Increasing Endometrial Thickness Beyond 8 mm Does Not Alter Clinical Pregnancy Rate After Single Euploid Embryo Transfer.

The aim of this study was to investigate if variation in endometrial thickness affects clinical pregnancy and live birth rates among patients undergoing single euploid embryo transfer (SET). A retrospective review of IVF cycles performed at a single private fertility institution between 2015 and 2020 was performed. Patients with normal uterine anatomy undergoing their first SET of a euploid embryo undergoing their first cycle at the center were included, for a total of 796 cycles. Endometrial thickness was measured by transvaginal ultrasound following 10-14 days of estradiol exposure. Specific infertility diagnoses did not significantly impact endometrial lining thickness with means across diagnoses ranging from 9.3 to 11.0 mm. Endometrial thickness was grouped into five categories: < 8 mm, 8-10 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm. Using 8-10 mm as the reference group, the odds ratio of live birth was 0.5, 1.22, 1.05, and 1.05 for < 8 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm groups, respectively. Risk of first trimester miscarriage was equivalent across groups. There was a trend toward an increased rate of biochemical pregnancies in patients with a < 8 mm and ≥ 15 mm endometrium; however, this was not statistically significant. The clinical pregnancy and live birth rate were lowest in patients with < 8-mm endometrial thickness. For single euploid embryo transfers, an endometrial lining greater than or equal to 8 mm confers optimal live birth rates following a medicated FET cycle. These data confirm the findings of prior studies in fresh embryo transfers without the confounders of supraphysiologic ovarian hormone concentrations and genetically untested embryos.

Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus-Like Inflammation.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression. Nevertheless, Th2 effector subsets have also been implicated in CLE. We have now assessed the role of specific T cell subsets in the initiation and persistence of skin disease using a T cell-inducible murine model of CLE, dependent on KJ1-26 T cell recognition of an ovalbumin fusion protein. We found that only Th2-skewed cells, and not Th1-skewed cells, induced the development of skin lesions. However, we provide strong evidence that the Th2 disease-initiating cells convert to a more Th1-like functional phenotype in vivo by the time the skin lesions are apparent. This phenotype is maintained and potentiates over time, as T cells isolated from the skin, following a second induction of self-antigen, expressed more IFN-γ than T cells isolated at the time of the initial response. Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. Further, injection of IFN-γ-/- T cells faied to induce skin disease in mice. We concluded that Th2 cells trigger skin lesion formation in CLE, and these cells switch to a Th1-like phenotype in the context of a TLR7-driven immune environment that is stable within the T cell memory compartment.

Access to Fertility Care in Geographically Underserved Populations, a Second Look.

Infertility has a prevalence of up to 16% worldwide and is on the rise in developed nations, largely due to pursuing childbearing at advanced reproductive ages. Advances in assisted reproductive technology have benefitted socioeconomically advantaged patients disproportionately. High costs of fertility care are largely responsible for this disparity; however, patients in rural areas also face barriers in accessing both gynecology and reproductive endocrinology subspecialty care. Here, focusing on the USA, we discuss fertility care in geographically underserved areas and low-resource settings, and the impact on reproductive outcomes. Increased innovation to improve patient access to fertility care such as assisted reproductive technology is critical for ensuring equity. Remote monitoring is frequently performed by fertility centers, but partnership with local gynecologists has also been demonstrated to be an effective assisted reproductive technology monitoring method. Telehealth is now in mainstream use and the continued application to reduce geographic barriers to infertility patients is imperative. Partnership between local gynecologists and reproductive endocrinology and infertility specialists may improve patient access to fertility care and provide the unique benefits of continuity and ongoing local social support.

Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet+, IFN-γ+, and FasL-expressing Th1 cells as well as autoantibody-producing B cells. Unexpectedly, contrary to what occurs in most models of SLE, they also developed skin lesions that are very similar to those of human cutaneous lupus erythematosus (CLE) as far as clinical appearance, histological changes, and gene expression. FasL was a key effector mechanism in the skin, as the transfer of FasL-deficient DO11gld T cells completely failed to elicit overt skin lesions. FasL was also upregulated in human CLE biopsies. Overall, our model provides a relevant system for exploring the pathophysiology of CLE as well as the negative regulatory role of TLR9.

IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells.

Type 2 effector production of IL-13, a demonstrated requirement in models of fibrosis, is routinely ascribed to CD4(+) Th2 cells. We now demonstrate a major role for CD8(+) T cells in a murine model of sterile lung injury. These pulmonary CD8(+) T cells differentiate into IL-13-producing Tc2 cells and play a major role in a bleomycin-induced model of fibrosis. Differentiation of these Tc2 cells in the lung requires IL-21, and bleomycin treated IL-21- and IL-21R-deficient mice develop inflammation but not fibrosis. Moreover, IL-21R-expressing CD8(+) cells are sufficient to reconstitute the fibrotic response in IL-21R-deficient mice. We further show that the combination of IL-4 and IL-21 skews naive CD8(+) T cells to produce IL-21, which, in turn, acts in an autocrine manner to support robust IL-13 production. Our data reveal a novel pathway involved in the onset and regulation of pulmonary fibrosis and identify Tc2 cells as key mediators of fibrogenesis.