ASSISTED CONCEPTION IN HIV-DISCORDANT COUPLES. Augusto E Semprini, MD University of Milan Medical School University College of London Chelsea & Westminster Hospital, London.
Augusto E Semprini, MD
University of Milan Medical School
University College of London
Chelsea & Westminster Hospital, London
Alessandra Vucetich, MD Simona Fiore, MDValeria Savasi, MD Claudio Castagna, MDSimonetta Giuntelli, MDMonica Oneta, BiologistTiziana Persico, Biologist
REMOVAL OF p18 IMMUNOREACTIVE CELLS FROM THE SEMEN HTLV-III/LAV SEROPOSITIVE MENAugusto E Semprini, A Vucetich, E Morandi, CL Parravicini, G Pardi and AE Beer. Colloque INSERM, Vol. 154, 1987, pp 462
A cytospin preparation of washed spermatozoa, supernatant and the second fraction of the ejaculate were tested against a monoclonal anti-p18 antibody by immunoperoxidase technique. Washed sperm of seropositive and seronegative men were non-reactive, while many mononuclear cells and those in the second fraction of seropositive males were strongly reactive. Experiments are under way to test the possibility of safe intrauterine insemination with processed semen of HIV-positive men desiring a child.
CMV 50 %
HIV 0.1 - 1 %
HBV 2 %
HHV8 10- 50 %
TTV 2 - 90 %
HGV 1.5 %
HCV 2 %
1. SHOULD IT BE DONE ?
2. HOW SAFE IT IS ?
3. HOW SHOULD WE DO IT ?
HIV/AIDS surveillance in Europe-Mid Year report 2000, n 63
HETEROSEXUAL TRANSMISSION HAS BECOME THE SECOND LEADING CAUSE OF HIV ACQUISITON AFTER USE OF INJECTING DRUGS
THREE OUT OF FOUR NEW CASES OF SEXUAL INFECTION ARE FEMALES
Natural conception in HIV-negative women with HIV-infected partnersL Mandelbrot, I Heard, E Henrion-Geant, R Henrion (Lancet 1997; 349: 850)
We followed 104 consecutive pregnancies in 92 HIV-negative women with HIV-positive partners. Couples were advised to pinpoint ovulation in order to reduce possible exposure. Seroconversion was observed in two women at 7 months of pregnancy and in two others post partum. Some authors advocate intrauterine insemination with semen from the HIV-infected males, but the risk of this must be measured against the low background risk of natural conception. Stringent standard of safety must be required before inseminating potentially infected semen.
hMG IUI 1428-2380 (9-14%)
Costs for 100 ATTEMPTS
IUI 500= 50 000 PREGNANCIES
hMG IUI 1900= 190 000 PREGNANCIES
3 to 100 adult HIV- infections (300 000 $ for an HIV infected adult) $ 900-000 to 30 000 000
Cost for an infected child 175 000 $100 Couples where the male is infected after two years (10.000 episodes)
2.500 IUI (Europe 3.100)
200 IVF (Europe 400)
100 ICSI (Europe 200)
SPECIAL CONSIDERATIONS REARDING HIV AND ASSISTED REPRODUCTIVE TECHNOLOGIESAmerican Society for Reproductive MedicineFertility and Sterility Vol. 62, No. 5, November 1994USE OF SEMEN FROM HIV-POSITIVE PARTNERS FOR INSEMINATION OF SERONEGATIVE WOMEN PARTNERS“The Committee recommends that the physician counsel the couple regarding the risks to the woman and offspring through homologous insemination by any means and that the couple consider the options of donor insemination, adoption, or child-free living.”
THERE IS NO REPORT OF ACQUISITION OF SEXUALLY TRANSMISSIBLE OR BLOODBORNE VIRUSES BY HEALTH CARE PROVIDERS DURING ART PROCEDURES
85 HIV-discordant couples were screened for fertility; 29 women were found suitable for a timed insemination course with the processed semen of their HIV-positive partner. None of the inseminated women seroconverted and 17 pregnancies were achieved in 15 women. All 10 infants born to these mothers remain HIV seronegative. The eldest child is now three years old, healthy and uninfected.
(Semprini et al. - Lancet 1992; 340: 1317-19)
AMOUNT OF HIV-1 IN SPERM FRACTION AFTER SPERM PROCESSING TECHNIQUES(normal semen spiked with 106 pg as by Abbot HIV-Ag ELISA)Anderson and Semprini, Fertil Steril 1993, abstract
Seminal fraction HIV-DNA HIV-RNA
Unprocessed semen 127/254 180/240
Washed spermatozoa 0/254 0/540
ABSENCE OF HEPATITIS C VIRUS AND DETECTION OF HEPATITIS G VIRUS/GB VIRUS C RNA SEQUENCES IN THE SEMEN OF INFECTED MENAE Semprini, T Persico, V Thiers, M Oneta, R Tuveri, P Serafini,A Boschini, S Giuntelli, G Pardi and C Brechot. J Infect Dis 1998; 177(4): 848-54
Serum and semen from 90 anti-HCV-positive drug users were tested (27 infected with HIV) for HCV and HGV/GBV-C RNAs by polymerase chain reaction (PCR) assay, hybridisation, and Sequence analysis. Semen was processed into round cells, seminal plasma and spermatozoa.
Fifty-six patients were HCV-viraemic, but HCV-RNA was not identify in their seminal fractions. However, PCR inhibitors were found in the semen of 34 of these men. Twenty-eight patients had HGV/GBV-C RNA in their blood and for 24 of them, ejaculates were available for analysis. HGV/GBV-C RNA was found in the seminal plasma of 6 of 12 samples free from PCR inhibitors.
These results agree with the low risk of sexual transfer of HCV and provide preliminary evidence for the presence of HGV/GBV-C in semen.
Chronic genital tract infections
Tubal damage up to bilateral obstruction
Poor spermatozoa recovery after washing
Complete washing procedure unfeasible
(necrospermia, severe asthenospermia)
No conception after repeated spontaneous
or IUI attempts
IUI TIMED ON SPONTANEOUS OVULATION
absence of infertility factors
woman with < 35 y.o.
normal hormonal profile
>1 million spermatozoa after washing
IUI WITH MULTIPLE FOLLICULAR INDUCTION
clinical indication for the use of fertility drugs
woman with > 35 y.o.
failure to conceive after 3 timed IUI attempts
>1 million spermatozoa after washing
severe pelvic infertility factor
< 1 million spermatozoa after washing
no pregnancy after repeated IUI attempts
< 0.5 million spermatozoa after washing
severe asthenospermia or necrospermia
(incompatible with complete washing processing)
semen washing and timed IUI does not requires intensive follicular monitoring, carries no risk of multifetality but has a 10% pregnancy rate per attempt
semen washing and IUI with induced multiple follicular maturation, requires follicular monitoring and expensive drugs, carries a 20% risk of multifetality but has a 15-20% pregnancy rate per attempt
semen washing and IVF requires all the above, plus egg retrieval under sedation, costly laboratory procedures, carries a 20-30% risk of multifetality and has a 25-40% pregnancy rate per cycle
semen washing and ICSI involves all the above plus additional laboratory costs, carries a 20-30 risk of multifetality and has a 30-60% pregnancy rate
FERTILITY OF THE COUPLE
EXPERIENCE OF THE CENTER
EXPECTED PREGNANCY RATE PER ART METHOD
TIMING OF PCR RESULTS
COSTS OF DIFFERENT ART PROCEDURES
ACCEPTANCE OF MULTIFETAL OUTCOME
LOGISTICS OF THE COUPLE
NUMBER OF PREVIOUS ART ATTEMPTS
CONFLICTING COUNSELLING FROM DIFFERENT PROVIDERS OF CARE
ANXIETY OVER THE POSSIBILITY OF INFECTION
DIFFICULTIES IN COMPLETING THE PRE-INSEMINATION SCREENING (COST, CONFIDENTIALITY, LOGISTICS)
DIFFICULTIES IN REACHING THE CENTER
LONG WAITING LIST LEADING TO SPONTANEOUS ATTEMPTS AT CONCEPTION
POSSIBILITY OF CYCLE CANCELLATION DUE TO POOR OVARIAN RESPONSE OR HIV PCR TECHNICAL PROBLEMS