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Open research questions in Reproductive System and Pregnancy

210 unresolved questions extracted from the limitations and future-work sections of 590 Reproductive System and Pregnancy papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Retrospective study design, - Limited to women undergoing fresh IVF/ICSI cycles, - No data on long-term outcomes

    Late follicular phase progesterone levels and in vitro fertilization and intracytoplasmic sperm injection outcomes · 2026 · DOI

  • Investigation of age-and protocol-specific progesterone thresholds for optimal perinatal outcomes, - Examination of the effect of progesterone on reproductive outcomes in frozen-thawed embryo transfer cycles, - Study of the mechanisms underlying the protocol-dependent divergence in the effect of progesterone on live birth

    Late follicular phase progesterone levels and in vitro fertilization and intracytoplasmic sperm injection outcomes · 2026 · DOI

  • the study had a relatively small sample size of 103 samples derived from 737 women, - the study was limited to women with a history of two or more first-trimester consecutive miscarriages, - the study did not control for other potential factors that may influence CD138 expression, - the study relied on patient-reported data for some variables

    CD138 expression in the endometrium associates with endometrial timing and inflammatory status but not microbiota composition · 2026 · DOI

  • further studies are needed to confirm the findings of this study and to explore the mechanisms underlying CD138 expression in the endometrium, - studies should investigate the relationship between CD138 expression and other factors that may influence reproductive outcomes, - research should focus on developing new diagnostic and therapeutic strategies for recurrent pregnancy loss based on CD138 expression

    CD138 expression in the endometrium associates with endometrial timing and inflammatory status but not microbiota composition · 2026 · DOI

  • investigating PRP in RPL subgroups characterized by endometrial or implantation-related dysfunction, - direct evidence that intrauterine PRP modifies oxidative stress in the human endometrium or in women with RPL

    Platelet-Rich Plasma in Recurrent Pregnancy Loss: Toward a Precision Medicine Framework for Biologically Guided Patient Selection · 2026 · DOI

  • The current evidence base for the use of PRP in RPL is limited, and there is a need for direct high-quality evidence. The extrapolation of findings from RIF and thin endometrium populations to RPL is a major limitation. There is a lack of understanding of the molecular mechanisms underlying the effects of PRP on endometrial decidualization and implantation.

    Platelet-Rich Plasma in Recurrent Pregnancy Loss: Toward a Precision Medicine Framework for Biologically Guided Patient Selection · 2026 · DOI

  • Cellular data imbalance, - Limited understanding of the precise immune coordination at the maternal-fetal interface, - Heterogeneity of RPL, - Focus on euploid RPL

    Machine learning–driven decoding of maternal immune signatures in repeated pregnancy loss · 2026 · DOI

  • Investigation of the role of CXCR4 and JUN in RPL, - Functional investigation of the candidate targets, - Further analysis of the immune coordination at the maternal-fetal interface

    Machine learning–driven decoding of maternal immune signatures in repeated pregnancy loss · 2026 · DOI

  • most of the signals remain mechanistic, preclinical, associative, or candidate-biomarker evidence rather than proof of clinical utility, - pooled heterogeneity is high, - peripheral NK cells do not reliably correlate with uNK cells, - current evidence remains dominated by associative studies and methodological exploration

    Endometrial receptivity failure in assisted reproduction: immune-cellular niches, mechanistic evidence, and translational boundaries · 2026 · DOI

  • standardized RIF phenotyping, - cycle-phase and sampling control, - external validation of cell-specific markers, - prospective trials, - live-birth endpoints, - safety follow-up

    Endometrial receptivity failure in assisted reproduction: immune-cellular niches, mechanistic evidence, and translational boundaries · 2026 · DOI

  • The absence of unified standardization in protocols for sampling, DNA extraction, and bioinformatics analysis, - Different researchers use different regions of the 16S rRNA gene, - The lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis

    Endometrial Microbiome and Reproductive Receptivity: Diverse Perspectives · 2025 · DOI

  • Further studies on the endometrial microbiome, - Investigation of the effects of geographic, ethnic, and hormonal factors on the endometrial microbiome, - Development of standardized protocols for sampling, DNA extraction, and bioinformatics analysis

    Endometrial Microbiome and Reproductive Receptivity: Diverse Perspectives · 2025 · DOI

  • Microbial cultures have limitations, including the inability to culture certain pathogens, - Hysteroscopy provides valuable information but its diagnostic accuracy is influenced by the operator's subjective judgment, - The exact etiology of CE remains unclear, - There is no consensus on the diagnostic criteria for CE via hysteroscopy

    The pathogenesis, diagnosis, and treatment of chronic endometritis: a comprehensive review · 2025 · DOI

  • Further studies on the etiology and pathogenesis of CE are needed, - Research on the development of standardized diagnostic criteria and treatment protocols for CE, - Investigation of emerging adjuvant approaches for CE management

    The pathogenesis, diagnosis, and treatment of chronic endometritis: a comprehensive review · 2025 · DOI

  • The existence of a core uterine microbiome is still unknown due to the inaccessibility of the uterine cavity. The specific roles of Lactobacillus species in reproductive outcomes are not well understood. The mechanisms by which the vaginal and endometrial microbiome affect reproductive health are not fully elucidated.

    Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss · 2024 · DOI

  • inter-and intraobserver variability may bias endometrial dating - the capacity for assessment remains limited - conflicting results are reported in the literature -

    When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation · 2024 · DOI

  • development of accurate, predictive, and personalized tests to identify the window of implantation and the best quality embryo - improvement of pregnancy outcomes through measures such as the identification of difficult procedures of embryo transfer and the standardization of morphological criteria to classify blastocyst competency -

    When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation · 2024 · DOI

  • Pregnancy drives uterine remodeling through rapid anatomical expansion and scar-free postpartum repair, yet how the organ reconstructs its cellular architecture after birth remains incompletely understood.

    Mapping Uterine Remodeling from Pregnancy to a New Homeostatic State · 2026 · DOI

  • However, how the uterus acquires the competence to respond to progesterone at the appropriate time remains poorly understood.

    ERBB2 establishes the timing of progesterone priming required for uterine receptivity · 2026 · DOI

  • However, current evidence remains inconsistent, and diagnostic criteria vary widely.

    Impact of chronic endometritis on assisted reproductive technology outcomes: a propensity score inverse probability weighting cohort study · 2026 · DOI

  • Routine CE screening in all ART candidates may be unnecessary, and targeted evaluation for high-risk subgroups warrants further investigation.

    Impact of chronic endometritis on assisted reproductive technology outcomes: a propensity score inverse probability weighting cohort study · 2026 · DOI

  • A direct comparison of pregnancy outcomes following in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) between patients with ETB and those with NSCE would help clarify whether differential management strategies are warranted and provide more precise guidance for clinical practice.

    Endometrial tuberculosis increases miscarriage risk after IVF/ICSI compared with non-specific chronic endometritis · 2026 · DOI

  • A receptive endometrium is essential for successful embryo implantation, yet its dynamic cellular and molecular features remain poorly understood due to limitations in current in vitro models.

    Establishment of a cell line-based 3D co-culture model of the endometrium for studying endometrial receptivity · 2026 · DOI

  • OBJECTIVE: Maternal immune activation has been proposed as a mechanism for adverse pregnancy outcomes, yet the mechanisms and effects of timing remain unclear.

    Maternal Immune Activation During Pregnancy and Obstetric Outcomes: A Population‐Based Cohort Study · 2025 · DOI

  • CONCLUSION: Comprehensive individualised interventions may improve clinical outcomes for patients with RIF, warranting further investigation.

    Effect of Comprehensive Individualised Interventions on the Clinical Outcomes of Patients With Recurrent Implantation Failure: A Single‐Centre Retrospective Cohort Study · 2025 · DOI

Most-cited papers in Reproductive System and Pregnancy

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210 open questions have been extracted from the limitations and future-work passages of 590 Reproductive System and Pregnancy papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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