Impaired expression of ectonucleotidases in ectopic and eutopic endometrial tissue is in favor of ATP accumulation in the tissue microenvironment in endometriosis

Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis

Conmemorando el Premio Nobel 2010 de Medicina. Transferencia selectiva de un embrión como prevención del embarazo múltiple

The development of Assisted Reproduction Techniques represents an important advance in the treatment of human infertility. However, their great effectiveness has brought with it an excessive increase in multiple pregnancy rates with the serious medical, financial and social consequences that they entail. Now, the scientific societies, the health professionals, and the infertile couples themselves are aware of these risks and have worked together to implement various strategies to deal with this situation. The result that is being obtained from the strategy of selectively reducing the number of embryos transferred is obvious. The pandemic of multiple pregnancies is being brought under control and so we have effective prevention of the obstetric and neonatal complications arising from it. It is to be hoped that it will also contribute to significantly reducing the rates of prematurity and thus of severe neonatal complications.El desarrollo de las Técnicas de Reproducción Asistida ha representado un importante avance en el tratamiento de la infertilidad humana. Sin embargo, la alta eficacia de las mismas ha traído consigo un incremento excesivo de las tasas de embarazo múltiple con las graves consecuencias médicas, económicas y sociales que ello comporta. Actualmente tanto las sociedades científicas como los profesionales de la salud como las propias parejas estériles son conscientes de estos riesgos y de forma coordinada se han establecido diversas estrategias para hacer frente a esta situación. El resultado que se está obteniendo de la estrategia de reducir selectivamente el número de embriones transferidos es evidente. La pandemia de embarazos múltiple se está controlando y con ello estamos haciendo una prevención eficaz de las complicaciones obstétricas y neonatales derivadas de los mismos. Esperamos que ello contribuirá también a reducir significativamente las tasas de prematuridad y por tanto de complicaciones neonatales severa

Presence of Adenomyosis Impairs Clinical Outcomes in Women Undergoing Frozen Embryo Transfer: A Retrospective Cohort Study

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes

Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

ObjectiveTo assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo. MethodSingle centre retrospective cohort study including 1247 PGT-A cycles. Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision-making. Outcomes after mosaic embryo transfer were assessed. ResultsTo date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high-degree mosaicism (>50%) seemed to be negatively associated with the decision to transfer (18.2% vs. 29.8%, p = 0.294; 10% vs. 32.2%, p = 0.052). ConclusionsNeither reproductive history nor information on mosaic embryo characteristics through counselling seems to be determinative for patients when deciding to transfer a mosaic embryo. Promising and increasing data on clinical outcomes after mosaic embryo transfer will be of utmost importance to soften risk perception regarding mosaic embryos and give a better, simplified and more evidence-based counselling

The effect of short term exposure to outdoor air pollution on fertility

Background There is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable. Methods This prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM2.5 [particulate matter (PM) ≤2.5 μm], PMcoarse (PM between 2.5 and 10μm), PM10 (PM≤10 μm), PM2.5 abs, and NO2 and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers. Results One hundred ninety-four women were recruited, contributing with data for 486 embryo transfers. Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM2.5 exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 on 3D. The second sensitivity analysis showed a significant risk of miscarriage for PM2.5 exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes. Conclusions Exposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success