Reproductive Technologies & Counseling

1. 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

2. Objectives • Transmission risks • Pregnancy options • Infertility • Treatment options

3. Transmission Risks • Heterosexual • Vertical

4. Risk of Transmission • Unprotected vaginal intercourse • Male to female = 3% to .01% per contact • Female to male = 10% to 17% less efficient

5. HIV in Body Fluids • Blood • Semen • Cervical secretions • Breast milk • Spinal fluid

6. 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

7. 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

8. 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

9. 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

10. Vertical Transmission • In utero - <10% • Peripartum – 40 – 70% • Breastfeeding – 0.5% per month risk • Most important factor is viral load

11. Vertical Transmission Rate • Total rate – 13% to 60% • U.S. – 25% to 30% • Europe – as low as 13% • Africa – 50% to 60%

12. 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.)

13. 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.)

14. 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

15. Viral load in Genital Secretions & MTCT (Thailand)

16. Cesarean Delivery

17. 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

18. Pregnancy Options

19. Pregnancy • Does not affect disease progression • Lowers CD4 count • Should not use Stavudine and ddi together • No Efavirenz in the first trimester

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

21. 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)

22. 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

23. 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)

24. 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

25. 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

26. 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.

27. 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

28. U.S. • Self insemination • Women inseminate themselves with fresh semen using syringe (without needle) or disposable Pasteur pipette (cheap, safe)

29. 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) $$$$

30. Sperm Washing • Infected male followed by intrauterine insemination • 29% success rate for pregnancy • No seroconversion of females

31. 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

32. 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

33. 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

34. U.S. • Assisted reproductive techniques • Expensive $10,000 to $17,000 per cycle • Many (most) cannot afford this expense • VL undetectable • CD4 >400

35. Goals of these Reproductive Options • Achieve pregnancy • Avoid transmission of HIV to mother, father or baby • Give woman choice regarding pregnancy

36. Risk to Fetus • Multiple fetuses • Low birth weight • Pre-term delivery

37. Infertility

38. Infertility • HIV positive and HIV negative workup is no different

39. Infertility • One year of unprotected intercourse • History/sexual practices • Sperm evaluation • Urologic evaluation • GYN evaluation • Appropriate treatment

40. Infertility Treatment • Based on problem • Many have no particular medical issue and diagnosis of etiology can’t be determined

41. Male Infertility Male causes • Sperm - poor quality - poor quantity - poor motility • Semen - poor quality - poor quantity

42. Male Infertility • Anatomical - obstruction - hypospadia - varicocele - injury - retrograde ejaculation • Endocrine - low testosterone • Genetic - Klinefelters, etc. • Psychiatric - depression - low libido

43. Male Infertility Suggestions • Stop smoking • Avoid tight fitting pants (male), bicycle riders • Timing of intercourse • Appropriate weight • Healthy life style

44. Female Infertility • Endocrine - thyroid, pituitary, adrenal insufficiency • Genetic - polycystic ovaries, Turners • Psychiatric - depression - low libido

45. 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

46. Treatment Options

47. Minimal MTCT Risk • With serum VL <1000 • No breastfeeding • Woman on HAART

48. Factors Associated with Vertical Transmission • High viral load • Acute HIV infection • Older maternal age • Cigarette smoking • Prolonged rupture of membranes

49. 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

50. 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