Increasing infertility rates represent a growing medical challenge in modern societies resulting from a complex interplay of sociocultural trends, lifestyle factors, exposure to environmental toxins, and underlying health problems. Women's fertility is particularly vulnerable to these shifts. The obesogenic lifestyle not only accelerates weight gain, but also disrupts ovulation driving the rise in infertility. Among several medications used for treating obesity and type 2 diabetes, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) show promising improvement in female fertility most likely by stimulating ovulation. However, the effects of GLP‐1RAs on the endometrium remain unclear. Further studies are needed to investigate the impact of GLP‐1RAs on endometrial receptivity and embryo implantation and early development. The aim of this study is to address the knowledge gap regarding the effects of GLP‐1RAs on human reproduction, with special focus on the endometrium. Understanding these mechanisms may help to develop new strategies for improving fertility treatment, reduce implantation failure and address potential safety concerns regarding teratogenicity and adverse developmental outcomes for children born to women conceiving during or soon after GLP‐1RA treatment.

The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcriptome-wide analyses have mainly been utilized to study endometrial receptivity, the prerequisite for successful implantation, with most studies, so far, comparing the endometrial transcriptomes between (i) secretory and proliferative endometrium or (ii) mid-secretory and early secretory endometrium. In the current study, we provide a complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points including the mid-proliferative, late proliferative (peri-ovulatory phase), early secretory, mid-secretory, and late secretory phases. Thus, we unveil exhaustively the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. The transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of coordinated gene activity, the expression profile of histone-encoding genes within the HIST cluster on chromosome 6 shows an increase in cluster activity during the late proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Our data analysis highlights significant transcriptomic and functional changes occurring during the late proliferative phase—an essential transition point from the proliferative phase to the secretory phase. Future studies should explore how the biology of the late proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.

Proposed renaming of polycystic ovary syndrome (PCOS) to polyendocrine metabolic ovarian syndrome (PMOS) aims to broaden multidisciplinary care. However, it may obscure reproductive manifestations and introduce phenotypic ascertainment bias. Historical examples of nomenclature changes suggest that clinical benefits depend heavily on diagnostic, therapeutic, and etiological advances and education. Although formal cost‐effectiveness analysis of nomenclature changes are lacking, our preliminary estimates suggest that implementation may entail substantial cost and healthcare resource requirements, while its clinical benefits remain uncertain.

Research question How accurate is minimally invasive assessment of endometrial receptivity from uterine fluid extracellular vesicles (UF-EVs) using only 68 RNA biomarkers. Study design Assessment of endometrial receptivity by applying the beREADY computational model on transcriptomic data derived from UF-EVs during the pre-receptive (LH+2) and receptive phases (LH+7) of a natural cycle. Results beREADY housekeeping gene transcript levels in UF-EV are not significantly different between LH+2 and LH+7 UF-EVs. Endometrial receptivity can be assessed from UF-EV transcriptomic data using beREADY computational model with specificity of 100% and sensitivity of 75%. Conclusion beREADY computational model can be used on UF-EVs instead of endometrial tissue biopsy to assess endometrial receptivity. However, further development is needed to fine-tune the model to show that this model can also be used on UF-EV samples from women undergoing hormone-replacement therapy.

The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcrip-tome-wide analyses have mainly been utilized to study the endometrial receptivity, the prerequisite for successful implantation, with most of the studies, so far, comparing the endometrial transcriptomes between (i) secretory versus proliferative endometrium or (ii) mid-secretory versus early-secretory endometrium. In the current study, we provide the complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points: mid-proliferative, late-proliferative (peri-ovulatory phase), early-secretory, mid-secretory, and late-secretory phases. Thus, we exhaustively unveil the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. Transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of the coordinated gene activity, the expression profile of his-tone-encoding genes within the HIST cluster on chromosome 6 showed an increase in cluster activity during the late-proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Data analysis highlights significant transcriptomic and functional changes occurring during the late-proliferative phase – an essential transition point from the proliferative to the secretory phase. Future studies should explore how the biology of the late-proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.