hiv & subfertility leila c g frodsham clinical research fellow assisted conception unit chelsea...
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HIV & SubfertilityHIV & Subfertility
Leila C G FrodshamClinical Research Fellow
Assisted Conception Unit
Chelsea and Westminster
Talk to UK-CAB (UK-Community Advisory Board)Talk to UK-CAB (UK-Community Advisory Board)25 October, 200225 October, 2002
HIV I-Base:HIV I-Base:http://www.I-base.org.ukhttp://www.I-base.org.uk
Talk to UK-CAB 25.10.02
Our TeamOur Team
Leila CG Frodsham Research Fellow
Bronwen Tamberlin Sperm washing Coordinator
Carole Gilling-SmithConsultant Gynaecologist+Director
Assisted Conception Unit
Chelsea and Westminster Hospital
Talk to UK-CAB 25.10.02
Who we treatWho we treat
HIV positive maleswith negative partners
HIV positive femaleswith negative partners
Couples where both partners are positive
Talk to UK-CAB 25.10.02
What treatments do we offer?What treatments do we offer?
IUI (intrauterine insemination)
IVF(in vitro fertilization)
ICSI(intracytoplasmic sperm injection)
Donor Insemination
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IUIIUI
In couples with normal/unexplained infertility
Ovulation predicted via ultrasound tracking
Sperm washed
Sperm injected into partners womb
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InVitroFertilizationInVitroFertilization
In subfertile couplesTubal disease/low sperm count
Superovulation by injection
Follicles tracked by scan
Eggs collected
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InVitroFertilizationInVitroFertilization
Sperm washed
Sperm and eggs mixed in the lab
Embryos replaced in womb
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Intracytoplasmic sperm Intracytoplasmic sperm injectioninjection
Very low sperm count
As IVF
Single washed sperm injected into egg
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Referral to the programmesReferral to the programmes
We are happy to consider anyone
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Referral to the programmesReferral to the programmes
Consider ‘welfare of the child’Detailed HIV history
Recent viral load and CD4
Drugs and resistance
Sexual health screenSmear/colposcopyIntended obstetric care
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Referral to the programmesReferral to the programmes
No storage of positive gametes/embryos
Gamete donation on named basis
Couples only will be considered
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Pre conceptual counselling & Pre conceptual counselling & HIVHIV
Stability of relationship Disease progression / health of infected parent High risk behaviour (drug abuse, unprotected sex) Social support
Understand & agree to comply with risk reduction treatment
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Welfare of the Child in HIV Welfare of the Child in HIV +ve+ve
In male partner:– Transmission of HIV in sperm
In female partner:– Vertical transmission risk (< 1%)
Use of antiretrovirals Mode of delivery Avoidance of breastfeeding
– Effect of antiretrovirals on fetus/child
In both:– Disease progression / health of infected parent– High risk behaviour (drug abuse, unprotected
sex)
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Sperm washing programmeSperm washing programme
Since April 1999
59 Couples treated
11 babies born
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Sperm washing-How safe?Sperm washing-How safe?
seminal fluidNSC
sperm
NSCNSC
NSC
NSC
sperm
?
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Validation of sperm washingValidation of sperm washing
sperm samples from 11 HIV +ve men tested for:– HIV RNA viral load– HIV proviral DNA (latent virus)– expression of CD4 receptor & HIV co-receptors CCR5
spermatozoa had no: – HIV RNA – HIV proviral DNA– CD4 or CCR5 expression
L Kim et al, AIDS 1999, 13: 645-51
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sperm washingsperm washing
semen centrifuged in density gradient
NASBA check for HIV-1 RNA (25 HIV-1 copies/106
sperm) 6% risk of positive
NASBA cancelled cycle
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Risks of unprotected Risks of unprotected intercourseintercourse
unprotected timed intercourse– 1 in 500 risk of infecting partner
series of 92 HIV +ve men /HIV -ve women carefully timed but unprotected intercourse
Mandlebrot et al, Lancet 1997; 349:850-851
4 seroconversions•2 during pregnancy•2 postpartum
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Fertility provision for HIV +ve Fertility provision for HIV +ve malesmales
Initial referralinfo pack sent out
1st appointment (GUM)sexual health screen
IUI3rd appointment (ACU)
treatment planned
Counselling2 sessions
2nd appointment (ACU)fertility screen
IVF or ICSI
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Pregnancy ratesPregnancy rates
IUI
36 patients=91 cycles: 20% pregnancyIVF
13 patients=19 cycles: 33.3% pregnancyICSI
10 patients=16 cycles: 12.5% pregnancy
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Pregnancy monitoringPregnancy monitoring
Pregnancy test
Serial scans from 5+4 weeks
3 monthly HIV tests during antenatal + post natal periods
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Female positive programmeFemale positive programme
Since April 2002
3 women treated
4 pregnancies-1 ongoing
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risk of vertical transmission– cannot ‘wash eggs’ – reduced to < 1% with good obstetric care
effect of antiretrovirals in uterohealth / life expectancy of parentpersistent drug abuse in parentfuture for child if born HIV positive
HIV-1 +ve women:welfare of the HIV-1 +ve women:welfare of the childchild
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equal or greater risks to offspring in:– older women
trisomy 21 and other chromosome abnormalities
– women with cardiac disease or cystic fibrosis
– diabetics– multiple pregnancy– severe oligoasthenospermia & ICSI
HIV+ve women and vertical HIV+ve women and vertical transmissiontransmission
HIV and infertility: time to treat. Gilling-Smith C, Smith JR, Semprini A. BMJ 2001, 322: 567-8
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Mother to child HIV Mother to child HIV transmissiontransmission
HAART+
Caesarean Section
+
No Breastfeeding
=
<2% Vertical transmission
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Mother to child HIV Mother to child HIV transmissiontransmission
Chelsea &Westminster (since 1995)50 births in HIV +ve womennone of the babies +ve
St Mary’s Paddington (since 1996)78 births in HIV +ve womentwo positive babies (in both cases mother did not comply and take medication & delivered elsewhere)
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Antenatal CareAntenatal Care
Must be optimal
Joint care from GU Physician
& HIV Specialist Obstetrician
C+W if insufficient locally
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Fertility provision for HIV positive Fertility provision for HIV positive femalesfemales
1st appointment (GUM)sexual health screen
3rd appointment (ACU)treatment planned
2nd appointment (ACU)fertility screen
Preconceptual counselling
Obstetric monitoring
•HAART•LSCS
•no breast feeding
pregnant
IUI
IVF or ICSI
Sperm washing
Talk to UK-CAB 25.10.02
Female positivesFemale positives
IUI-3 cycles
1 pregnancy; early miscarriage
IVF-5 cycles
3 pregnancies-1 ongoing pregnancy
ICSI-0 cycles
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Females:when to referFemales:when to refer
Provided Negative partner regular cycle no history PID/STD or abdominal surgery No other known fertility factors
>35 years: 6 months self-insemination
<35 years: 6-12 months self-insemination
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Couples where both are Couples where both are positivepositive
Sperm washing required
Extra counselling
3 couples ready for/undergoing treatment
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CREAThECREAThE
Centres for Reproductive Assistance Techniques in HIV in Europe
7 centres in 6 countries to pool data to assess:– safety of risk reduction options– efficacy in relation to fertility factors in this population– epidemiology– behavioural and psychosocial aspects
draw up guidelines for counselling and treatment