HIV Subfertility Leila C G Frodsham Clinical Research

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 l Leila CG Frodsham Research Fellow l Bronwen Tamberlin Sperm washing Coordinator l Carole Gilling-Smith Consultant Gynaecologist+Director Assisted Conception Unit Chelsea and Westminster Hospital Talk to UK-CAB 25. 10. 02

Who we treat l HIV positive males with negative partners l HIV positive females with negative partners l Couples where both partners are positive Talk to UK-CAB 25. 10. 02

What treatments do we offer? l IUI (intrauterine insemination) l IVF (in vitro fertilization) l ICSI (intracytoplasmic sperm injection) l Donor Insemination Talk to UK-CAB 25. 10. 02

IUI l In couples with normal/unexplained infertility l Ovulation predicted via ultrasound tracking l Sperm washed l Sperm injected into partners womb Talk to UK-CAB 25. 10. 02

Natural cycle IUI/SWP 18 mm Day 8 Day 11 Day 13 Talk to UK-CAB 25. 10. 02

In. Vitro. Fertilization l In subfertile couples Tubal disease/low sperm count l Superovulation l Follicles l Eggs by injection tracked by scan collected Talk to UK-CAB 25. 10. 02

In. Vitro. Fertilization l Sperm washed l Sperm and eggs mixed in the lab l Embryos replaced in womb Talk to UK-CAB 25. 10. 02

Intracytoplasmic sperm injection l Very l As low sperm count IVF l Single washed sperm injected into egg Talk to UK-CAB 25. 10. 02

Referral to the programmes l We are happy to consider anyone Talk to UK-CAB 25. 10. 02

Referral to the programmes l Consider ‘welfare of the child’ l Detailed HIV history Recent viral load and CD 4 Drugs and resistance l Sexual health screen l Smear/colposcopy l Intended obstetric care Talk to UK-CAB 25. 10. 02

Referral to the programmes l No storage of positive gametes/embryos l Gamete donation on named basis l Couples only will be considered Talk to UK-CAB 25. 10. 02

Pre conceptual counselling & HIV Stability of relationship l Disease progression / health of infected parent l High risk behaviour (drug abuse, unprotected sex) l Social support l l Understand & agree to comply with risk reduction treatment Talk to UK-CAB 25. 10. 02

Welfare of the Child in HIV +ve l In male partner: – Transmission of HIV in sperm l In female partner: – Vertical transmission risk (< 1%) l l l Use of antiretrovirals Mode of delivery Avoidance of breastfeeding – Effect of antiretrovirals on fetus/child l In both: – Disease progression / health of infected parent to UK-CAB 25. 10. 02 – High risk behaviour (drug abuse, Talk unprotected sex)

Sperm washing programme l Since April 1999 l 59 Couples treated l 11 babies born Talk to UK-CAB 25. 10. 02

Sperm washing-How safe? sperm NSC ? sperm NSC seminal fluid NSC NSC Talk to UK-CAB 25. 10. 02

Validation of sperm washing l sperm for: samples from 11 HIV +ve men tested – HIV RNA viral load – HIV proviral DNA (latent virus) – expression of CD 4 receptor & HIV co-receptors CCR 5 l spermatozoa had no: – HIV RNA – HIV proviral DNA – CD 4 or CCR 5 expression L Kim et al, AIDS 1999, 13: 645 -51 Talk to UK-CAB 25. 10. 02

sperm washing semen centrifuged in density gradient l NASBA check for HIV-1 RNA l (25 HIV-1 copies/106 sperm) 6% risk of positive NASBA Ù cancelled cycle l Talk to UK-CAB 25. 10. 02

Risks of unprotected intercourse l unprotected timed intercourse – 1 in 500 risk of infecting partner series of 92 HIV +ve men /HIV -ve women l carefully timed but unprotected intercourse l 4 seroconversions • 2 during pregnancy • 2 postpartum Mandlebrot et al, Lancet 1997; 349: 850 -851 Talk to UK-CAB 25. 10. 02

Fertility provision for HIV +ve males Initial referral info pack sent out 1 st appointment (GUM) sexual health screen Counselling 2 sessions 2 nd appointment (ACU) fertility screen IVF or ICSI 3 rd appointment (ACU) treatment planned IUI Talk to UK-CAB 25. 10. 02

Pregnancy rates l IUI 36 patients=91 cycles: 20% pregnancy l IVF 13 patients=19 cycles: 33. 3% pregnancy l ICSI 10 patients=16 cycles: 12. 5% pregnancy Talk to UK-CAB 25. 10. 02

Pregnancy monitoring l Pregnancy l Serial test scans from 5+4 weeks l 3 monthly HIV tests during antenatal + post natal periods Talk to UK-CAB 25. 10. 02

Female positive programme l Since April 2002 l 3 women treated l 4 pregnancies-1 ongoing Talk to UK-CAB 25. 10. 02

HIV-1 +ve women: welfare of the child l risk of vertical transmission – cannot ‘wash eggs’ – reduced to < 1% with good obstetric care l effect of antiretrovirals in utero l health / life expectancy of parent l persistent drug abuse in parent l future for child if born HIV positive Talk to UK-CAB 25. 10. 02

HIV+ve women and vertical transmission l equal or greater risks to offspring in: – older women l trisomy 21 and other chromosome abnormalities – women with cardiac disease or cystic fibrosis – diabetics – multiple pregnancy – severe &JR, ICSI HIV and infertility: timeoligoasthenospermia to treat. Gilling-Smith C, Smith Semprini A. BMJ 2001, 322: 567 -8 Talk to UK-CAB 25. 10. 02

Mother to child HIV transmission HAART + Caesarean Section + No Breastfeeding = <2% Vertical transmission Talk to UK-CAB 25. 10. 02

Mother to child HIV transmission Chelsea &Westminster (since 1995) 50 births in HIV +ve women none of the babies +ve St Mary’s Paddington (since 1996) 78 births in HIV +ve women two positive babies (in both cases mother did not comply and take medication & delivered elsewhere) Talk to UK-CAB 25. 10. 02

Antenatal Care l Must be optimal l Joint care from GU Physician & HIV Specialist Obstetrician l C+W if insufficient locally Talk to UK-CAB 25. 10. 02

Fertility provision for HIV positive females 1 st appointment (GUM) sexual health screen Preconceptual counselling 2 nd appointment (ACU) fertility screen IUI 3 rd appointment (ACU) treatment planned Sperm washing IVF or ICSI pregnant Obstetric monitoring • HAART • LSCS Talk to UK-CAB 25. 10. 02 • no breast feeding

Female positives l IUI-3 cycles 1 pregnancy; early miscarriage l IVF-5 cycles 3 pregnancies-1 ongoing pregnancy l ICSI-0 cycles Talk to UK-CAB 25. 10. 02

Females: when to refer l Provided Negative partner l regular cycle l no history PID/STD or abdominal surgery l No other known fertility factors l >35 years: 6 months self-insemination <35 years: 6 -12 months self-insemination Talk to UK-CAB 25. 10. 02

Couples where both are positive l Sperm l Extra l 3 washing required counselling couples ready for/undergoing treatment Talk to UK-CAB 25. 10. 02

CREATh. E Centres for Reproductive Assistance Techniques in HIV in Europe l 7 centres in 6 countries to pool data to assess: l – safety of risk reduction options – efficacy in relation to fertility factors in this population – epidemiology – behavioural and psychosocial aspects l draw up guidelines for counselling and treatment Talk to UK-CAB 25. 10. 02

Who to contact l Bronwen Tamberlin /Dr Leila Frodsham Happy to take any enquiries Thankyou Talk to UK-CAB 25. 10. 02