1. 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

2. Talk to UK-CAB 25.10.02 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

3. Talk to UK-CAB 25.10.02 Who we treat HIV positive males with negative partners HIV positive females with negative partners Couples where both partners are positive

4. Talk to UK-CAB 25.10.02 What treatments do we offer? IUI (intrauterine insemination) IVF (in vitro fertilization) ICSI (intracytoplasmic sperm injection) Donor Insemination

5. Talk to UK-CAB 25.10.02 IUI In couples with normal/unexplained infertility Ovulation predicted via ultrasound tracking Sperm washed Sperm injected into partners womb

6. Talk to UK-CAB 25.10.02 Natural cycle IUI/SWP Day 8 Day 11 Day 13 18mm

7. Talk to UK-CAB 25.10.02 InVitroFertilization In subfertile couples Tubal disease/low sperm count Superovulation by injection Follicles tracked by scan Eggs collected

8. Talk to UK-CAB 25.10.02 InVitroFertilization Sperm washed Sperm and eggs mixed in the lab Embryos replaced in womb

9. Talk to UK-CAB 25.10.02 Intracytoplasmic sperm injection Very low sperm count As IVF Single washed sperm injected into egg

10. Talk to UK-CAB 25.10.02 Referral to the programmes We are happy to consider anyone

11. Talk to UK-CAB 25.10.02 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

12. Talk to UK-CAB 25.10.02 Referral to the programmes No storage of positive gametes/embryos Gamete donation on named basis Couples only will be considered

13. Talk to UK-CAB 25.10.02 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

14. Talk to UK-CAB 25.10.02 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)

15. Talk to UK-CAB 25.10.02 Sperm washing programme Since April 1999 59 Couples treated 11 babies born

16. Talk to UK-CAB 25.10.02 Sperm washing-How safe? seminal fluid NSC sperm NSC sperm ?

17. Talk to UK-CAB 25.10.02 Validation 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

18. Talk to UK-CAB 25.10.02 sperm washing semen centrifuged in density gradient NASBA check for HIV- 1 RNA (25 HIV-1 copies/10 6 sperm) 6% risk of positive NASBA Ù cancelled cycle

19. Talk to UK-CAB 25.10.02 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 Mandlebrot et al, Lancet 1997; 349:850-851 4 seroconversions 2 during pregnancy 2 postpartum

20. Talk to UK-CAB 25.10.02 Fertility provision for HIV +ve males Initial referral info pack sent out 1st appointment (GUM) sexual health screen IUI 3rd appointment (ACU) treatment planned Counselling 2 sessions 2nd appointment (ACU) fertility screen IVF or ICSI

21. Talk to UK-CAB 25.10.02 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

22. Talk to UK-CAB 25.10.02 Pregnancy monitoring Pregnancy test Serial scans from 5+4 weeks 3 monthly HIV tests during antenatal + post natal periods

23. Talk to UK-CAB 25.10.02 Female positive programme Since April 2002 3 women treated 4 pregnancies-1 ongoing

24. Talk to UK-CAB 25.10.02 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-1 +ve women:welfare of the child HIV-1 +ve women:welfare of the child

25. Talk to UK-CAB 25.10.02 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 transmission HIV and infertility: time to treat. Gilling-Smith C, Smith JR, Semprini A. BMJ 2001, 322: 567-8

26. Talk to UK-CAB 25.10.02 Mother to child HIV transmission HAART + Caesarean Section + No Breastfeeding = <2% Vertical transmission

27. 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)

28. Talk to UK-CAB 25.10.02 Antenatal Care Must be optimal Joint care from GU Physician & HIV Specialist Obstetrician C+W if insufficient locally

29. Talk to UK-CAB 25.10.02 Fertility provision for HIV positive females 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

30. Talk to UK-CAB 25.10.02 Female positives IUI-3 cycles 1 pregnancy; early miscarriage IVF-5 cycles 3 pregnancies-1 ongoing pregnancy ICSI-0 cycles

31. Talk to UK-CAB 25.10.02 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

32. Talk to UK-CAB 25.10.02 Couples where both are positive Sperm washing required Extra counselling 3 couples ready for/undergoing treatment

33. Talk to UK-CAB 25.10.02 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

34. Talk to UK-CAB 25.10.02 Who to contact Bronwen Tamberlin /Dr Leila Frodsham Happy to take any enquiries Thankyou