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HIV & Subfertility. Leila C G Frodsham Clinical Research Fellow Assisted Conception Unit Chelsea and Westminster. Talk to UK-CAB (UK-Community Advisory Board) 25 October, 2002 HIV I-Base: http://www.I-base.org.uk. Our Team. Leila CG Frodsham Research Fellow Bronwen Tamberlin
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HIV & Subfertility Leila C G Frodsham Clinical Research Fellow Assisted Conception Unit Chelsea and Westminster Talk to UK-CAB (UK-Community Advisory Board)25 October, 2002HIV I-Base:http://www.I-base.org.uk
Our Team • Leila CG Frodsham Research Fellow • Bronwen Tamberlin Sperm washing Coordinator • Carole Gilling-Smith Consultant Gynaecologist+Director Assisted Conception Unit Chelsea and Westminster Hospital
Who we treat • HIV positive males with negative partners • HIV positive females with negative partners • Couples where both partners are positive
What treatments do we offer? • IUI (intrauterine insemination) • IVF (in vitro fertilization) • ICSI (intracytoplasmic sperm injection) • Donor Insemination
IUI • In couples with normal/unexplained infertility • Ovulation predicted via ultrasound tracking • Sperm washed • Sperm injected into partners womb
18mm Natural cycle IUI/SWP Day 8 Day 11 Day 13
InVitroFertilization • In subfertile couples Tubal disease/low sperm count • Superovulation by injection • Follicles tracked by scan • Eggs collected
InVitroFertilization • Sperm washed • Sperm and eggs mixed in the lab • Embryos replaced in womb
Intracytoplasmic sperm injection • Very low sperm count • As IVF • Single washed sperm injected into egg
Referral to the programmes • We are happy to consider anyone
Referral to the programmes • Consider ‘welfare of the child’ • Detailed HIV history Recent viral load and CD4 Drugs and resistance • Sexual health screen • Smear/colposcopy • Intended obstetric care
Referral to the programmes • No storage of positive gametes/embryos • Gamete donation on named basis • Couples only will be considered
Pre conceptual counselling & HIV • 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
Welfare of the Child in HIV +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)
Sperm washing programme • Since April 1999 • 59 Couples treated • 11 babies born
Sperm washing-How safe? seminal fluid NSC sperm NSC ? sperm NSC NSC NSC
Validation of sperm washing • sperm samples from 11 HIV +ve men tested for: • HIV RNA viral load • HIV proviral DNA (latent virus) • expression ofCD4 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
sperm 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
4 seroconversions • 2 during pregnancy • 2 postpartum Mandlebrot et al, Lancet 1997; 349:850-851 Risks of unprotected intercourse • unprotected timed intercourse • 1 in 500 risk of infecting partner • series of 92 HIV +ve men /HIV -ve women • carefully timed but unprotected intercourse
1st appointment (GUM) sexual health screen Counselling 2 sessions 2nd appointment (ACU) fertility screen 3rd appointment (ACU) treatment planned IVF or ICSI IUI Fertility provision for HIV +ve males Initial referral info pack sent out
Pregnancy rates • IUI 36 patients=91 cycles: 20% pregnancy • IVF 13 patients=19 cycles: 33.3% pregnancy • ICSI 10 patients=16 cycles: 12.5% pregnancy
Pregnancy monitoring • Pregnancy test • Serial scans from 5+4 weeks • 3 monthly HIV tests during antenatal + post natal periods
Female positive programme • Since April 2002 • 3 women treated • 4 pregnancies-1 ongoing
HIV-1 +ve women:welfare of the child • risk of vertical transmission • cannot ‘wash eggs’ • reduced to < 1% with good obstetric care • effect of antiretrovirals in utero • health / life expectancy of parent • persistent drug abuse in parent • future for child if born HIV positive
HIV+ve women and vertical transmission • 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 and infertility: time to treat. Gilling-Smith C, Smith JR, Semprini A. BMJ 2001, 322: 567-8
Mother to child HIV transmission HAART + Caesarean Section + No Breastfeeding = <2% Vertical transmission
Mother to child HIV transmission Chelsea &Westminster (since1995) 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)
Antenatal Care • Must be optimal • Joint care from GU Physician & HIV Specialist Obstetrician • C+W if insufficient locally
1st appointment (GUM) sexual health screen 2nd appointment (ACU) fertility screen IUI • Obstetric • monitoring • HAART • LSCS • no breast feeding 3rd appointment (ACU) treatment planned pregnant IVF or ICSI Fertility provision for HIV positive females Preconceptual counselling Sperm washing
Female positives • IUI-3 cycles 1 pregnancy; early miscarriage • IVF-5 cycles 3 pregnancies-1 ongoing pregnancy • ICSI-0 cycles
Females: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
Couples where both are positive • Sperm washing required • Extra counselling • 3 couples ready for/undergoing treatment
CREAThE • 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
Who to contact • Bronwen Tamberlin /Dr Leila Frodsham Happy to take any enquiries Thankyou