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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

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Reproductive technologies counseling l.jpg

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


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Objectives

  • Transmission risks

  • Pregnancy options

  • Infertility

  • Treatment options


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Transmission Risks

  • Heterosexual

  • Vertical


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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

  • Blood

  • Semen

  • Cervical secretions

  • Breast milk

  • Spinal fluid


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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


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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 STD

  • Cervical ectopy

  • Male partner not circumcised

  • Sex during menses

  • Bleeding during intercourse

  • Receptive anal intercourse

  • Partner 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 risk

  • Most 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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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.)


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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.)


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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 baby

  • Or equivalent AZT dose


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Viral load in Genital Secretions & MTCT (Thailand)


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Cesarean Delivery


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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 progression

  • Lowers CD4 count

  • Should not use Stavudine and ddi together

  • No 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 partner

  • Time 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 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)


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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

  • 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


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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.


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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 pregnancy

  • No 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 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


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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 pregnancy

  • Avoid transmission of HIV to mother, father or baby

  • Give woman choice regarding pregnancy


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Risk to Fetus

  • Multiple fetuses

  • Low birth weight

  • Pre-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 intercourse

  • History/sexual practices

  • Sperm evaluation

  • Urologic evaluation

  • GYN evaluation

  • Appropriate treatment


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Infertility Treatment

  • Based on problem

  • Many have no particular medical issue and diagnosis of etiology can’t be determined


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Male Infertility

Male causes

  • Sperm- poor quality

    - poor quantity

    - poor motility

  • Semen - 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

Suggestions

  • Stop smoking

  • Avoid tight fitting pants (male), bicycle riders

  • Timing of intercourse

  • Appropriate weight

  • Healthy 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 <1000

  • No breastfeeding

  • Woman on HAART


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Factors Associated with Vertical Transmission

  • High viral load

  • Acute HIV infection

  • Older maternal age

  • Cigarette smoking

  • Prolonged 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 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


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Conclusion

  • With appropriate education

  • With minimal risk it is possible for many HIV positive persons to become the parents of HIV negative babies


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