUND OF UV FILTERS.
ANYBODY USE COLORED DISH SOAP?
OKAY.
SO THESE ARE COMPOUNDS THAT ARE
BEING--THEY'RE THE SPF FACTORS
IN OUR SUNSCREEN, THEY'RE BEING
ADDED TO ALL PERSONAL CARE
PRODUCTS, BUG REPELLANTS YOU
MAKE IT BUT ALSO THESE UV
FILTERS ARE ADD BECAUSE WHERE DO
WOMEN KEEP THEIR DISH SOAP, NEAR
THE WINDOW, RIGHT?
AND YOU WOULDN'T WANT THE DISH
SOAP TO FADE AND THESE ARE
HIGHLY EFFECTIVE AT ABSORBING UV
RADIATION BUT WE'RE RECENTLY
DISCOVERING THEY'RE SO PREVALENT
IN THE POPULATION ON BASIS OF
BIOMONITORRING DATA THAT CDC
DOES FOR NHANES AND IT'S
CONCERNING AND THE BASIC
RESEARCHERS ARE FINDING THAT
SOME OF THESE ARE VERY HIGHLY
ESTRO GENIC AMONG OTHER
BIOLOGICAL PROPERTIES AND SO IN
OUR STUDY, WE DECIDED TO LOOK AT
THEM, SOME OF THE FIRST DATA AND
WE'RE SEEING ON TIME TO
PREGNANCY, THIS LEVEL, REALLY IS
WHAT'S DRIVING THE COUPLE'S KIND
OF PREGNANCY, NOT HERS AT ALL.
SO WE THOUGHT, WELL, WHAT ABOUT
SEMEN QUALITY, SO WE JUST
SUBMITTED THIS PAPER AND WE'RE
SEEING VERY STRONG SIGNALS OF
SEMEN QUALITY ALL FOCUS ON
ALTERATIONS IN THE HEAD.
SO AT THE JOINT MODELING, THE
NEXT THING WE'RE WORKING ON, WE
CAN SAY, MALES, EXPOSE TOWER UV
FILTER, SEMEN QUALITY AND DOES
IT TRANSLATE ACTUALLY TO A
LONGER TIME TO PREGNANCY SO WE
COULD BEGIN TO GET THOSE
ANSWERED.
SO WE'RE NOT GOING TO BE TALKING
ABOUT IT BUT THE E. U. JUST HAS
A SERIES OF PAPERS WHERE THEY'RE
ATTRIBUTE MALE FACTOR
INFERTILITY, NEURAL
DEVELOPMENTAL DISEASES IN
CHILDREN.
I KNOW THERE'S A CANCER ONE, I
CAN'T REMEMBER WHICH ONE.
ATTRIBUTING THE CAUSE TO
ENVIRONMENTAL CHEMICALS AND THEN
THEY COST IT OUT WHAT IT COSTS
THE UNION, SO THEY JUST COME
OUT, I ENCOURAGE TO YOU TAKE A
LOOK.
I THINK THEY'RE AT JCEM, SO I
KNOW THIS IS GOING TO BE A HOT
ONE FOR THE U.S. TO FOLLOW
THROUGH WITH.
>> A FEW YEARS AGO WHEN SHAVING
CREAMS ALL HAD--WHAT WAS IT?
>> I DON'T KNOW.
>> WHAT WAS IT ALAN, THE STUFF
THAT CLOSED THE OZONE, THEY WERE
CONCERNED WITH ITS RELEASE IN
THE ATMOSHPHERE.
>> AEROSOL.
>> WELL THAT DISAPPEARED
INDUSTRIALLY WITHIN A COUPLE OF
YEARS.
>> RIGHT.
RIGHT.
BECAUSE OF GOOD, REALLY PUBLIC
REACTION.
I DON'T THINK THERE WERE ANY
COMPANIES OUT THERE.
>> SAME THING EITHER WAY, THE
BPA WHICH MAKES PLASTIC STUFF--
>> THE POINT WE'RE GETTING AT IS
HOW DO YOU CONVEY THIS
INFORMATION TO THE GENERAL
PUBLIC, NOT JUST TO PEOPLE WHO
GO TO A DOCTOR, BUT YOU DON'T
READ ABOUT ANYTHING LIKE THIS
THAT YOU'RE TALKING ABOUT WHERE
YOUR READ IS THE MORE HYSTERICAL
STUFF.
>> A LOT OF THE LAY MAGAZINES DO
A NICE JOB.
NEW YORK TIMES WRITES A LOT ON A
QUESTION OF ENVIRONMENTAL
CHEMICALS AND I THINK THEY DO, I
HAVE TO SAY A FABULOUS JOB.
THERE ARE LOTS OF WEB SITES,
COALITIONS, AMERICAN COLLEGES OF
GYNECOLOGY, ENDOCRINE SOCIETY,
THERE'S ANOTHER ONE I CAN'T
REMEMBER, IT'S AFRM, ALL THE
PRESIDENTS HAVE COME TOGETHER TO
SAY THAT WE NEED TO GET FINITE
ANSWERS BECAUSE, YOU KNOW THERE
ISN'T A LOT OF RESEARCH, STILL.
SO I MEAN, BUT I THINK, PEOPLE
HAVE--WE CAN CERTAINLY ANSWER
THIS QUESTION, BUT WE JUST NEED
TO BE ABLE TO DO THE STUDIES.
>> OKAY.
>> YOU.
DON'T GO AWAY.
[ APPLAUSE ] 
>> I'M NOT.
>> OKAY, AND GREAT.
OKAY, GOOD.
>> OKAY, SO I WILL SKIP OVER A
LOT OF SLIDES BECAUSE I DON'T
HAVE A LOT OF TIME BUT I WILL
HIT THE HIGHLIGHTS.
>> NO, NO, THESE PEOPLE WANT TO
GET OUT OF HERE.
COME ON.
IT'S THE END OF A LONG DAY.
SO NUMBER ONE, THE ONLY REASON
THAT WE'RE HERE, BIOLOGICALLY IS
TO REPRODUCE, SO WHEN YOU'RE
DONE REPRODUCING BIOLOGICALLY,
YOU FILL FILLED YOUR OBLIGATION
AS TO BEING BORN.
NOW, IS INFERTILITY A DISEASE OR
NOT?
MOST PEOPLE THINK THAT IT IS A
DISEASE, BUT THE GOVERNMENT DOES
NOT THINK IT'S A DISEASE AND FOR
THAT REASON, IT'S NOT BEEN VERY
WELL COVERED AS FAR AS INSURANCE
IS CONCERNED.
SO A BIG PROBLEM WITH
INFERTILITY TREATMENT IS THAT
IT'S ALL OUT OF POCKET AND IT'S
A VERY EXPENSIVE TREATMENT, A WE
WILL KNOW MORE ABOUT THAT IN A
MINUTE.
LET'S SEE, THE CAUSES OF
FERTILITY AT THIS, BUT AS FAR AS
FEMALE IS CONCERNED, OCCLUDED
FALOPENNIAN TUBE SYSTEM
IMPORTANT, THE FACTOR IS A
RESULT OF INFECTION, MALE FACTOR
WAS COVERED QUITE WELL, A LARGE
PART OF WOMEN THAT DON'T
OVULATE, HAVE THE REGULAR CYCLES
AND THEY DON'T PRODUCE EGGS AND
IF A WOMAN LIFE--WELL A WOMAN
WITH POLYCYSTIC OVARY SYNDROME,
OVULATING ONLY FOUR OR FIVE
TIMES A YEAR, SO HER ABILITY TO
CONCEIVE IS CUT IN HALF COMPARED
TO THE NORMAL WOMAN WHO OVULATES
13 TIMES A YEAR AND OF COURSE
THERE IS THAT UNEXPLAINED
INFERTILITY GROUP THAT GERMANE
MENTIONED.
NOW THIS IS WHAT THE BIOLOGY
CONSISTS OF.
I CAN COME OUT HERE, RIGHT?
, YES.
>> OKAY.
>> SO HERE'S THE OVARY, START
OUT WITH PRIMORDIAL FOLLICLES,
THESE ARE FORMED FOUR MONTHS
BEFORE THEY ARE PRODUCED AND
THEY ARE INDEPENDENT OF
GENERATEDAT O TROPEINS AND THIS
IS PROBABLY AN AREA WHERE TOXINS
HAVE A PRETTY STRONG INPUT.
THEN, THE CYCLE STARTS ON DAY
ONE AND ON DAY 14, THE EGG IS
RELEASED INTO THE FALOPENNIAN
TUBE, AND THE SPERM HAS TO BE IN
THERE BEFORE THE EGG GETS
RELEASED.
THE AVERAGE SPERM COUNT AND
200 MILLION SPERM IS ONLY A
THOUSAND EVER GET INTO THE
FALOPENNIAN TUBE, SO IT'S A
DIFFICULT TRIP FOR THE SPERM.
FERTILIZATION OCCURS IN THE END
OF THE FALOPENNIAN TUBE, THE
EMBRYO THEN STAYS IN THE
FALOPENNIAN TUBE FOR ABOUT THE
FOUR DAYS TTHEN COMES INTO THE
UTEXOUS AND CONSTANTLY
DEDIVIDING AND I'LL SHOW YOU
SOME BLASTOCYSTS IN JUST A FEW
MINUTES AND THEN IT IMPLANT AND
YOU CAN SEE IMPLANTATION HERE.
NOW IF A HUNDRED EGGS ARE
OVULATED, ONLY 20 OF THOSE WILL
TURN OUT TO BE PREGNANCIES.
SO THERE'S A GIANT LOSS IN THE
FALOPENNIAN TUBE OF FERTILIZED
EGGS.
NOW WE DON'T KNOW THAT, WE DON'T
KNOW THAT OF OUR PATIENTS BUT
IT'S PROBABLY SOMETHING THAT
WE'LL LEARN IN A FUTURE AND
GIANT CAUSE OF INFERTILITY, WHAT
CAUSES THOSE EGGS TO FERTILIZE
BUT NEVER MAKE IT TO THE POINT
WHERE THEY GO ON TO--GO ON TO
THE EGG.
AND THIS GOES THROUGH THE
PARADIGM OF OVULATION, THE
NUMBER OF CHROMOSOMES, SPLITTING
AND EVENTUALLY A HAPLOTYPE YOU
SEE IN THE OOCYTE THAT'S FINALLY
OVULATED IN THE FAR LEFT.
NOW SPERM, ARE INTERESTING AS
WELL.
SPERM PENETRATE THROUGH THE
 CAN
WALL, OUTSIDE WALL, BUT TH]
ONLY--ONLY ONE SPERM CAN GET
INTO THE--GET INTO THE EGG TO
FERTILIZE THE OOCYTE NUCLEUS, IF
NOT YOU WOULD HAVE PROBLEMS SO
AS SOON AS THE SPERM
PENETRATES--THERE'S A LASER HERE
RIGHT?
WELL IT DOESN'T MATTER.
AS SOON AS THE SPERM PENETRATES
THOSE CORTICAL GRANULES YOU SEE
ACTIVATE AND NO OTHER SPERM CAN
GET IN.
YES THERE ARE DISEASES WHERE THE
CORTICAL GRANULES DON'T WORK BUT
IN THOSE CASES OF COURSE, THOSE
CASES OF POLYSPERMIA AND THOSE
EMBRYOS ARE NOT VIABLE.
SO IT'S A VERY COMPLICATED
SYSTEM, IT'S AMAZING IT WORKS AT
ALL BUT OBVIOUSLY IT WORKS IN
MOST PATIENTS AND IT WORKS MOST
OF THE TIME AND THIS IS JUST AN
ULTRASOUND OF AN OOCYTE, YOU CAN
SEE THE BLACK WHOLE AND OF
COURSE THIS IS A LAPROSCOPY OF
THE PELVIS, YOU CAN SEE THE
UTERROUS, CAN YOU SEE THE FLAIL
OPENNIAN TUBES AND YOU CAN SEE
THE OVARIES.
NOW THE EGGS GET INTO THE
FALOPENNIAN TUBE BY HAPPEN
STANCE.
THERE'S NO MECHANISM BY WHICH
THE TUBE SPEAKS TO THE OOCYTE
AND THERE'S NO WAY THAT
THE--THAT WE KNOW THAT THE EGG
AND SPERM TALK TO EACH OTHER, SO
IT'S JUST A CASE WHERE THE
FALOPENNIAN TUBE ENCASES THE
OVARY, AND THE EGG GETS INTO THE
PALE OPENNIAN TUBE, USUALLY ONLY
ONE EGG MATURELY AND MADE
PERCYCLE AND THE SAME WITH THE
SPERM, HERE'S THE EGG HERE AND
THE SPERM IS SWIMMING AROUND AND
IT'S JUST MASS ACTION THAT THAT
SPERM GETS IN AND UNEXPLAINING
PERFILLITY TO GIVE MEDICATIONS
THAT THAT MAKE FOUR OR FIVE EGGS
AND IT NEWELLERICALLY INCREASES
THE CHANCE, IF YOU HAVE FOUR OR
FIVE EGGS WERE LIKELY THAT THE
SPERM GET IN AND IT'S MORE
LIKELY THAT THE FALOPENNIAN TUBE
WILL PICK UP THE EGGS SO THAT'S
ONE OF THE TREATMENTS FOR
PATIENTS WITH UNEXPLAINED
FERTILITY.
NOW MALE FACTOR.
THIS IS A MAN WITH A FREE
RADICALSON JOCK STRAP, ONE OF
THE REASONS WELL, THE TESTICLES
ARE DESCENDED IN THE MALE, IN
ORDER TO KEEP THE TEMPERATURE 1
DEGREE BELOW NORMAL BASAL
INTERIOR TEMPERATURE, BECAUSE IF
YOU, IF THE TESTICLES WERE
INTERIOR AND WE HAVE CASES WHERE
THEY'RE NOT DISTENDED THEN THE
TESTICLES WOANCHT MAKE SPERM SO
THAT'S WHY THEY'RE DISTENDED.
NOW I WILL TELL YOU THIS FACT
THAT YOU WILL REMEMBER FOREVER
THERE ARE TWO MAMMALS THAT DON'T
HAVE DESCENDED TESTICLES.
ONE IS THE WHALE.
AND THE REASON THAT THE
WHALE--WELL, THE WHALE AND THE
DOLPHIN, MAMMAL, THE DOLPHIN
THAT'S A MAMMAL AND OF COURSE
THAT MAKES SENSE BECAUSE THE
WATER WAS VERY COLD AND THAT'S
JUST AS HARMFUL FOR MAKING SPERM
AS THE CORE BASAL TEMPERATURE,
THE OTHER IS THE ELEPHANT AND
THE REASON FOR THE ELEPHANT WAS
ONCE AN AQUATIC ANIMAL AND THE
TRUNK WAS A SNORKEL AND FOR THAT
REASON, THE ELEPHANT HAS EVOLVED
TO HAVE INTERNAL TESTICLES EVEN
THOUGH IT'S A--EVEN THOUGH IT'S
A LAND MAMMAL--LAND MAMMAL NOW.
NOW OF COURSE, THE SPERM COUNT
IS CRITICAL.
IT'S THE PHYSICAL EXAMINATION OF
THE FETTERILE MALE, TO LOOK AT
SPERM COUNT, IT IS
CONTROVERSIAL, THERE ARE WAYS TO
MEASURE SPERM AND I DON'T WANT
TO GO INTO THE DETAILS BUT MOST
ARE DONE BY THIS TECHNIQUE WHERE
IT'S A STROBE LIGHT AND AND YOU
CAN SEE THAT THE MOVING SPERM,
THIS IS JUST ONE SPERM AND YOU
CAN SEE IT MOVING AND IF YOU SEE
A SPERM LIKE THIS, IT'S NOT
MOVING, IT'S A DEAD SPERM.
AND MOST SPERM COUNTS ARE DOWN
THIS WAY.
THE LEAST IMPORTANT IMPORTANT
FACTOR IN THIS SPERM COUNT IS
THE WAY THAT SPERM LOOKS.
THE MORPHOLOGY.
THE MOST IMPORTANT FEATURE OF
THE FIRM IS THE ABILITY TO SWIM.
IT'S MOTILITY OBVIOUSLY, IT HAS
TO GET TO WHERE IT'S INVOLVED IN
THIS ACTION.
NOW THIS IS A STUDY THAT WAS
DONE AT THE UNIVERSITY OF
WASHINGTON; IT'S A ONE--THIS IS
ONE MALE, THEY STUDIED FIVE
MAILS AND THEY HAD THEM DO SPERM
COUNTS OVER 120 WEEKS.
THEY WERE NOT ALLOWED TO HAVE
ANY OTHER, EVERY TIME THEY
EJACULATED IT HAD TO BE FOR THE
SAKE OF THE SPERM COUNT AND WHAT
CAN YOU SEE VERY INTERESTINGLY
S&P THAT THE SPERM COUNT CHANGES
DRAMATICALLY, PROBABLY AROUND 70
OR 80 WEEKS.
WELL FROM THE DAY THE SPERM IS
RELEASED IT WAS FORMED 70 DAYS
AGO, SO THAT PROBABLY INDICATES
THAT THAT MALE HAD A COLD OR A
PEB ROLE EPISODE THAT DROVE THE
SPERM COULD YOU RECOLLECT DOWN.
SO WE GET TWO SPERM COUNTS ON
THAT TO MAKE SURE THAT WE'RE
GETTING THE NORMAL IS, AND THE
FREQUENCY OF THEY'RE HAVING
INTERCOURSE, IF THEY'RE HAVING
EVERY TYPH DAYS IF THEY'RE EVERY
FIVE DAYS, IF IT'S EVERY DAY,
IT'S EVERY DAY.
OF OTHER THING IS HERE IT SHOWS
HOW DESPERATE SOME SUBMITTAL
STUDENTS ARE TO GET THROUGH
MEDICAL SCHOOL THAT THEY'RE
WILLING TO PARTICIPATE IN THIS
STUDY.
NOW GERMANE MENTIONED OLDER MEN,
THIS IS OWEN O'NEILL, BUT THE
FACT IS A GOOD ONE.
MALE FACTOR PERTILITY DOES
INCREASE WITH AGE AS DOES SINGLE
GENE DEFECTS.
BUT IN WOMEN, IT'S A LITTLE BIT
MORE INTERESTING OR MAYBE
INTERESTING IS THE WRONG WORD
BUT IT'S A LITTLE MORE
UNDERSTANDABLE BECAUSE IT'S AN
OLFACTORY.
WHAT HAPPENS IN WOMEN AS THEY
AGE, THE FIVE RULES BREAK DOWN
MORE EASILY AND THEN YOU GET
NONDISJUNCTION OF THE PROEM
STUDIES OF 
-CHROMOSOMES, SO WHAT AN
EXAMPLE OF THAT IS DOWNS
SYNDROME WHERE IN OLDER WOMEN
IT'S MORE COMMON BECAUSE THE
CHROMOSOMES BREAK AWAY IN
TAKEN--THEY FASHION.
NOW WHAT YOU SEE IN OLDER WOMEN
IS NOT ONLY IS FERTILITY ANDA
WE'LL TALK ABOUT HA IN A MINUTE
NOT ONLY DOES FERTILITY DECLINE
BUT ALSO THE RATE OF MISCARRIAGE
BECAUSE THESE ARE VERY HIGH IN
OLDER WOMEN AS LIKE TURNER
SYNDROME AND THOSE THAT BREAK
NOW IT'S INTERESTING BECAUSE IT
WAS ALWAYS THOUGHT THAT THAT WAS
THE WOMEN'S PROBLEM, THAT THOSE
BREAK BECAUSE IT'S IN AN OLDER
EGG, BUT THE TRUTH IS 15% OF THE
TIME, THEY'RE THE BREAK IS DUE
TO THE MALE, THAT THE MALE
CONTRIBUTES TO THOSE FIB RULES
AS WELL, BECAUSE THEY BREAK,
THIS SHOWS AGE AND IT SHOWS THE
MISCARRIAGE RATE AS WOMEN GO ON
TO GET OLDER.
NOW, UNFORTUNATELY A LOT OF DATA
WE WORK WITH, AS GERMANE MENTION
SIDE LOOKING AT THE INFERTILE
POPULATION, THERE'S NOT A LOT OF
POPULATIONOT FETTERILE
POPULATION, THIS HAPPENS TO BE A
STUDY THAT'S NOT A BAD STUDY, IT
DOES COME FROM A GENERAL
POPULATION, BUT MOST OF THE
STUDIES COME FROM INFERTILE
POPULATIONS SO ONE HAS TO TAKE
THAT INTO CONSIDERATION.
NEXT PROBLEM OF COURSE IS
OVULATION, THIS STICKS AT THE
TOP, THIS IS BASIAN DECODER AT
BODY TEMPERATURE, AFTER
TEMPERATURE, THE BASAL BODY
TEMPERATURE, BECAUSE OF THE
PRODUCTION OF PROJECT ROAN DOES
UP 610thS OF A DEGREE AND YOU
CAN SEE--.6-10thS OF A DEGREE
AND YOU LOOK AT THE SURGE, NOW
WHEN YOU HAD THE L. A. SURGE,
THE PATIENT DOESN'T OVULATE FOR
36 HOURS, SO WHEN THE STICK
TURNS COLOR THEY SHOULDN'T HAVE
INTERCOURSE FOR 36 HOURS OR 24
HOURS AND MOST PEOPLE DON'T
BELIEVE THAT AND THEY HAVE
INTERCOURSE AS SOON AS THE STICK
TURNS BLUE BECAUSE THEY THINK
WELL THAT HAS TO BE BECAUSE
THAT'S THE WAY THE TEST IS
DESIGNED AND IT TAKES AT LEAST
24-36 HOURS FOR THAT SURGE TO
CAUSE THE [INDISCERNIBLE] TO BE
RELEASED.
NOW TUBAL DISEASE USED TO BE
TREATED BY TUBAL SURGERY.
THIS IS A TUBE THAT WAS
ONSTRUCTURALLY INDEED THE MIDDLE
AND YOU WILL DO AN ANAST MOWSIS,
PUT THE TWO TOGETHER, SO IT
OPEN, THE BRACE TO BRING IT
TOGETHER, THE TUBAL SURGERY HAS
DISAPPEARED TO A GREAT DEGREE
AND IT'S BEEN REPLACED BY
INVITRO FETTERRIZEALIZATION, SO
IN 1978, BABY BROWN WAS BORN IN
ENGLAND, STEP FORD AND EDWARDS,
AFTER REPORTEDLY A HUNDRED
HUNDRED TRIES, A THOUSAND TRIES
FOR ALL WE KNOW, THEY HAD A
PREGNANCY BASED ON PUTTING THIS
SPERM AND EGG IN A PETARY DISH
ALLOWING THE EMBRO O TO FORM AND
PUTTING IT BACK INTO THE
UTERROUS AND YOU CAN SEE HERE,
THE EGG, THE SPERM, THAT'S WHERE
THE SPERM IS INJECTED INTO THE
EGG, IT WAS MOTILITY OF THE
SPERM IS NOT GOOD ENOUGH TO GET
IN.
CAN YOU SEE THE TWO NUCLEI HERE,
CAN YOU SEE AN EARLY EMBRYO AND
YOU CAN SEE A BLASTOCYST HAS
ABOUT 150 CELLS, HERE THE EMBRYO
HAS SIX-EIGHT CELLS.
AND THIS IS JUST THE
IMPLANTATION, CAN YOU SEE THIS
PERSONAL FLUID WHERE THE--WHERE
THE EMBRYO WAS PLACED INSIDE THE
UTERINE CAVITY.
NOW HERE, THIS IS ALL THE
DIFFERENT TREATMENTS, AS FAR AS
FERTILITY IS CONCERNED.
YOU CAN DO IUI, WHICH MEANS
WASHING THE SPERM AND PUTTING IT
UP IN THE UTERROUS, SO INSTEAD
OF A THOUSAND, 10,000 GET UP IN
THE FALOPENNIAN TUBE.
IT'S THE LEAST SUCCESSFUL OR
LEAST HELPFUL TREATMENT.
THE NEXT IS CLOUGH MID, AND IT
CAUSES YOU--CAUSES THE PATIENT
TO MAKE MORE EGGS, YOU DO
CLOMID, AND IUI, AND THERE'S
DIFFERENCE THERE, SO HMG IS
INJECTABLE, SO INSTEAD OF FOUR
EGGS YOU MAKE 10 OR 20.
LOOKING AT THE NUMBERS IT
REINTEGRATED SERVICES CREASES
PREGNANCY RATE AND THE LAST IS
IVF WHERE THE PUT THE EMBRYO
BACK IN THE UTERTERROUS SO IT'S
NOT UNKNOWN AS FAR AS EGG AND
SPERM IS CONCERNED.
NOW THE PROBLEM OF COURSE, IS
THE BETTER THE TREATMENT, AS FAR
AS THE OUTCOME IS CONCERNED THE
MORE EXPENSIVE SAID.
AND YOU CAN SEE HERE, IVF IS
$9000, HORMONAL TREATMENT IS A
$2000, JUST FOR--JUST AS AN
EXAMPLE.
SO THIS IS AN EXPENSIVE PROCESS.
I NOW WANT TO--THAT'S THE
BIOLOGY, I HAVE MORE BIOLOGY BUT
IT'S MORE ETHICS AND QUESTIONS
THAN IT IS LOOKING AT THE ACTUAL
BIOLOGY.
SO A GOOD PROBLEM IS, HAVING
TWINS.
MOST INFERILE PATIENTS WANT TO
HAVE TWINS.
THERE IS SEIVET% OF INFERTILE
PATIENTS THAT HAVE IVF, THEY
WANT TO ARE TWINS.
REASON THEY WANT TWINS, THEY'VE
WAITED A LONG TIME AND IT'S
ECONOMICALLY BETTER AND YOU GO
THROUGH ONE CYCLE OF IVF AND
HAVE YOU TWO CHILDREN, THE
PROBLEM IS FOR THE OBSTETRICIAN,
TWINS ARE A PROBLEM BECAUSE
TWINS ARE ASSOCIATED, YES THEY
LOOK CUTE WHEN YOU KIND OF WALK
INTO THE GROCERY STORE OR
SUPERMARKET AND THEY'RE THERE,
BUT TWINS OF COURSE HAVE
PROBLEMS AND MAINLY BASED ON AN
INCREASED PREMATURITY RATE, BUT
MOST PATIENTS WANT--MOST
PEOPLEMENT TWINS.
BUT LUCKILY OR IN A RESPONSIBLE
WAY, MOST OF US THROUGH SINGLE
EMBRYO TRANSFER NOW.
YOU PUT ONE EMBRYO BACK, IT'S
VERY RARE THAT HAVE YOU TWINS
AND--THOSE ARE JUST IDENTICAL
TWINS AND THAT'S A HAPPEN
STANCE.
SO SINGLE EMBRYO TRANSFER IS
VERY IMPORTANT.
IT'S A VERY IMPORTANT--VERY
IMPORTANT CONCEPT AND I GUESS
AND ACCEPT IT AS A REASONABLE
FORM OF TREATMENT.
THIS IS A STUDY THAT WE'VE BEEN
LOOKING AT SINGLE VERSES DOUBLE
EMBRYO TRANSFER AND YOU CAN SEE
THAT THE SINGLE--EVENTUALLY THE
SINGLE TRANSFER HAS DONE JUST AS
WELL, AS THE--PUTTING BACK TO.
NOW THE OTHER THING THAT'S
IMPORTANT IS NOW THAT WE GROW
EMBRYOS, INSTEAD OF PUTTING THEM
BACK ON DAY THREE, WE PUT THEM
BACK ON DAY FIVE.
SO WE KNOW THE HEALTHIER
EMBRYOS, THE STRONGER--STRONGER
EMBRYOS HAVE MADE IT TO DAY
FIVE, THEREFORE PUTTING ONE BACK
IS SUCCESSFUL.
NOW OF COURSE, THIS IS A
TECHNOLOGY THAT'S GONE AWRY. 
WE'RE VERY HIGHLY SCRUTINIZED.
ONE OF THE REASONS IS THAT KIND
OF EVERYBODY IS PARTICIPATE
NOTHING REPRODUCTION IN SOME WAY
OR ANOTHER SO PEOPLE ARE
INTERESTED IN THAT, BUT
NEVERTHELESS WE HAD PROBLEMS.
THIS WAS ONE OF THEM THIS, WAS A
PATIENT THAT HAD MULTIPLE EGGS,
IT WASN'T IVF IF WAS OVULATION
INDUCTION AND FERTILIZATION THAT
WAY BUT YOU CAN--YOU KNOW THE
PRESS SHOW THIS IS CUTE PICTURE
WITH EVERYBODY, EVERYBODY WITH
MILK ON THEIR UPPER LIPS BUT THE
TRUTH IS ALL THESE BABIES ARE
SEVERELY DAMAGED.
SOME OF THEM ARE DEAF, ONE IS
BLIND AND DEAF, MOST OF THEM ARE
FEED BY FEEDING TUBES BECAUSE
THEY WERE BORN AT JUST ABOUT A
POUND.
SO THIS IS SOMETHING WE LIKE TO
AVOID BUT IT MAKES IT INTO THE
PRESS QUITE OFTEN.
SO NOW LET'S TALK ANY SOME OF
THE LEGAL ASPECTS OF THIS.
WHO OWNS THE EMBRYO?
FAMOUS CASE COUPLE OF TREATED IN
NORFOLK, THEY HAD A FROZEN
EMBRYO, THE COUPLE MOVED TO
CALIFORNIA, THEY WANTED THE
PEOPLE IN NORFOLK TO SHIP THEIR
EMBRYO BY WAY OF FEDEX, TO
CALIFORNIA.
THE GROUP IN NORFOLK, CAN'T DO
THAT, SUPPOSE THE EMBRYO SITS ON
THE TARMAC AND BECOMES HOT AND
THE EMBRYO IS DESTROYED, WE'RE
NOT GOING TO RELEASE IT, IT WAS
ACTUALLY A DOCTOR THAT WAS THE
OWNER, DOCTOR AND HIS WIFE WERE
THE OWNER OF THAT EMBRYO BUT THE
COURT SAID THAT THE COUPLE OWNS
THE EMBRYO AND THEY CAN
DETERMINE WHAT HAPPENS TO IT.
SURO GASY IS A GIANT ISSUE WHERE
A THIRD PARTY IS INVOLVED.
EMBRYO RESEARCH IS SOMETHING
THAT'S VERY INTERESTING TO US
HERE.
--SO WHEN YOU DO IVF, EVERY
EMBRYO IS NOT PERFECT, DON'T PUT
THEM BACK, BUT WE DON'T DO IVF
HERE AT THE NIH.
CLONING OF COURSE, IS AN
INTELLECTUAL DISCUSSION.
NO ONE DOES CLONING AND NO ONE'S
PARTICULARLY INTERESTED IN IT,
THE ORIGINAL WHEN
[INDISCERNIBLE] WAS BORN, PEOPLE
SAID CLONING WOULD BE GREAT
BECAUSE WE COULD MAKE A COPY OF
YOU SO THAT WHEN YOU WERE 80 AND
YOUR COPY WAS 20 AND YOU NEEDED
A KIDNEY, THEY COULD TAKE THE
KIDNEY FROM THE 20 YEAR-OLD AND
GIVE IT TO THE 80 YEAR-OLD.
WELL THAT'S RIDICULOUS BECAUSE
THE 20 YEAR-OLD WOULD BE A
PERSON AND NOT NECESSARILY--NOT
AN ORGAN GROWER.
AND NOW REGULATION, REGULATION
IS VERY INTERESTING.
WE'RE THE ONLY SPECIALTY THAT
HAS A REGISTRY WHERE EVERY IVF
CYCLE IS REGISTERED.
THERE ARE FALSE IN IT, BUT
NEVERTHELESS IT IS A REGULATED
INDUSTRY AND WE WILL TALK ONE
MINUTE ABOUT THAT THAT IT WILL
BECOME MORE REGULATED.
NOW SOME OF THE ETHICAL
QUESTIONS.
IS SEX SELECTION SOMETHING WE
CAN DO?
IT IS SUCCESSFUL, IF YOU CAME IN
AND SAID YOU WANTED A MALE, A
CHILD, WE COULD PUT ONLY THE
MALE EMBRYOS BACK, WE CAN SEX
EMBRYOS BUT MOST PEOPLE, IT'S A
MUTE QUESTION BECAUSE MOST
PEOPLE DON'T WANT TO PAY $12,000
TO HAVE THE GENDER, IF THEY CAN
AFFORD IT, THE GENDER THEY
PARTICULARLY WANT.
NOW WHAT ABOUT POSTMORTEM
REPRODUCTION, WHERE A MAN IS
KILLED IN AN ACCIDENT AND THE
UROLOGY GOES AND COLLECTS THAT
SPERM AND FREEZES THAT SPERM SO
THAT THEY CAN HAVE--SO THAT
FAMILY CAN HAVE THAT GENETIC
MATERIAL PROCREATED.
STORAGE, WHAT HAPPENS TO THE
EMBRYOS, HOW DO YOU DESTROY THEM
AND WHAT HAPPENS TO THE EMBRYOS
AND TREATING PATIENTS AS FAR AS
DISEASE IS CERTAINED, I WILL
GIVE YOU ONE EXAMPLE OF THAT.
I SPOKE TO THE LITTLE PEOPLE OF
AMERICA A NUMBER OF YEARS OKAY
AND SEEDS THAT ACHOND ROUGH ATOM
PLACIA COULD BE ELIMINATE INDEED
ONE GENERATION, IT'S A SINGLE
GENE, MAKES ABNORMAL CARTILAGE,
WELL THEY WENT NUTS BECAUSE THEY
DON'T VIEW IT AS A DISEASE.
THEY GET MARRIED, THEY HAVE
CHILDREN, THEY WORK, THEY HAVE
LIVES, AND SO I DISEASE
PERPETUATION IS A QUESTION AND
ONE OF THEM STILL, EACH AFTER 20
YEARS ONE OF THE MOST
CONTROVERSIAL THINGS WE DO IS
SINGLE WOMEN INSEMESTER NATION
WHERE A WOMAN GOES TO A SPERM
BANK, SHE'S NOT MARRIED OF
COURSE NOW FREEZING EGG SYSTEM
ANOTHER ISSUE.
SO THE LAST THING I WANT TO TALK
ABOUT IS MITOCHONDRIAL,
TREATMENT OF MITOCHONDRIAL
DISEASE AND THIS IS A VERY
CURRENT ISSUE AND IT TIES THIS
ALL TOGETHER.
MITOCHONDRIAL DISEASE IS A
SERIOUS SPECTRUM OF DECEASES
TEFFECTS ALMOST EVERY ORGAN,
SOME PEOPLE ARE BLIND, SOME
PEOPLE HAVE NO MUSCLE STRENGTH,
SOME PEOPLE ARE BLIND AND HAVE
NO MUSCLE STRENGTH, SOME PEOPLE
HAVE HEARING DEFECTS.
IT CAN BE VERY PROFOUND.
IT CAN BE VERY MILD.
BUT IT'S USUALLY PRETTY
PROFOUND.
IT'S CARRIED IN THE
MITOCHONDRIA.
SO THE TREATMENT IS IS TO TAKE
OUT THE NUCLEUS OF THE EFFECTED
EMBRYO, AND PUT IT IN--TAKE OUT
THE NUCLEUS OF A
HEALTHY--HEALTHY EGG, THAT HAS
NORMAL MITOCHONDRIA AND PUT THAT
IN THERE AND LET THAT--THAT
PATIENT--LET THAT CHILD BE BORN
FREE OF MITOCHONDRIAL DISEASE. 
NOW THERE'S A COUPLE QUANDARYS
HERE, ONE IS ONCE THAT PERSON
NOW--YOU'VE CHANGED THE GERM
LINE IN THAT PATIENT BECAUSE IF
IT'S A FEMALE, THE NEW
MITOCHONDRIA AND THAT'S WHY IT'S
CALLED THIRD PARENT PROCREATION
IS THAT THIRD--THAT NOW THAT
MITOCHONDRIAL PASSED ON FROM
GENERATION TO GENERATION.
BECAUSE THIS IS COMPLICATED
BECAUSE THE MITOCHONDRIA,
DOESN'T GIVE YOU MUCH, IT'S NOT
IDENTIFIABLE.
YOU DON'T LOOK A SPECIAL WAY
BECAUSE OF THE MIGHT O CHOND
RIATHERE IS ONE CAVEAT HERE IN
THAT IT COULD--THERE ARE ANIMAL
EXPERIMENTS THAT SHOW THAT ONE
MILT O CHOND RIA IS DIFFERENT
THAN A MITOCHONDRIA AND THAT
SOME MITOCHONDRIA HAVE MORE
ENERGY ASSOCIATED WITH IT.
SO YOU KNOW, IF YOU HAVE--YOU
WANT TO HAVE AN ATHLETE, YOU
TAKE THE MITOCHONDRIA FROM A
WOMAN WHO'S A MAR RAATHON
RUNNENER THE--MARATHON RUNNER IN
THE OLYMPIRKS.
SO THAT'S ONE FACET OF THIS.
THE OTHER IS THAT THE FDA
BECAUSE IT'S THE RESULT OF A
TRANSPLANT, THE FDA IS GOING TO
WEIGH IN ON THIS AND TO REGULATE
IT.
SO IT'S ALSO INTERESTING BECAUSE
IT WILL TRICKLE DOWN TO THE
WHOLE FIELD.
SO THIS IS--THIS IS A
DYNAMICALLY GROWING FIELD.
THERE ARE LOTS OF QUESTIONS.
WE'VE DONE GREAT.
WE'VE DONE GREAT THINGS IN THE
LAST 30 YEARS BUT WE'VE RAISED A
NUMBER OF INTERESTING QUESTIONS.
NOW I'LL GIVE MY ANSWER TO THE
MITOCHONDRIAL QUESTION AS FAR AS
ETHICS ARE CONCERNED.
THE CHILD HAS THREE OPTIONS TCAN
BE BORN WITH SEVERE
MITOCHONDRIAL DISEASE, BORN FREE
OF DISEASE, OR NOT BE HERE AT
ALL AND AS A PHYSICIAN, THE
MIDDLE ONE IS THE BEST ONE TO BE
AND ON THAT NOTE I'LL STOP.
THANKS.
[ APPLAUSE ]
[INAUDIBLE QUESTION FROM
AUDIENCE]
>> THOSE THAT MAKE SPERM SURVIVE
AND THOSE THAT DIDN'T MAKE
SPERM, THAT BRAND DISAPPEARED SO
IT'S SURVIVAL OF THE FITTEST
ESSENTIALLY.
>> OKAY, THANK YOU.
>> SO WHAT ABOUT--THERE'S THIS
QUESTION OF--THAT POPS UP IN THE
NEWSPAPERS AND MORE JOURNALS OF
THE CLAIM WHEN THEY FOLLOW KIDS
WHO WERE BORN BY INVITRO
FERTILIZATION THAT THEY'RE
SHORTER OR NOT SO SMART OR GREEN
HAIR OR ALL KINDS OF BUSINESS,
IS THERE ANYTHING TO THAT? 
>> THE'S NO EVIDENCE OF ANY
PROBLEM, THESE KIDS THAT ARE
BORN THAT WAY.
NOW, THERE IS--THE ONLY THING
THAT'S DOCUMENTED IS THAT
THERE'S A SLIGHT INCREASE IN
CONGENITAL ANOMALIES IN THESE
OFFSPRING.
AND THERE ARE METHYLATION
PROBLEMS LIKE DECAWEED MEN OR
HAD--I'M NOT TRYING TO MINIMIZE
IT BUT THESE ARE ALL.
NOW LET'S SAY CONGENITAL
ANOMALIES, THE AVERAGE
CONGENITAL ANOMALY RATE IN A
NORMAL CONCEPTION IS FOUR%.
IN A--WELL POST IVF SEEM
PARALLEL AND 7 PERCENT, SO THE
PAPER SAYS IT'S TWICE AS HIGH,
IF YOU GO FROM FOUR TO SEVEN,
THAT'S FAIR ENOUGH THAT THIS
PLACE IS HIGH, BUT TO A COUPLE
WHEN YOU TELL THEM YOU HAVE THE
93% CHANCE OF A INARMAL CHILD,
COMPARED TO A 90--96% CHANCE
THAT IT DOESN'T DISSUADE, I MEAN
WE INFORM THEM BUT IT DOESN'T
DISSUADE PATIENTS BUT I'LL TELL
YOU AN INTERESTING PAPER, WE
DIDN'T PUBLISH IN THE--ACTUALLY
IT WAS JUST KIND OF PUBLISHED, I
DON'T KNOW IF IT WAS THE SAME
PEOPLE OR NOT, BUT IN THE BAY
AREA, FAYE FOBBED THAT PATIENTS
THAT WERE BORN FROM IVF HAD A
HIGHER INCIDENCE OF AUTISM THAN
THE GENERAL POPULATION.
BUT THE TRUTH IS, THIS IS A BAD
POPULATION STUDY AUTISM, NUMBER
ONE THE PEOPLE THAT  CAN AFFORD
IT ARE PRETTY MUCH IN THE
COMPUTER INDUSTRY IN THAT AREA,
THEY'RE USUALLY IN THE COMPUTER
AREA WHEN THEY'RE OLDER BECAUSE
THEY'RE SLIGHTLY NOT SOCIALLY
WELL ADEPT AND MANY PEOPLE IN
THAT AREA, IN THAT INDUSTRY, YOU
OW HAVE--THEY'RE COMPROMISED.
THEIR AUTISM SPECTRUM PATIENTS
ANYWAY.
>> SO, IT'S HARD TO
DIFFERENTIATE WHETHER THIS IS
PRECLUDED OR WHETHER IT IS AN
EFFECT OF IVF, BUT OTHER
POPULATIONS HAVE--THEY'VE LOOKED
FOR THAT AND THEY HAVEN'T FOUND
THAT.
SO IT'S--BY AND LARGE, THIS IS A
GOOD OUTCOME.
THIS IS A--IT'S A GOOD OUTCOME
FOR PATIENTS BUT THAT DOESN'T
MINE IT SHOULDN'T BE CONTINUED
TO BE STUDIED AND ONCE THE FDA
GETS INVOLVED, IN THIS, THEN
THERE WILL BE CERTAINLY BETTER
MONITORED.
>> SO WE SHOULD ADD TO THE
FORMULA THAT IT SHOULD BE A
YOUNG MAN, A YOUNG WOMAN AND
SOMEBODY WHO'S NOT IN THE
COMPUTER INDUSTRY.
[LAUGHTER]
>> WELL I TRIED TO DO AN
EXPERIMENT, HAVE AN ISLAND
SOMEWHERE IN THE CARIBBEAN, WITH
YOUNG WOMEN AND BRING OLDER MEN
IN, HAVE THEM PROCREATE THESE
WOMEN SO WE CAN SEE--WE HAVE
MANY, MANY MEN VOLUNTEERING BUT
NO WOMEN WOULD VOLUNTEER FOR THE
STUDY.
>> HOW LONG HAVE YOU HAD ANY
OTHER QUESTIS?
>> [LAUGHTER]
>> MICROSOFT ANNOUNCED TODAY, I
READ IT QUICKLY IN THE PAPER
THIS MORNING THAT THEY ARE GOING
TO BE HIRING FOLKS WITH
ASPERGERS, BECAUSE THEY REAL
REAL HAVE FANTASTIC ATTENTION TO
THE LEVEL OF DETAIL ESPECIALLY
LIKE FOR COMPUTER DEBUGGING.
>> YEAH, I SAW THAT WELL THATTA
A FACT.
MANY PEOPLE IN THAT INDUSTRY ARE
ASPERGERS, AND YOU KNOW THEY
HAVE SPECIAL TALENTS.
>> WELL, WAIT A MINUTE WE
SHOULDN'T GET INTO THAT--LISTEN,
THANK YOU.
>> DON'T FORGET WHERE YOU WORK.
>> WE'LL CUT THAT OUT JOSEPH.
>> LISTEN, THANK YOU BOTH, VERY,
VERY MUCH.
THAT WAS VERY INFORMATIVE AND
EXCITING.
01:19:49.600,00:00:00.000
[ APPLAUSE ]
