To the Editor:
Sauer et al. (1) reported, in a recent Fertility and Sterility issue, 10 years’ experience of an ICSI program in 181 HIV-serodiscordant couples. One hundred three deliveries were reported. It’s noteworthy that the multiple pregnancy (MP) rate was 41%, and 43% of infants were born preterm. Twenty-one infants weighed less than 1500 grams. No female HIV-seroconversions occurred.
The authors affirm that their work provides “evidence that IVF-ICSI is indeed reasonable, safe, and effective alternative for managing the fertility needs of HIV-serodiscordant couples.”
We cannot agree with these conclusions.
1. The choice of ICSI method was not “reasonable.” In this context, one must remember that the majority of serodiscordant couples, with HIV-infected males using condoms to avoid female contamination, were fertile. In our opinion, there is no justification for systematic use of the ICSI in these couples. Since the pioneering study from Semprini et al. (2), several teams have developed IUI programs with efficiency and no female contamination (3). While the debate on HIV presence on spermatozoa is not definitively closed, the safety of ART methods was clearly demonstrated in a published European multicenter study (4). The sperm abnormalities sometimes reported in the literature cannot justify ICSI for all serodiscordant couples.
2. The choice of ICSI method in this context cannot be regarded as “safe.” With respect to the HIV-transmission risk, the current literature supports ICSI as being as safe, but no safer than IUI. Compared to IUI, superovulation and oocyte retrieval in IVF-ICSI carry risks to the women. However, the main concern with IVF-ICSI is the significantly increased MP and resulting complications, such as increased rate of preterm delivery and increased risk of maternal morbidity and mortality. Multiple-birth infants have significantly increased risks of adverse health outcomes, predominantly as a result of preterm delivery, such as low birth weight, infant death and physical and neurological disabilities. The literature on ART has clearly established that practitioners should strive to avoid MP. Because of that, performing IVF or ICSI in serodiscordant couples when there is no sound medical basis for it cannot be justified.
3. ICSI did not prove to be an “effective” treatment. The live-birth rate in the ICSI group (56.9%) was comparable to the cumulative live-birth rate reported in IUI programs. From a public health perspective, if we integrate the cost of ICSI on the effectiveness, ICSI was less effective than IUI programs for HIV-serodiscordant couples, even when the cost of viral testing of semen is taken into account. Moreover, if we add the huge financial burden associated with MP and prematurity, ICSI then becomes a very costly treatment.
In countries where health insurance companies often do not cover infertility treatment, the cost of ICSI may prohibit ART to reduce transmission risk during reproduction for many serodiscordant couples, which may in turn lead to such couples attempting to conceive through unprotected intercourse. From this aspect, we believe systematic use of ICSI in such couples carries ethical implications.
In conclusion, we believe that the systematic use of ICSI in serodiscordant couples, where the male partner is HIV infected, is not reasonable, safe, effective or ethical. We believe that patients should be informed about all the options for reducing the risk of HIV transmission and that the choice of ART methods should be related only to the fertility status (5).
Louis Bujan, MD Associate Professor of Reproductive Biology University Toulouse III Paul Sabatier, EA 3694, Research Group on Human Fertility CECOS Midi-Pyrénées, and CREAThE Network University Hospital Paule de Viguier TSA 70034, 31059 Toulouse Cedex 9, France
Carole Gilling-Smith, MD Department of Obstetrics and Gynaecology, Chelsea & Westminster Hospital, and CREAThE network London, England
Lital Hollander, MSc Enrico A. Semprini, MD ESMAN Medical Consulting and CREAThE network Milan, Italy
Pietro Veranzza; MD, PhD Infectious Diseases, Department of Medicine and CREAThE network Kantonsspital St Gallen, Switzerland
1. Sauer MV, Wang JG, Douglas NC, Nakhuda GS, Vardhana P, Jovanovic V, et al. Providing fertility care to men seropositive for human immunodeficiency virus: reviewing 10 years of experience and 420 consecutive cycles of in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2008 Jun 12.
2. Semprini AE, 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(8831):1317-9.
3. Gilling-Smith C, Nicopoullos JD, Semprini AE, Frodsham LC. HIV and reproductive care–a review of current practice. Bjog. 2006;113(8):869-78.
4. Bujan L, Hollander L, Coudert M, Gilling-Smith C, Vucetich A, Guibert J, et al. Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network. Aids. 2007;21(14):1909-14.
5. Bujan L, Daudin M, Pasquier C. Choice of ART programme for serodiscordant couples with an HIV infected male partner. Hum Reprod. 200621(5):1332-3; author reply 3-4.
The Author Replies:
I was disappointed to read the response of CREAThE to the detailed report of our 10 years of work. Columbia University has labored to provide a reproductive “alternative” for Americans with HIV since 1997, within an environment very different from that existing in Europe and the United Kingdom. We have never advocated for a “systematic” approach using either IVF or IUI therapy, and in fact, I have published on the value of utilizing both methods (1). However, in providing an alternative to no care, we chose to allow open access to HIV-infected patients despite recommendations against the practice by the Centers for Disease Control and Prevention (CDC), when few if any U.S. centers offered services, and accepting of the fact that it might be considered illegal in various parts of this country to treat them. We chose ICSI to avoid prohibitions against “insemination,” and to negate the need to test individual samples for HIV with assays that are expensive and not licensed or commercially approved to be used on semen.
Our patients elect to come here. They are fully informed of the risks and the benefits. Their risks are no different from other patients who also choose IVF, many of whom could also have consented to less invasive approaches but may prefer the enhanced success rates, expedited approach and ability to cryopreserve embryos that remain an advantage of IVF over IUI therapies.
We have been transparent in our attempts to advocate for treatment of HIV infected patients, publishing our protocols and updating our experience regularly along the way. This includes reports of complications of the use of IVF for this purpose (2). More than any other American program, and with numbers that rival any of the individual centers within the CREAThE network, Columbia University has gained an experience that is large and deep in both its clinical aspects and cultural importance. To question our method is one thing; to question our ethics is quite another.
Mark V. Sauer, MD Professor and Chief Reproductive Endocrinology Columbia University New York, NY
1. Sauer MV. Sperm washing techniques address the fertility needs of HIV-seropositive men: a clinical review. Reprod Biomedicine Online 2005; 10:135-140.
2. Pena JE, Thornton MH, Sauer MV. Complications of IVF-ICSI in HIV serodiscordant couples. Arch Gynecol Obstet 2003; 268:198-201.