This study aimed to determine whether consecutive ovarian stimulation in follicular and luteal phases within a single menstrual cycle (dual stimulation) is achievable and superior to conventional stimulation for poor ovarian responders (PORs). Data of 260 PORs were retrospectively collected and divided into three groups. Group A comprised of cycles with dual ovarian stimulation (n = 76), which were divided into two subgroups (follicular [group A-F] and luteal phase stimulation [group A-L]); group B comprised of cycles with ovarian stimulation that was performed only in the luteal phase (n = 52). Group C comprised of mild ovarian stimulation cycles (n = 132). Baseline parameters were not different among the three groups. The numbers of oocytes and embryo obtained were less in group A-F than group B and C, while group A overall had significantly more oocytes and viable embryo retrieved than did group B and C. Group A-L consumed significantly less gonadotropin than group B, without compromising the number of retrieved oocytes and embryo. The pregnancy outcomes of transfer of embryo from different stimulation phases were similar. We conclude that dual ovarian stimulation protocol is effective and potentially optimal for PORs.

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Cutaneous T cell lymphoma (CTCL) represents a heterogeneous group of non-Hodgkin lymphoma distinguished by the presence of clonal malignant T cells. The heterogeneity of malignant T cells and the complex tumor microenvironment remain poorly characterized. With single-cell RNA analysis and bulk whole-exome sequencing on 19 skin lesions from 15 CTCL patients, we decipher the intra-tumor and inter-lesion diversity of CTCL patients and propose a multi-step tumor evolution model. We further establish a subtyping scheme based on the molecular features of malignant T cells and their pro-tumorigenic microenvironments: the TCyEM group, demonstrating a cytotoxic effector memory T cell phenotype, shows more M2 macrophages infiltration, while the TCM group, featured by a central memory T cell phenotype and adverse patient outcome, is infiltrated by highly exhausted CD8+ reactive T cells, B cells and Tregs with suppressive activities. Our results establish a solid basis for understanding the nature of CTCL and pave the way for future precision medicine for CTCL patients.

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