Current applications of indocyanine green (ICG) in abdominal, gynecologic and urologic surgery: a meta-review and quality analysis with use of the AMSTAR 2 instrument.

BACKGROUND: Indocyanine green (ICG) is an injectable fluorochrome that has recently gained popularity as a means of assisting intraoperative visualization during laparoscopic and robotic surgery. Many systematic reviews and meta-analyses have been published. We conducted a meta-review to synthesize the findings of these studies. METHODS: PubMed and Embase were searched to identify systematic reviews and meta-analyses coping with the uses of ICG in abdominal operations, including Metabolic Bariatric Surgery, Cholecystectomy, Colorectal, Esophageal, Gastric, Hepato-Pancreato-Biliary, Obstetrics and Gynecology (OG), Pediatric Surgery, Surgical Oncology, Urology, (abdominal) Vascular Surgery, Adrenal and Splenic Surgery, and Interdisciplinary tasks, until September 2023. We submitted the retrieved meta-analyses to qualitative analysis based on the AMSTAR 2 instrument. RESULTS: We identified 116 studies, 41 systematic reviews (SRs) and 75 meta-analyses (MAs), spanning 2013-2023. The most thoroughly investigated (sub)specialties were Colorectal (6 SRs, 25 MAs), OG (9 SRs, 15 MAs), and HPB (4 SRs, 12 MAs). Interestingly, there was high heterogeneity regarding the administered ICG doses, routes, and timing. The use of ICG offered a clear benefit regarding anastomotic leak prevention, particularly after colorectal and esophageal surgery. There was no clear benefit regarding sentinel node detection after OG. According to the AMSTAR 2 tool, most meta-analyses ranked as "critically low" (34.7%) or "low" (58.7%) quality. There were only five meta-analyses (6.7%) that qualified as "moderate" quality, whereas there were no "high" quality reviews. CONCLUSIONS: Regardless of the abundance of pertinent literature and reviews, surgeons should be cautious when interpreting their results on ICG use in abdominal surgery. Future reviews should focus on ensuring methodological vigor; establishing clear protocols of ICG dose, route of administration, and timing; and improving reporting quality. Other sources of data (e.g., registries) and novel methods of data analysis (e.g., machine learning) might also contribute to an enhanced role of ICG as a decision-making tool in surgery.

Maternal and neonatal outcomes following magnesium sulfate in the setting of chorioamnionitis: a meta-analysis.

PURPOSE: Magnesium sulfate (MgSO4) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence. METHODS: We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers. RESULTS: Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO4 and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO4. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO4 in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death. CONCLUSION: Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.

Efficacy and safety of oral and sublingual versus vaginal misoprostol for induction of labour: a systematic review and meta-analysis.

OBJECTIVE: Misoprostol is a synthetic PGE1 analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit maternal and neonatal adverse outcomes. The present meta-analysis investigates the efficacy and safety of oral compared to vaginally inserted misoprostol in terms of induction of labor and adverse peripartum outcomes. METHODS: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till April 2022. Randomized controlled trials that assessed the efficacy of oral misoprostol (per os or sublingual) compared to vaginally inserted misoprostol. Effect sizes were calculated in R. Sensitivity analysis was performed to evaluate the possibility of small study effects, p-hacking. Meta-regression and subgroup analysis according to the dose of misoprostol was also investigated. The methodological quality of the included studies was assessed by two independent reviewers using the risk of bias 2 tool. Quality of evidence for primary outcomes was evaluated under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, ranging from very low to high. RESULTS: Overall, 57 studies were included that involved 10,975 parturient. Their risk of bias ranged between low-moderate. There were no differences among the routes of intake in terms of successful vaginal delivery within 24 h (RR 0.90, 95% CI 0.80) and cesarean section rates (RR 0.92, 95% CI 0.82, 1.04). Sublingual misoprostol was superior compared to vaginal misoprostol in reducing the interval from induction to delivery (MD - 1.11 h, 95% CI - 2.06, - 0.17). On the other hand, per os misoprostol was inferior compared to vaginal misoprostol in terms of this outcome (MD 3.45 h, 95% CI 1.85, 5.06). Maternal and neonatal morbidity was not affected by the route or dose of misoprostol. CONCLUSION: The findings of our study suggest that oral misoprostol intake is equally safe to vaginal misoprostol in terms of inducing labor at term. Sublingual intake seems to outperform the per os and vaginal routes without increasing the accompanying morbidity. Increasing the dose of misoprostol does not seem to increase its efficacy. CLINICAL TRIAL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/V9JHF ).

Prenatal Exposure to Bisphenol A: Is There an Association between Bisphenol A in Second Trimester Amniotic Fluid and Fetal Growth?

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual's diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = -0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

Serum LDH values in hypertensive disorders of pregnancy and their association with maternal and neonatal morbidity: A meta-analysis.

BACKGROUND: Serum lactate dehydrogenase has been extensively studied in hypertensive disorders of pregnancy. However, to date, its clinical usefulness in the field remains unknown. The present meta-analysis has been designed to evaluate differences in serum LDH values among patients with hypertensive disorders of pregnancy and to help determine its diagnostic accuracy as well its predictive accuracy in determining adverse pregnancy outcomes. METHODS: We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from their inception till 18 March 2021. Observational studies that assessed differences in serum LDH levels among women with hypertensive disorders of pregnancy and healthy controls were included. Meta-analysis was performed using Rstudio. Pooled mean differences (MD) were calculated with the Hartung-Knapp-Sidik-Jonkman. Meta-regression analyses, publication bias assessment and Trim and Fill function were also performed. The adequacy of the sample size was evaluated with Trial Sequential Analysis. RESULTS: Fifty-two articles were included that comprised 5340 women with hypertensive disorders of pregnancy and 2890 healthy controls. The meta-analysis revealed significant differences among patients with preeclampsia (either mild or severe) compared with controls, as well as among patients with mild and severe preeclampsia. Significant asymmetry was noted after examining funnel plots, however, and the trim and fill analysis revealed that differences were significant only among cases with severe preeclampsia and healthy controls. Morbidity outcomes increased with LDH levels >600 IU/L and particularly when these exceeded 800 IU/L. However, confidence and prediction intervals indicated an underpowered sample size for the accurate determination of the odds of developing maternal morbidity. CONCLUSION: Despite the extensive research in the field of hypertensive disorders of pregnancy, there is still lack of evidence concerning the diagnostic performance of serum LDH in clinical practice; hence, research should expand in this direction to evaluate its clinical utility.

Meta-analysis of GnRH-antagonists versus GnRH-agonists in poor responder protocols.

PURPOSE: Considering the insufficient evidence supporting an ideal protocol for poor responder management in IVF/ICSI cycles, the aim of the current meta-analysis was to compare GnRH-antagonist versus GnRH-agonist protocols in poor responders, evaluating effectiveness and safety. METHODS: Meta-analysis was conducted using Medcalc 16.8 version software. Standardized mean differences (SMD), odds ratios (OR), and the respective 95% confidence intervals (CI) were determined appropriately. The Cochran Q statistic and the I2 test were used to assess studies' heterogeneity. RESULTS: GnRH-agonists were shown to correlate with fewer cancelled IVF/ICSI cycles (p = 0.044, OR = 1.268 > 1, 95% CI 1.007, 1.598), a larger number of embryos transferred (p = 0.008, SMD = - 0.230, 95% CI - 0.400, - 0.0599), and more clinical pregnancies (p = 0.018, OR = 0.748 < 1, 95% CI 0.588, 0.952). However, GnRH-antagonists resulted in a significantly shorter duration of ovarian stimulation (p = 0.007, SMD = - 0.426. 95% CI - 0.736, - 0.115). The number of oocytes and mature oocytes retrieved in both protocols did not differ statistically (p = 0.216, SMD = - 0.130, 95% CI - 0.337, 0.0763 and p = 0.807, SMD = - 0.0203, 95% CI - 0.183, 0.142, respectively). Moreover, a high heterogeneity among studies was observed regarding duration of ovarian stimulation (I2 = 90.6%), number of oocytes (I2 = 82.83%)/mature oocytes retrieved (I2 = 70.39%), and embryos transferred (I2 = 72.83%). CONCLUSIONS: Based on the present meta-analysis, agonist protocols could be suggested as a first choice approach, in terms of effectiveness. Due to the high studies' heterogeneity, results should be considered with caution. Accordingly, larger cohort studies and meta-analyses like the present one will enhance the robustness of the emerging results to identify the ideal protocol for poor responders.

Culture of Human Embryos at High and Low Oxygen Levels.

One of the parameters potentially affecting the in vitro growth of preimplantation embryos is the oxygen concentration in the culture environment. An increased oxygen concentration causes the generation of ROS which in turn can cause damage to the cells and seriously disrupt the embryonic development. Previous studies have assessed oxygen concentrations in the fallopian tubes of several mammals of between 5 and 8%, while the oxygen levels in the uterus were found to be even lower; similar measurements have been confirmed in humans. In addition, studies in mammalian embryos showed that low oxygen concentrations improve embryo development. Multiple studies on the effect of the oxygen concentration on human embryos have been conducted so far with diverse methodologies and objectives. Data from these have been included in three meta-analyses. All meta-analyses indicate the potential benefit in favor of a low oxygen concentration, though data are considered to be of a low methodological quality and further studies are considered necessary. However, based on the existing evidence, it is suggested that a low oxygen concentration should be adopted in the routine of the IVF laboratory, especially in the case of blastocyst culture.

Follicle-Stimulating Hormone Receptor (FSHR) Ser680Asn Genotype Does Not Affect the Follicular Fluid Hormonal Profile in Stimulated Cycles Using Different Gonadotropin Preparations for Ovulation Induction: A Pilot Study.

BACKGROUND: The existing literature lacks consensus on the effectiveness of utilizing polymorphisms to enhance outcomes in in vitro fertilization (IVF), particularly regarding ovulation induction protocols, oocyte and embryo quality, and pregnancy rates. Therefore, the present pilot study aims to assess whether the composition of different gonadotropin preparations affects the ovarian stimulation protocol concerning follicle-stimulating hormone receptor (FSHR) Ser680Asn genotypes (Ser/Ser, Ser/Asn, and Asn/Asn), in terms of ovulation induction parameters, including oocyte maturation rate, embryo quality, and pregnancy rate. METHODOLOGY: A total of 94 IVF patients underwent treatment using a GnRH antagonist protocol with four distinct gonadotropin preparations: HMG, HMG/hCG, rFSH, and rFSH/hCG. Follicular fluid (FF) samples were pooled for each patient for analysis. RESULTS: No statistical differences in the FF hormonal profile (progesterone, testosterone, androstenedione, estradiol, FSH, hCG) among the FSHR genotypes were reported either separately for each protocol or in combination for the four different preparations of gonadotropins. The maturation rate of MII oocytes and embryo quality did not differ among women carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype (p-value=0.475, and p-value=1.000, respectively). Moreover, no statistically significant correlation was revealed among Ser/Ser, Ser/Asn, and Asn/Asn carriers and pregnancy rate (p = 0.588). CONCLUSIONS: FF hormonal analysis of women undergoing IVF using different ovulation induction protocols and carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype revealed no significant correlations, in terms of maturation rate of MII oocytes, embryo quality, and pregnancy rate, indicating that the FSHR Ser680Asn genotype does not constitute a biomarker for a positive pregnancy outcome. Therefore, the existence of a different mechanism for the expression of FSHR Ser680Asn genotypes in the FF hormonal profile related to stimulated cycles is implied.

Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice.

Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility.

Ectopic pregnancy with full implantation of the gestational sac in the caesarean section scar managed successfully with laparotomy.

Caesarean scar pregnancy represents one of the rarest locations of ectopic pregnancies. It occurs when the blastocyst is implanted in a scar from a previous caesarean section. A dramatic increase of its prevalence has been observed for the last decades, reaching about 21% globally. Early diagnosis and treatment are crucial to avoid maternal morbidity and mortality. Our case presents the characteristic appearance of a caesarean scar pregnancy with full implantation of the gestational sac in the scar, which was managed successfully with laparotomy.

The Contribution of Proteomics in Understanding Endometrial Protein Expression in Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) poses a significant challenge in assisted reproductive technology (ART) outcomes. The endometrium plays a crucial role in embryo implantation, and its protein expression profile is integral in determining receptivity. Proteomics has emerged as a valuable tool in unraveling the molecular intricacies underlying endometrial receptivity and RIF. The aim of the present review is to analyze the contribution of proteomics to the understanding of endometrial protein expression in women with RIF, based on the results of significant proteomic studies. Medline/Pubmed databases were searched using keywords pertaining to proteomics combined with terms related to RIF. 15 studies were included in the present review. Several proteins have been found to exbibit differential expression in endometrial biopsies and fluid samples between fertile women and women with RIF during the receptive endometrial phase. The profile of endometrial proteins varied significantly among the studies. Nevertheless, similar changes in the expression levels of annexin-6, progesterone receptor, MMP-2, and MMP-9 in the endometrium of women with RIF, were found in more than one study indicating that certain proteins could potentially be effective biomarkers of endometrial receptivity. Proteomics contributes significantly to the understanding of protein expression in the endometrium of women with RIF and the analysis of proteins in endometrial fluid are promising for improving the clinical management of RIF.

Association of Obesity with Telomere Length in Human Sperm.

Background: Telomere attrition and mitochondrial dysfunction are two fundamental aspects of aging. Calorie restriction (CR) is the best strategy to postpone aging since it can enhance telomere attrition, boost antioxidant capacity, and lower the generation of reactive oxygen species (ROS). Since ROS is produced by mitochondria and can readily travel to cell nuclei, it is thought to be a crucial molecule for information transfer between mitochondria and cell nuclei. Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). Telomere damage results from mitochondrial failure, whereas nuclear DNA remains unaffected. This research aims to investigate potential associations between these three variables and how they might relate to body mass index. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, male participants who were categorized into three body mass index (ΒΜΙ) groups-normal, overweight, and obese-had their sperm samples tested. Results: For both the normal and overweight groups, our results show a negative connection between relative telomere length and ΒΜI. As an illustration of a potential connection between mitochondrial health and telomere maintenance, a positive correlation was found for the obese group. Only the obese group's results were statistically significant (p < 0.05). More evidence that longer telomeres are associated with lower mitochondrial content can be found in the negative connection between telomere length and mitochondrial content in both the normal and overweight groups. However, the obese group showed a positive association. The data did not reach statistical significance for any of the three groups. These associations may affect sperm quality since telomere length and mitochondrial concentration are indicators of cellular integrity and health. Moreover, the ratio of mtDNA to nDNA was positively correlated with the relative telomere lengths of the obese group, but negatively correlated with the normal and overweight groups. In every group that was studied, the results were not statistically significant. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome compared to the nuclear DNA in sperm. Conclusions: Essentially, the goal of our work is to determine whether mitochondria and telomere length in human sperm interact. Understanding these connections may aid in the explanation of some male infertility causes and possibly contribute to the creation of new treatment modalities for problems pertaining to reproductive health. The functional implications of these connections and their applications in therapeutic settings require further investigation.

Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes.

BACKGROUND: Infertility affects about 80 million individuals worldwide and 10-15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. METHODS: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. RESULTS: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. CONCLUSIONS: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children.

Infant, Neonatal, and Post-neonatal Mortality in Greece: A Nationwide Time-Trend Analysis.

INTRODUCTION: Infant mortality is a crucial perinatal measure and is also regarded as an important public health indicator. This study aimed to comprehensively present time trends in infant, neonatal, and post-neonatal mortality in Greece. METHODS: The annual infant mortality rate (IMR), the neonatal mortality rate (NMR), and the post-neonatal mortality rate (PNMR) were calculated based on official national data obtained from the Hellenic Statistical Authority, spanning 67 years from 1956 to 2022. The time trends of the mortality rates were evaluated using joinpoint regression analysis, and the annual percent changes (APC) and the overall average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI). RESULTS: The IMR exhibited accelerating declines over more than 50 years, with an APC of -1.9 (-2.8 to -1.0) from 1956 to 1968, -5.4 (-5.6 to -5.2) from 1968 to 1999, and -7.3 (-8.9 to -5.7) between 1999 and 2008. In 2008, IMR reached its all-time low of 2.7 per 1,000 live births, down 16.6-fold from its peak at 44.1 per 1,000 live births in 1957. This improving trend was reversed following the onset of the economic crisis in the country, leading to a 57% increase in IMR from 2008 to 2016, with an upward trend APC of 3.4 (1.2 to 5.5). In the recent period 2016-2022, there was an improvement with an APC of -3.7 (-6.2 to -1.1), resulting in an IMR of 3.1 per 1,000 live births in 2022. The decrease in IMR was estimated to have prevented 209,109 infant deaths in the country from 1958 to 2022. From 1956 to 2022, the IMR decreased with an AAPC of -3.9 (-4.3 to -3.4), while the PNMR saw a decline with an AAPC of -4.5 (-5.1 to -3.9) and the NMR with an AAPC of -3.2 (-3.7 to -2.6). CONCLUSION: Greece achieved an impressive decrease in infant mortality rates, but this progress was halted and completely reversed during the economic crisis. Although there have been some recent improvements after the country's economic recovery, the rates have yet to reach pre-crisis levels.

The Contribution of Multiple Pregnancies in Stillbirths in Greece: A Time-Trend Analysis.

Introduction Multiple pregnancy is an established risk factor for fetal death. This study aimed to examine the impact of multifetal pregnancies on stillbirth rates (SBRs) in the Greek population. Methods Data on live births and stillbirths by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. The SBR for multiple and single gestations, and the population attributable risk (%) (PAR (%)) stillbirth attributable to multifetal gestations were calculated, and temporal trends were assessed using joinpoint regression analysis, with annual percentage changes (APC) and 95% confidence interval (95% CI). Results In the period 1957-2021, multiple pregnancies accounted for 9.4% of total stillbirths in Greece and the overall relative risk of fetal death among multifetal gestations was 3.34, in comparison with singletons. The SBR in multiple births remained unchanged from 1957 to 1976 and showed downward trends from 1976 to 2021 (APC = -3.0, 95% CI: -3.4 to -2.7, p < 0.001). PAR (%), after two decades of stability, showed an increasing trend over the period 1975-2011 (APC = 3.4, 95% CI: 2.8 to 4.0, p < 0.001), which was reversed in the more recent decade 2011-2021 (APC = -6.1, 95% CI: -9.6 to -2.5, p = 0.001), with PAR (%) decreasing from a historical high of 19.3% in 2012 to 8.6% in 2021. Conclusion The high incidence of multiple births has a considerable impact on stillbirth rates in the Greek population. The recent downward trends of SBR and PAR (%) of multiple gestations are encouraging, however more measures and targeted interventions are needed to improve perinatal outcomes in multifetal gestation.

Maternal Blood Adipokines and Their Association with Fetal Growth: A Meta-Analysis of the Current Literature.

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines.

Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes.

As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children.

Correlation of Serum Prolactin Levels With Metabolic and Cardiovascular Risk in Greek Women With Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood. AIM: This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. METHODS: The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels. CONCLUSION: The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target.