reproductive technologies & counseling patricia kloser, md, mph, facp professor of medicine...
TRANSCRIPT
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Reproductive Technologies &
Counseling
Patricia Kloser, MD, MPH, FACP
Professor of Medicine
Professor of Public HealthJune 2006
UMDNJ, a Local Performance Site
of the NY/NJ AETC
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Objectives
Transmission risksPregnancy optionsInfertilityTreatment options
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Transmission Risks
HeterosexualVertical
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Risk of Transmission
Unprotected vaginal intercourse– Male to female = 3% to .01% per contact– Female to male = 10% to 17% less efficient
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HIV in Body Fluids
BloodSemenCervical secretionsBreast milkSpinal fluid
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HIV in Semen
Higher in acute HIV infection in menCorrelation between viral levels of HIV in blood
and semenMen hyperinfectious before symptoms of HIV
infection occur (lasts 6 weeks)Could infect 7 to 24% of partners during first 2
months of infectionSTD would increase this rate (in either partner)
JID 2004; 189:1785-1792
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U.S.
HIV-1 RNA in Cervical Secretions– Varies in menstrual cycle (due to hormone variation)– Highest just before menses start– Risk of transmission riskiest as menses approach– Lowest level at mid-cycle– Explains increase of HIV in cervical secretions in
women on oral contraceptives– No increase of cervical shedding in menses– Less variation in serum than genital secretions– Less virus in vaginal than cervical in secretions
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Heterosexual Transmission Risks Increase With
Genital ulcer or STDCervical ectopyMale partner not circumcisedSex during mensesBleeding during intercourseReceptive anal intercoursePartner with high viral load
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Risk of Vertical-Transmission
Mother - cigarette smoking - older maternal age
- high viral load - low CD4 - vaginal delivery - prolonged rupture of membranes
>4hrs- acute HIV infection
Baby - prematurity- breastfeeding
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Vertical Transmission
In utero - <10%Peripartum – 40 – 70%Breastfeeding – 0.5% per month riskMost important factor is viral load
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Vertical Transmission Rate
Total rate – 13% to 60%U.S. – 25% to 30%Europe – as low as 13%Africa – 50% to 60%
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MTCT with ARV (U.S.)
Treatment– None
– AZT
– HAART
– HAART
Transmission– 24.5% (WITS 1993)
– 7.6% (ACTG 076 1994)
– <1% (2006)
– 7 cases NJ (2004)
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Viral load and MTCT (U.S.)
Mother’s viral load– <1000– 1000 to 10,000– 10,000 to 50,000– 50,000 to 100,000– More than 100,000
– Garcia, et al NEJM 1990;341:394
Transmission rate– 0%
– 16.5%
– 21.3%
– 30.9%
– 40.6%
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Vertical Transmission with Treatment
U.S. – with HAART <1%Developing Countries
– PMTCT reduces transmission by 50%
Nevirapine – 200mg to mother
- 6ml to babyOr equivalent AZT dose
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Viral load in Genital Secretions & MTCT (Thailand)
Plasma VL HIV in CVL Transmission rate
>10,000 Yes 28.7%
>10,000 No 1.5%
<10,000 Yes 15.0%
<10,000Chuachoowong et al
JID 2000:181-105
No 1.0%
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Cesarean Delivery
AZT C/S Transmission rate
No
No
Yes
Yes
International Perinatal HIV Group NEJM
1999:340-977
No
Yes
No
Yes
18%
10.4%
7%
2%
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Cesarean Section
Elective cesarean section before rupture of membranes or onset of labor usually at 37-39 weeks may further decrease vertical transmission
Not routinely done unless mother requests or if the viral load is high
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Pregnancy Options
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Pregnancy
Does not affect disease progressionLowers CD4 countShould not use Stavudine and ddi togetherNo Efavirenz in the first trimester
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In unprotected vaginal intercourse leading to pregnancy the risks are twofold:– Partner’s risk of infection– Baby’s risk of infection
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Risk to Partners
Expense (depending on method)Possibility of HIV infection (depending on
method used)Possibility of passing “resistant” HIV to
infected partnerTime consuming (depending on method
used)
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Negative FemalePositive Male
Timed unprotected intercourse (as above) not recommended
Intrauterine insemination (IUI) after “sperm washing”
Intracytoplasmic sperm injection (ICSI) one sperm-one egg with zygote implanted in uterus (aliquots tested for cell free virus) via laser manipulation
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Negative MalePositive Female
Timed unprotected intercourse (using basal body temperature monitoring)
“Turkey baster” method self inseminationOvarian stimulation with artificial
insemination (partner/donor)In vitro fertilization (ova harvested and
fertilized outside of body and then implanted in hormonally stimulated uterus)
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Positive MalePositive Female
Remember undetectable viral load in serum does not mean undetectable genital viral load
It may be possible to impart resistant virus from one partner to the other
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Superinfection
Controversial5 published verified casesAppears to occur but difficult to verifyUsually occurs shortly after initial infection less
likely later onPositive partners study on-goingHIV positive people prefer other HIV positive
people
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Reproductive Decisions
Artificial insemination Invitro fertilization Intracytoplasmic sperm injection – most
expensiveSelf inseminationTimed intercourseTransmission rates MTCT <1% in women with
VL <1000 copies in U.S.
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U.S.
Timed intercourse:– Condoms at all times
– No condom during fertile times
– 4% transmission rate (for female if male HIV+)
– Men – semen sample – count motility, progression, morphology
– Women – ultrasound during follicular phase and endocrine profile
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U.S.
Self insemination– Women inseminate themselves with fresh
semen using syringe (without needle) or disposable Pasteur pipette (cheap, safe)
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U.S.
IVF – for infected male for uninfected female sperm processed and single sperm used to fertilize egg of HIV infected woman
No seroconversion and no HIV+ infants(intracytoplasmic sperm injection) $$$$
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Sperm Washing
Infected male followed by intrauterine insemination
29% success rate for pregnancyNo seroconversion of females
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Sperm Washing
For use in cases where male is HIV+ Ejaculate is processed in laboratory separating
semen from sperm cells These cells are then reinserted into female (in
vivo) or inserted into ovum (in vitro) for fertilization
This process will reduce possibility of infecting HIV negative woman
This process will reduce chance of re-infection of HIV positive woman with resistant viral strain
Problems – expense, technical availability, needs cooperative couple and committed obstetrician
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Patient Considerations
Healthy No active OI CD4 >350 VL <50,000 Woman must have normal PAP or normal colposcopy If Hepatitis C must have normal liver enzymes and
hepatology consult Been on HAART for 1 year Male semen sample No unprotected sex during this time
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Laboratory Considerations
Cross contamination is a concernMust have separate freezers and storage for
samplesMay be difficult regarding food facilitiesMilan, Italy criteria and Columbia
University in NYC doing this work
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U.S.
Assisted reproductive techniques– Expensive $10,000 to $17,000 per cycle– Many (most) cannot afford this expense– VL undetectable– CD4 >400
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Goals of these Reproductive Options
Achieve pregnancyAvoid transmission of HIV to
mother, father or babyGive woman choice regarding
pregnancy
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Risk to Fetus
Multiple fetusesLow birth weightPre-term delivery
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Infertility
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Infertility
HIV positive and HIV negative workup is no different
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Infertility
One year of unprotected intercourseHistory/sexual practicesSperm evaluationUrologic evaluationGYN evaluationAppropriate treatment
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Infertility Treatment
Based on problemMany have no particular medical
issue and diagnosis of etiology can’t be determined
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Male Infertility
Male causesSperm - poor quality
- poor quantity
- poor motilitySemen - poor quality
- poor quantity
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Male Infertility
Anatomical - obstruction
- hypospadia
- varicocele
- injury
- retrograde ejaculation Endocrine - low testosterone Genetic - Klinefelters, etc. Psychiatric - depression
- low libido
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Male Infertility
SuggestionsStop smoking Avoid tight fitting pants (male), bicycle
ridersTiming of intercourseAppropriate weightHealthy life style
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Female Infertility
Endocrine - thyroid, pituitary, adrenal insufficiency
Genetic - polycystic ovaries, Turners
Psychiatric - depression
- low libido
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Female Infertility
Female causes Ova - poor quantity - poor quality – age,
nutrition, injury, illness Anatomical - obstructed fallopian tubes
- poor motility of cilia in fallopian tubes
- uterine lining abnormality fibroid- endometriosis
- uterine anatomy
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Treatment Options
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Minimal MTCT Risk
With serum VL <1000No breastfeedingWoman on HAART
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Factors Associated with Vertical Transmission
High viral loadAcute HIV infectionOlder maternal ageCigarette smokingProlonged rupture of membranes
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U.S.
Pregnancy– Lopinavir with Ritonavir – levels 50% lower
in third trimester– Levels still adequate but study needed– Efavirenz – not in 1st trimester– Nevirapine – watch liver function– D4T/DDI – do not combine – lactic acidosis
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Counsel Woman
Importance of adherence to careImportance to take every pill every daySeek care of experienced OBS/ID team for
the best resultObtain all laboratory tests on scheduleFollow up immediately for any new
symptoms or signs
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Conclusion
With appropriate educationWith minimal risk it is possible for many
HIV positive persons to become the parents of HIV negative babies