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Open research questions in Reproductive Biology and Fertility

367 unresolved questions extracted from the limitations and future-work sections of 1,505 Reproductive Biology and Fertility papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Precise figures for developmental failures in IVF remain undetermined. Current assessment methods have a shortcoming in evaluating embryo viability. The study used a narrative methodology to consolidate existing knowledge.

    When Fertilization Is Not Enough: Maternal-Zygotic Transition as a Determinant of Embryo Competence in IVF · 2026 · DOI

  • Identifying molecular markers to enhance the selection of embryos in IVF. Investigating the molecular pathways that control transcript regulation, translation, chromatin remodelling, and genome activation.

    When Fertilization Is Not Enough: Maternal-Zygotic Transition as a Determinant of Embryo Competence in IVF · 2026 · DOI

  • The study faced challenges in differentiating between true absence of pronuclei, early fading of pronuclei, or asynchronous appearance of pronuclei in 0PN embryos. The lack of time-lapse imaging systems limited the ability to assess fertilization dynamics. The study had to account for the potential presence of embryos with abnormal fertilization in the 0PN group.

    Cleavage-stage stratification reveals the clinical and developmental potential of 0PN embryos compared with 2PN embryos in IVF · 2026 · DOI

  • The limitations of current diagnostic techniques for fertility preservation, - The lack of comprehensive evaluation of ovarian reserve markers, - The financial barriers and social factors influencing the utilization of fertility preservation options

    Editorial: Fertility preservation and restoration in oncologic and non-oncologic patients · 2026 · DOI

  • The clinical and developmental potential of 0PN embryos is not well understood. The gap in knowledge is the lack of understanding of the impact of early cleavage dynamics on subsequent embryonic development and clinical outcomes. The study aims to address this gap by comparing the developmental competence and clinical outcomes of 0PN and 2PN embryos.

    Cleavage-stage stratification reveals the clinical and developmental potential of 0PN embryos compared with 2PN embryos in IVF · 2026 · DOI

  • This effect has not yet been tested on bovine oocytes; therefore, this study aimed to evaluate rapid warming's influence on mitochondrial functionality, nuclear DNA integrity, and IVEP efficiency.

    Rapid warming improves blastocyst production of vitrified bovine oocytes while significantly affecting mitochondrial activity · 2026 · DOI

  • However, how these cytokines affect early follicular development remains poorly understood.

    Pro-inflammatory cytokines disrupt in vitro preantral follicle development by targeting granulosa and theca cell functions · 2026 · DOI

  • However, the function of these age-associated immune cells and their potential contributions to the inflammaging phenotype remain unclear.

    Multicellular origins of murine ovarian inflammaging · 2026 · DOI

  • However, the specific role of IGF1 signaling mediated by its cognate receptor IGF1R during mammalian preimplantation development remains unclear and unexplored.

    Insulin-like growth factor 1 receptor (IGF1R)-dependent signaling regulates blastocyst formation during early embryonic development · 2026 · DOI

  • However, the role of mitochondrial proteostasis in determining oocyte quality is underexplored.

    Mitochondrial unfoldase ClpX regulates oocyte competence during ovarian aging · 2026 · DOI

  • Since patients could undergo cleavage or blastocyst stage embryo transfer, the threshold value of peak estradiol level for each transfer stage that impacts the pregnancy outcomes of fresh versus frozen embryo transfer remains unclear.

    The threshold of estradiol level for fresh embryo transfer differs between blastocyst and cleavage‐stage embryo · 2025 · DOI

  • Eriodictyol, a natural flavonoid, possesses potent anti-inflammatory properties, but its effects on POF remain unexplored.

    Eriodictyol alleviates ovarian dysfunction in a mouse model of premature ovarian failure via the PI3K/Akt/NF-κB pathway and suppression of macrophage inflammation · 2025 · DOI

  • While GCs facilitate follicle development and ovulation through estrogen and progesterone secretion, the role of AMH in sheep GCs and its impact on follicle development remains unclear.

    AMH regulates granulosa cell function via ESR2/ p38-MAPK signaling pathway in sheep · 2025 · DOI

  • However, our understanding of the regulatory mechanisms underlying the cellular and developmental programs of oogenesis is lacking.

    An mTOR-Stat3-Stathmin pathway controls centrosome and microtubule dynamics for oocyte polarization · 2025 · DOI

  • In aged mice, CoQ10 restored mitochondrial activity and reduced chromosomal abnormalities, while preliminary human studies noted improved embryo quality in poor responders, though randomized controlled trials (RCTs) remain inconclusive.

    Oocyte and dietary supplements: a mini review · 2025 · DOI

  • Whether the efficiency and quality of oocyte maturation can be improved by optimizing cell volume regulation by adjusting the osmolality of the culture medium in the presence of the organic osmolyte of glycine remains to be determined.

    Stage-dependent changes in culture medium osmolality promote porcine oocyte maturation in vitro · 2025 · DOI

  • While the long-term consequences of low-protein diets during early development have been reported in the context of DOHaD (Developmental Origins of Health and Disease) theory, the relationship between nutrient supply via autophagy during preimplantation development and these long-term effects remains unclear.

    Chloroquine mitigates long-term effects of in vitro culture in mouse embryos · 2025 · DOI

  • Although the mechanisms involved in the regulation of sperm capacitation and acrosome reaction are not fully understood, it has been reported that Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is an important regulator of these processes.

    Heat shock affects the Ca2+/calmodulin-dependent protein kinase II dynamic during bovine sperm capacitation and acrosome reaction · 2025 · DOI

  • Despite its critical role in reproductive performance, the transcriptional regulatory mechanisms governing ovine BMPR1B expression remain poorly understood.

    ELK1 regulates BMPR1B transcriptional activity in ovine granulosa cells · 2025 · DOI

  • However, the complex molecular stress responses evoked by vitrification remain poorly understood.

    Multi-omics analysis reveals a protective role of endogenous proline in sheep oocyte vitrification and its therapeutic application · 2025 · DOI

  • However, the intrinsic regulatory mechanisms governing MQC during bovine oocyte maturation remain incompletely characterized.

    Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency · 2025 · DOI

  • While fertility-sparing surgery can allow pregnancy, those who undergo a hysterectomy are limited to adoption, surrogacy, or the emerging possibility of uterus transplantation.

    The complexity and challenges of fertility preservation in women with cervix cancer—A prospective cohort study reporting on reproductive outcome and overall survival · 2024 · DOI

  • However, the link between SERa+ and neonatal outcomes remains controversial and open for debate.

    Smooth endoplasmic reticulum aggregates in oocytes associated with increased risk of neonatal birth defects: A meta‐analysis · 2024 · DOI

  • In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic.

    Primary ovarian insufficiency: update on clinical and genetic findings · 2024 · DOI

  • These pathways include but are not limited to the MAPK signaling pathway, Hippo signaling pathway, Wnt signaling pathway, Calcium signaling pathway, Aldosterone synthesis and secretion, Cellular senescence, and NF-kappa B signaling pathway-essentially encompassing signal transduction pathways crucial to reproductive processes.

    Differential age-related transcriptomic analysis of ovarian granulosa cells in Kazakh horses · 2024 · DOI

Most-cited papers in Reproductive Biology and Fertility

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367 open questions have been extracted from the limitations and future-work passages of 1,505 Reproductive Biology and Fertility 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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