Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
OBJECTIVE: Male factor is the sole cause of infertility in about 20% of cases and is at least partially involved in up to 40% of cases. Sperm total normal motile count (TNMC) integrates the semen analysis components of morphology, motility, and total count to yield a single clinical value. The objective of this study is to assess whether a relationship exists between TNMC and preimplantation genetic testing for aneuploidy (PGT-A) as well as in vitro fertilization (IVF) outcomes.DESIGN: Retrospective, observational study. MATERIALS AND METHODS: In this retrospective, observational study, unidentified data sets were included of couples who visited our fertility center between October 2012 to December 2018 and had PGT-A (N¼ 1492) and elective single embryo transfer (N¼242) performed. Inclusion was limited to those with a semen analysis within 90 days of IVF start. TNMC was calculated by multiplying total sperm count by percent motility and percent normal forms (Kruger's strict criteria). For analyses, we categorized TNMC into three groups: Group 1 (<1 million), 2 (1-4.99 million), and 3 (R5 million). Primary endpoint was IVF outcomes. Secondary endpoints included embryo quality, morphology, ploidy, and gender. Pearson's chi-squared test was used for statistical analysis with p<0.05 considered significant.RESULTS: A total of 1492 embryos (Group 1 N¼395, 2 N¼558, and 3 N¼539) were analyzed. For all groups, embryos were more likely to be female; however, embryos from the <1 million group had the highest percentage of female embryos (58.5% vs 50.4% and 54.2%; p¼0.046), and were more likely to be high-grade (69.1% vs 62.7% and 63.5%; p¼0.015), compared to Groups 2 and 3, respectively. Embryos from the 1-4.99 million group were more likely to be low-grade (21.0% vs 14.4% and 15.8%; p¼0.015), have a poor inner cell mass grading (14.9% vs 9.6% and 9.8%; p¼0.027), and a poor trophectoderm grading (16.8% vs 12.2% and 12.4%; p¼0.039), compared to those in Groups 1 and 3, respectively. There was no difference in embryo development (p¼0.076), day of blastocyst transformation (p ¼ 0.368) or ploidy status (p¼0.324) among the different TNMC groups.Subpopulation analysis of 242 transferred embryos (Group 1 N¼50, 2 N¼92, and 3 N¼100), showed no statistical difference in implantation (p¼0.311), clinical pregnancy (p¼0.214), chemical pregnancy (p¼0.426), miscarriage (p¼0.685), ectopic pregnancy (p¼0.417), or ongoing pregnancy rates (p¼0.069) between the different TNMC groups.CONCLUSIONS: This large-scale study is the first to examine the relationship of sperm TNMC to PGT-A and IVF outcomes. While it is possible that TNMC may impact certain embryo characteristics, such as gender, inner cell mass, trophectoderm, and overall grade, TNMC does not appear to impact IVF outcomes. Further studies are needed to further elucidate these relationships. REFERENCES:Practice Committee of American Society for Reproductive Medicine. 2015. "Diagnostic evaluation of the infertile male: a committee opinion". Fertility and Sterility. 103 (3): e18-25.
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