Portal de Periódicos da CAPES

American physicians remain slow to embrace the reproductive needs of human immunodeficiency virus–infected patients

2006; Elsevier BV; Volume: 85; Issue: 2 Linguagem: Inglês

10.1016/j.fertnstert.2005.08.019

1556-5653

Mark V. Sauer,

LGBTQ Health, Identity, and Policy

Nearly 1 million Americans are infected with HIV. Most are living well and enjoying productive lives. Yet few programs in the United States permit unrestricted access to assisted reproduction for HIV-seropositive patients. Some of these individuals have conventional problems causing infertility. Many others are attempting to minimize viral transmission to their spouse or offspring. European centers remain far ahead of those in the United States in advancing techniques and offering services to safeguard the uninfected while providing effective, affordable care to the HIV-seropositive patient. Nearly 1 million Americans are infected with HIV. Most are living well and enjoying productive lives. Yet few programs in the United States permit unrestricted access to assisted reproduction for HIV-seropositive patients. Some of these individuals have conventional problems causing infertility. Many others are attempting to minimize viral transmission to their spouse or offspring. European centers remain far ahead of those in the United States in advancing techniques and offering services to safeguard the uninfected while providing effective, affordable care to the HIV-seropositive patient. Frodsham et al. (1Frodsham L.C.G. Boag F. Barton S. Gilling-Smith C. Human immunodeficiency virus infection and fertility care in the United Kingdom demand and supply.Fertil Steril. 2006; 85: 285-289Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar) detail efforts by fertility care providers in the United Kingdom to address the reproductive needs of HIV-infected patients. They profile the inadequate resources of a health care system attempting to service an increasingly large population of HIV-seropositive patients. The lack of uniformity in policy noted in the screening and therapy of these individuals suggests that a general strategy for treatment remains to be embraced by most physicians there. Yet, reviewing this experience, it should be readily apparent to clinicians in the United States just how far behind we are in meeting the similar challenge that faces our own populace.For many years now, the topic of providing assisted reproductive care to couples in whom one or both partners is known to be HIV-seropositive has generated intense controversy (2Englert Y. Van Vooren J.P. Place I. Liesnard C. Laruelle C. Delbaere A. et al.ART in HIV-infected couples. Has the time come for a change in attitude?.Hum Reprod. 2001; 16: 1309-1315Crossref PubMed Scopus (58) Google Scholar, 3Anderson D.J. Assisted reproduction for couples infected with the human immunodeficiency virus type 1.Fertil Steril. 1999; 72: 592-594Abstract Full Text PDF PubMed Scopus (34) Google Scholar). Despite 15 years of published experience in Europe, American centers have largely refused services to patients known to be virally infected (4Sauer M.V. Sperm washing techniques address the reproductive needs of HIV-seropositive men a clinical review.Reprod Biomed Online. 2005; 10: 135-140Abstract Full Text PDF PubMed Scopus (63) Google Scholar). As best as I can ascertain, to date there are still fewer than 10 centers that admit to actively treating men with HIV, which represents less than 3% of the practices registered with the Society for Assisted Reproductive Technology. Similarly, there have been but a handful of abstracts detailing any clinical experience with HIV-seropositive patients at the annual meeting of the American Society for Reproductive Medicine over the past 5 years, and almost all of them have come from one center, that being Columbia University in New York.Undoubtedly, U.S. programs cannot ignore these patients indefinitely. Human immunodeficiency virus infection occurs primarily in young, reproductively competent individuals, many of whom are at a stage in their lives when they normally would desire children. A report of 2,864 HIV-infected adults in the United States interviewed as part of the HIV Cost and Services Utilization Study confirmed this presumption, with approximately one third of participants stating a strong desire to have a baby (5Chen J.L. Phillips K.A. Kanouse D.E. Collins R.L. Miu A. Fertility desires and intentions of HIV-positive men and women.Fam Plann Perspect. 2001; 33: 144-152Crossref PubMed Scopus (248) Google Scholar). However, practicing safe sex requires the use of condoms. Obviously, following these guidelines essentially precludes any hope of pregnancy without physician assistance.Physicians trained in reproductive endocrinology and infertility in the United States have been slow to offer care or assistance. I believe there are many reasons for this bias. First, few physicians trained in reproductive endocrinology and infertility are well acquainted with the biology of HIV and how it affects reproductive tract tissue. There is the unfounded belief that the HIV known to exist in semen is also carried by sperm and therefore that any attempt at insemination or IVF is risky. This bias is not supported by evidence in the medical literature (6Politch J.A. Anderson D.J. Preventing HIV-1 infection in women.Infertil Reprod Med Clin North Am. 2002; 13: 249-262Google Scholar). Second, the Centers for Disease Control and Prevention have not endorsed treatments such as IUI or IVF for HIV-infected patients, and therefore physicians are reasonably concerned with liability exposure (7Centers for Disease Control and PreventionHIV-1 infection and artificial insemination with processed semen.MMWR Morb Mortal Wkly Rep. 1990; 39 (255–6): 249PubMed Google Scholar, 8Duerr A. Assisted reproductive technologies for discordant couples.Am J Bioethics. 2003; 3: 45-47Crossref PubMed Scopus (18) Google Scholar). Third, in many states, knowingly placing material that might harbor HIV into a patient might be interpreted as a criminal act, which essentially outlaws efforts at reform. Fourth, it costs money to outfit laboratories with duplicate systems to house the virally infected patients' material. Finally, the majority of ART in this country is provided by private practitioners. These aforementioned factors deter interest in personally investing in such bold initiatives.Thus, in the United States, reproductive options for HIV-seropositive patients remain limited. Couples wishing to have children are usually recommended donor sperm insemination or adoption. However, sperm-washing techniques followed by IUI or IVF, as practiced throughout western Europe and the United Kingdom, have been offered as a means to reduce horizontal transmission of HIV for many years (4Sauer M.V. Sperm washing techniques address the reproductive needs of HIV-seropositive men a clinical review.Reprod Biomed Online. 2005; 10: 135-140Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 9Semprini A.E. Levi-Setti P. Bozzo M. Ravizza M. Taglioretti A. Sulpizio P. et al.Insemination of HIV-negative women with processed semen of HIV-positive partners.Lancet. 1992; 340: 1317-1319Abstract Full Text PDF PubMed Scopus (290) Google Scholar). The success of these clinical trials has led the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine to revise earlier statements against caring for HIV-seropositive patients. Despite the apparent lack of membership support, both groups now recommend the adoption of more tolerant policies of nondiscrimination (10American College of Obstetricians and GynecologistsHIV: ethical guidelines for obstetricians and gynecologists. ACOG committee opinion 255. ACOG, Washington, DC2001Google Scholar, 11Ethics Committee of the American Society for Reproductive MedicineHIV and infertility treatment.Fertil Steril. 2002; 77: 218-222Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar).Although more cases of IUI have been reported, it remains unclear whether one technique is superior to the other in terms of safety. Intrauterine insemination is easier, much less expensive, and with repetitive applications, its success rates approach the efficacy of IVF in well-selected patients. However, IUI therapy requires millions of spermatozoa, and likely some other cellular debris, to be placed above the natural protective barrier of the cervix. Catheters inserted through the endocervix and into the endometrial cavity might create bleeding, which potentially could further increase risk. It is difficult to ensure that all CD4+ cells are eliminated from the "washed" preparation (12Hanabusa H. Kuji N. Kato S. Tagami H. Kaneko S. Tanaka H. et al.An evaluation of semen processing methods for eliminating HIV-1.AIDS. 2000; 14: 1611-1616Crossref PubMed Scopus (67) Google Scholar). Choosing patients according to the viral loads seen in their blood is not recommended, because paired semen samples obtained from HIV-seropositive men commonly express virus, even when plasma viral counts are very low (13Coombs R.W. Speck C.E. Hughes J.E. Lee W. Sampoleo R. Ross S.O. et al.Association between culturable human immunodeficiency virus type 1 in semen and HIV-1 RNA levels in semen and blood evidence for compartmentalization of HIV-1 between semen and blood.J Infect Dis. 1998; 177: 320-330Crossref PubMed Scopus (267) Google Scholar). As mentioned in the Frodsham et al. report (1Frodsham L.C.G. Boag F. Barton S. Gilling-Smith C. Human immunodeficiency virus infection and fertility care in the United Kingdom demand and supply.Fertil Steril. 2006; 85: 285-289Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar), it is prudent to test for the presence of virus when using washed samples for IUI. Unfortunately, HIV testing adds complexity and cost to a normally simple and inexpensive procedure. It is reasonable to assume that neither developing countries nor poorly funded centers serving indigent patients will incorporate such methodology into standard practice.Men with chronic HIV infection often have abnormal semen profiles, and hypogonadism has been described in up to 20% of men receiving highly active antiretroviral therapy (14Pena J.E. Thornton M.H. Sauer M.V. Reversible azoospermia anabolic steroids may profoundly affect HIV seropositive men undergoing assisted reproduction.Obstet Gynecol. 2003; 101: 1073-1075Crossref PubMed Scopus (13) Google Scholar, 15Sellmeyer D.E. Grunfeld C. Endocrine and metabolic disturbances in human immunodeficiency virus infection and the acquired immunodeficiency syndrome.Endocr Rev. 1996; 17: 518-552PubMed Google Scholar). Additionally, they might be using androgens to improve well-being and lessen muscle wasting (16Bhasin S. Storer T.W. Javanbakt M. Berman N. Yarasheski K.E. Phillips J. et al.Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels.JAMA. 2000; 283: 763-770Crossref PubMed Scopus (303) Google Scholar). In such instances, IUI therapy might be less desirable because pregnancy success is generally reduced in men with persistently abnormal semen analyses (17Ohl J. Partisani M. Wittemer C. Schmitt M.P. Cranz C. Stoll-Keller F. et al.Assisted reproduction techniques for HIV serodiscordant couples 18 months experience.Hum Reprod. 2003; 18: 1244-1249Crossref PubMed Scopus (91) Google Scholar). Thus, IUI therapy cannot be universally applied as a treatment option.In 1997, Columbia University began offering IVF-intracytoplasmic sperm injection (ICSI) to HIV-seropositive men to limit viral exposure to a few motile sperm cells (18Sauer M.V. Chang P.L. Establishing a program to assist HIV-1 seropositive men to have children using IVF-ICSI.Am J Obstet Gynecol. 2002; 186: 627-633Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). Intracytoplasmic sperm injection has commonly been used to address male factor infertility and is available at practically all centers providing assisted reproduction. Because "insemination" is not used, it can be argued that IVF-ICSI does not contradict recommendations published by the Centers for Disease Control and Prevention or states with laws prohibiting introducing HIV-infected material into noninfected individuals. Individual spermatozoa are injected, making the risk of inadvertently placing white cells or macrophages into the embryo culture system negligible, which arguably might obviate the need for routine HIV testing of the final motile fraction. The downside to IVF-ICSI relates to its high cost and the increased risk of complications known to exist when ovarian hyperstimulation is used and multiple embryos are transferred (19Pena J.E. Thornton M.H. Sauer M.V. Complications of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus serodiscordant couples.Arch Gynecol Obstet. 2003; 268: 198-201Crossref PubMed Scopus (7) Google Scholar).At Columbia University, new equipment costing more than $100,000 was purchased to perform the procedures and to house embryos obtained from HIV-infected patients separately from those of the general population. Precautions were taken to reduce fears of nosocomial infection. We have now performed more than 200 treatment cycles in HIV-serodiscordant couples, without complication. A seroconversion has not occurred in any of the treated women or the 100 delivered infants.Needless to say, these are very happy and grateful families. However, as in the United Kingdom, the majority of U.S. centers do not offer treatment, and for the few that do, there exist no uniform approaches to care. Every week, we see new patients in New York with HIV, many of whom traveled a great distance to access assisted reproduction from locations in which IVF centers exist.Twenty years into this epidemic, our specialty should accept that HIV-infected patients with fertility needs exist. They are survivors and are tenacious in seeking treatment. For years these couples traveled to Europe to seek care not offered by American physicians fully capable of delivering it. They deserve to be treated better; they deserve to be treated fairly; they deserve to be treated here; and they deserve to be treated now. Frodsham et al. (1Frodsham L.C.G. Boag F. Barton S. Gilling-Smith C. Human immunodeficiency virus infection and fertility care in the United Kingdom demand and supply.Fertil Steril. 2006; 85: 285-289Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar) detail efforts by fertility care providers in the United Kingdom to address the reproductive needs of HIV-infected patients. They profile the inadequate resources of a health care system attempting to service an increasingly large population of HIV-seropositive patients. The lack of uniformity in policy noted in the screening and therapy of these individuals suggests that a general strategy for treatment remains to be embraced by most physicians there. Yet, reviewing this experience, it should be readily apparent to clinicians in the United States just how far behind we are in meeting the similar challenge that faces our own populace. For many years now, the topic of providing assisted reproductive care to couples in whom one or both partners is known to be HIV-seropositive has generated intense controversy (2Englert Y. Van Vooren J.P. Place I. Liesnard C. Laruelle C. Delbaere A. et al.ART in HIV-infected couples. Has the time come for a change in attitude?.Hum Reprod. 2001; 16: 1309-1315Crossref PubMed Scopus (58) Google Scholar, 3Anderson D.J. Assisted reproduction for couples infected with the human immunodeficiency virus type 1.Fertil Steril. 1999; 72: 592-594Abstract Full Text PDF PubMed Scopus (34) Google Scholar). Despite 15 years of published experience in Europe, American centers have largely refused services to patients known to be virally infected (4Sauer M.V. Sperm washing techniques address the reproductive needs of HIV-seropositive men a clinical review.Reprod Biomed Online. 2005; 10: 135-140Abstract Full Text PDF PubMed Scopus (63) Google Scholar). As best as I can ascertain, to date there are still fewer than 10 centers that admit to actively treating men with HIV, which represents less than 3% of the practices registered with the Society for Assisted Reproductive Technology. Similarly, there have been but a handful of abstracts detailing any clinical experience with HIV-seropositive patients at the annual meeting of the American Society for Reproductive Medicine over the past 5 years, and almost all of them have come from one center, that being Columbia University in New York. Undoubtedly, U.S. programs cannot ignore these patients indefinitely. Human immunodeficiency virus infection occurs primarily in young, reproductively competent individuals, many of whom are at a stage in their lives when they normally would desire children. A report of 2,864 HIV-infected adults in the United States interviewed as part of the HIV Cost and Services Utilization Study confirmed this presumption, with approximately one third of participants stating a strong desire to have a baby (5Chen J.L. Phillips K.A. Kanouse D.E. Collins R.L. Miu A. Fertility desires and intentions of HIV-positive men and women.Fam Plann Perspect. 2001; 33: 144-152Crossref PubMed Scopus (248) Google Scholar). However, practicing safe sex requires the use of condoms. Obviously, following these guidelines essentially precludes any hope of pregnancy without physician assistance. Physicians trained in reproductive endocrinology and infertility in the United States have been slow to offer care or assistance. I believe there are many reasons for this bias. First, few physicians trained in reproductive endocrinology and infertility are well acquainted with the biology of HIV and how it affects reproductive tract tissue. There is the unfounded belief that the HIV known to exist in semen is also carried by sperm and therefore that any attempt at insemination or IVF is risky. This bias is not supported by evidence in the medical literature (6Politch J.A. Anderson D.J. Preventing HIV-1 infection in women.Infertil Reprod Med Clin North Am. 2002; 13: 249-262Google Scholar). Second, the Centers for Disease Control and Prevention have not endorsed treatments such as IUI or IVF for HIV-infected patients, and therefore physicians are reasonably concerned with liability exposure (7Centers for Disease Control and PreventionHIV-1 infection and artificial insemination with processed semen.MMWR Morb Mortal Wkly Rep. 1990; 39 (255–6): 249PubMed Google Scholar, 8Duerr A. Assisted reproductive technologies for discordant couples.Am J Bioethics. 2003; 3: 45-47Crossref PubMed Scopus (18) Google Scholar). Third, in many states, knowingly placing material that might harbor HIV into a patient might be interpreted as a criminal act, which essentially outlaws efforts at reform. Fourth, it costs money to outfit laboratories with duplicate systems to house the virally infected patients' material. Finally, the majority of ART in this country is provided by private practitioners. These aforementioned factors deter interest in personally investing in such bold initiatives. Thus, in the United States, reproductive options for HIV-seropositive patients remain limited. Couples wishing to have children are usually recommended donor sperm insemination or adoption. However, sperm-washing techniques followed by IUI or IVF, as practiced throughout western Europe and the United Kingdom, have been offered as a means to reduce horizontal transmission of HIV for many years (4Sauer M.V. Sperm washing techniques address the reproductive needs of HIV-seropositive men a clinical review.Reprod Biomed Online. 2005; 10: 135-140Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 9Semprini A.E. Levi-Setti P. Bozzo M. Ravizza M. Taglioretti A. Sulpizio P. et al.Insemination of HIV-negative women with processed semen of HIV-positive partners.Lancet. 1992; 340: 1317-1319Abstract Full Text PDF PubMed Scopus (290) Google Scholar). The success of these clinical trials has led the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine to revise earlier statements against caring for HIV-seropositive patients. Despite the apparent lack of membership support, both groups now recommend the adoption of more tolerant policies of nondiscrimination (10American College of Obstetricians and GynecologistsHIV: ethical guidelines for obstetricians and gynecologists. ACOG committee opinion 255. ACOG, Washington, DC2001Google Scholar, 11Ethics Committee of the American Society for Reproductive MedicineHIV and infertility treatment.Fertil Steril. 2002; 77: 218-222Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar). Although more cases of IUI have been reported, it remains unclear whether one technique is superior to the other in terms of safety. Intrauterine insemination is easier, much less expensive, and with repetitive applications, its success rates approach the efficacy of IVF in well-selected patients. However, IUI therapy requires millions of spermatozoa, and likely some other cellular debris, to be placed above the natural protective barrier of the cervix. Catheters inserted through the endocervix and into the endometrial cavity might create bleeding, which potentially could further increase risk. It is difficult to ensure that all CD4+ cells are eliminated from the "washed" preparation (12Hanabusa H. Kuji N. Kato S. Tagami H. Kaneko S. Tanaka H. et al.An evaluation of semen processing methods for eliminating HIV-1.AIDS. 2000; 14: 1611-1616Crossref PubMed Scopus (67) Google Scholar). Choosing patients according to the viral loads seen in their blood is not recommended, because paired semen samples obtained from HIV-seropositive men commonly express virus, even when plasma viral counts are very low (13Coombs R.W. Speck C.E. Hughes J.E. Lee W. Sampoleo R. Ross S.O. et al.Association between culturable human immunodeficiency virus type 1 in semen and HIV-1 RNA levels in semen and blood evidence for compartmentalization of HIV-1 between semen and blood.J Infect Dis. 1998; 177: 320-330Crossref PubMed Scopus (267) Google Scholar). As mentioned in the Frodsham et al. report (1Frodsham L.C.G. Boag F. Barton S. Gilling-Smith C. Human immunodeficiency virus infection and fertility care in the United Kingdom demand and supply.Fertil Steril. 2006; 85: 285-289Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar), it is prudent to test for the presence of virus when using washed samples for IUI. Unfortunately, HIV testing adds complexity and cost to a normally simple and inexpensive procedure. It is reasonable to assume that neither developing countries nor poorly funded centers serving indigent patients will incorporate such methodology into standard practice. Men with chronic HIV infection often have abnormal semen profiles, and hypogonadism has been described in up to 20% of men receiving highly active antiretroviral therapy (14Pena J.E. Thornton M.H. Sauer M.V. Reversible azoospermia anabolic steroids may profoundly affect HIV seropositive men undergoing assisted reproduction.Obstet Gynecol. 2003; 101: 1073-1075Crossref PubMed Scopus (13) Google Scholar, 15Sellmeyer D.E. Grunfeld C. Endocrine and metabolic disturbances in human immunodeficiency virus infection and the acquired immunodeficiency syndrome.Endocr Rev. 1996; 17: 518-552PubMed Google Scholar). Additionally, they might be using androgens to improve well-being and lessen muscle wasting (16Bhasin S. Storer T.W. Javanbakt M. Berman N. Yarasheski K.E. Phillips J. et al.Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels.JAMA. 2000; 283: 763-770Crossref PubMed Scopus (303) Google Scholar). In such instances, IUI therapy might be less desirable because pregnancy success is generally reduced in men with persistently abnormal semen analyses (17Ohl J. Partisani M. Wittemer C. Schmitt M.P. Cranz C. Stoll-Keller F. et al.Assisted reproduction techniques for HIV serodiscordant couples 18 months experience.Hum Reprod. 2003; 18: 1244-1249Crossref PubMed Scopus (91) Google Scholar). Thus, IUI therapy cannot be universally applied as a treatment option. In 1997, Columbia University began offering IVF-intracytoplasmic sperm injection (ICSI) to HIV-seropositive men to limit viral exposure to a few motile sperm cells (18Sauer M.V. Chang P.L. Establishing a program to assist HIV-1 seropositive men to have children using IVF-ICSI.Am J Obstet Gynecol. 2002; 186: 627-633Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). Intracytoplasmic sperm injection has commonly been used to address male factor infertility and is available at practically all centers providing assisted reproduction. Because "insemination" is not used, it can be argued that IVF-ICSI does not contradict recommendations published by the Centers for Disease Control and Prevention or states with laws prohibiting introducing HIV-infected material into noninfected individuals. Individual spermatozoa are injected, making the risk of inadvertently placing white cells or macrophages into the embryo culture system negligible, which arguably might obviate the need for routine HIV testing of the final motile fraction. The downside to IVF-ICSI relates to its high cost and the increased risk of complications known to exist when ovarian hyperstimulation is used and multiple embryos are transferred (19Pena J.E. Thornton M.H. Sauer M.V. Complications of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus serodiscordant couples.Arch Gynecol Obstet. 2003; 268: 198-201Crossref PubMed Scopus (7) Google Scholar). At Columbia University, new equipment costing more than $100,000 was purchased to perform the procedures and to house embryos obtained from HIV-infected patients separately from those of the general population. Precautions were taken to reduce fears of nosocomial infection. We have now performed more than 200 treatment cycles in HIV-serodiscordant couples, without complication. A seroconversion has not occurred in any of the treated women or the 100 delivered infants. Needless to say, these are very happy and grateful families. However, as in the United Kingdom, the majority of U.S. centers do not offer treatment, and for the few that do, there exist no uniform approaches to care. Every week, we see new patients in New York with HIV, many of whom traveled a great distance to access assisted reproduction from locations in which IVF centers exist. Twenty years into this epidemic, our specialty should accept that HIV-infected patients with fertility needs exist. They are survivors and are tenacious in seeking treatment. For years these couples traveled to Europe to seek care not offered by American physicians fully capable of delivering it. They deserve to be treated better; they deserve to be treated fairly; they deserve to be treated here; and they deserve to be treated now.