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Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital
British Journal of Obstetrics and Gynaecology June 2001, Vol. 108, pp. 654±656
SHORT COMMUNICATION
Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital R. Hart*, Y. Khalaf, R. Lawson, H. Bickerstaff, A. Taylor, P. Braude The Human Fertilisation and Embryology Authority requires all sperm donors to be screened for human immunode®ciency virus (HIV), hepatitis B and C and their semen quarantined for six months. No guidelines exist for screening prior to in vitro fertilisation or intracytoplasmic sperm injection. We prospectively analysed the prevalence of these viruses in our patients. Screening detected one case of HIV (0.13%), four of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population at this time was 1.4% and 0.8%, respectively. Knowledge allows measures to be taken to reduce the risk of transmission to partner, fetus, new born baby, or by cross-contamination during embryo cryostorage and enables couples to make an informed decision regarding proceeding with treatment. Detection of infection in one partner should no longer preclude fertility treatment.
Introduction The prevalence of human immunodefeciency virus (HIV) in an inner London antenatal population was 0.28% in 1995 1. The UK antenatal prevalence of hepatitis B ranges from 0.03-1.75%. The prevalence of hepatitis C is upto 2% in the United States, although routine antenatal screening is not advocated. Fifty-one percent of patients infected with HIV have been exposed to other sexually transmitted diseases 2 and there is speculation that infertility may be more prevalent in women who are HIV positive. This has implications for those offering fertility services. If one or both partners seeking assisted conception is infected with HIV, hepatitis B or C, they maybe denied access to the service of embryo storage due to the theoretical risk of crosscontamination. If an assisted conception cycle is successful, infection with HIV and hepatitis B and C has implications for both the mother and her infant, with respect to reducing exposure of the baby to the virus at birth or vaccination in hepatitis B infection. In August 1999 the UK government issued a commitment to reduce the numbers of children acquiring HIV infection in England by 80% by the end of 2002. The Human Fertilisation and Embryology Authority (HFEA) requires that all sperm donors should be screened and their semen quarantined for 180 days prior to the most recent blood test. The Authority has not issued any guidelines for HIV screening before
Guy's and St. Thomas' Assisted Conception Unit, St Thomas' Hospital, London UK * Correspondence: Mr R. Hart, Reproductive Medicine Unit, Obstetric Hospital, University College Hospital, London WC18 6HX, UK. q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S03 06-5456(00)0014 6-7
proceeding with assisted conception and future guidance may be required. From January 1999 we undertook a prospective programme in which all couples were tested for HIV, hepatitis B and hepatitis C infection before proceeding with assisted conception treatment. Our aim was to assess the prevalence of HIV, hepatitis B and hepatitis C infection in an infertile population seeking assisted conception and to compare it with the prevalence in the antenatal population in the same hospital during the same study period. Methods Before the introduction of the programme, discussions were held with virologists, genitourinary medicine physicians and HIV counsellors as to how the tests should be performed, how frequently the patients ought to be tested, and how the results were to be conveyed to patients with both negative and positive tests. A decision was made that a positive test in one partner did not preclude the offer of treatment in the unit. However, it would provide an opportunity for the couple to discuss the issue with a counsellor to decide whether they wished to proceed with treatment and the treatment options available to them. The reasons for our mandatory testing policy were presented to patients at a routine pretreatment patient information evening which is attended by all patients. All couples are routinely asked to consent to be tested for hepatitis B and C and HIV before proceeding with a treatment cycle of in vitro fertilisation (IVF). The virology reports of all couples considered for assisted conception between 1 January and 31 December 1999 were reviewed. We de®ned a low risk for hepatitis B infection as being www.bjog-elsevier.com
SHORT COMMUNICATION 655
hepatitis B core antibody positive and surface antigen positive (core Ab 1ve, SAg 1ve), and high risk when positive for both the e antigen and the surface antigen (e Ag 1 ve, SAg 1ve). We used our antenatal population as a control group although we do not screen routinely for hepatitis C. Results The prevalence of hepatitis B, C and HIV in our IVF population and HIV, and hepatitis B in our antenatal population at St. Thomas' Hospital are shown in Table 1. In our unit 815 people were screened (408 couples). The male partner of a couple, who were known to be HIV discordant and who chose our unit for the purpose of sperm washing, was excluded from the analyses. Nobody declined to be screened. Screening detected one new case of HIV positive serology (0.13%), four new cases of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population during the study period was 95 of 6854 (1.4%) and 33 of 4291 patients tested (0.8%), respectively. Discussion In this study we found an incidence of newly diagnosed hepatitis C of 0.5%, hepatitis B of 1.7% and of HIV of 0.13%, similar to those in our antenatal population (1.4% and 0.8% for hepatitis B and HIV, respectively). A similar study reported an incidence of newly diagnosed HIV of 0.06%, of hepatitis B of 0.5% and of hepatitis C of 0.54% 4. Forty-two percent of UK assisted conception centres tested for HIV 3 in 1999. In 1995 the number was 40%, with 41% and 14% testing for hepatitis B and C respectively 5. It is important to test couples before assisted conception so they can make an informed decision as to whether they wish to proceed with treatment. There is evidence
that women infected with HIV still do and that where a person infected with HIV has children their quality of life is enhanced. The majority of couples with positive screening in our study were discordant for infection (only two of our patients were concordant for infection, both with hepatitis B). The knowledge that one of them could potentially infect their partner is important for counselling regarding safe sexual practice and on the appropriate method of assisted conception. If the female partner is the carrier of either HIV or hepatitis C, the couple may prefer to remain childless rather than take the low risk of passing on the infection to an offspring or partner. The risk of contracting hepatitis B can be overcome after a course of vaccination for the unaffected partner and infant. Couples in whom the female partner is a carrier of HIV infection can be taught self-insemination using a syringe at the time of ovulation to minimise risk to their partner. They should be informed of the risk of vertical transmission of the HIV infection (15% to 30%), which can be reduced to less than 5% by anti-retroviral agents and by elective caesarean section, and by avoidance of intrapartum invasive procedures and breastfeeding. Techniques which can reduce the risk of vertical transmission of Hepatitis B and C consist of avoidance of intrapartum fetal blood sampling and instrumental delivery, if possible. Infants of a couple carrying hepatitis B surface antigen should receive prophylaxis in the form of immunoglobulin and vaccination if they are at high risk (mother positive for both hepatitis B surface antigen and core antigen positive). Vaccination only should be administered if they are at low risk (mother positive for both the hepatitis B surface antigen and core antibody). Breastfeeding does not appear to be a major route of transmission of hepatitis C and hepatitis B if the infant is immunised. If the male partner is a carrier of hepatitis B virus a course of vaccination of the female partner should be offered and treatment commenced once immunity is established. If the male partner is infected with HIV, the couple could potentially opt for donor insemination.
Table 1. The prevalance of HIV, Hepatitis B and C in the IVF and antenatal populations of Guy's and St. Thomas' NHS Trust in 1999. HIV IVF population (N 815)
Antenatal population a b
1 (0.13%)
33 (0.8%) (n 4291) b
Hepatitis B i. 2 patients evidence of vaccination ii. 3 patients a core Ab1ve, SAg -ve (previous exposure and immune) iii. 8 patients core Ab1ve, SAg1ve (low infection risk) iv. 3 patients e Ag1ve, SAg1ve (high infection risk) Total 14 new cases detected (1.7%) 95 patients in total SAg1ve (1.39%) (n 6854)
Two of these patients were in a relationship together. Proportion of antenatal population screened for HIV was 62.5%.
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 654±656
Hepatitis C
4 (0.5%)
Not tested
656 SHORT COMMUNICATION
However, most couples prefer to have a child that is genetically their own, therefore sperm washing is an option for couples with unexplained infertility 6. Timed intercourse without sperm washing carries a risk of female seroconversion. Sperm washing reduces the viral load in the semen in most cases to undetectable levels as recorded by a nucleic acid sequence base assay 6. It is advised that an aliquot of the washed semen should be tested and the sample only used if the virus is undetectable. There are no recorded cases of HIV transmission by the procedure of sperm washing. Some women with an HIV positive partner may require IVF treatment because of fallopian tube damage or previous unsuccessful intrauterine insemination treatment. In the procedure of IVF spermatozoa are mixed with each oocyte. If HIV is present in this sample, there is the potential risk of infection of the oocyte and female partner after embryo transfer. This risk can be reduced by sperm washing and testing the spermatozoal fraction for HIV prior to insemination. As with couples where one of the partners is infected with Hepatitis B and C, embryo storage should only be considered in these cases if cryostorage is available separate from other embryos to prevent the risk of contamination. For a man seropositive for HIV with sub-optimal sperm parameters intracytoplasmic sperm injection (ICSI) maybe required to avoid fertilisation failure. The ®rst pregnancy achieved in a seronegative woman using ICSI from an HIV seropositive man has been reported. However, despite prior testing of the sample, if the virus is adherent to the sperm or contained within it, ICSI could risk the direct introduction of the virus into the oocyte. The HFEA code of practice requires that prior to licensable assisted reproduction, account should be taken of the welfare of any child born as a result of the treatment. There are inevitable concerns about the treatment for a couple where one of the partners has a life threatening disease. HIV should be managed no differently to other life threatening diseases. The decision regarding treatment depends on the supportive measures in place for the child once born should one partner die.
Conclusions Our study demonstrates that the incidence of HIV and hepatitis B infection is low and comparable to that in our antenatal population. Screening provides a useful function as it increases patient choice. A study addressing the psychological implications of the mandatory screening of a couple before assisted conception needs to be performed. It is important that when routine testing is implemented that expert counselling is available.
Acknowledgements The authors would like to thank senior midwife Jane Kennedy for her help in obtaining the virology reports for our antenatal population.
References 1. Unlinked Anonymous Surveys Steering Group. Unlinked Anonymous HIV Prevalence Monitoring Programme: England and Wales: Data to the End of 1993. London: Department of Health, 1995. 2. Madge S, Philips AN, Grif®oen A, Olaitan A, Johnson MA. Demographic, clinical and social factors associated with human immunde®ciency virus infection and other sexually transmitted diseases in a cohort of women from the United Kingdom and Ireland, MRC Collaborative Study of women with HIV. Int J Epidemiol 1998;27:1068±1071. 3. Marcus SF, Avery SM, Abusheikha N, Marcus NK, Brinsden PR. The case for routine HIV screening before IVF treatment. A survey of UK IVF centre policies. Hum Reprod 2000;15:1657±1661. 4. Abusheikha N, Akagbosu F, Marcus S, Lass A, Cousins C, Brinsden P. Viral screening and assisted conception treatment ± The Bourn Hall experience. J Assist Reprod Genet 1999;16:337±339. 5. Balet R, Lower AM, Wilson C, Anderson J, Grudzinskas JG. Attitudes towards routine human immunode®ciency virus (HIV) screening and fertility treatment in HIV positive patients ± a UK survey. Hum Reprod 1998;13:1085±1087. 6. Semprini AE, Levi-Setti P, Bozzo M, Ravizza M, Taglioretti A, Sulpizio P, Albani E, Oneta M, Pardi G. Insemination of HIV±negative women with processed semen of HIV±positive partners. Lancet 1992;340:1317± 1319. Accepted 19 January 2001
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 654±656
SHORT COMMUNICATION
Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital R. Hart*, Y. Khalaf, R. Lawson, H. Bickerstaff, A. Taylor, P. Braude The Human Fertilisation and Embryology Authority requires all sperm donors to be screened for human immunode®ciency virus (HIV), hepatitis B and C and their semen quarantined for six months. No guidelines exist for screening prior to in vitro fertilisation or intracytoplasmic sperm injection. We prospectively analysed the prevalence of these viruses in our patients. Screening detected one case of HIV (0.13%), four of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population at this time was 1.4% and 0.8%, respectively. Knowledge allows measures to be taken to reduce the risk of transmission to partner, fetus, new born baby, or by cross-contamination during embryo cryostorage and enables couples to make an informed decision regarding proceeding with treatment. Detection of infection in one partner should no longer preclude fertility treatment.
Introduction The prevalence of human immunodefeciency virus (HIV) in an inner London antenatal population was 0.28% in 1995 1. The UK antenatal prevalence of hepatitis B ranges from 0.03-1.75%. The prevalence of hepatitis C is upto 2% in the United States, although routine antenatal screening is not advocated. Fifty-one percent of patients infected with HIV have been exposed to other sexually transmitted diseases 2 and there is speculation that infertility may be more prevalent in women who are HIV positive. This has implications for those offering fertility services. If one or both partners seeking assisted conception is infected with HIV, hepatitis B or C, they maybe denied access to the service of embryo storage due to the theoretical risk of crosscontamination. If an assisted conception cycle is successful, infection with HIV and hepatitis B and C has implications for both the mother and her infant, with respect to reducing exposure of the baby to the virus at birth or vaccination in hepatitis B infection. In August 1999 the UK government issued a commitment to reduce the numbers of children acquiring HIV infection in England by 80% by the end of 2002. The Human Fertilisation and Embryology Authority (HFEA) requires that all sperm donors should be screened and their semen quarantined for 180 days prior to the most recent blood test. The Authority has not issued any guidelines for HIV screening before
Guy's and St. Thomas' Assisted Conception Unit, St Thomas' Hospital, London UK * Correspondence: Mr R. Hart, Reproductive Medicine Unit, Obstetric Hospital, University College Hospital, London WC18 6HX, UK. q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S03 06-5456(00)0014 6-7
proceeding with assisted conception and future guidance may be required. From January 1999 we undertook a prospective programme in which all couples were tested for HIV, hepatitis B and hepatitis C infection before proceeding with assisted conception treatment. Our aim was to assess the prevalence of HIV, hepatitis B and hepatitis C infection in an infertile population seeking assisted conception and to compare it with the prevalence in the antenatal population in the same hospital during the same study period. Methods Before the introduction of the programme, discussions were held with virologists, genitourinary medicine physicians and HIV counsellors as to how the tests should be performed, how frequently the patients ought to be tested, and how the results were to be conveyed to patients with both negative and positive tests. A decision was made that a positive test in one partner did not preclude the offer of treatment in the unit. However, it would provide an opportunity for the couple to discuss the issue with a counsellor to decide whether they wished to proceed with treatment and the treatment options available to them. The reasons for our mandatory testing policy were presented to patients at a routine pretreatment patient information evening which is attended by all patients. All couples are routinely asked to consent to be tested for hepatitis B and C and HIV before proceeding with a treatment cycle of in vitro fertilisation (IVF). The virology reports of all couples considered for assisted conception between 1 January and 31 December 1999 were reviewed. We de®ned a low risk for hepatitis B infection as being www.bjog-elsevier.com
SHORT COMMUNICATION 655
hepatitis B core antibody positive and surface antigen positive (core Ab 1ve, SAg 1ve), and high risk when positive for both the e antigen and the surface antigen (e Ag 1 ve, SAg 1ve). We used our antenatal population as a control group although we do not screen routinely for hepatitis C. Results The prevalence of hepatitis B, C and HIV in our IVF population and HIV, and hepatitis B in our antenatal population at St. Thomas' Hospital are shown in Table 1. In our unit 815 people were screened (408 couples). The male partner of a couple, who were known to be HIV discordant and who chose our unit for the purpose of sperm washing, was excluded from the analyses. Nobody declined to be screened. Screening detected one new case of HIV positive serology (0.13%), four new cases of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population during the study period was 95 of 6854 (1.4%) and 33 of 4291 patients tested (0.8%), respectively. Discussion In this study we found an incidence of newly diagnosed hepatitis C of 0.5%, hepatitis B of 1.7% and of HIV of 0.13%, similar to those in our antenatal population (1.4% and 0.8% for hepatitis B and HIV, respectively). A similar study reported an incidence of newly diagnosed HIV of 0.06%, of hepatitis B of 0.5% and of hepatitis C of 0.54% 4. Forty-two percent of UK assisted conception centres tested for HIV 3 in 1999. In 1995 the number was 40%, with 41% and 14% testing for hepatitis B and C respectively 5. It is important to test couples before assisted conception so they can make an informed decision as to whether they wish to proceed with treatment. There is evidence
that women infected with HIV still do and that where a person infected with HIV has children their quality of life is enhanced. The majority of couples with positive screening in our study were discordant for infection (only two of our patients were concordant for infection, both with hepatitis B). The knowledge that one of them could potentially infect their partner is important for counselling regarding safe sexual practice and on the appropriate method of assisted conception. If the female partner is the carrier of either HIV or hepatitis C, the couple may prefer to remain childless rather than take the low risk of passing on the infection to an offspring or partner. The risk of contracting hepatitis B can be overcome after a course of vaccination for the unaffected partner and infant. Couples in whom the female partner is a carrier of HIV infection can be taught self-insemination using a syringe at the time of ovulation to minimise risk to their partner. They should be informed of the risk of vertical transmission of the HIV infection (15% to 30%), which can be reduced to less than 5% by anti-retroviral agents and by elective caesarean section, and by avoidance of intrapartum invasive procedures and breastfeeding. Techniques which can reduce the risk of vertical transmission of Hepatitis B and C consist of avoidance of intrapartum fetal blood sampling and instrumental delivery, if possible. Infants of a couple carrying hepatitis B surface antigen should receive prophylaxis in the form of immunoglobulin and vaccination if they are at high risk (mother positive for both hepatitis B surface antigen and core antigen positive). Vaccination only should be administered if they are at low risk (mother positive for both the hepatitis B surface antigen and core antibody). Breastfeeding does not appear to be a major route of transmission of hepatitis C and hepatitis B if the infant is immunised. If the male partner is a carrier of hepatitis B virus a course of vaccination of the female partner should be offered and treatment commenced once immunity is established. If the male partner is infected with HIV, the couple could potentially opt for donor insemination.
Table 1. The prevalance of HIV, Hepatitis B and C in the IVF and antenatal populations of Guy's and St. Thomas' NHS Trust in 1999. HIV IVF population (N 815)
Antenatal population a b
1 (0.13%)
33 (0.8%) (n 4291) b
Hepatitis B i. 2 patients evidence of vaccination ii. 3 patients a core Ab1ve, SAg -ve (previous exposure and immune) iii. 8 patients core Ab1ve, SAg1ve (low infection risk) iv. 3 patients e Ag1ve, SAg1ve (high infection risk) Total 14 new cases detected (1.7%) 95 patients in total SAg1ve (1.39%) (n 6854)
Two of these patients were in a relationship together. Proportion of antenatal population screened for HIV was 62.5%.
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 654±656
Hepatitis C
4 (0.5%)
Not tested
656 SHORT COMMUNICATION
However, most couples prefer to have a child that is genetically their own, therefore sperm washing is an option for couples with unexplained infertility 6. Timed intercourse without sperm washing carries a risk of female seroconversion. Sperm washing reduces the viral load in the semen in most cases to undetectable levels as recorded by a nucleic acid sequence base assay 6. It is advised that an aliquot of the washed semen should be tested and the sample only used if the virus is undetectable. There are no recorded cases of HIV transmission by the procedure of sperm washing. Some women with an HIV positive partner may require IVF treatment because of fallopian tube damage or previous unsuccessful intrauterine insemination treatment. In the procedure of IVF spermatozoa are mixed with each oocyte. If HIV is present in this sample, there is the potential risk of infection of the oocyte and female partner after embryo transfer. This risk can be reduced by sperm washing and testing the spermatozoal fraction for HIV prior to insemination. As with couples where one of the partners is infected with Hepatitis B and C, embryo storage should only be considered in these cases if cryostorage is available separate from other embryos to prevent the risk of contamination. For a man seropositive for HIV with sub-optimal sperm parameters intracytoplasmic sperm injection (ICSI) maybe required to avoid fertilisation failure. The ®rst pregnancy achieved in a seronegative woman using ICSI from an HIV seropositive man has been reported. However, despite prior testing of the sample, if the virus is adherent to the sperm or contained within it, ICSI could risk the direct introduction of the virus into the oocyte. The HFEA code of practice requires that prior to licensable assisted reproduction, account should be taken of the welfare of any child born as a result of the treatment. There are inevitable concerns about the treatment for a couple where one of the partners has a life threatening disease. HIV should be managed no differently to other life threatening diseases. The decision regarding treatment depends on the supportive measures in place for the child once born should one partner die.
Conclusions Our study demonstrates that the incidence of HIV and hepatitis B infection is low and comparable to that in our antenatal population. Screening provides a useful function as it increases patient choice. A study addressing the psychological implications of the mandatory screening of a couple before assisted conception needs to be performed. It is important that when routine testing is implemented that expert counselling is available.
Acknowledgements The authors would like to thank senior midwife Jane Kennedy for her help in obtaining the virology reports for our antenatal population.
References 1. Unlinked Anonymous Surveys Steering Group. Unlinked Anonymous HIV Prevalence Monitoring Programme: England and Wales: Data to the End of 1993. London: Department of Health, 1995. 2. Madge S, Philips AN, Grif®oen A, Olaitan A, Johnson MA. Demographic, clinical and social factors associated with human immunde®ciency virus infection and other sexually transmitted diseases in a cohort of women from the United Kingdom and Ireland, MRC Collaborative Study of women with HIV. Int J Epidemiol 1998;27:1068±1071. 3. Marcus SF, Avery SM, Abusheikha N, Marcus NK, Brinsden PR. The case for routine HIV screening before IVF treatment. A survey of UK IVF centre policies. Hum Reprod 2000;15:1657±1661. 4. Abusheikha N, Akagbosu F, Marcus S, Lass A, Cousins C, Brinsden P. Viral screening and assisted conception treatment ± The Bourn Hall experience. J Assist Reprod Genet 1999;16:337±339. 5. Balet R, Lower AM, Wilson C, Anderson J, Grudzinskas JG. Attitudes towards routine human immunode®ciency virus (HIV) screening and fertility treatment in HIV positive patients ± a UK survey. Hum Reprod 1998;13:1085±1087. 6. Semprini AE, Levi-Setti P, Bozzo M, Ravizza M, Taglioretti A, Sulpizio P, Albani E, Oneta M, Pardi G. Insemination of HIV±negative women with processed semen of HIV±positive partners. Lancet 1992;340:1317± 1319. Accepted 19 January 2001
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 654±656