Background: Time-lapse monitoring (TLM) technology has been implemented in the clinical setting for the culture and selection of human embryos. Many studies have assessed the association between sperm DNA fragmentation (sDNAf) and clinical outcomes after ART, but little is known about the influence of sDNA on embryo morphokinetics. Objectives: The objective of this retrospective study, which includes 971 embryos from 135 consecutive ICSI cycles (56 cases with own oocytes, 79 with oocytes from young and healthy donors), was to assess if sDNAf has an impact on embryo morphokinetics. Materials and methods: Samples used to perform ICSI were analyzed by the flow cytometry TUNEL assay, and embryo development was assessed through an EmbyoScope â system. The association between sDNAf and the timings of cell cleavage was analyzed by categorizing the first variable into quartiles: ≤6.50%; 6.51-10.70%; 10.71-20.15%; >20.15%. Results: In cases where sDNAf was above 20.15% (the upper quartile), embryos derived from donated oocytes (n = 644) showed significantly slower divisions. Such association was not observed in embryos obtained from the patients' own oocytes (n = 327). The embryo cleavage pattern (either normal, direct from 1 to 3 blastomeres, direct from 1 to 4 blastomeres, incomplete, reversed or asynchronous) was independent of the sDNAf level. Blastocyst arrival rate was 63.0% and the rate of good quality embryos (transferred and frozen embryos divided by the number of zygotes) was 45.49%. Neither parameter was related to the levels of sDNAf. Discussion: According to our results, the association between high sDNAf and donated oocytes led to delayed cell division. To our knowledge, this is the first study suggesting that sDNAf can delay human embryo cleavage timings when oocytes from donors are inseminated.Conclusions: This finding may indicate that, in the presence of increased DNA damage, time is needed before the first embryonic cell division for the activation of the optimal DNA repairing machinery in higher quality oocytes.
BACKGROUNDOvarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.METHODSA randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 µg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17–21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset ≤9 days after hCG administration) in 182 IVF patients with ≥20 but less than 30 follicles ≥10 mm.RESULTSThe incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 µg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09–0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10–0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.CONCLUSIONSQuinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability.ClinicalTrials.gov Identifier: NCT00329693.
Renal failure persisting after renal transplant is known as delayed graft function (DGF). DGF predisposes the graft to acute rejection and increases the risk of graft loss. In 2010, Irish et al. developed a new model designed to predict DGF risk. This model was used to program a web-based DGF risk calculator, which can be accessed via http://www.transplantcalculator.com . The predictive performance of this score has not been tested in a different population. We analyzed 342 deceased-donor adult renal transplants performed in our hospital. Individual and population DGF risk was assessed using the web-based calculator. The area under the ROC curve to predict DGF was 0.710 (95% CI 0.653-0.767, p < 0.001). The "goodness-of-fit" test demonstrates that the DGF risk was well calibrated (p = 0.309). Graft survival was significantly better for patients with a lower DGF risk (5-year survival 71.1% vs. 60.1%, log rank p = 0.036). The model performed well with good discrimination ability and good calibration to predict DGF in a single transplant center. Using the web-based DGF calculator, we can predict the risk of developing DGF with a moderate to high degree of certainty only by using information available at the time of transplantation.
Colloidal super-paramagnetic microbeads conjugated with annexin V are effective for separating apoptotic spermatozoa by MACS as a result of the high affinity of annexin V for externalized PS molecules. The effectiveness of the procedure in reducing the percentage of sperm with fragmented DNA and abnormal morphology has also been reported. However, it is still unknown if it could decrease the percentage of aneuploid spermatozoa. The objective of our prospective study, performed on 16 males with abnormal FISH on spermatozoa, was to assess if MACS columns were useful tools to retain spermatozoa carrying chromosomal abnormalities in semen samples processed after density gradient centrifugation (DGC). The pellet obtained after DGC was subjected to MACS, and sperm FISH analyses were performed both in the eluded fraction and in the fraction retained in the column. The observed frequencies of disomy and nullisomy 13, 18, and 21, X and Y, as well as the diploidy rates in the MACS eluded fraction and the fraction retained in the MACS column were recorded. We observed that the frequencies of aneuploidies in the eluded fraction were lower than in the fraction retained in the MACS column (0.59% vs. 0.75%; p = 0.010). DGC determined a significant reduction in sperm concentration (z-ratio = 2.83; p = 0.005) and a significant increase in sperm progressive motility (z-ratio = -3.5; p < 0.001). MACS also led to a significant reduction in sperm concentration (z-ratio = 3.14; p = 0.002) and a significant increase in progressive motility (z-ratio = -2.59; p = 0.01) when compared with the post-DGC sample. Sperm concentration was similar in the two fractions generated by MACS (z-ratio = 0.63; p = 0.52), while progressive motility was significantly higher in the MACS eluded fraction (z-ratio = 2.42; p = 0.02). According to our results, MACS columns are able to selectively retain spermatozoa carrying chromosomal abnormalities. Furthermore, the performance of DGC and MACS on semen samples leads to an enrichment of progressive motility.
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