Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin

BACKGROUND: To compare the frequency of Y-chromosome microdeletions in Japanese and African azoospermic and oligozoospermic men and describe embryo characteristics and reproductive outcome following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). METHODS: Our study was performed prospectively at two centers, a private IVF clinic and a university hospital. Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and oligozoospermia (concentration < 5 × 10(6 )/ml) were evaluated for Y-chromosome microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were then compared with those of 19 IVF+ICSI cycles performed on couples with Y-chromosome intact males/tubal factor infertility which served as a control group. RESULTS: Seven azoospermic and oligozoospermic patients had Y-chromosome deletions; the total number of deletions in the AZFc region was five. There was only one deletion in the AZFa region and one complete deletion involving all three regions (AZFa, b, and c) within AZF. In our study population, microdeletion frequency among Japanese men was 6.2% (95% CI, 4.25% – 14.45%), whereas no deletions were identified in the African group (95% CI, 0.0% – 7.27%). The difference between the two groups was not statistically significant, however. Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed reduced rates of fertilization, blastocyst development, implantation, and pregnancy compared to the Y-chromosome intact group, although these observed differences were not statistically significant. CONCLUSION: The observed frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and oligozoospermic males; no microdeletions were identified among our African study patients. In this population of couples undergoing IVF+ICSI, there was no statistically significant difference in embryo characteristics or pregnancy outcome between patients with Y-chromosome microdeletion and those with an intact Y-chromosome

Variable effect of co-infection on the HIV infectivity: Within-host dynamics and epidemiological significance

<p>Abstract</p> <p>Background</p> <p>Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals.</p> <p>Methods</p> <p>We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface.</p> <p>Results</p> <p>Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased.</p> <p>Conclusion</p> <p>Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.</p