Is biochemical pregnancy loss associated with embryo or endometrium? A retrospective cohort study in frozen single embryo transfer of own and donated oocytes.

STUDY QUESTION: Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? SUMMARY ANSWER: Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. WHAT IS KNOWN ALREADY: BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined BPL as a pregnancy diagnosed only by serum ß-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. WIDER IMPLICATIONS OF THE FINDINGS: BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov (NCT04549909).

TRANSDISCIPLINARITY IN STRATEGIC DECISIONS FOR ONCOLOGICAL TREATMENTS.

The current models for equity and access to new oncological treatments are under strain due to the economic and demographic crisis in Europe as well as the rising costs of innovative drugs. Cancer treatment needs a model of patient-centered care in which an interdisciplinary care plan, based on evidence-based practice is essential for patient wellbeing. Physicians should be focused in the doctor-patient relationship and informed consent is important, especially when new medicines are prescribed. Related with informed consent, there is therapeutic privilege. Moreover, utilitarianism and social justice have to be considered without compromising human dignity and the principle of economy cannot be ignored in the provision of public services. An interdisciplinary approach is essential for the new oncological drugs approval. Therefore, transdisciplinary decision between civil society, pharmaceuticals, healthcare professionals and policy makers is essential in order to assure quality, access to innovation and equity in oncological care.

Annoyance evaluation and the effect of noise on the health of bus drivers.

In the present study, we evaluated annoyance and the effects of noise on the health of bus drivers. For that, 200 bus drivers from a public transport company participated in a cross-sectional study. Annoyance and effects on health was measured with analog scale: Sleep quality, occurrence of tinnitus, headache, irritation, and annoyance from bus engine, traffic, and passengers. Data of age and working time of bus drivers also were obtained. For noise exposure, LA eq was evaluated in 80 buses. Statistical analysis consisted of mean, standard deviation, minimum, and maximum, Kruskal-Wallis test with post-hoc Dunn, one-way ANOVA with post-hoc Tukey and Spearman's correlation coefficient. Results indicate three groups of bus drivers (not annoyed: (N.A.), a little annoyed (L.A.) and highly annoyed (H.A.)). The group H.A. was younger and with less working time in relation to others, with a significant difference only for age. Regarding sleep quality, there was no significant difference. For results on the occurrence of tinnitus, headache and irritation after work, group H.A. had significantly higher means. Result of annoyance to the bus engine was significantly higher in H.A. than in L.A. and N.A. Annoyance to traffic and passengers, no significant differences were found, but the highest results were found for L.A., followed by H.A. and N.A. Equivalent sound pressure level in buses was above of the limit for occupational comfort. It was concluded that bus drivers has considerable level of noise annoyance and some health effects are perceived. The noise is a factor discomfort ergonomic that may cause effects on health of bus drivers. This study aims to evaluate annoyance and the effects of noise on the health of bus drivers. Cross-sectional study with buses and bus drivers. For that, 200 bus drivers from a public transport company participated in a cross-sectional study. Annoyance and effects on health was measured with analog scale: Sleep quality, occurrence of tinnitus, headache, irritation and annoyance from bus engine, traffic, and passengers. Data of age and working time of bus drivers also were obtained. For noise exposure, LA eq was evaluated in 80 buses. Statistical analysis consisted of mean, standard deviation, minimum and maximum, Kruskal-Wallis test with post-hoc Dunn, one-way ANOVA with post-hoc Tukey and Spearman's correlation coefficient. Results indicate three groups of bus drivers (N.A., a L.A. and H.A.). The group H.A. was younger and with less working time in relation to others, with a significant difference only for age. Regarding sleep quality, there was no significant difference. For results on the occurrence of tinnitus, headache and irritation after work, group H.A. had significantly higher means. Result of annoyance to the bus engine was significantly higher in H.A. than in L.A. and N.A. Annoyance to traffic and passengers, no significant differences were found, but the highest results were found for L.A., followed by H.A. and N.A. Equivalent sound pressure level in buses was above of the limit for occupational comfort. It was concluded that bus drivers has considerable level of noise annoyance and some health effects are perceived.

sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis.

The glycoconjugates expressed by cancer cells frequently contain sialylated oligosaccharide chains. Among these oligosaccharides the sialyl Lewis a (sLe(a)) and sialyl Lewis x (sLe(x)) antigens are found to be overexpressed in tumours of different origin. The current study assesses sLe(a) and sLe(x) expression in different colorectal specimens in order to establish the correlation of these biomarkers with both malignant transformation of colorectal mucosa and the progression of colorectal cancer (CRC). Healthy disease-free and inflammatory mucosa specimens showed no presence of the antigens. sLe(a) was expressed in 6.7% of the healthy tissue from CRC patients, in 20.8% of the adenomas, and in 33.3% and 42.6% of the transitional tissue and tumour tissue, respectively. sLe(x) expression was observed in 6.7% of the healthy tissue from CRC patients, in 27.0% of the adenomas, and in 25.6% and 74.8% of the transitional and the tumour tissue, respectively. The expression of the sLe(a) and sLe(x) antigens was correlated in adenomas, as well as in healthy and tumour tissue from CRC. Moreover, the high expression of sLe(x) in adenomas was correlated with a high degree of dysplasia (p=0.042). Finally, the survival analysis suggested that sLe(a) expression may be a prognostic factor for predicting disease-free survival in colorectal cancer (p=0.012).

α(1,6)Fucosyltransferase expression is an independent prognostic factor for disease-free survival in colorectal carcinoma.

We previously reported that α(1,6)fucosyltransferase (Enzyme class 2.4.1.68) activity and expression are increased in colorectal cancer, suggesting a role for this enzyme in tumor development and progression. However, the possible impact of α(1,6)fucosyltransferase activity or expression on clinical outcomes in colorectal cancer patients has never been studied. Thus, the present study was conducted to determine the value of α(1,6)fucosyltransferase as a prognostic factor for colorectal cancer. α(1,6)Fucosyltransferase expression was analyzed using immunohistochemistry in 141 colorectal tumors, and α(1,6)fucosyltransferase activity was determined in 39 tumors. A complete standardized follow-up of patients was documented until the end of the observation period of 5 years or patient death. Univariate analysis demonstrated the absence of a correlation between enzyme activity and disease evolution. However, in patients with moderate or strong α(1,6)fucosyltransferase expression, a significant decrease in the overall (P = .04) and disease-free (P = .03) survival rates was observed. In addition, when local and distant disease recurrence were considered separately, enzyme expression was found to correlate with local tumor recurrences (P = .01). Furthermore, multivariate analysis showed that α(1,6)fucosyltransferase expression has independent value for predicting tumor recurrences and, specifically, local recurrences. These findings suggest that α(1,6)fucosyltransferase expression may be a good indicator of poor prognosis in colorectal cancer and, therefore, a helpful tool to choose the most effective treatment.

Stage pT3a of renal clear cell carcinoma: do tumors with sinus fat involvement behave the same as those with perinephric fat involvement?

INTRODUCTION: In this report, we review our series of patients with pT3a clear cell renal carcinoma (CCRC) and comment on their outcome. MATERIALS AND METHODS: We have reviewed 260 cases of CCRC operated in the Móstoles General Hospital, Madrid, between 2000 and 2004. We have found 30 cases with pT3a tumors. Eleven of them were invading the perinephric fat, nine were invading the renal sinus fat and ten were pT3a locally but showed metastasis at the moment of diagnosis (cM1, TNM stage IV). We have analyzed the prognostic influence of histopathological parameters (vascular invasion, size, Fuhrman grade) and also immunohistochemical ones (p53, cyclin D1, proliferation index with Ki67, bcl-2 and vascular density with CD34). RESULTS: Only six of 10 patients with perinephric fat involvement died of disease compared with all the patients with sinus fat involvement, suggesting a worse prognosis for the latter. However, this difference did not reach statistical significance, probably due to the small number of cases. Of all the clinical, histological and immunohistochemical factors analyzed, only cyclin D1 was a strong indicator of worse prognosis in pT3a CCRC (p=0.02). We could not show any statistically significant relation between vascular density and prognosis. Vascular invasion was the only histological parameter that showed a trend toward significance (p=0.09). CONCLUSIONS: Sinus fat involvement might be underestimated in some series. A protocol for nephrectomy specimen handling could improve the detection rate of sinus fat involvement and allow the performance of randomized prospective studies to determine whether these tumors behave similarly.