From Conception to Birth: Embryonic Development and Disease

Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of clinically stable preterm neonates by Rotational Thromboelastometry [ROTEM; (EXTEM, INTEM, FIBTEM assays)], (b) establishing reference ranges, and (c) investigating potential differences in comparison to healthy term neonates. We also evaluated the impact of clinical and perinatal factors on the haemostatic status of this vulnerable population. Materials and Methods: 69 premature neonates with no underlying morbidity and 226 healthy term neonates were the study subjects. In term neonates, blood was collected on the 2nd-3rd day of life, if sampling was required for any other reason (hyperbilirubinemia, ABO blood group incompatibility screening, maternal thyroid antibodies, or insufficient prenatal care), whereas in premature neonates, blood was collected between the 4nd-10th day after stabilisation. The parameters measured for each ROTEM assay included Clotting Time (CT), Clot Formation Time (CFT), Alpha angle (α, degrees), Clot Amplitude at 5 and 10 min (A5, A10), Maximal Clot Firmness (MCF), and Lysis Index at 30, 45 and 60 min (Li30, Li45, and Li60 respectively). Results: The data analysis demonstrated a prothrombotic profile in preterm neonates, characterized by increased values of A5, A10, (MCF), and α-angle, and shortened CT and CFT across all assays (EXTEM, INTEM, FIBTEM), when compared to term neonates. A statistically significant inverse correlation was observed between gestational age and clot lysis parameters (INTEM Li45, Li60). Additionally, hematocrit levels were negatively correlated with clot amplitude and kinetics of clot development, while platelet count was positively associated with clot firmness parameters (A5, A10, MCF) and α-angle. Mode of delivery and the presence of gestational diabetes did not significantly affect ROTEM assay values. Preterm neonates with a history of respiratory distress syndrome (RDS) exhibited a more pronounced hypercoagulable profile compared to those without RDS, as reflected by the enhanced clot strength and reduced CT, findings that may be attributed to postnatal pulmonary inflammation and its systemic effects on coagulation. Conclusions: This study introduces for the first time reference values for the parameters of ROTEM assays (EXTEM, INTEM, FIBTEM) in clinically stable preterm neonates—a highly vulnerable patient group with a distinct need for accurate and individualized monitoring of their haemostatic status. The combined assessment of these assays enhances diagnostic precision, and offers a more comprehensive evaluation of neonatal haemostasis. By defining reference ranges in whole blood, this work provides novel data that support the integration of ROTEM into clinical transfusion algorithms. Full article

Male infertility affects nearly 15% of couples worldwide, with chromosomal abnormalities representing a major underlying cause. This review explores how numerical and structural chromosomal anomalies, along with environmental exposures, lifestyle factors, and age-related genetic changes, disrupt spermatogenesis and contribute to infertility. It synthesizes findings from cytogenetic, molecular, and clinical studies, with particular focus on mechanisms such as meiotic nondisjunction, spindle assembly checkpoint dysfunction, and alterations in cohesin and synaptonemal complex proteins. Chromosomal abnormalities, both numerical and structural, emerge as key contributors to male infertility by impairing chromosomal segregation and recombination, often leading to azoospermia or oligospermia. Meiotic checkpoint failures and recombination errors further exacerbate the production of aneuploid sperm. Environmental toxins, oxidative stress, and poor nutrition disrupt hormonal balance and chromatin integrity, while advancing paternal age is associated with increased sperm aneuploidy and impaired meiotic control, with implications for assisted reproduction. Specific syndromes, including AZF deletions, Kallmann syndrome, and 46,XX testicular DSD, exemplify the direct genetic impact on male fertility. Overall, chromosomal abnormalities are central to the pathophysiology of male infertility, arising from intrinsic meiotic errors as well as extrinsic environmental and lifestyle factors. Integrating cytogenetic diagnostics, genetic counseling, and lifestyle interventions is essential for comprehensive fertility assessment and management. Further research into molecular biomarkers and targeted therapies could enhance diagnosis, improve treatment strategies, and lead to better reproductive outcomes. Full article

Fertility-sparing treatments (FSTs) have gained importance for young female cancer patients, especially those with early-stage cervical, ovarian, and endometrial cancers. However, concerns about the long-term safety of these procedures, particularly in more advanced cancers, persist. A literature review was conducted using databases such as PubMed, Scopus, and Web of Science. The search terms included “fertility preservation” and “gynaecological cancer”. Articles published between 2014 and 2024 were considered, with 39 articles cited in the paper. The inclusion criteria were female patients undergoing FST. Studies were excluded if prior treatments impacted fertility or if oncological outcomes were inadequately reported. Radical trachelectomy, laparoscopic fertility-sparing surgeries, and cryopreservation techniques, such as ovarian tissue vitrification and oocyte cryopreservation, offer viable options for preserving fertility in early-stage gynecological cancer patients. Radical trachelectomy and cryopreservation showed positive reproductive outcomes, with pregnancy rates of 30–50% in early-stage cases. GnRH analogs during chemotherapy also demonstrated benefits in maintaining fertility. Despite these advances, recurrence in more advanced stages (FIGO IA2 and beyond) remains a concern. Minimally invasive surgeries like robotic-assisted procedures demonstrated comparable fertility outcomes to traditional methods but with fewer complications. FST is a promising option for women with early-stage cancer, offering favorable reproductive and survival outcomes. However, further research is needed to confirm long-term oncological safety in advanced stages. Multidisciplinary approaches and individualized treatment planning are essential for optimizing outcomes. Full article

Assisted reproduction technology (ART) has advanced significantly over the past four decades, leading to improved pregnancy outcomes and a reduction in complications, particularly those associated with multiple pregnancies. These improvements largely stem from advances in understanding embryonic physiology, which has enabled better culture conditions. As a result, embryologists can now efficiently culture embryos to the blastocyst stage and successfully cryopreserve them for future use. However, while incubators aim to replicate the maternal environment of the oviduct and uterus, embryos in vitro are cultured in static conditions, unlike the dynamic, constantly changing environment they experience in vivo. Key factors such as pH, temperature, osmolality, and gas concentrations are crucial for establishing optimal embryo development and implantation potential. Moreover, the vitrification procedure for gametes or embryos can introduce oxidative stress, as well as osmotic shock and cryoprotectant toxicity, which may affect embryo viability and increase the risk of birth defects. Since the first successful ART birth in 1978, over 10 million babies have been conceived through these techniques. Although most of these children are healthy, concerns exist about potential birth defects or changes linked to the handling of gametes and embryos. The preimplantation period is marked by significant epigenetic reprogramming, which can be influenced by ART procedures such as ovarian stimulation, in vitro fertilization, embryo culture, and cryopreservation. However, the long-term health implications for offspring remain uncertain. Epigenetic reprogramming during early embryogenesis is essential for proper embryo development and can be changed by ART-related conditions. These concerns have raised questions about the possible connection between ART and a higher risk of birth defects or other changes in children born through these methods. Therefore, we conducted a scoping review following PRISMA-ScR guidelines to map evidence on ART-related risks, including epigenetic and birth defect outcomes. Full article

Fetal surgery has emerged as a viable option for the management of selected congenital anomalies that result in severe or lethal outcomes if left untreated until birth. Conditions such as spina bifida, urinary tract obstruction, congenital cystic adenomatoid malformation, diaphragmatic hernia, sacrococcygeal teratoma, and twin–twin transfusion syndrome have shown improved prognosis after in utero intervention, open, or fetoscopically. Despite significant advances in surgical methods and anesthesia, preterm labor remains a primary concern. Stem cell transplantation and in utero gene therapy are developing, and they have the potential to expand the treatment window, as they minimize maternal complications. Hematopoietic stem cell transplantation, which is based on the immaturity of the fetal immune system, is a promising treatment for inherited disorders. Although many procedures of fetal interventions are now established, their safety and efficacy must be ensured and this requires optimal patient selection and choice of appropriate timing for intervention, adherence to ethical principles, and continuous research. Therefore, a multidisciplinary team, including specialists in maternal–fetal medicine, pediatric surgery, anesthesiology, neonatology, psychosocial support, and bioethics, is essential to guide comprehensive, patient-centered care. Fetal surgery is an evolving field that offers hope for conditions previously considered untreatable before birth. Full article

High-risk pregnancies (HRPs) constitute a significant global health issue due to their strong association with increased maternal and neonatal morbidity and mortality. Although pregnancy is generally characterized by positive expectations, the presence of maternal comorbidities, gestational complications, or adverse socioeconomic and environmental conditions can markedly elevate the probability of unfavorable outcomes. HRPs contribute disproportionately to complications such as preterm birth, fetal growth restriction, low birth weight, and congenital anomalies, which are key determinants of neonatal mortality and long-term developmental and health challenges. A broad spectrum of risk factors as well as insufficient prenatal care, underscores the complex nature of HRPs. These conditions necessitate a multidisciplinary management approach encompassing early risk identification, continuous monitoring, and individualized interventions. The neonatal prognosis in such contexts is strongly influenced by gestational age at delivery, birth weight, the standard of neonatal care, and the underlying etiological factors driving preterm or complicated deliveries. Preventive strategies including comprehensive prenatal screening, systematic antenatal follow-up, and timely referral to specialized perinatal care centers are essential for reducing the burden of HRPs. Furthermore, addressing social determinants of health—such as low socioeconomic status and limited access to healthcare—is critical for optimizing maternal and neonatal outcomes. This review consolidates current evidence on the epidemiology, etiological factors, and clinical implications of high-risk pregnancies, emphasizing the necessity of an integrative, preventive, and multidisciplinary framework to mitigate adverse neonatal outcomes and improve long-term health trajectories. Full article

Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis on how its distinctive structural domains facilitate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂) and the induction of calcium (Ca²⁺) oscillations in the oocyte. Notably, PLCζ exhibits unique sensitivity to basal Ca²⁺ levels and the capacity to sustain repetitive intracellular Ca²⁺ transients that drive meiotic progression and block polyspermy. Clinically, PLCζ deficiency—whether caused by genetic mutations, reduced expression, or improper localization—represents a unifying explanation for certain forms of male infertility, including total fertilization failure (TFF) following intracytoplasmic sperm injection (ICSI). Globozoospermia is a prime example; this condition is characterized by round-headed sperm devoid of acrosomes and exhibiting significantly reduced or absent PLCζ and often results in fertilization failure. Diagnostic methods such as immunofluorescence, Western blotting, and the mouse oocyte-activation test collectively support the identification and characterization of PLCζ-related defects, while genetic testing for mutations in the PLCZ1 gene has proven valuable for identifying hereditary causes of sperm-borne oocyte-activation deficiency (OAD). Therapeutic approaches range from assisted oocyte activation (AOA) with calcium ionophores to emerging interventions that introduce functional PLCζ protein or mRNA directly into the oocyte. These advancements demonstrate the rapid translation of foundational discoveries into clinically actionable interventions. Future investigations are poised to refine diagnostic assays, standardize measurement protocols, and explore the potential of gene therapy or CRISPR/Cas9-mediated correction for heritable PLCζ abnormalities. By addressing both the molecular basis and translational applications of PLCζ, recent findings underscore its indispensable role in fertility care and lay out a path toward further innovation in assisted reproductive technologies. Full article