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Artificial insemination in HIV-discordant couples by dfhdhdhdhjr

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									Assisted Reproductive Technology in
      Resource-Poor Settings




            Arlene D. Bardeguez, MD, MPH
  Dept. of Obstetrics, Gynecology & Women’s Health
             New Jersey Medical School
Definitions

   Assisted Reproductive Technologies (ART)
    include all fertility treatments in which
    both eggs and sperm are handled.



FCSRCA Publication # 102-493, October 24, 1992.
Reproductive Options for HIV-infected
Women: Historical Perspective USA

     1985 Recommendation from CDC: Women
      known to be HIV(+) should defer pregnancy
      – concerns disease progression
      – concerns lethality of disease
      – concerns of risk perinatal transmission

     1990 CDC Reported that Use of Assisted
      Reproductive Technologies could lead to
      horizontal transmission
Reproductive Options for HIV-infected
Women: Historical Perspective
   1994: Use of antiretroviral therapy and/or
    operative delivery lead to a dramatic decrease in
    perinatal HIV-1 transmission

   1996: Introduction of HAART in clinical practice
     – decrease mortality
     – increase life-span
     – increase pool of individuals with stable HIV
       disease
     – decrease Perinatal HIV-1 Transmission
Advocates for use of assisted
reproductive technologies in HIV-
1 infertile couples
 Perinatal HIV-1 Transmission
 in the HAART Era
               Perinatal HIV-1 Transmission Rate
45%


40%


35%                                                                       Garcia

30%                                                                       Mofenson

25%                                                                       Sperling-T

20%                                                                       Sperling-P

15%


10%


5%


0%
      <1,000       1000-10,000   10-50,000   50-100,000   >100,000

                                                                     @ABardeguez
   Mode of Delivery and the Risk
   of Perinatal HIV-1 Transmission
   [Meta-Analysis NEJM 1999]



                      Perinatal transmission Rate among
                        HIV-infected pregnant women

Elective C/S      Elective C/S +              NSVD or other    NSVD or other +
    only       Antiretroviral [ZDV]               only        Antiretroviral [ZDV]
   10.4%               2.0%                      19.0%                7.3%
                                Management of the
                               HIV+ Pregnant Woman
Diagnosed Before Pregnancy              Diagnosed in Pregnancy      Diagnosed in Labor
      Case Scenario 2                       Case Scenario 1          Case Scenario 3

                 No ARV                VL <1,000      VL >100,000
                                       CD4 >350        CD4 <350
                                                                           Offer
      On ARV                                                           short-course
     VL <1,000                                                         regimen ZDV
                                                                      Nevirapine [Nev]
                                  ZDV, 2 NRTI                           ZDV+ Nev.
                                 HAART [ZDV]       HAART (+ZDV)
                                                                         Combivir
      Keep same
    regimen unless
      concern for
         toxicity                      VL at term >1,000                     Infant
      or teratogen                                                         Regimen
                                                                          Refer Mother
                                                                           and Baby
Guidelines re: HAART                     Consider C/S
Courtesy of A. Bardeguez, MD                                        The Academy of Medicine of New Jersey
Patient’s   Fetal
Autonomy    Beneficence
Opponents on the use of
assisted reproductive
technologies in HIV-1 infertile
couples
Other arguments

   Lack of Perinatal transmission can’t be
    guaranteed
   Horizontal transmission risk of available
    procedures is uncertain [1st do no harm]
   Overall cost of Intervention
    – Individual
    – Society
Risk/Benefits of Assisted Reproductive
Technologies in HIV-Infected Subjects

   Could decrease the risk of horizontal transmission
    for discordant couples
    – decrease risk of unprotected intercourse
    – increase conception rate [25% cycle 35% IVF]
   Use of reproductive technologies can increase
    perinatal risk
    – preterm labor
    – low birthweight
   Could increase morbidity if operative interventions
    are needed
   Increase cost of the interventions?
Assisted Reproductive
Technologies should not be
denied to HIV-infected couples
solely on the basis of their
positive serostatus
Committee on Ethics of ACOG 2001
American Society for Reproductive Medicine 2002
Something to Think About!


By 1999, more than 97% of all ART
procedures in the United States
were IVF + ICSI.


Fertil Steril 78:918, 2002.
Pregnancy Rates According to
Procedure Used
                                            Pregnancy/Cycle

    Fecundability                                 25 %
          ICI-IUI1                                2-5 %
       SO-SO/IUI1                                 4-9 %
            IVF2                                  35 %

  1 Guzick, et al., N Engl J Med 340:177, 1999.
  2 Fertil Steril 78:918, 2002.
 COST
   IVF cycle (1 cycle):          $9,226.00

   SO-IUI (1 cycle):             $1,800.00

   SO-IUI (4 cycles):            $7,200.00


Semin Reprod Med 331:244, 1994.
Fertil Steril 67:830, 1997.
Multiple Gestations per IVF
Retrievals-US 1999
70

60

50
                              Singleton
40                            Twins
30                            Triplets
                              Multiples
20

10

0

Fertil Steril 78:918, 2002.
Assisted Reproductive Technology for Men
and Women Infected with Human
Immunodeficiency Virus Type 1




    Clinical Infectious Diseases
    2003; 36: 195-200
    January 15, 2003
Case Scenario 1: HIV-Infected
Female & Negative Male Partner
   Goals
    – Prevent horizontal transmission
      • Artificial insemination with/without ovarian
        stimulation
      • Donor Insemination
      • IVF
    – Prevent perinatal transmission
    – Infertility work-up if needed
      • Anovulation [PCO, Substance use, Hypothalamic
        disorders, HIV?]
Case Scenario 2: HIV-Infected Male
& Negative Female Partner
Goals
   Prevent horizontal transmission
    – Cell associated and cell free virus can be source of
      infection
    – There is a relation between serum and genital viral load
      but imperfect!
   Techniques used
    – Intrauterine insemination after “Sperm wash”
    – Intracytoplasmic Sperm Injection [ICSI]
    – Oocyte donation
Bedford Research Foundation*
Special Program of Assisted Reproduction-SPAR

Pregnancies and Births as of January 2005

• 39 pregnancies have been achieved through SPAR and IVF, procedures,
  6 are ongoing.

• 3 pregnancies and 3 births have been achieved using the new
  Oligospermic Cup procedure, both are ongoing.

• 26 babies have been born using SPAR and IVF procedures
   • 5 sets of twins
   • 16 singletons



  *Formerly Duncan Holly Biomedical Inc.
Intrauterine insemination after
“Sperm wash”
   Semprini et al
    – Over 1,000 IUI in 350 discordant couples
    – 200 pregnancies
    – No horizontal transmission
   Marina et al
    –   63 HIV+ men without AIDS
    –   + HIV RNA 5.6% samples [discarded]
    –   49% success IUI, 37 children
    –   All women HIV(-) 6 months after IUI
Intracytoplasmic Sperm Injection
[ICSI]
    Sauer et al Complications
     – Multiple pregnancies
     – Ovarian stimulation syndrome
    Sauer 1997-2002
     –   25 couples conceived 27 pregnancies
     –   40 neonates
     –   C/S rate 70%
     –   Mean gestational age at delivery 37 weeks
     –   7 cases Preterm delivery
     –   8 cases low birth weight
Case Scenario 3: Both partners
HIV-Infected

    Risk/Benefits?
    Optimal Management?
    Options
     – IUI
     – ICSI
     – Oocyte Donation
     – Adoption
Laboratory Issues

   Sample processing
    – Sperm washing
    – DNA/RNA testing
   Prevent Cross-contamination
    – Timing procedures
    – Separate freezers for storage
    – Liquid nitrogen vapors
Criteria and Recommendations for Use of
Assisted Reproductive Technologies-I

   Disclosure of serostatus between partners
   Pre-conceptional Counseling
   Informed consent [risk, benefits, alternatives explained]
   Absence of OI or prophylaxis
   CD4>350cells/mm3, HIVRNA <50,000 copies/ml
   Normal pap and/or colpo if abnormal
   If Hepatitis C+:
    – normal liver enzymes
    – hepatology consult
Criteria and Recommendations for Use of
Assisted Reproductive Technologies-II

Patients receiving HAART:
 HIV RNA<400 copies/ml
 Regimen without teratogenic drugs
 Adequate tolerance to regimen
    – No toxicities
   Adequate response to regimen [CD4, VL] at least
    1 year
   Semen analysis by HIV PCR prior to
    insemination/IVF
Criteria and Recommendations for Use
of Assisted Reproductive
Technologies-III

   Intrapartum ZDV prophylaxis
   Close follow-up during pregnancy and after
    birth by HIV experts
   Follow-up of child and HIV negative partner
    after procedure/delivery to verify lack of
    transmission
Optimal procedures                            Optimal candidates
Sperm washing                   Patients      Access
Drug penetration                              Attitudes/Beliefs
Ethics:Risk/Benefits                          Education
Access
                Technology


                                  Outcomes

                       Data collection
                       Monitor outcomes
                       Modify Approaches based on evidence
                       Financial Support
Contrast between US or
International Guidelines, Access to Care

    Treatment started if           Treatment started id
     Cd4<350 or viral load           AIDS or CD4<200
     >100,000                       Preferred options for
    Unlimited regimens              treatment
    Access to HAART during         HAART access limited
     pregnancy                       women with advance
    Access to Intrapartum ZDV       disease
    C/S done routinely             NEV used intrapartum
                                    Limited access to C/S
Technology Transfer from
Develop to Under-develop Countries:
Cost, Simplicity

     Insemination – Sperm Wash
     Oligo-spermic cap-Sperm Wash
     IVF
     ICSI
Ideal Candidate-Individual

   Committed couple
   Younger couple
   No STI’s
   Able to use post-exposure prophylaxis
   Cultural beliefs will not hinder condom use during
    pregnancy
   Able to not breastfeed postpartum
   Will have access to treatment if disease progress
Ideal Candidate-Community

   Access to treatment prior to AIDS diagnosis:
    diversity of options
   Access to IV ZDV in labor or effective
    antiretroviral for MTCT
   Timely and safe access to C/S
   Access to neonatal antiretrovirals for MTCT
    prevention and follow up
   Long term assessment-cost to society
Ideal Candidate-Site

    Assisted reproduction technologies on site
    Quality control assessment
    Ongoing training
    Culturally acceptable
    Criteria for qualification not link to patient’s
     resources
Unknowns!!

   Cost effectiveness of averting horizontal and
    perinatal transmission versus cost intervention
   Will current technology for sperm wash be equally
    effective all clades
   Ethics of limiting access to younger population
    based on fertility rate and life potential
   Should access be limited to 1 pregnancy per
    couple

								
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