Amy Criniti's Presentation


Published on

Published in: Health & Medicine
1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide
  • Women who are hep c positive have a higher risk of liver toxicity on antiretrovirals Also increased risk of perinatal HIV transmission in women who are coinfected
  • Vertical transmission rates as high as 45% in developing factors Data show no reduction in the transmission rate if C/S is performed after the onset of labor or ROM Number of children that would die of malnutrition far surpasses number infected with HIV from breastfeeding
  • Women and Infants Transmission Study 1.2% transmission Pediatric AIDS Clinical Trials Group Protocol 1.2% transmission rate AZT has documented benefit in reduction of perinatal transmission independent of viral load Even women with VL less than 1000 have significant reduction in perinatal transmission rates
  • Efavirenz associated with neural tube defects ddI + d4T is associated with increased risk of lactic acidosis in pregnant women Nevirapine can be associated with hepatotoxicity Emerging debate of risk of premature delivery in women on HAART Still debate about using them in the first trimester Need to consider each patient individually and choice of initiation and timing of therapy depends on the clinical status of the patient
  • Devised 15 years ago by Augusto Semprini in Milan who has been one of the world’s leaders in offering care to HIV discordant couples. Initially there was no way to evaluate presence of virus after washing. First 500 cycles done preceeded ability to do PCR on samples. No seroconversions. Currently PCR is done on an aliquot of the final sample and only confirmed negative samples are used. Gradient step filters the liquefied specimen. Wash eliminates the seminal plasma and non motile sperm
  • Nested PCR is when another round of amplification is performed using primers internal to the ones used in the first round.
  • Inconsistent condom use, before HAART
  • General Indications for ART Apply ART when less invasive and less expensive therapies for infertility have not been successful
  • Over 66% of cycles involved the transfer of 3 or more embryos Many programs have limited the number of embryos to 2. Has not significantly reduced the number of twins
  • Emotional currency also spent ESHRE consensus report 2003 states that the essential goal of IVF is singleton pregnancy and that twins are considered a complication
  • Amy Criniti's Presentation

    1. 1. Fertility options for HIV discordant couples Amy Criniti MD Fellow Reproductive Endocrinology and Infertility University of Washington Medical Center [email_address]
    2. 2. <ul><li>“ We hope to have a vaccine ready for testing in about 2 years. Yet another terrible disease is about to yield to patience, persistence, and outright genius.” </li></ul>Margaret Heclker, US Health & Human Services, April 23, 1984
    3. 3. HIV statistics <ul><li>Nearly 42 million persons affected worldwide </li></ul><ul><li>75% of those affected are between the ages of 20 and 40 </li></ul><ul><li>Antiretroviral treatment has significantly changed prognosis </li></ul>
    4. 4. Antiretrovirals <ul><li>AZT approved in 1987 </li></ul><ul><li>Saquinavir approved in 1995 </li></ul><ul><li>1996 AIDS deaths in U.S.  by 42% </li></ul><ul><li>Mortality Rate: Mortality Rate per 100 Patient Years — Not on therapy 65 — HAART therapy 3.4 </li></ul>
    5. 5. Desire to conceive <ul><li>28% of HIV infected adults desire to have biologic children </li></ul><ul><li>High priority for many HIV positive women </li></ul>Chen et al, Family Planning Perspectives, 2001
    6. 6. HIV Discordant Couples <ul><li>20% had engaged in unprotected intercourse to achieve pregnancy </li></ul><ul><li>50% did not consider donor sperm a reasonable option </li></ul><ul><li>Many would consider unprotected intercourse if fertility treatment was not an option </li></ul><ul><li>More than 50% feel that their reproductive options have not been addressed sufficiently </li></ul>
    7. 7. Previous Recommendations <ul><li>1985: CDC encourages HIV infected women to avoid pregnancy </li></ul><ul><li>1987: ACOG encourages HIV infected women to avoid pregnancy </li></ul><ul><li>1994: ASRM presents donor sperm or adoption as options </li></ul>
    8. 8. New Recommendations <ul><li>ACOG states that ART should not be denied to HIV infected couples solely on the basis of HIV status </li></ul><ul><li>CDC recommends that HIV positive women receive nondirective counseling about all options </li></ul>
    9. 9. HIV positive female partner <ul><li>Risk to child </li></ul><ul><li>Risk to unaffected partner </li></ul>
    10. 10. Preconception Counseling <ul><li>Discussion of risk of vertical transmission </li></ul><ul><li>Assessment of status of HIV infection </li></ul><ul><li>CD4 count and viral load </li></ul><ul><li>History of prior or current antiretroviral therapy </li></ul><ul><li>Hepatitis C status </li></ul><ul><li>Discussion about breast feeding </li></ul>
    11. 11. Perinatal HIV Transmission 15% Breastfeeding <2% HAART and viral load <1000 < 2% AZT + scheduled C/S 5-8% AZT 25-40% No intervention Risk Vertical Transmission Delivery Mode/Factors
    12. 12. Antiretrovirals in Pregnancy <ul><li>Perinatal transmission  with viral load </li></ul><ul><li>Transmission <2% in women on HAART </li></ul><ul><li>If already on meds, continue </li></ul><ul><li>If not on meds, defer to after 1 st trimester </li></ul>
    13. 13. Antiretrovirals in pregnancy <ul><li>Combination therapy recommended when viral load > 1000 </li></ul><ul><li>Always include AZT </li></ul><ul><li>Avoid Efavirenz </li></ul><ul><li>ddI +d4T </li></ul><ul><li>Nevirapine </li></ul><ul><li>Amprenavir </li></ul><ul><li>Risks </li></ul>
    14. 14. ACOG Recommendations <ul><li>Elective C/S if viral load>1000 copies/mL </li></ul><ul><li>C/S should be performed at 38 weeks </li></ul><ul><li>Intrapartum AZT prophylaxis </li></ul><ul><li>If viral load <1000 and receiving HAART, vaginal delivery may be considered </li></ul><ul><li>AROM, scalp electrodes and other invasive procedures to be avoided </li></ul>
    15. 15. Reducing Risk to Male Partner <ul><li>Timed intercourse </li></ul><ul><li>Self insemination </li></ul><ul><li>Intrauterine Insemination </li></ul>
    16. 16. HIV positive male partner <ul><li>Risk to female partner </li></ul><ul><li>Effect of HIV infection and treatment on sperm function </li></ul><ul><li>Ability to detect virus in semen </li></ul><ul><li>Semen washing techniques </li></ul><ul><li>“ ART” (Assisted Reproductive Technologies) </li></ul>
    17. 17. Risks of HIV transmission <ul><li>Male to female 1/1000 </li></ul><ul><li>Female to male <1/1000 </li></ul><ul><li>Increased risk with advanced disease, genital infection, STD </li></ul>
    18. 18. Semen vs Blood <ul><li>Genital tract thought to act as a distinct reservoir for HIV </li></ul><ul><li>4-10% of men with undetectable viral loads still have viral shedding in semen </li></ul>Vernazza et al, AIDS 2000 Bujan et al, AIDS 2004
    19. 19. Impact of viral load on seminal viral excretion <ul><li>Estimated risk of infection per act of unprotected intercourse not known </li></ul><ul><li>Longitudinal Ugandan study in 415 discordant couples </li></ul><ul><li>- no seroconversions when VL<1500 </li></ul><ul><li>- probability of transmission rose to </li></ul><ul><li>.0023 per act at VL >38,500 </li></ul>Gray et al, Lancet 2001
    20. 20. HIV and Semen Parameters <ul><li>Majority of HIV+ men have normal parameters </li></ul><ul><li>However all parameters impaired compared to HIV- </li></ul><ul><li>Parameters correlate with CD4 count </li></ul>Nicopoullos et al, Human Reprod 2004
    21. 21. Sperm Washing <ul><li>Based on theory that HIV virus exists in seminal fluid and not within sperm cells </li></ul><ul><li>Cell associated form in the seminal leukocytes </li></ul><ul><li>Cell free form in seminal plasma </li></ul>
    22. 22. Semen Washing <ul><li>Gradient Centrifugation </li></ul><ul><li>Washing </li></ul><ul><li>Spontaneous Migration (aka Swim Up) </li></ul>
    23. 23. Detection of virus in semen <ul><li>RT-PCR of seminal plasma has limitations </li></ul><ul><li>Inhibitors in semen reduce the sensitivity of the assay </li></ul><ul><li>Nested PCR improves sensitivity </li></ul>
    24. 24. Timed Intercourse <ul><li>1997 Lancet study followed 96 HIV discordant couples attempting pregnancy </li></ul><ul><li>104 pregnancies with 2 seroconversions </li></ul><ul><li>Infection rate significantly higher than expected </li></ul>
    25. 25. Intrauterine Insemination (IUI) <ul><li>Sperm is collected, washed, and motile fraction separated </li></ul><ul><li>Sample placed into uterine cavity around the time of the LH surge </li></ul><ul><li>Success rate approx 8% per cycle </li></ul>
    26. 26. Intrauterine Insemination <ul><li>Used extensively in Europe </li></ul><ul><li>10 clinics have used this method </li></ul><ul><li>3166 inseminations performed in 1263 women </li></ul><ul><li>571 pregnancies w/o seroconversion </li></ul><ul><li>Pregnancy rates per cycle 10-20% </li></ul>
    27. 27. Is Intrauterine Insemination Safe? <ul><li>Unclear whether it is safer than intercourse </li></ul><ul><li>Places millions of sperm above the immunological barrier of the cervix </li></ul><ul><li>Need more cases to demonstrate safety </li></ul><ul><li>CDC does not currently support IUI </li></ul>
    28. 28. Assisted Reproductive Technology
    29. 29. State of the ART <ul><li>Includes IVF and ICSI </li></ul><ul><li>Involves extensive screening </li></ul><ul><li>May be cost prohibitive for many couples </li></ul><ul><li>Involves risk </li></ul>
    30. 30. Cycle Specifics <ul><li>Patient stimulated with gonadotropins </li></ul><ul><li>Eggs aspirated from ovary by ultrasound guided procedure </li></ul><ul><li>Eggs fertilized with sperm from partner </li></ul>
    31. 31. IVF Monitoring
    32. 32. Sonographic Egg Recovery
    33. 33. ICSI
    34. 34. Embryo Development <ul><li>Fertilization and early embryo development occurs in the lab </li></ul><ul><li>Embryos transferred into uterus of on day 3 or 5 of development </li></ul>
    35. 35. Embryo Transfer <ul><li>Done under ultrasound guidance </li></ul><ul><li>Soft catheter used </li></ul><ul><li>No anesthesia needed </li></ul><ul><li>Full bladder helps </li></ul>
    36. 36. Extensive Screening <ul><li>Ovarian reserve testing (antral follicle count and Day 3 FSH) </li></ul><ul><li>Uterine evaluation (HSG, SHG, OH) </li></ul><ul><li>Semen analysis </li></ul><ul><li>Genetic history </li></ul>
    37. 37. IVF/ICSI Trial Discordant Couples N=61 Cycles = 113 HIV testing 3 and 6 mos After Embryo Transfer Infants and mothers tested at delivery and 3 mos No seroconversions ! IVF and ICSI Sauer et al, Fert Stert 2003
    38. 38. Cycle Outcome
    39. 39. Advantages of IVF/ICSI <ul><li>Reduces exposure from millions to a single sperm cell </li></ul><ul><li>Only motile spermatozoa used </li></ul><ul><li>Routine laboratory testing of semen for HIV virus is relatively experimental </li></ul><ul><li>Higher success rates than with IUI (fewer exposures) </li></ul><ul><li>Can be used even if sperm parameters are poor </li></ul>
    40. 40. Disadvantages of IVF/ICSI <ul><li>Invasive </li></ul><ul><li>Expensive </li></ul><ul><li>Risk of Ovarian Hyperstimulation </li></ul><ul><li>Risk of Multiple Pregnancy </li></ul><ul><li>Questions about the safety of IVF and ICSI </li></ul>
    41. 41. Cost of IVF/ICSI <ul><li>Pre Cycle Evaluation $2000 </li></ul><ul><li>Medications $3500 </li></ul><ul><li>IVF Procedures $8000 </li></ul><ul><li>ICSI $1500 </li></ul><ul><li>________ </li></ul><ul><li>$15,000 </li></ul>
    42. 42. Ovarian Hyperstimulation Syndrome <ul><li>Severe cases are rare </li></ul><ul><li>Can cause fluid shifts, hemoconcentration, and ARDS </li></ul><ul><li>Can require ICU admission </li></ul>
    43. 43. Multiple Pregnancy
    44. 44. Number of Embryos Transferred CDC Assisted Reproductive Technology Success Rates, 2001 6.2% 27.3% 34.5% 20.6% 11.4%
    45. 45. Embryo Transfer Guidelines ASRM/SART (11/99) Female Recommended Age Transfer No. <35 1–2 35–38 2–3 38–40 3–4 >40 4–6
    46. 46. Twins are not an ideal ART outcome <ul><li>Fetal and maternal complications </li></ul><ul><li>12 fold increase in cerebral palsy </li></ul><ul><li>5-10 fold increase in perinatal mortality </li></ul><ul><li>$600 million excess cost in year 2000 </li></ul>Kinzler et al, 2000
    47. 47. Conclusions <ul><li>Fertility counseling and treatment options should be presented to HIV discordant couples </li></ul><ul><li>IUI and ICSI both appear to be safe options, although numbers are still relatively small </li></ul><ul><li>Neither are yet the standard of care and prevention can not be guaranteed. </li></ul><ul><li>IUI is not widely available in the United States </li></ul>
    48. 48. Ethical Issues <ul><li>Risk of transmission to the seronegative partner </li></ul><ul><li>Risk of transmission to the infant </li></ul><ul><li>Early death of one or both parents </li></ul><ul><li>Possible need for third party parenting </li></ul><ul><li>Posthumous reproduction </li></ul>