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Uterine microbiota may be involved in reproductive health and disease. This study aims to describe and compare the vaginal and endometrial microbiome patterns between women who became pregnant and women who did not after in vitro fertilization. We also compared the vaginal and endometrial microbiome patterns between women with and without a history of repeated implantation failures (RIF). This pilot prospective cohort study included 48 women presenting to the fertility clinic for IVF from May 2017 to May 2019. Women who achieved clinical pregnancy presented a greater relative abundance of Lactobacillus spp. in their vaginal samples than those who did not (97.69% versus 94.63%, p = 0.027. The alpha and beta diversity of vaginal and endometrial samples were not statistically different between pregnant and non-pregnant women. The Faith alpha diversity index in vaginal samples was lower in women with RIF than those without RIF (p = 0.027). The alpha diversity of the endometrial microbiome was significantly higher in women without RIF (p = 0.021). There were no significant differences in the vaginal and endometrial microbiomes between pregnant and non-pregnant women. The relative abundance of the genera in women with RIF was different from those without RIF. Statistically significant differences in the endometrial microbiome were found between women with and without RIF.

Background:The vaginal microbiome plays an important role in maintaining health, and there is evidence that microbial colonization of the upper genital tract can also influence successful embryo transfer. The aim of this study is to determine whether the vaginal and endometrial microbiome in people undergoing assisted reproduction techniques could affect the pregnancy rate.Results:Regarding the microbiome dynamics during the cycle, we observed a decrease in alpha diversity from the follicular to luteal phase in the control group, in contrast to a stable pattern in the repetitive implantation failure group. As for endometrial and vaginal microbiome, alpha diversity was higher in the endometrium (Shannon p = 0.0139, Simpson p = 0.046); differences were also observed in beta diversity (p = 0.001). Compared to the endometrium, the vagina showed a greater relative abundance of Lactobacillus spp. (83.17% vs 84.82%, p Streptococcus spp. (1.59% vs 7.74%, p = 0.014) and Ureaplasma spp. (0% vs. 0.89%, p = 0.006), and a lower abundance of Delftia spp. (0.95% vs 0%, p = 0.0003), Anaerobacillus spp. (1.59% vs 0%, p = 0.0004), and Ralstonia spp. (3.17% vs 0%, p = 0.0006). We also observed differences in both alpha diversity (Shannon p = 0.0206, Simpson p = 0.0206) and beta diversity between groups, along with differences for Ralstonia spp. (0.09% study group and 0.73% control, p = 0.0012). Finally, the relative abundance of Lactobacillus spp. differed between patients that did not versus did achieve pregnancy (91% vs 99%, p = 0.0445 visit 1, 94.63% vs. 97.69%, p = 0.0268 visit 2, 97.73% vs 99.74%, p = 0.0492 visit 3). The relative abundance of L.reuteri was also different between groups (0.39% vs 0.17%, p = 0.0397 visit 1, 0.15% vs 0.30%, p = 0.0491 visit 3).Conclusions:The vaginal and endometrial microbiome pattern correlates with the pregnancy rate, and it is different in patients who do versus do not have repetitive implantation failures. No significant differences in the composition of the microbiome were observed through the different visits. The lack of dynamism in the microbiome pattern of repetitive implantation failure patients might reflect an impaired adaptation to endometrial changes. A greater relative abundance of Lactobacillus spp. and L. reuteri is correlated with higher chances of pregnancy.*MC Díaz Martínez and A Bernabeu García share equal responsibility for authorship.

Purpose: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. Materials and Methods: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. Results: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean +/- SD age of 70.5 +/- 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. Conclusions: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.

The mapping method detailed here is based on the multiplex polymerase chain reaction (PCR) coamplification of 32 molecular markers, using fluorescently labeled oligonucleotides as primers. For the genotyping of a single plant from a mapping population, only two simultaneous amplifications are required, the products of which are finally electrophoresed in an automated DNA sequencer controlled by fragment analysis software. An analysis of the genotypes of 50 plants allows mapping of the mutation of interest within a candidate genomic interval of about 15 cM (3 Mb, corresponding to about 40 BAC clones).