Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

Mapping frailty in people living with HIV: A nationwide study in Greece.

OBJECTIVES: Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data. METHODS: Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored. RESULTS: The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/µl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty. CONCLUSIONS: Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

OBJECTIVES: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis. METHODS: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B. RESULTS: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks. CONCLUSIONS: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.

Making obstetrics more environmentally sustainable during and beyond the COVID-19 pandemic.

The climate crisis has increased the burden of obstetrical care due to the negative impact of environmental disruption on the health of pregnant women, new mothers, foetuses and neonates. During the COVID-19 pandemic, the ecological footprint of obstetrical care has significantly increased due to the use of personal protective equipment and the provision of large-scale testing and vaccination of pregnant women and healthcare personnel against COVID-19. The situation calls for coordinated action to make obstetrics more resource efficient. To achieve this goal, obstetricians need to rationalise the use of electricity, water, paper and plastic, adopt green surgical practices and integrate environmental sustainability in their working culture and personal life at large. The present article discusses the main sources of environmental pollution in obstetrical care and proposes evidence-based solutions.

Migration and newborn screening: time to build on the European Asylum, Integration and Migration Fund?

PURPOSE: The authors discuss the need for newborn screening in the context of the migration policy of the European Union, and particularly, the European Asylum, Migration and Integration Fund. METHODS: The authors searched scholarly databases (Pubmed, Scopus, Google scholar) and grey literature (LexEuropa, Policy reports) to identify original peer-reviewed research examining the migration to the European Union and the provision of healthcare to infants born to refugees and immigrant mothers. Resources in language different from English, French, German and Greek were not taken into consideration. RESULTS: Every year, a large number of refugees and immigrants from sub-Saharan Africa and Middle East countries travel to and enter in Europe. It has been estimated that two thirds of those seeking asylum are women and children. Many of these children have been born on the way to Europe or in migrant camps. Essential newborns' health screening is not accessible in most cases. Congenital conditions such as hypothyroidism and phenylketonuria may remain untreated, and once these infants are diagnosed, the organic damage could be irreversible. Prolonged necessary hospitalisation might be out of consideration at a time when clinics and hospitals are overstrained with COVID-19 patients. CONCLUSIONS: It is essential to ensure that newborn screening will be performed in a timely and evidence-based manner as well as that the information will be communicated between hospitals and within countries' health networks. In order to achieve these goals interdisciplinary and international technical and logistical collaboration are required.

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece.

OBJECTIVES: Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. METHODS: Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. RESULTS: A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. CONCLUSIONS: Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

Hospital-wide antifungal prescription in Greek hospitals: a multicenter repeated point-prevalence study.

The aim of the study was to evaluate antifungal prescriptions among hospitalized adult patients in Greek hospitals. This multicenter two-times, 1-day, point-prevalence study was carried out in 2015 and 2017 in five and six hospitals, respectively. Among the 5812 patients screened in both periods, antifungals were prescribed in 129 patients (73 in 2015 and 56 in 2017); antifungals were used as prophylaxis in 31 patients (24%), pre-emptively in 32 (25%), empirically in 38 (30%), and as targeted therapy in 28 (22%). Triazoles were the class most commonly used (65 patients; 50%), followed by echinocandins (59; 46%) and liposomal amphotericin B (12; 9%). The use of echinocandins was higher (P 0.009) in the ICU (16 out of 22 patients), as compared with those in other departments (40%). Antifungal treatment was deemed inappropriate in 32/129 patients (25%) (16% in 2015 versus 36% in 2017; P 0.014). Inappropriate antifungal administration was more common if indicated by the primary physician, as compared with an infectious disease specialist (35% versus 5%; P < 0.001). Candidemia represented the majority of microbiologically documented infections (12 out of 28). Only two cases of proven pulmonary aspergillosis were diagnosed. Fluconazole and echinocandins were most frequently prescribed for identified or presumptive fungal infections, while fluconazole or posaconazole was given most frequently as prophylaxis. Antifungal treatment has been, ultimately, proven unnecessary in one-fourth of cases, underlining the need of a nationwide antifungal stewardship program.

The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: A meta-analysis of randomised trials.

BACKGROUND: Vitamin D deficiency is frequently manifested in women with polycystic ovarian syndrome (PCOS). To date, supplementation of deficient patients has not been correlated with the hormonal and metabolic status of these patients. PURPOSE: We aimed to investigate the impact of vitamin D supplementation on the hormonal and metabolic profile of PCOS women. MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases for published randomised controlled trials. The meta-analysis was performed with the RevMan 5.3.5 software. RESULTS: Nine studies were included in the present meta-analysis which investigated the impact of vitamin D supplementation in 647 patients. According to our meta-analysis neither serum testosterone (MD 0.04 ng/mL, 95% CI -0.09 to 0.17) nor serum LH (MD -0.48 IU/mL, 95% CI -1.97 to 1.00) were significantly affected by vitamin D supplementation in any of the subgroup comparisons. On the contrary, serum DHEAS was significantly affected by vitamin D (MD -32.24 µg/dL, 95% CI -32.24 to -14.01) an effect which was mainly affected by the vitamin D vs placebo comparison. Vitamin D supplementation did not have an impact on fasting glucose (MD 0.42 mg/dL, 95% CI -2.75 to 3.60) or fasting insulin (MD 1.27 µU/mL, 95% CI -1.42 to 3.97) levels. HOMA-IR was, however, increased among patients that received placebo compared to vitamin D (MD 0.52, 95% CI 0.39-0.65). CONCLUSION: There is no evidence to support that vitamin D supplementation significantly benefits PCOS patients. However, given the relatively small number of enrolled patients further studies are needed to elucidate this field.

Update on ischemic colitis: from etiopathology to treatment including patients of intensive care unit.

Ischemic colitis is the result of colonic hypoperfusion and is regarded as a relatively rare condition. It can be roughly classified as occlusive and non-occlusive. Pathogenesis includes a usually transient compromise in the colonic vasculature, with a parallel activation of an inflammatory cascade caused primarily by reperfusion. Diagnosis of ischemic colitis remains often difficult and requires a combination of diagnostic techniques, whereas clinical signs are occasionally only seen late as complications. Gold standard is considered to be colonoscopy. Clinical presentation and treatment of ischemic colitis vary widely depending on the degree of ischemia. Patients of intensive care unit (ICU) with ischemic colitis are often under-diagnosed, since the parallel co-morbidities and the nonspecific nature of symptoms that mimic almost any abdominal pathology, can mislead the doctor. Moreover, sedated or ventilated patients can mask many of the characteristic features of ischemic colitis and make the diagnosis challenging. Bedside colonoscopy and diagnostic laparoscopy in ICUs are two options, which seem lately to be reliable and promising in diagnosing ischemic colitis in critically ill patients.

Metabolic syndrome in Greek women with polycystic ovary syndrome: prevalence, characteristics and associations with body mass index. A prospective controlled study.

PURPOSE: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI). METHODS: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF). RESULTS: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p < 0.05). Women with PCOS presented statistically higher BMI in comparison with the controls (p < 0.001). Subsequently, the prevalence of MetS was estimated in three groups: normal, overweight and obese subdivided according to BMI. The latter two groups showed significant differences compared with the healthy controls (24.5 vs. 8.8 %, p = 0.050). CONCLUSION: In conclusion, this study showed high prevalence of MetS and increased BMI in Greek PCOS women. In addition, it demonstrated the higher prevalence of MetS in obese PCOS women in comparison with the controls. These results are placing them at increased risk for cardiovascular disease and diabetes in the future and underline the necessity of periodic screening, appropriate diet and exercise program.

The contribution of sildenafil (Viagra) to ovarian stimulation with gonadotropins in a woman with poor ovarian response.

We aim to present the first case of a pregnancy achieved by administering sildenafil (Viagra) to a woman not responding to controlled ovarian hyperstimulation (COH) with the sole use of gonadotropins. A 37-year-old woman underwent COH, as part of an intracytoplasmic sperm injection (ICSI) cycle, with the combination of r-FSH and HMG for 13 d, without evidence of follicular growth. The addition of oral sildenafil at a dose of 50 mg per day for a total of five doses improved the ovarian response and resulted in the retrieval of 10 oocytes. Three embryos were transferred to the uterine cavity resulting in a successful pregnancy and, eventually, the delivery of a healthy neonate. Conclusively, the use of sildenafil as an adjunct to COH protocols may enhance ovarian response in a woman with poor ovarian response (POR) and merits further research.

Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece.

BACKGROUND: Antibiotic resistance, a major public health problem, has been linked to antibiotic consumption. In Greece both consumption and resistance rates are among the highest in Europe. A multifaceted campaign targeting both physicians and parents of school children was implemented for the first time in order to educate the public and update doctors, aiming to promote judicious use of antibiotics and hopefully decrease its consumption. METHODS: The programme consisted of a public education campaign and academic detailing of primary care physicians in the district of Corinth in Peloponnese. The experience and perceptions of parents were recorded in the meetings in the form of course evaluation and assessment, anonymous questionnaires. The use of Rapid Antigen Detection Test (RADT) for streptococcal pharyngitis by primary care physicians was also assessed by use of anonymous questionnaires. Antibiotic consumption was compared before and after the programme between the district of Corinth and the other districts of Peloponnese, as well as at a national level. RESULTS: Antibiotic consumption remained unaltered at 26 Defined daily doses per 1000 Inhabitants per Day (DID) in accordance with the trend in other regions and at a national level. However, the utilization of Amoxycillin and Penicillin was increased by 34.3%, while the use of other antimicrobial classes including macrolides, cephalosporins and fluoroquinolones decreased by 6.4-21.9%. The use of RADT did not lead to a significantly decreased antimicrobial consumption. CONCLUSIONS: A multifaceted educational programme targeting both the general public and primary care physicians was associated with rationalization in the choice of antimicrobial. A reduction in the total antimicrobial consumption was not achieved.

Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections.

The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections.

Early Infirmaries in Methoni During the Venetian Occupation.

INTRODUCTION: In the High Middle Ages, Venetian sovereignty was recognized in Methoni and Koroni (in Greece). It helped lay the foundations for the prevalence of democracy in Venice in the Eastern Mediterranean. The development of these two decadent regions of Messinia, had to be supported by social welfare infrastructure. Today, the search for these social welfare infrastructures in Venetian Methoni at the beginning of the conquest turns mainly to the monasteries of the Latin monastic orders that settled there during that time. These spiritual institutions, which provided shelter, hospitality, and even medical care to those in need, have not been identified to date. OBJECTIVES AND METHODS: The goal of this paper is to propose two possible locations based on bibliographic and on-site research. With the help of bibliographies, Venetian files, and relevant wills from the time, an effort was made to identify these ruins. On-field research was carried out to consolidate the findings that arose from the analysis of bibliographic references, the evidence arising from them, as well as local tradition. RESULTS AND CONCLUSION: The monastery of the Cistercian nuns shows that, in the context of charity, medical care was provided to those in need. The monastery in Paliomothoni was one of the earliest infirmaries in Venetian Methoni. The location of the first infirmary of Venetian Methoni within the Cistercian monastery of Paliomothoni is highly probable. Additionally, it was found to be operating there by Dominican monks at a later time.

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.

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.

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.

Oocyte Maturation and miRNAs: Studying a Complicate Interaction to Reveal Possible Biomarkers for Female Infertility.

Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.