Assisted Reproductive Technology in Resource-Poor Settings Arlene D. Bardeguez, MD, MPH Dept. of...
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Transcript of Assisted Reproductive Technology in Resource-Poor Settings Arlene D. Bardeguez, MD, MPH Dept. of...
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 Transmissionin the HAART Era
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
<1,000 1000-10,000 10-50,000 50-100,000 >100,000
Garcia
Mofenson
Sperling-T
Sperling-P
Perinatal HIV-1 Transmission Rate
@ABardeguez
Mode of Delivery and the Riskof Perinatal HIV-1 Transmission[Meta-Analysis NEJM 1999]
Perinatal transmission Rate among HIV-infected pregnant women
Elective C/Sonly
10.4%
Elective C/S +Antiretroviral [ZDV]
2.0%
NSVD or otheronly
19.0%
NSVD or other +Antiretroviral [ZDV]
7.3%
The Academ y of Medicine of New Jersey
Management of the Management of the HIV+ Pregnant WomanHIV+ Pregnant Woman
Diagnosed Before PregnancyDiagnosed Before PregnancyCase Scenario 2Case Scenario 2
No ARVNo ARV
Diagnosed in PregnancyDiagnosed in PregnancyCase Scenario 1Case Scenario 1
VL >100,000VL >100,000CD4 <350CD4 <350
Diagnosed in LaborDiagnosed in LaborCase Scenario 3Case Scenario 3
Offer Offer shortshort --course course regimen ZDVregimen ZDV
Nevirapine [Nevirapine [ NevNev ]]ZDV+ Nev.ZDV+ Nev.CombivirCombivir
ZDVZDV , 2 NRTI, 2 NRTIHAART [ZDV]HAART [ZDV] HAART (+ZDV)HAART (+ZDV)
On ARVOn ARVVL <1,000VL <1,000
Keep same Keep same regimen unless regimen unless
concern forconcern fortoxicitytoxicity
or or teratogenteratogenVL at term >1,000VL at term >1,000 Infant Infant
RegimenRegimenRefer Mother Refer Mother
and Baby and Baby
Consider C/SConsider C/S
VL <1,000VL <1,000CD4 >350CD4 >350
Guidelines re: HAART
Courtesy of A. Bardeguez, MD
Patient’s Autonomy
Fetal 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.
COSTCOST
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
0
10
20
30
40
50
60
70
SingletonTwinsTripletsMultiples
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
Patients
Technology
Outcomes
Optimal candidates
Access
Attitudes/Beliefs
Education
Optimal procedures
Sperm washing
Drug penetration
Ethics:Risk/Benefits
Access
Data collectionMonitor outcomes Modify Approaches based on evidenceFinancial Support
Contrast between US orInternational Guidelines, Access to Care
Treatment started if Cd4<350 or viral load >100,000
Unlimited regimens Access to HAART during
pregnancy Access to Intrapartum ZDV C/S done routinely
Treatment started id AIDS or CD4<200
Preferred options for treatment
HAART access limited women with advance disease
NEV used intrapartum Limited access to C/S
Technology Transfer fromDevelop 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