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

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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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Natural cycle IUI/SWP

Day 8 Day 11 Day 13

18mm

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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

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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

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Who to contactWho to contact

Bronwen Tamberlin /Dr Leila Frodsham

Happy to take any enquiries

Thankyou