Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
WELL WOMAN EXAM
Trying to become pregnant
Try to not become pregnant
Not at risk to become pregnant
Start folic acid if at risk to become pregnant
PRE CONCEPTUAL COUNSELING
-FOLIC ACID TO PREVENT NEURAL TUBE DEFECT
-RUBELLA STATUS
-CYSTIC FIBROSIS SCREENING,TAY-SACH (Jewish Heritage),SICKLE
CELL
-DIABETICS: NEED FOR STRICT CONTROL BEFORE TRYING TO
BECOME PREGNANT
-DISCUSS RISK OF SMOKING, ALCOHOL AND DRUGS
-DISCUSS AGE RELATED GENETIC RISK
FERTILITY UPDATE
20-25% OF COUPLES WANTING A BABY MAY HAVE PROBLEMS
GETTING PREGNANT
INFERTILITY
WHEN PREGNANCY DOES NOT OCCUR WHILE ACTIVELY TRYING
TO BECOME PREGNANT FOR GREATER THAN ONE YEAR
WHEN TO SEEK HELP SOONER
VERY IRREGULAR MENSTRAL CYCLES
PAST HISTORY OF SERIOUS PELVIC INFECTION
AGE GREATER THAN 35 YEARS
CHECKING THE BASICS, SPERM--MALE FACTOR
ADEQUATE NUMBERS
ADEQUATE MOVERS
GOOD SWIMMERS
GOOD QUALITY
GOOD AMOUNT
>2O MILLION /CC
>50% MOTILITY
GRADE III OR IV (motility)
>30% OVAL
VOLUME 2-5 CC
FERTILE PERIOD
LIFE SPAN OF SPERM 5 DAYS
LIFE SPAN OF EGG 12-24 HRS
SPERM PROCESSING LIFE SPAN 10-12HRS?
CHECK THE BASICS UTERINE TUBAL
-IS THE UTERINE CAVITY NORMAL?
POLYPS -- FIBROIDS -- ADHESIONS --ABNORMAL SHAPE
-IS THE TUBE NORMAL AND CAN IT PICK UP THE EGG?
-CAN THE FERTILIZED EGG PASS DOWN THE TUBE INTO THE UTERUS TO IMPLANT?
-ARE THERE OTHER PERITONEAL FACTORS SUCH AS
ENDOMETRIOSIS?
HYSTEROSALPINGOGRAM
-SMALL CATHETER INSERTED INTO THE UTERUS
-SMALL BALLOON KEEPS THE DYE FROM RUNNING BACK OUT
-INJECT DYE TO SEE THE UTERINE CAVITY AND SEE IF ONE OR
BOTH TUBES FILL AND SPILL
-MAY BE BENEFICIAL TO “FLUSH THE TUBES”
Hysterosalpingogram
Balloon filling lower
segment (uterus), look for
die in surrounding areas,
don’t want to see dumbbell
shape, stretching, that
would be a hydrosalphinx.
HYSTEROSCOPE
-TELESCOPE USED TO VIEW INSIDE OF THE UTERUS
-MAY REMOVE POLYPS, FIBROIDS OR IMPROVE SHAPE OF THE
UTERUS
-USUALLY DONE WITH LAPAROSCOPY UNDER ANESTHESIA
MALE FACTOR TREATMENT
-EVALUATION BY UROLOGIST OR ENDOCRINOLOGIST
-VARICOCELE
-HORMONE STUDIES?
-SPERM PROCESSING WITH INTRAUTERINE INSEMINATION
(WASH AND SPIN)
-ASSISTED REPRODUCTION WITH ICSI (INTRACYTOPLASMIC
SPERM INJECTION) – Last resort bc of price.
CHECKING THE BASICS CERVICAL MUCOUS FACTOR
-GOOD QUALITY MUCOUS
-100 MILLION SPERM DEPOSITED IN THE VAGINA WITH
INTERCOURSE
-500,000 MAKE IT INTO THE UTERUS
-100,000 GET INTO THE TUBE TO FIND THE EGG
-WASH AND SPIN DEPOSIT MILLIONS OF SPERM INTO THE
UTERUS (safe, hasn’t seen one chemical rxn in his pts)
Post Coital Test
-Mid cycle test to see if the sperm are alive and moving 2-6 hrs after
intercourse
-Aspirate mucous from the cervical OS with a small catheter
-Place mucous on a slide and observe under a microscope
-Want to see more than 15 motile sperm per HPF
-Result of this test does not correlate well with whether or not one
achieves pregnancy
TREATMENT OF ABNORMAL POST COITAL TEST
IMPROVE THE MUCOUS
ESTROGEN
ROBITUSSIN (ALSO AVAILABLE IN PILL FORM)
BYPASS THE MUCOUS
“WASH AND SPIN”
Broad based area, cut across septum, can see space is open on top R.
LAPAROSCOPY
TELESCOPE THROUGH THE UMBILICUS TO LOOK DIRECTLY AT
THE UTERUS, TUBES AND OVARIES
MAY BE ABLE TO CUT ADHESIONS, OPEN BLOCKED TUBES AND
TREAT ENDOMETRIOSIS
REQUIRES GENERAL ANESTHESIA
Very expensive! See fibroids, endometriosis, pain, etc. than do it.
Many image examples of laparoscopy followed in the lecture..
Injected blue dye. It doesn’t spill out. Cutting off of adhesions. Pt
conceived a month after surgery. There is also an example of
endometriosis (brown spots), cauterize them. Large chocolate cyst
is also seen on ovary, cut it open it would be brown. Can pull wall
of cyst away from the ovary. Leave ovary open and it heals without
significant scarring.
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Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
OPEN MICROSURGERY
-INCISION TO REMOVE LARGE OVARIAN CYSTS OR LARGE
FIBROIDS
-MICROSCOPE MAY BE NEEDED IF EXTENSIVE ADHESSIONS
AROUND THE TUBES
-TREATMENT OF EXTENSIVE ENDOMETRIOSIS OR TO REMOVE
LARGE FIBROIDS
-DR TED NAGEL CONSULTS FROM UNIV. OF MINN. EVERY OTHER
MONTH
CHECKING THE BASICS OVULATION
-PITUITARY GLAND RELEASES FSH TO STIMULATE THE OVARY TO
MAKE EGG/EGGS
-EGG GROWS IN A FOLLICLE WHICH PRODUCES ESTROGEN TO
STIMULATE GROWTH OF THE UTERINE LINING TO GET READY
FOR PREGNANCY
-PITUITARY TELLS THE OVARY TO RELEASE THE EGG(S) (LH
SURGE)
-OVARY: FOLLICLE BECOMES THE CORPUS LUTEUM PRODUCING
PROGESTERONE TO CHANGE THE UTERINE LINING TO GET
READY FOR PREGNANCY.
EGG IS RELEASED IN 36-40. HRS IF NO PRIOR LH SURGE HAD
OCCURRED.
-PROGESTERONE BLOOD TEST - IF > 5 NGM OVULATION HAS
OCCURRED
CLEAR PLAN BLUE FERTILITY MONITER
-HAND HELD FERTILITY MONITER (COMPUTER THAT CAN
PERFORM ASSAYS)
-DISPOSABLE TEST STRIPS THAT DETERMINE BOTH ESTROGEN
AND LH LEVELS IN THE URINE
-HOLD STRIP IN URINE STREAM FOR 3 SECS
-PLACE IN THE MONITER AND GET RESULTS IN 5 MIN:
LOW FERTILITY
HIGH FERTILITY 1-5 DAYS
PEAK FERTILITY 1-2 DAYS (99%)
-IF HIGH GREATER THAN 3-5 DAYS,ULTRASOUND WILL
GENERALLY CONFIRM A GOOD FOLLICLE AND HCG TRIGGER CAN
BE GIVEN TO INDUCE OVULATION
Monitor goes up when estrogen is above a threshold.
Pit gland gonadotropin releasing factors, release FSH, at mid cycle follicle is
size quarter, ovary produces E, thickens lining. Waiting for LH surge,
detectable in urine for two days, tells the proper time for insemination.
POD pts don’t have LH, but can supplement B-hCG to assimilate LH release.
Retrieve eggs at 36 h. Corpus luteum produces progesterone, so that
menstruation does not occur & preg can carry. Prog less than five may be
assctd with ectopic or tubal pregnancy. It needs to be higher for a good
pregnancy. Can supplement progesterone at the time and pregnancy may
be normal.
PREGNANCY
IF PREGNANCY OCCURS, THE PREGNANCY HORMONE (HCG)
TELLS THE OVARY TO KEEP MAKING PROGESTERONE TO
PREVENT MISCARRIAGE
-IF < 5 NGMS POOR PREGNANCY OUTCOME
-IF >25 NGMS USUALLY GOOD OUTCOME
-IF BETWEEN 5 AND 15 PROGERTERONE MAY REDUCE -THE CHANCE OF MISCARRIAGE ESPECIALLY IF
BLEEDING AND /OR CRAMPING IS PRESENT
CHECKING THE BASICS OVULATION
-BASAL BODY TEMPERATURE - DAILY TEMP / GOES UP AFTER
OVULATION / HARD TO INTERPRET
-OVULATION STICKS - DAILY URINE CHECK FOR LH / GIVES 24-40
HR WARNING THAT THE EGG(S) IS GOING TO BE RELEASED /
HARD TO INTREPRET IF PCO AS THE LH MAY ALWAYS BE
ELEVATED
-ULTRASOUND - VAG. PROBE TO OBSERVE THE OVARIES / AT MID
CYCLE FOLLICLE >16 MM DIAMETER SHOULD PASS WITH LH
SURGE OR HCG TRIGGER SHOT
-HCG IS VERY SIMILAR STRUCTURALLY TO LH AND MAY BE GIVEN
IN ITS PLACE. AFTER 10,000 IU OF HCG IS ADMINISTERED,THE
OVULATORY Disorders Who Classification
-CLASS 1 HYPOGONADOTRPIC-HYPOGONADOL ANAVULATION (510%)
-CLASS 2 NORMOGONADOTROPHIC-NORMOESTROGENIC ANOVULATION (70-85%)
CLASS 3 HYPERGONADOTROPIC-HYPOESTROGENIC
ANOVULATION (10-30%) – High FSH, LH & low E (menopause,
premature ovarian failure)
USs: lining greater than 8 mm is good if trying to get preg (uterus).
Looking at the ovary, follicles are black circles that represent fluid.
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Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
Class1 HYPOGONADOTROPIC-HYPOGONADAL (dec FSH, LH
hormones, dec Testosterone)
DO NOT GENERALLY WITHDRAW TO PROGESTERONE
LOW BODY WT (BMI <17 KG/M2)
EXCESSIVE EXERCISE
EATING DISORDERS
GENERALLY WILL NOT RESPOND TO CLOMIPHENE
WILL RESPOND TO INJECTABLE FSH
Class 3 HYPERGONADOTROPIC-HYPOESTROGENIC (inc FSH, LH,
dec E)
DO NOT WITHDRAW TO PERGESTERONE
DO NOT RESPOND TO CLOMIPHENE
DO NOT RESPOND TO FSH INJECTION
CONSIDER INVITRO-DONOR EGGS
Class 2 NORMOGONADOTROPIC-NORMOESTROGENIC (norm FSH,
LH & normal E)
WITHDRAW TO PROGESTERONE (worry about uterine hyperplasia)
OFTEN OBESE (BMI.>27KG/M2)
MAY RESPOND TO WT LOSS (5-10% BODY WT)
GENERALLY RESPOND TO CLOMIPHENE
RESPOND TO FSH INJECTION
MAY RESPOND TO METFORMIN
POLYCYSTIC OVARIAN DISEASE
POLYCYSTIC OVARY SYNDROME
6-10% WOMEN OF CHILDBEARING AGE
IRREGULAR MENSES
ANOVULATION
INSULIN RESISTANCE
ANDROGEN EXCESS
(OBESITY)
INSULIN RESISTANCE AND PCO
-INCREASED INSULIN LEVELS STIMULATE THE OVARY TO
PRODUCE MORE ANDROGENS
-INCREASED ANDROGENS IMPEDE OVULATION
METFORMIN AND INSULIN RESISTANCE
LOWERS INSULIN LEVEL IN PCO PATIENTS
REDUCES LH LEVELS
INCREASES FSH AND SHBG (SEX HORMONE BINDING GLOBULIN)
REDUCES FREE TESTOSTERONE 49%
REDUCES TOTAL TESTOSTERONE 52%
MAJORITY RESUME NORMAL MENSES BY 8 WEEKS
MAY NOT WORK IN MORBIDLY OBESE
METFORMIN VS CLOMID
OVULATION METFORMIN 12/35 34%
PLACEBO/CLOMID 2/25 8%
PLACEBO
1/26 4%
METFORMIN/+- CLOMID 83%OVULATED / 39% PREGNANCY
METFORMIN IN PREGNANCY
STOP METFORMIN 64% SPONT AB
CONT METFORMIN 12% SPONT AB
PCO NO METFORMIN 58% GEST DIAB
PCO CONT METFORMIN 4% GEST DIAB
PLASMINOGEN ACTIVATOR INHIBITOR (PAI) CAUSES PLACENTAL
INSUFFICIENCY BY REDUCING THE LYSIS OF THROMBI IN THE
PLACENTA INCREASES AS INSULIN LEVELS INCREASE.
METFORNIN REDUCES PAI ACTIVITY
Side effects of diarrhea, bloating, rare lactic acidosis, so do renal
analysis.
Stay on it once preg. Less risk for miscarriage.
OVULATION ENHANCERS - CLOMIPHENE
-CLOMIPHENE – SELECTIVE ESTROGEN RECEPTOR
MODULATORS – binds recs in hypoth and uterus. Has long half-life,
lose negative feedback, can result in many follicles being ready to pass.
-HAS BOTH ESTROGEN ANTAGONISTIC AND AGONIST EFFECTS
THAT INCREASE GONADOTROPIN (FSH) RELEASE
-MAY PRODUCE MULTIPLE EGGS
-NEGATIVE EFFECT ON CERVICAL MUCOUS AND ENDOMETRIAL
LINING
-TWINS 2-5%, OCCASSIONAL TRIPLETS OR HIGHER ORDER
MULTIPLES
-HYPERSTIMULATION SYNDROME POSSIBLE
-QUESTION OVARIAN CANCER RISK AFTER 12 CYCLES
CLOMOPHENE
-ADMINISTRATION OF CLOMID RESULTS IN EST RECEPTOR
DEPLETION AT PITUITARY AND MEDIOBASAL HYPOTHALMOS
-CLOMID PROLONGED EFFECT OF ER DEPLETION PREVENTS
NEG EST FEEDBACK THEREFORE MORE EGGS, GREATER RISK
OF MULTIPLES
OVARIAN ENHANCERS AROMATASE INHIBITORS
-AROMATASE IS A MICROSOMAL CYTOCHROME P450 –
CONTAINING ENZYME (P450arom), THE PRODUCT OF THE CYP19
GENE THAT CATALYZES THE RATE LIMITING STEP IN THE
PRODUCTION OF ESTROGENS: THE CONVERSION OF
ANDROSTENEDIONE AND TESTOSTERONE VIA THREE
HYDROXYLATION STEPS TO ESTRONE AND ESTRIOL.
-LETROZOLE IS APPROVED FOR THE TREATMENT OF BREAST
CANCER
LETROZOLE
-LETROZOLE TAKEN DAY 3-7 REDUCES ESTROGEN LEVELS BY
97% BUT IS RAPIDLY CLEARED (30-60HR ½ LIFE) ALLOWING
RETURN OF NEG EST FEEDBACK AND GENERALLY RELEASE OF
ONLY 1 EGG
-AROMATASE INHIBITORS MAY ALLOW INCREASED SENSITIVITY
TO FSH BY ALLOWING TEMPORARY ACCUMULATION OF
INTRAOVARIAN ANDROGENS
-LETROZOLE HAS LESS SIDE EFFECTS (HOT FLASHES, NAUSEA
EMESIS,HEADACHE,BACKACHE) THAN CLOMIPHENE
-LETEROZOLE LESS NEGATIVE EFFECT ON UTERINE LINNING
AND CERVICAL MUCOUS
-PREGNANCY RATE LET 16.7% CC 6.5%
-TWIMS LETROZOLE 2% CC 5-% /OCC TRIPLETS
Letrozole Warning True or False?
-Novartis durg manufacturer warns against use as ovulation inductor
-Montreal Fertility Clinic study reports 4.7% rate of major anomalies
compared with control of 1.6% of 36,000 low risk deliveries. (study
group 150 babies 2x usual dose of letrozole) 15% OF STUDY
PREGNANCIES WERE TWINS
Letrozole Warning True or False
-Terminal elimination half life 2 days
-Steady state is not reached for 2-6 weeks
-Fetal exposure to letrozole more likely to result in abnormal female
sexual development
-One breast cancer patient exposed to letrozole during second trimester
had genital abnormalities
-FDA approval of letrozole is only for treatment of breast cancer
-Dr Casper Univ of Toronto no birth defects in 200 letrozole births
-Growing body of literature supporting aromatase inhibitors in fertility
therapy
-Most major anomalies in Biljans control group would have been referred
to specialist prenatally and may not have shown up as adverse
outcomes
OC-CLOMID VS CLOMID
CLOMID ONLY 2/24 8% OVULATED
OC-CLOMID
17/24 71% OVULATED
CLOMID ONLY 1/24 4% PREGNANT
OC-CLOMID
14/24 60% PREGNANT
INJECTABLE RX
BASELINE US ESTRADIOL
INJECTIONS FSH X4-5 DAYS
REPEAT US /ESTRADIOL
INJECTIONS 2-3 DAYS
HCG TRIGGER WHEN 1-3 FOLLICLES >16MM
W&S INSEMINATION
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Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
INJECTABLE RX
COST $3500
PREGNANCY RATES 10-15%
RISK MULTIPLES TWINS >20% TRIPLETS +
RISK HYPERSTIMULATION SYNDROME
1% CAN BE LIFE THREATENING
INCREASING THE ODDS IN VITRO MODEL
GET MORE EGGS
CLOMIPHENE
FSH INJECTIONS
GET MORE SPERM INTO THE UTERUS
WASH AND SPIN
BYPASS THE MUCOUS
INTRAUTERINE INSEMINATION
BETTER TIMING
ULTRASOUND AND HCG TRIGGER
CLEAR PLAN MONITER
SUPPORT THE LINING
ORAL PROGESTERONE
VAGINAL PROGESTERONE (CRINONE)
PROGESTERONE INJECTIONS
EARLY PREGNANCY TESTING
EARLY PREGNANCY ULTRASOUND
DRUG COSTS
METFORMIN 500MG TID
METFORMIN 1000MG BID
LETROZOLE 2.5MG D 3-7
CLOMID 50MG D3-7
CLOMID 100MG D3-7
INJECTABLES
$58.59/MO
$76.79/MO
$43.99/MO
$27.19/MO
$48.99/MO
>$1000/MO
OTHER NORTHLAND OB GYN PROGRAMS
-ADOPT A SPERM
FROZEN DONOR SPERM PROGRAM
-ADOPT AN EMBRYO
SNOWFLAKE.COM
-ART SATELLITE FOR DR. NAGEL UNIV. OF MINN. PROGRAM
-REFER FOR ADOPTION
ASSISTED REPRODUCTION
OVULATION STIMULATION
MONITER CYCLE
HCG TRIGGER
RETRIEVAL AND FERTILIZATION
EMBRYO TRANSFER
LUTEAL PHASE SUPPORT
PREGNANCY SUPPORT
RMIA ART STATISTICS
Age Retrievals Chem
Clinical
<30
345
231(67%)
193(56)
30-34 928
578(62%)
485(52)
35-40 746
451(60%)
365(48)
>40
137
53 (39%)
39(28)
Cumulative 2156 1313(61) 1018(50)
Ongo
177(51)
438(47)
298(40)
27(20)
940(43.6)
ART:COST SHARING
$3,000 ADM COST(NON REFUNDABLE)
$14.000 ESCROW ACCOUNT
$3,000 PER CYCLE COST
USE FROZEN EMBRYOS
$3000 SECOND CYCLE PLUS FROZEN
$3,000 THIRD CYCLE PLUS FROZEN
REFUND ESCROW IF NO VIABLE PREGNANCY
(PER CYCLE COST $10,000)
ASSISTED REPRODUCTION
Base cost $6,000 +$3000(meds)
Additional options:
ICSI $1,000
ASSISTED HATCHING $400
FROZEN EMBRYO TRANSFER $1,330
EMBRYO CRYOPRESERVE $1,000
EMBRYO STORAGE
$480/YR
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Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
HOPE PROGRAM RMIA
MATERNAL AGE <35
COST $25,000
3CYLCLES WITH ANY FROZEN EMBRYOS TRANSFERRED
TOTAL REFUND IF NO VIABLE PREGNANCY
ECONOMICS AND INFERTILITY
INSURANCE MAY OR MAY NOT COVER FERTILITY TREATMENT
MAY COVER DIAGNOSIS ONLY
MAY LIMIT TREATMENT TO SIX CYCLES
MAY COVER INJECTABLES ($3,000/CYCLE)
USUALLY WILL NOT COVER ART
MAY HAVE TOTAL $ AMOUNT
ETHICAL CONSIDERATIONS
IS PREGNANCY A RIGHT?
ADOPTION REQUIRES HOME VISIT
PSYCHOLOGIC ASSESSMENT?
MARRIAGE IS BETWEEN ONE MAN-ONE WOMEN. SAME SEX
COUPLES?
SHOULD MEDICAL ASSISTANCE PAY FOR FERTILITY TREATMENT?
MULTIPLE PREGNANCY ASSOCIATED WITH FERTILITY RX
Questions:
1. What should you have our patient start if at risk to become
pregnant?
a.
Riboflavin
b. Iron
c.
Folic Acid
d. Vitamin B12
e.
Thiamine
2. What is the definition of infertility?
3. What is used to view inside the uterus and may remove polyps,
fibroids, or improve shape of the uterus?
4. Progesterone should be greater than ____ for a pregnancy to have
a good outcome.
5. A pt with a BMI <17 kg/m2 who is training for a marathon is
having troubles conceiving is most likely in which Classification
of Ovulatory Disorders.
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Fertility Update. Sebastian. Katelyn Rogers. 03.09.10.
Answers:
1. C
2. WHEN PREGNANCY DOES NOT OCCUR WHILE ACTIVELY
TRYING TO BECOME PREGNANT FOR GREATER THAN ONE
YEAR
3. Hysteroscope. Also note this is usually done with laparoscopy
under anesthesia.
4. 25
5. Class 1 Hypogonadotroic-Hypogonadal.
6