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Reproductive Technologies & Counseling. Patricia Kloser, MD, MPH, FACP Professor of Medicine Professor of Public Health June 2006. UMDNJ, a Local Performance Site of the NY/NJ AETC. Objectives. Transmission risks Pregnancy options Infertility Treatment options. Transmission Risks.

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reproductive technologies counseling

Reproductive Technologies & Counseling

Patricia Kloser, MD, MPH, FACP

Professor of Medicine

Professor of Public Health

June 2006

UMDNJ, a Local Performance Site

of the NY/NJ AETC

objectives
Objectives
  • Transmission risks
  • Pregnancy options
  • Infertility
  • Treatment options
transmission risks
Transmission Risks
  • Heterosexual
  • Vertical
risk of transmission
Risk of Transmission
  • Unprotected vaginal intercourse
    • Male to female = 3% to .01% per contact
    • Female to male = 10% to 17% less efficient
hiv in body fluids
HIV in Body Fluids
  • Blood
  • Semen
  • Cervical secretions
  • Breast milk
  • Spinal fluid
hiv in semen
HIV in Semen
  • Higher in acute HIV infection in men
  • Correlation between viral levels of HIV in blood and semen
  • Men hyperinfectious before symptoms of HIV infection occur (lasts 6 weeks)
  • Could infect 7 to 24% of partners during first 2 months of infection
  • STD would increase this rate (in either partner)

JID 2004; 189:1785-1792

slide7
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
heterosexual transmission risks increase with
Heterosexual Transmission Risks Increase With
  • Genital ulcer or STD
  • Cervical ectopy
  • Male partner not circumcised
  • Sex during menses
  • Bleeding during intercourse
  • Receptive anal intercourse
  • Partner with high viral load
risk of vertical transmission
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

vertical transmission
Vertical Transmission
  • In utero - <10%
  • Peripartum – 40 – 70%
  • Breastfeeding – 0.5% per month risk
  • Most important factor is viral load
vertical transmission rate
Vertical Transmission Rate
  • Total rate – 13% to 60%
  • U.S. – 25% to 30%
  • Europe – as low as 13%
  • Africa – 50% to 60%
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)

MTCT with ARV (U.S.)
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%

Viral load and MTCT (U.S.)
vertical transmission with treatment
Vertical Transmission with Treatment
  • U.S. – with HAART <1%
  • Developing Countries
    • PMTCT reduces transmission by 50%
  • Nevirapine – 200mg to mother

- 6ml to baby

  • Or equivalent AZT dose
cesarean section
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
pregnancy
Pregnancy
  • Does not affect disease progression
  • Lowers CD4 count
  • Should not use Stavudine and ddi together
  • No Efavirenz in the first trimester
slide20
In unprotected vaginal intercourse leading to pregnancy the risks are twofold:
    • Partner’s risk of infection
    • Baby’s risk of infection
risk to partners
Risk to Partners
  • Expense (depending on method)
  • Possibility of HIV infection (depending on method used)
  • Possibility of passing “resistant” HIV to infected partner
  • Time consuming (depending on method used)
negative female positive male
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
negative male positive female
Negative MalePositive Female
  • Timed unprotected intercourse (using basal body temperature monitoring)
  • “Turkey baster” method self insemination
  • Ovarian stimulation with artificial insemination (partner/donor)
  • In vitro fertilization (ova harvested and fertilized outside of body and then implanted in hormonally stimulated uterus)
positive male positive female
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
superinfection
Superinfection
  • Controversial
  • 5 published verified cases
  • Appears to occur but difficult to verify
  • Usually occurs shortly after initial infection less likely later on
  • Positive partners study on-going
  • HIV positive people prefer other HIV positive people
reproductive decisions
Reproductive Decisions
  • Artificial insemination
  • Invitro fertilization
  • Intracytoplasmic sperm injection – most expensive
  • Self insemination
  • Timed intercourse
  • Transmission rates MTCT <1% in women with VL <1000 copies in U.S.
slide27
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
slide28
U.S.
  • Self insemination
    • Women inseminate themselves with fresh semen using syringe (without needle) or disposable Pasteur pipette (cheap, safe)
slide29
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) $$$$
sperm washing
Sperm Washing
  • Infected male followed by intrauterine insemination
  • 29% success rate for pregnancy
  • No seroconversion of females
sperm washing31
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
patient considerations
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
laboratory considerations
Laboratory Considerations
  • Cross contamination is a concern
  • Must have separate freezers and storage for samples
  • May be difficult regarding food facilities
  • Milan, Italy criteria and Columbia University in NYC doing this work
slide34
U.S.
  • Assisted reproductive techniques
    • Expensive $10,000 to $17,000 per cycle
    • Many (most) cannot afford this expense
    • VL undetectable
    • CD4 >400
goals of these reproductive options
Goals of these Reproductive Options
  • Achieve pregnancy
  • Avoid transmission of HIV to mother, father or baby
  • Give woman choice regarding pregnancy
risk to fetus
Risk to Fetus
  • Multiple fetuses
  • Low birth weight
  • Pre-term delivery
infertility38
Infertility
  • HIV positive and HIV negative workup is no different
infertility39
Infertility
  • One year of unprotected intercourse
  • History/sexual practices
  • Sperm evaluation
  • Urologic evaluation
  • GYN evaluation
  • Appropriate treatment
infertility treatment
Infertility Treatment
  • Based on problem
  • Many have no particular medical issue and diagnosis of etiology can’t be determined
male infertility
Male Infertility

Male causes

  • Sperm - poor quality

- poor quantity

- poor motility

  • Semen - poor quality

- poor quantity

male infertility42
Male Infertility
  • Anatomical - obstruction

- hypospadia

- varicocele

- injury

- retrograde ejaculation

  • Endocrine - low testosterone
  • Genetic - Klinefelters, etc.
  • Psychiatric - depression

- low libido

male infertility43
Male Infertility

Suggestions

  • Stop smoking
  • Avoid tight fitting pants (male), bicycle riders
  • Timing of intercourse
  • Appropriate weight
  • Healthy life style
female infertility
Female Infertility
  • Endocrine - thyroid, pituitary, adrenal insufficiency
  • Genetic - polycystic ovaries, Turners
  • Psychiatric - depression

- low libido

female infertility45
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

minimal mtct risk
Minimal MTCT Risk
  • With serum VL <1000
  • No breastfeeding
  • Woman on HAART
factors associated with vertical transmission
Factors Associated with Vertical Transmission
  • High viral load
  • Acute HIV infection
  • Older maternal age
  • Cigarette smoking
  • Prolonged rupture of membranes
slide49
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
counsel woman
Counsel Woman
  • Importance of adherence to care
  • Importance to take every pill every day
  • Seek care of experienced OBS/ID team for the best result
  • Obtain all laboratory tests on schedule
  • Follow up immediately for any new symptoms or signs
conclusion
Conclusion
  • With appropriate education
  • With minimal risk it is possible for many HIV positive persons to become the parents of HIV negative babies
ad