To investigate the role of the 'male factor' in the pathogenesis of recurrent spontaneous abortion (RSA), especially sperm morphology abnormalities, 120 previously selected couples with unexplained RSA were studied for sperm parameters retrospectively and prospectively. The patients were subdivided into three subgroups, depending on their reproductive outcome during the 3 years of follow-up study: (i) 48 RSA couples who achieved a successful pregnancy; (ii) 39 RSA couples who experienced further abortions, and (iii) 33 RSA couples who experienced infertility during the follow-up period. A semen analysis was performed twice at the time of inclusion in this study, and twice again during the 3 year follow-up period. No significant differences in semen parameters were observed between RSA males and fertile controls. Instead, significant differences were observed between the group of RSA couples who experienced infertility during the follow-up and the other two groups (RSA couples who achieved successful pregnancy and RSA couples who experienced miscarriages and no live birth during the follow-up) for sperm concentration (P < 0.01 and P < 0.01 respectively), sperm motility (P < 0.01 and P < 0.01 respectively) and sperm morphology abnormalities (P < 0.01 and P < 0.01 respectively). Sperm morphology abnormalities do not seem to be involved in determining RSA; instead, they are an aetiological factor in determining infertility in patients, along with the other semen parameters, in the RSA couple's subsequent reproductive life. Semen analysis is an important test in the clinical management of RSA couples.
We have demonstrated previously that hyaluronic acid (HA) improves the velocity and the retention of motility in freshly ejaculated human spermatozoa. In the present work, we examined the effect of HA on cryopreserved/ thawed spermatozoa in four paradigms: (i) effect of HA on sperm motility and velocity in semen; (ii) stabilizing effect of HA after 4 h of incubation when the decline of sperm motility is already detectable; (iii) the duration of improved motility after the separation of spermatozoa from HA by Percoll gradient centrifugation; and (iv) motility of sperm cryopreserved in the presence of HA. HA improved the retention of sperm motility in thawed spermatozoa. Indeed, the motility values after 30 h were approximately 100% higher in the HA compared with the control samples. This effect of HA was also evident in the stabilization of spermatozoa with already declining motility. After removal of the HA from the incubation medium, significantly increased motility in the HA-exposed spermatozoa was still detectable for at least 4 h. Cryopreservation of spermatozoa in the presence of HA did not improve the recovery of motility. The data indicate that HA improves the retention of motility of cryopreserved/thawed spermatozoa, even after the removal of HA from the incubation medium. The utilization of HA will probably prove beneficial in assisted reproduction: in intrauterine insemination and in in-vitro fertilization (IVF), the extended sperm motility and velocity will enhance the fertilizing efficiency; in intracytoplasmic sperm injection (ICSI), the improved motility will facilitate the identification of viable spermatozoa. Because HA is a physiological component of the cumulus and of the female and male reproductive tracts, administration of HA should not cause ethical concerns.
To our knowledge, this is the first report of two patients with documented IR with panitumumab being desensitized successfully with cetuximab. Though anecdotal reports suggest safety of panitumumab in patients following IR with cetuximab, panitumumab can also cause severe IR. Our experience suggests that in case of limited options, such patients can be successfully challenged with cetuximab in a hospital after appropriate desensitization and premedication. Further studies focusing on desensitization and identifying hypersensitivity profile of different anti-epidermal growth factor receptor antibodies are warranted.
The results suggest that gene(s) disadvantageous for reproduction may exist between the HLA-B and -DR chromosomal region which influences the pregnancy outcome in RSA couples, and that HLA-antigen sharing itself does not influence the outcome.
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