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

Objectives

Transmission risksPregnancy optionsInfertilityTreatment options

Transmission Risks

HeterosexualVertical

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

BloodSemenCervical secretionsBreast milkSpinal fluid

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

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

Genital ulcer or STDCervical ectopyMale partner not circumcisedSex during mensesBleeding during intercourseReceptive anal intercoursePartner with high viral load

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

In utero - <10%Peripartum – 40 – 70%Breastfeeding – 0.5% per month riskMost important factor is viral load

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)

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%

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

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%

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%

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 Options

Pregnancy

Does not affect disease progressionLowers CD4 countShould not use Stavudine and ddi togetherNo Efavirenz in the first trimester

In unprotected vaginal intercourse leading to pregnancy the risks are twofold:– Partner’s risk of infection– Baby’s risk of infection

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)

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 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)

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

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

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.

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

U.S.

Self insemination– Women inseminate themselves with fresh

semen using syringe (without needle) or disposable Pasteur pipette (cheap, safe)

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

Infected male followed by intrauterine insemination

29% success rate for pregnancyNo seroconversion of females

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

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

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

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

Achieve pregnancyAvoid transmission of HIV to

mother, father or babyGive woman choice regarding

pregnancy

Risk to Fetus

Multiple fetusesLow birth weightPre-term delivery

Infertility

Infertility

HIV positive and HIV negative workup is no different

Infertility

One year of unprotected intercourseHistory/sexual practicesSperm evaluationUrologic evaluationGYN evaluationAppropriate treatment

Infertility Treatment

Based on problemMany have no particular medical

issue and diagnosis of etiology can’t be determined

Male Infertility

Male causesSperm - poor quality

- poor quantity

- poor motilitySemen - poor quality

- poor quantity

Male Infertility

Anatomical - obstruction

- hypospadia

- varicocele

- injury

- retrograde ejaculation Endocrine - low testosterone Genetic - Klinefelters, etc. Psychiatric - depression

- low libido

Male Infertility

SuggestionsStop smoking Avoid tight fitting pants (male), bicycle

ridersTiming of intercourseAppropriate weightHealthy life style

Female Infertility

Endocrine - thyroid, pituitary, adrenal insufficiency

Genetic - polycystic ovaries, Turners

Psychiatric - depression

- low libido

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

Treatment Options

Minimal MTCT Risk

With serum VL <1000No breastfeedingWoman on HAART

Factors Associated with Vertical Transmission

High viral loadAcute HIV infectionOlder maternal ageCigarette smokingProlonged rupture of membranes

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

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

Conclusion

With appropriate educationWith minimal risk it is possible for many

HIV positive persons to become the parents of HIV negative babies