REFLECTIONS Why are we still, 20 years later, depriving human immunodeficiency virus-serodiscordant couples of equal access to fertility care? Since acquired immunodeficiency syndrome (AIDS) was first described by the U.S. Centers for Disease Control and Prevention (CDC) in a group of five young gay men in 1981, more than 75 million people have contracted the human immunodeficiency virus (HIV) worldwide. There are currently more than 35 million people living with HIV/AIDS, with 2.3 million new infections reported in 2012. Over 80% of people infected with HIV are of reproductive age (15–44 years old), and heterosexual transmission accounts for up to 80% of all new infections in women. Owing to advances in early diagnosis and treatment, especially since the introduction and widespread use of highly active antiretroviral treatment (HAART) in 1996, HIV/AIDS is no longer a death sentence; it has been reclassified as a chronic disease with significant improvement in life quality and expectancy. As a result, HIV patients are living much longer than before and have partners who are not always HIV positive. Reports suggest that there are currently more than 140,000 HIV-serodiscordant heterosexual couples in the United States, approximately half of whom wish to have children. In a survey of 50 consecutive serodiscordant couples who presented at the Center for Women's Reproductive Care at Columbia University seeking fertility care to minimize their risk of HIV transmission, 20% of couples reported having had unprotected intercourse aiming at conception, 40% would have unprotected intercourse to achieve pregnancy in the absence of alternatives, and 92% had discussed the potential risk of HIV transmission to their partner or child (1). According to the National Perinatal HIV Hotline and Clinicians Network, calls pertaining to HIV-serodiscordant couples and their options for safer conception have increased significantly between 2006 and 2011 (2). Out of the calls related to couples with an HIV-positive man/HIV-negative woman (>80% of all calls), 63% were regarding referrals to fertility clinics. In cases when assisted reproduction options were not available or affordable, couples inquired about alternatives such as pre-exposure prophylaxis (PrEP). Furthermore, HIV-positive patients, both men and women, have higher rates of infertility than their HIV-negative counterparts. This is primarily due to HIV-associated decreased semen parameters and hypogonadism in males as well as a higher incidence of tubal disease and pelvic infections in women, especially when the virus was acquired sexually. According to the American Society for Reproductive Medicine (ASRM), the rate of HIV transmission in serodiscordant couples is approximately 1 per 500–1,000 episodes of unprotected intercourse (3). This risk increases significantly if the HIV-positive partner's viral load is high, or if the HIVnegative partner has a concomitant genital infection, inflammation, or abrasions. Semen washing (SW) techniques were thus developed in the 1980s to aid serodiscordant couples who desired conception. This process employs centrifugation and density gradient separation of sperm from the seminal fluid that contains HIV. Unfortunately, one isolated case of documented seroconversion after incorrect use of SW in an intra352
uterine insemination (SW-IUI) led to the CDC in 1990 and the ASRM in 1994 recommending against insemination of HIVnegative women with their HIV-positive partners' sperm (4). In the meantime, Canada, Europe, and Australia adopted SW-IUI as the standard of care for HIV-serodiscordant couples, and reports have repeatedly confirmed no seroconversion events. The meta-analysis by Barnes et al. (5) published in this issue of Fertility and Sterility, the largest study to date, summarizes our collective published experience with SW-IUI and SW-IVF in serodiscordant couples. This amounts to over 8,200 IUI cycles and over 1,200 IVF cycles with satisfactory reproductive outcomes and, even more importantly, a 0% HIV transmission rate (5). As inferred by these investigators, the upper 95% confidence limit would be 4.5 transmissions per 10,000 seropositive male and seronegative female IUI cycles. As more encouraging evidence has accumulated throughout the years, the ASRM Ethics Committee reexamined its earlier guidelines from 2002 and has since revised them in 2006 and 2010 to reflect the recommended use of SW and assisted reproductive techniques in HIV-serodiscordant couples (3). Moreover, the updated 2014 U.S. Department of Health and Human Services (DHHS) recommendations also support the use of SW-IUI and IVF-ICSI for this population. However, the CDC maintains its original position against SW, despite the available evidence and notwithstanding specific requests for recommendation revision (2). What is far more disheartening is the resistance that is still presented by U.S. fertility clinics, despite the changes in the ASRM and DHHS recommendations, when it comes to treatment of serodiscordant couples. Historically, HIV patients have encountered little support or encouragement when pursuing conception. One would thus expect that emerging evidence of SW safety and consensus guidelines would change this attitude dramatically. Instead, over 80% of U.S. fertility clinics are not supportive of services provided to HIV-positive patients. According to the Perinatal HIV Hotline, as of March 2013 there were only seven known fertility clinics in the United States willing to offer SW-IUI, and only 17 were willing to offer IVF to these couples. When geographic, financial, and accessibility limitations are factored in, that leaves the majority of serodiscordant couples in the United States with no access to fertility care (2). This realization leads us to a consideration of alternative options available to these couples. These include [1] treatment of the HIV-positive partner with HAART to minimize viral load to ideally undetectable levels, [2] timing unprotected intercourse around ovulation, and/or [3] screening of both partners for sexually transmitted infections as they have been shown to increase HIV shedding and susceptibility to infection. None of these methods offer 100% protection from transmission and are thus not supported by ASRM. Furthermore, the efficacy and safety of PrEP is based on a few studies and remains controversial, especially in heterosexual serodiscordant couples. The use of PrEP is also limited by the potential for development of resistant strains, as well as for issues of durability of protection, adverse effect profile, and long-term compliance. It is true that no randomized controlled trial has been published yet investigating the safety and effectiveness of
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Fertility and Sterility® fertility treatments in HIV-serodiscordant couples, nor is one likely to be published soon, given the strong ethical implications. However, the rest of the developed world has reviewed the evidence and adopted these changes, and ASRM has endorsed them since 2002. More than 10 years later, most of us are still denying these patients their basic right of access to fertility care. I think it is about time we reconsidered! Vasiliki A. Moragianni, M.D., M.S. Fertility Solutions, Dedham, Massachusetts http://dx.doi.org/10.1016/j.fertnstert.2014.05.023 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/moragianniv-hivserodiscordant-equal-access/
REFERENCES 1.
2.
3.
4.
5.
~a JE, Thornton MH, Sauer MV. Understanding the motivations, Klein J, Pen concerns, and desires of human immunodeficiency virus 1-serodiscordant couples wishing to have children through assisted reproduction. Obstet Gynecol 2003;101:987–94. Cohan D, Weber S, Aaron E. CDC should reverse its recommendation against semen washing-intrauterine insemination for HIV-serodifferent couples. Am J Obstet Gynecol 2013;209:284. Ethics Committee of the American Society for Reproductive Medicine. Human immunodeficiency virus and infertility treatment. Fertil Steril 2010;94: 11–5. Centers for Disease Control and Prevention. HIV-1 infection and artificial insemination with processed semen. MMWR Morb Mortal Wkly Rep 1990; 39:249, 255–6. Barnes A, Ricke D, Mena L, Sison T, Barry L, Reddy R, et al. Efficacy and safety of intrauterine insemination and assisted reproductive technology in populations serodiscordant for human immunodeficiency virus: a systematic review and meta-analysis. Fertil Steril 2014;102:424–34.
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
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uterine insemination (SW-IUI) led to the CDC in 1990 and the ASRM in 1994 recommending against insemination of HIVnegative women with their HIV-positive partners' sperm (4). In the meantime, Canada, Europe, and Australia adopted SW-IUI as the standard of care for HIV-serodiscordant couples, and reports have repeatedly confirmed no seroconversion events. The meta-analysis by Barnes et al. (5) published in this issue of Fertility and Sterility, the largest study to date, summarizes our collective published experience with SW-IUI and SW-IVF in serodiscordant couples. This amounts to over 8,200 IUI cycles and over 1,200 IVF cycles with satisfactory reproductive outcomes and, even more importantly, a 0% HIV transmission rate (5). As inferred by these investigators, the upper 95% confidence limit would be 4.5 transmissions per 10,000 seropositive male and seronegative female IUI cycles. As more encouraging evidence has accumulated throughout the years, the ASRM Ethics Committee reexamined its earlier guidelines from 2002 and has since revised them in 2006 and 2010 to reflect the recommended use of SW and assisted reproductive techniques in HIV-serodiscordant couples (3). Moreover, the updated 2014 U.S. Department of Health and Human Services (DHHS) recommendations also support the use of SW-IUI and IVF-ICSI for this population. However, the CDC maintains its original position against SW, despite the available evidence and notwithstanding specific requests for recommendation revision (2). What is far more disheartening is the resistance that is still presented by U.S. fertility clinics, despite the changes in the ASRM and DHHS recommendations, when it comes to treatment of serodiscordant couples. Historically, HIV patients have encountered little support or encouragement when pursuing conception. One would thus expect that emerging evidence of SW safety and consensus guidelines would change this attitude dramatically. Instead, over 80% of U.S. fertility clinics are not supportive of services provided to HIV-positive patients. According to the Perinatal HIV Hotline, as of March 2013 there were only seven known fertility clinics in the United States willing to offer SW-IUI, and only 17 were willing to offer IVF to these couples. When geographic, financial, and accessibility limitations are factored in, that leaves the majority of serodiscordant couples in the United States with no access to fertility care (2). This realization leads us to a consideration of alternative options available to these couples. These include [1] treatment of the HIV-positive partner with HAART to minimize viral load to ideally undetectable levels, [2] timing unprotected intercourse around ovulation, and/or [3] screening of both partners for sexually transmitted infections as they have been shown to increase HIV shedding and susceptibility to infection. None of these methods offer 100% protection from transmission and are thus not supported by ASRM. Furthermore, the efficacy and safety of PrEP is based on a few studies and remains controversial, especially in heterosexual serodiscordant couples. The use of PrEP is also limited by the potential for development of resistant strains, as well as for issues of durability of protection, adverse effect profile, and long-term compliance. It is true that no randomized controlled trial has been published yet investigating the safety and effectiveness of
VOL. 102 NO. 2 / AUGUST 2014
Fertility and Sterility® fertility treatments in HIV-serodiscordant couples, nor is one likely to be published soon, given the strong ethical implications. However, the rest of the developed world has reviewed the evidence and adopted these changes, and ASRM has endorsed them since 2002. More than 10 years later, most of us are still denying these patients their basic right of access to fertility care. I think it is about time we reconsidered! Vasiliki A. Moragianni, M.D., M.S. Fertility Solutions, Dedham, Massachusetts http://dx.doi.org/10.1016/j.fertnstert.2014.05.023 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/moragianniv-hivserodiscordant-equal-access/
REFERENCES 1.
2.
3.
4.
5.
~a JE, Thornton MH, Sauer MV. Understanding the motivations, Klein J, Pen concerns, and desires of human immunodeficiency virus 1-serodiscordant couples wishing to have children through assisted reproduction. Obstet Gynecol 2003;101:987–94. Cohan D, Weber S, Aaron E. CDC should reverse its recommendation against semen washing-intrauterine insemination for HIV-serodifferent couples. Am J Obstet Gynecol 2013;209:284. Ethics Committee of the American Society for Reproductive Medicine. Human immunodeficiency virus and infertility treatment. Fertil Steril 2010;94: 11–5. Centers for Disease Control and Prevention. HIV-1 infection and artificial insemination with processed semen. MMWR Morb Mortal Wkly Rep 1990; 39:249, 255–6. Barnes A, Ricke D, Mena L, Sison T, Barry L, Reddy R, et al. Efficacy and safety of intrauterine insemination and assisted reproductive technology in populations serodiscordant for human immunodeficiency virus: a systematic review and meta-analysis. Fertil Steril 2014;102:424–34.
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
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