Reply to ‘The effect of human immunodeficiency virus on semen parameters and intrauterine insemination outcome’
1 Assisted Conception Unit, Chelsea & Westminster Hospital, London, SW10 9NH and 2 Clinical Director of Surgery, Charring Cross Hospital, London W6 8RF, UK
3 To whom correspondence should be addressed. Email: james.nicopoullos{at}chelwest.nhs.uk
Sir,
We read with great interest the letter by van Leeuwen et al., and thank them for their interest in our research. We will address their comments in turn.
First, they suggest that differences other than the presence of an human immunodeficiency virus (HIV) infection may exist between our study group and controls that could explain the observed differences in semen quality. However, as Table I of our paper demonstrated, there was no significant difference in age between the groups (37.3 and 37.2 years respectively) and although the data are not presented, there was no significant difference in alcohol, tobacco or recreational drug use reported between the two groups (Nicopoullos et al., 2004
). Furthermore, both groups would have undergone similar pre-treatment investigation. Although Guzick et al. (2001) do suggest ‘that caution must be used in interpreting the significance of any given subfertile or indeterminate semen measurement’, this is with regard to the ability of a given parameter to predict fertility potential per se.
Although their case report (van Leeuwen et al., 2004) is able to demonstrate a series of semen variables in an individual prior to, and following, HIV seroconversion and diagnosis, it also highlights the difficulties of longitudinal studies. First, they were only able to present such interesting data as a semen donor happened to seroconvert during the course of donation. The use of larger longitudinal cohort studies to assess the effect of the diagnosis of HIV on semen parameters would therefore be impossible. Second, longitudinal studies would, as they suggest, be of use in assessing the effect of ‘disease progession’ on parameters but would not in fact be addressing the same question as our study. Furthermore, such longitudinal studies would also be complicated by the effect of the ‘dependent variables’ they discuss.
Two small studies have presented such longitudinal data. Crittenden et al. (1992) demonstrated no difference in semen parameters in five men followed after AZT administration, and Robbins et al. (2001) demonstrated an increase in sperm motility in men with early disease (CD4 >200), and an increase in normal morphology in men with late disease with antiretroviral treatment (n=26). These benefits are likely to be as a consequence of improved health status with treatment (supported by the increase in CD4 and decrease in viral load seen), but Robbins et al. (2001) also demonstrated no change in lymphocyte genetic endpoints or sperm aneuploidy rates with treatment, which supports the findings of most studies of no detrimental effect on semen of antiretroviral treatment (Politch et al., 1994; Lasheeb et al., 1997; Nicopoullos et al., 2004).
Although some reports do indeed use an average of available semen analysis, there is no clear consensus with other reports assessing the impact of HIV on semen parameters also using a single analysis. However, reanalysis of our data using the method suggested by van Leeuwen et al. does not alter our conclusions, with significant impairments in semen volume (P=0.02), concentration (P=0.003), total count, total motility, progressive motility and morphology (all P<0.0001) still demonstrated in the HIV positive group.
The first aim of our paper was to present data from the largest group of HIV positive men seeking fertility treatment in the UK to add to the limited data on the effect of HIV on semen. In our opinion, there is a clear consensus amongst the published data of a detrimental effect of HIV on semen parameters in a number of studies that have used a number of different control groups as we have described (Nicopoullos et al., 2004).
The second aim was to present the first data on the outcome and predictors of outcome of sperm washing/intrauterine insemination (IUI). This also enabled us to use IUI groups for comparison. Although the difference in total count was diluted by the minimum criteria acceptable for IUI, differences in motility and morphology persist.
Our choice of thresholds for CD4 count and HIV-RNA viral load for analysis of outcome were made clinically, e.g. CD4 count dichotomization was based on CDC (Centres for Disease Control) classification of HIV/AIDS. As the numbers of HIV positive men seeking fertility treatment continues to expand, we will go on to report the outcome from a significantly larger number of cycles, and as suggested aim to confirm our current findings on the predictive capacity of these individual variables on the outcome of IVF and ICSI, as well as IUI using a multivariable approach.
In conclusion, we remain of the opinion that our data confirms the deleterious effect of HIV on semen parameters whilst accepting that there remain difficulties in study design as we have discussed. Similarly, we believe that the outcome of fertility treatment of HIV positive men may be significantly improved when undertaken whilst HIV RNA viral load is undectable.
References
Crittenden JA, Handelsman DJ and Stewart GJ (1992) Semen analysis in human immunodeficiency virus infection. Fertil Steril 57, 1294–1299.[Web of Science][Medline]
Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, Carson SA, Cisneros P, Steinkampf MP, Hill JA et al. (2001) Sperm morphology, motility, and concentration in fertile and infertile men. New Engl J Med 345, 1388–1393.
Lasheeb AS, King J, Ball JK, Curran R, Barratt CLR, Afnan M and Pillay D (1997) Semen characteristics in HIV-1 positive men and the effect of semen washing. Genitourin Med 73, 303–305.[Web of Science][Medline]
Nicopoullos JDM, Ramsay JWA, Almeida PA and Gilling-Smith C (2004) The effect of HIV on sperm parameters and the outcome of IUI following sperm-washing. Hum Reprod 19, 2289–2297.
Politch JA, Mayer KH, Abbott AF and Anderson DJ (1994) The effects of disease progression and zidovudine therapy on semen quality in human immunodeficiency virus type 1 seropositive men. Fertil Steril 61, 922–928.[Web of Science][Medline]
Robbins WA, Witt KL, Haseman JK, Dunson DB, Troiani L, Cohen MS, Hamilton CD, Perreault SD, Libbus B and Beyler SA (2001) Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection. J Infect Dis 184, 127–135.[CrossRef][Web of Science][Medline]
Van Leeuwen E, Cornelissen M, de Vries JW, Lowe SH, Jurriaans S, Repping S and van der Veen (2004) Semen parameters of a semen donor before and after infection with human immunodeficiency virus type 1: Case report. Hum Reprod 19, 2845–2848.
Submitted on February 21, 2005; accepted on February 25, 2005.
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