Background:Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown.Methods:Global RNA sequencing was applied to obtain the transcriptomic profile of endometrial biopsies collected from nonpregnant women who suffer sPE in a previous pregnancy and women who did not develop this condition. Samples were randomized in two cohorts, the training and the test set, to identify the fingerprinting encoding defective decidualization in sPE and its subsequent validation. Gene Ontology enrichment and an interaction network were performed to deepen in pathways impaired by genetic dysregulation in sPE. Finally, the main modulators of decidualization, estrogen receptor 1 (ESR1) and progesterone receptor B (PGR-B), were assessed at the level of gene expression and protein abundance.Results:Here, we discover the footprint encoding this decidualization defect comprising 120 genes—using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signature allowed us to effectively segregate samples into sPE and control groups. ESR1 and PGR were highly interconnected with the dynamic network of the defective decidualization fingerprint. ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE.Conclusions:Thus, the transcriptomic signature of impaired decidualization implicates dysregulated hormonal signaling in the decidual endometria in women who developed sPE. These findings reveal a potential footprint that could be leveraged for a preconception or early prenatal screening of sPE risk, thus improving prevention and early treatments.Funding:This work has been supported by the grant PI19/01659 (MCIU/AEI/FEDER, UE) from the Spanish Carlos III Institute awarded to TGG. NCM was supported by the PhD program FDGENT/2019/008 from the Spanish Generalitat Valenciana. IMB was supported by the PhD program PRE2019-090770 and funding was provided by the grant RTI2018-094946-B-100 (MCIU/AEI/FEDER, UE) from the Spanish Ministry of Science and Innovation with CS as principal investigator. This research was funded partially by Igenomix S.L.

While non-invasive prenatal testing is a screening method and confirmatory results must be obtained by ultrasound or genetic diagnosis, the sex-score determination presented herein offers an accurate and useful approach to characterizing fetus sex in twin pregnancies in a non-invasive manner early on in pregnancy.

ElsevierClemente Císcar, M.; San Matías Izquierdo, S.; Giner Bosch, V. (2014). A methodology based on profitability criteria for defining the partial defection of customers in noncontractual settings. AbstractThe defection or churn of customers represents an important concern for any company and a central matter of interest in customer base analysis. An additional complication arises in non-contractual settings, where the characteristics that should be observed to saying that a customer has totally or partially defected are not clearly defined. As a matter of fact, different definitions of the churn situation could be used in this context. Focusing on non-contractual settings, in this paper we propose a methodology for evaluating the short-time economic effects that using a certain definition of churn would have on a company. With this aim, we have defined two efficiency measures for the economic results of a marketing campaign implemented against churn, and these measures have been computed using a set of definitions of * Corresponding author. 1 Prof. Susana San Matías sadly passed away in the Summer of 2012 while this paper was under review. We deeply regret the loss of such a brilliant researcher and good person and feel fortunate to have had the opportunity to work with her. Susana will be deeply missed. February 7, 2014 partial defection. Our methodology finds that definition maximizing both efficiency measures and moreover, the monetary amount that the company should invest per customer in the campaign for achieving the optimal solution. This has been modelled as a multiobjective optimization problem that we solved using compromise programming. Numerical results using real data from a Spanish retailing company are presented and discussed in order to Preprint submitted to European Journal of Operational Researchshow the performance and validity of our proposal.

Highly sensitive next-generation sequencing (NGS) platforms applied to preimplantation genetic testing for aneuploidy (PGT-A) allow the classification of mosaicism in trophectoderm biopsies. However, the incidence of mosaicism reported by these tests can be affected by a wide number of analytical, biological, and clinical factors. With the use of a proprietary algorithm for automated diagnosis of aneuploidy and mosaicism, we retrospectively analyzed a large series of 115,368 trophectoderm biopsies from 27,436 PGT-A cycles to determine whether certain biological factors and in vitro fertilization (IVF) practices influence the incidence of overall aneuploidy, whole uniform aneuploidy, mosaicism, and TE biopsies with only segmental aneuploidy. Older female and male patients showed higher rates of high-mosaic degree and whole uniform aneuploidies and severe oligozoospermic patients had higher rates of mosaicism and only segmental aneuploidies. Logistic regression analysis identified a positive effect of female age but a negative effect of embryo vitrification on the incidence of overall aneuploid embryos. Female age increased whole uniform aneuploidy rates but decreased only segmental aneuploidy and mosaicism, mainly low-mosaics. Conversely, higher ovarian response decreased whole uniform aneuploidy rates but increased only segmental aneuploidies. Finally, embryo vitrification decreased whole uniform aneuploidy rates but increased mosaicism, mainly low-mosaics, compared to PGT-A cycles with fresh oocytes. These results could be useful for clinician’s management of the IVF cycles.

OBJECTIVE: The diagnosis of endometrial receptivity is being used as a clinical test to manage the endometrial factor in patients with implantation failure. Yet, this procedure is invasive and it delays personalized embryo transfer (pET) until the next cycle. We aim to develop a non-invasive approach based on the analysis of the transcriptomic signature in the endometrial fluid (EF).DESIGN: Fifty-six patients with implantation failure that underwent Endometrial Receptivity Analysis (ERA) test leading to successful pET, and the transcriptomic signature of their paired EF samples was analyzed blindly to compare receptivity diagnoses.MATERIALS AND METHODS: EF was aspirated immediately before endometrial biopsy using a flexible catheter (Wallace, SMI) inserted into the uterine cavity obtaining 10-20 ml of EF per patient that were snap frozen and stored. RNA was extracted using RNeasy mini-kit (Qiagen) and qualitychecked using Fragment Analyzer (AATI, USA). Gene expression was analysed using Ion AmpliSeq RNA for ERA custom panel in an Ion S5 system (Life Tech, USA) coupled to a computational predictor.RESULTS: Paired samples of EF and endometrial biopsy from the same patients (n¼56) were analysed separately. In 13 EF samples (23.2%) RNA quantity and/or quality were poor (mean: concentration 28.5 ng/ml; RIN 1.75). The remaining 43 EFs (76.8%) with mean concentration of 108.3 ng/ml and RIN of 4.3, generated good-quality libraries for sequencing. These 43 EFs yielded results concordant with their paired endometrial biopsies analysed by ERA: 33 were confirmed receptive (76.7%), 7 pre-receptive (16.3%), and 3 post-receptive (7.0%). EF testing resulted in 100% sensitivity and specificity with no false positive or negatives vs ERA.CONCLUSIONS: Transcriptomic profiling of EF samples gave high sensitivity and specificity vs the invasive test. Technical improvement in the collection and shipment of EF is necessary to avoid RNA degradation. Thus, EF offers a non-invasive alternative to diagnose endometrial receptivity for personalized embryo transfer without a need for endometrial biopsy.