Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study.

PURPOSE: The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events. METHODS: The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use. RESULTS: Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score. CONCLUSION: The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

Chemotherapy response score as a predictor of survival in ovarian cancer patients.

OBJECTIVE: The chemotherapy response score (CRS) has been widely adopted as a predictive tool for ovarian cancer survival. In the present study, we seek to define differences in survival rates among patients grouped in the traditionally established three-tiered system and those who have not been offered debulking surgery. STUDY DESIGN: We designed a retrospective cohort study involving women treated with chemotherapy and offered interval or late debulking surgery for ovarian cancer. Twenty-eight women were not considered for a debulking procedure for various reasons. Of the 89 women who were finally offered interval debulking or late debulking surgery, 28 had a CRS 1 score, 34 had a CRS 2 score and 27 had a CRS 3 score. RESULTS: Significant differences were noted in the progression-free survival (PFS) and overall survival (OS) of patients based on the CRS stratification, although survival rates were considerably longer for all three groups compared to those of patients who were not offered surgery. Cox regression univariate analysis revealed that suboptimal debulking and CRS 1 or no surgery had a significant negative impact on PFS and OS rates. The binary stratification of CRS (CRS 1-2 vs CRS 3) revealed comparable differences in the PFS and OS to those in the groups that were stratified as platinum resistant and platinum sensitive. CONCLUSION: The chemotherapy response score is a significant determinant of ovarian cancer survival that helps evaluate the risk of early disease relapse and death and may soon be useful in guiding patient-tailored treatment.

Proteomics in the study of female fertility: an update.

INTRODUCTION: Female fertility has been a field of interest for the scientific community throughout the years. The contribution of proteomics in the study of female fertility as well as female infertility and in vitro fertilization (IVF) has been significant. Proteomics is a recently developed field, extensively applied to the identification and quantification of proteins, which could be used as potential biomarkers in a diagnostic, prognostic, or predictive manner in a variety of medical conditions. AREAS COVERED: The present review focuses on proteomic studies of the oocyte and endometrial environment as well as on conditions related to infertility, such as polycystic ovarian syndrome, endometriosis, obesity, and unexplained infertility. Moreover, this review presents studies that have been done in an effort to search for fertility biomarkers in individuals following the IVF procedure. EXPERT OPINION: The comprehension of the molecular pathways behind female fertility and infertility could contribute to the diagnosis, prognosis, and prediction of infertility. Moreover, the identification of proteomic biomarkers for IVF cycles could predict the possible outcome of an IVF cycle, prevent an unsuccessful IVF, and monitor the IVF cycle in a personalized manner, leading to increased success rates. [Figure: see text].

Thoracic epidural analgesia as part of an enhanced recovery program in gynecologic oncology: a prospective cohort study.

OBJECTIVE: To evaluate the safety and the effectiveness of thoracic epidural analgesia as part of the enhanced recovery after surgery (ERAS) multimodal analgesic protocol in patients with gynecologic oncology who have undergone laparotomy for suspected or confirmed malignancy. METHODS: We conducted a prospective cohort study, following an enhanced recovery after surgery pathway, among patients who had undergone laparotomy for confirmed or suspected gynecological malignancy between January 2020 and September 2021. All patients who underwent laparotomy at the gynecologic oncology department for the aforementioned reason during that time were considered eligible. Patients (n=217) were divided into two groups: epidural (n=118) and non-epidural (n=99) group. Both groups were treated with the standard ERAS departmental analgesic protocol. The primary outcomes were length of hospital stay, complications, and readmission rates. RESULTS: Data from 217 patients (epidural group, n=118 vs non-epidural group, n=99) with median age of 61 years (IQR 53-68) were analyzed. The most common type of cancer was of ovarian origin (85/217, 39.2%, p=0.055) and median (Aletti) surgical complexity score was 3 (p=0.42). No differences were observed in the patients' demographics, clinical, and surgical characteristics. Primarily, median length of stay was 4 days in both groups with statistically significant lower IQR in the epidural group (3-5 vs 4-5, p=0.021). Complication rates were more common in the non-epidural group (38/99, 38.3% vs 36/118, 30.5%, p<0.001) with similar rates of grade III (p=0.51) and IV (0%) complications and readmission rates (p=0.51) between the two groups. Secondarily, the epidural group showed lower pain scores (p<0.001) on the day of surgery and in the first post-operative day (p<0.001), higher mobilization rates on the day of surgery (94.1% vs 57.6%, p<0.001), faster removal of urinary catheter (p<0.001), shorter time to flatus (p<0.001), and less nausea on the day of surgery (p<0.001). CONCLUSION: In this study we showed that thoracic epidural analgesia, when used as part of an ERAS protocol, is safe and offers more favorable pain relief along with a number of additional benefits, improving the peri-operative experience of patients with gynecologic cancer.

Ovarian Stimulation with FSH Alone versus FSH plus a GnRH Antagonist for Elective Freezing in an Oocyte Donor/Recipient Programme: A Protocol for a Pilot Multicenter Observational Study.

Preliminary data have shown that it is possible to attempt in vitro fertilization (IVF) treatment in fresh cycles without the use of a gonadotropin-releasing hormone (GnRH) antagonist or any other medication to prevent the luteinizing hormone (LH) surge during ovarian stimulation. To date, there is no information on this topic in the context of a prospective controlled trial. However, as prevention of the LH surge is an established procedure in fresh cycles, the question is whether such a study can be performed in frozen cycles. We aim to perform a pilot study in order to compare the efficacy of a protocol using FSH alone with that of a protocol using follicle-stimulating hormone (FSH) plus a GnRH antagonist for controlled ovarian hyperstimulation (COH) in cycles of elective freezing in the context of a donor/recipient program. This is a seven-center, two-arm prospective pilot cohort study conducted at the respective Assisted Reproductive Units in Greece. The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of the clinical outcome in a donor/recipient model. The results of the present study are expected to show whether the addition of the GnRH antagonist is necessary in terms of the frequency of LH secretory peaks and progesterone elevations >1 ng/mL during the administration of the GnRH antagonist according to the adopted frequency of blood sampling in all Units.

Chemotherapy Response Score in Ovarian Cancer Patients: An Overview of Its Clinical Utility.

The chemotherapy response score has been developed over the last few years as a predictive index of survival outcomes for patients with advanced-stage epithelial ovarian cancer undergoing interval debulking surgery. While its importance in predicting patients at risk of developing recurrences earlier seems to be important, its accuracy in determining patients with a shorter overall survival remains arbitrary. Moreover, standardization of the actual scoring system that was initially developed as a 6-tiered score and adopted as a 3-tiered score is still needed, as several studies suggest that a 2-tiered system is preferable. Given its actual importance in detecting patients with shorter progression-free survival, research should also focus on the actual predictive value of determining patients with platinum resistance, as a suboptimal patient response to standard neoadjuvant chemotherapy might help determine patients at risk of an earlier recurrence. In the present review, we summarize current knowledge retrieved from studies addressing outcomes related to the chemotherapy response score in epithelial ovarian cancer patients undergoing neoadjuvant chemotherapy and discuss differences in outcome reporting to help provide directions for further research.

The Effect of the Allelics of Ser680Asn Polymorphisms of Follicle-Stimulating Hormone Receptor Gene in IVF/ICSI Cycles: a Systematic Review and Meta-analysis.

A significant number of single-nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHr) can modify the response to exogenous FSH administration. A significant diversity in response to controlled ovarian stimulation (COS) in assisted reproductive technologies (ART) according to the type of allelic has been reported. We aimed to evaluate the relation between the Asn680Ser allelics and COS. A total of 4 electronic databases were searched for articles published up to August 2021. Prospective and retrospective comparative studies which reported outcomes after COS in patients who underwent genotyping for the detection of FSHr polymorphisms were considered eligible. A total of 11 studies including 4343 patients with Asn680Ser polymorphisms of the FSHr were included. Patients carrying the Asn/Asn allelic provide elevated E2 on the day of human chorionic gonadotropin (hCG) administration (1549 patients MD 262.39 pg/ml, p = 0.0007), but less transferrable embryos as compared with Ser/Ser genotype (283 patients MD - 0.11 embryos, p = 0.04). Ans/Ser versus Ser/Ser genotypes showed a higher E2 on the day of hCG administration (1799 patients, MD 207.86 pg/ml, p = 0.02). Pregnancy rates were similar in all combination of genotypes. There is currently no strong evidence suggesting that the examination of one gene in relation to genotypes can be effectively used as single tool to improve COS. However, polygenic analysis of different polymorphisms by analyzing the genetic profile of each individual could be useful. Further research is warranted to develop an algorithm that will enable simultaneous analysis of many genes, which combined with hormonal profile could promote treatment individualization.

PDE5 inhibitors and male reproduction: Is there a place for PDE5 inhibitors in infertility clinics or andrology laboratories?

The objective of this review study is to evaluate the therapeutic role of PDE5 inhibitors (PDE5is) in the amelioration of oligoasthenospermia in infertile males. PDE5is have a beneficial influence on the secretory function of the Leydig and Sertoli cells, the biochemical environment within the seminiferous tubule, the contractility of the testicular tunica albuginea, and the prostatic secretory function. In several studies, the overall effect of sildenafil and vardenafil increased quantitative and qualitative sperm motility. Furthermore, some studies indicate that PDE5is influence positively the sperm capacity to undergo capacitation under biochemical conditions that are known to induce the sperm capacitation process. Additional research efforts are necessary in order to recommend unequivocally the usage of sildenafil, vardenafil, or avanafil for the alleviation of male infertility.

Comparison of the Fetal Fraction of Cell-Free DNA in In-Vitro Fertilization (IVF) Versus Natural Conception Evaluation of the Fetal Fraction With IVF Parameters.

Background As the offspring of assisted reproduction techniques (ARTs) have become a substantial proportion of the population, increased attention has been placed on the safety of ART. Investigators have focused on identifying a tool that combines molecular or biological tests that can predict the outcomes of in-vitro fertilization (IVF) or intracytoplasmic sperm injection and the resulting pregnancy after ART-mediated embryo implantation. This study aimed to answer the following questions: is there a difference between natural conception and IVF pregnancies regarding fetal fraction (FF) of cell-free DNA (cfDNA) in maternal age, birth weight, gender, and gestational age? Is there a difference between FF concentration regarding the parameters of IVF as possible predictive factors affecting the outcomes of IVF? Methodology This study included 31 women with singleton pregnancies conceived via IVF who underwent cell-free fetal DNA (cffDNA) screening for trisomy 13, 18, and 21; sex determination; and FF. The control group included 55 women who experienced natural conception. For all women, anthropometric characteristics such as age, weight, height, and body mass index (BMI) were recorded. For the IVF group, early follicular phase values of follicle-stimulating hormone, luteinizing hormone, prolactin, anti-müllerian hormone, thyroid-stimulating hormone, and estradiol were recorded. Results The natural conception and IVF groups were similar regarding maternal age, BMI of the mother, gender, birth weight, and gestational age. FF was not significantly different between the natural conception and IVF groups (10 (3.8) vs. 9 (2.6); p = 0.144). The results were similar after adjusting for maternal age via regression analysis. cfDNA was not associated with maternal age, birth weight, gender, or gestational age in the entire study sample or separately for the natural conception and IVF groups. No significant correlation was found between cfDNA and IVF parameters. Conclusions The FF is an important factor for non-invasive prenatal testing (NIPT) accuracy. Several studies have found a reduction in FF in pregnancies following ART compared with natural conception, while other studies have presented no differences in the FF. All researchers agree on the importance of NIPT; however, knowledge on how the FF is affected in ART pregnancies compared with naturally conceived pregnancies is very limited. In this study, no difference in FF for the IVF group compared with natural conception women was observed. The cffDNA concentrations in maternal serum do not appear to be affected in IVF conception. We suggest that FF is an independent factor compared with IVF parameters.

Implementing a preimplantation proteomic approach to advance assisted reproduction technologies in the framework of predictive, preventive, and personalized medicine.

The evolution of the field of assisted reproduction technology (ART) in the last 40 years has significantly contributed to the management of global infertility. Despite the great numbers of live births that have been achieved through ART, there is still potential for increasing the success rates. As a result, there is a need to create optimum conditions in order to increase ART efficacy. The selection of the best sperm, oocyte, and embryo, as well as the achievement of optimal endometrial receptivity, through the contribution of new diagnostic and treatment methods, based on a personalized proteomic approach, may assist in the attainment of this goal. Proteomics represent a powerful new technological development, which seeks for protein biomarkers in human tissues. These biomarkers may aid to predict the outcome, prevent failure, and monitor in a personalized manner in vitro fertilization (IVF) cycles. In this review, we will present data from studies that have been conducted in the search for such biomarkers in order to identify proteins related to good sperm, oocyte, and embryo quality, as well as optimal endometrial receptivity, which may later lead to greater results and the desirable ART outcome.

Effectiveness of maternal vaccination with quadrivalent inactivated influenza vaccine in pregnant women and their infants in 2019-2020.

OBJECTIVES: Influenza is associated with an increased risk for serious illness, hospitalization, and death in pregnant women and young infants. Our aim was to estimate the effectiveness of a quadrivalent inactivated influenza vaccine (QIV) in pregnant women and their infants during 2019-2020. METHODS: A QIV vaccine was offered to pregnant women followed in a maternity hospital. Women were contacted weekly during the influenza season and asked about symptoms. Polymerase chain reaction testing in pharyngeal samples was offered to pregnant women and infants with influenza-like illness. A Bayesian beta-binomial model was used. RESULTS: We studied 636 pregnant women (406 vaccinated and 230 unvaccinated) and 474 infants (281 of mothers vaccinated in pregnancy and 193 of unvaccinated mothers). Using a Bayesian beta-binomial model, it was estimated that influenza vaccination of pregnant women reduced their logit to develop laboratory-confirmed influenza by -4.2 (95% CI -3,7 - 4,7) and the logit of their infants to develop laboratory-confirmed influenza by -4.2 (95% CI -3.6, -4.9). The QIV effectiveness against laboratory-confirmed influenza was 43.5% in pregnant women and 31.4% in infants. CONCLUSION: Maternal influenza vaccination with QIV in pregnancy reduced the odds of pregnant women and their infants to develop influenza. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04723771.

Male Age and Progressive Sperm Motility Are Critical Factors Affecting Embryological and Clinical Outcomes in Oocyte Donor ICSI Cycles.

This retrospective cohort study aimed to explore whether paternal age and semen quality parameters affect the embryological and clinical outcomes of ICSI with oocyte donation. A total of 339 oocyte donation (OD)-ICSI cycles were categorized into four groups according to the semen parameter profiles of the male counterparts: normozoospermia (NS, n = 184), oligozoospermia (OS, n = 41), asthenozoospermia (AS, n = 50), and oligoasthenozoospermia (OAS, n = 64). The effect of age, total sperm count, and progressive motility was separately analyzed for reproductive outcomes and compared between the study groups: fertilization, blastulation, and top-quality embryo rate, biochemical and clinical pregnancy, live birth, and miscarriage. A negative correlation between male age and fertilization rate was observed (rs = - 0.23, p < 0.0001), while male age was a significant factor for biochemical pregnancy (p = 0.0002), clinical pregnancy (p = 0.0017), and live birth (p = 0.0038). Reduced total sperm count and lowered progressive motility led to poorer fertilization rates (rs = 0.19 and 0.35, respectively, p < 0.0001) and affected embryo quality (rs = 0.13, p = 0.02, and rs = 0.22, p < 0.0001, respectively). OD-ICSI cycles with asthenozoospermia had significantly lowered success rates in biochemical pregnancy, clinical pregnancy, and live birth (p < 0.05). Our study demonstrated that both advanced male age and reduced progressive motility of spermatozoa exert a significant negative influence on the outcome of assisted reproduction, even in controlled procedures with gamete selection and optimization such as in OD-ICSI. Improvement in treatment strategies and male fertility evaluation requires incorporation of such evidence to obtain better prognosis towards personalized management.

A Randomized Controlled Trial on the Efficacy and Safety of Low-Dose hCG in a Short Protocol with GnRH Agonist and Ovarian Stimulation with Recombinant FSH (rFSH) During the Follicular Phase in Infertile Women Undergoing ART.

Τhis study aims to investigate whether the addition of low-dose hCG throughout stimulation in infertile women undergoing IVF improves IVF outcome parameters. This is a prospective, multicenter, randomized, double-blind, placebo-controlled, Phase IIIb clinical study, conducted in three university IVF units. We studied whether the addition of 100 IU hCG/day to a short GnRH agonist IVF protocol from the onset of the follicular phase (group 1, n=40) or placebo (group 2, n=41) had any impact on the number of high-quality transferred embryos at day 2 and clinical pregnancy rates. The comparison encompassed descriptive statistics, and univariate and multivariate analyses. Concerning the primary outcomes, we found no differences in both the number of high-quality embryos (≥2) at day 3 [21/40 (52.5%) vs. 14/41 (34.2%), p=0.095] and clinical pregnancy rates [10/40 (25%) vs. 10/41 (24.4%), p=0.949], respectively. Similarly, there were no differences concerning the secondary outcomes preset for this trial. According to the results of the multivariate logistic regression analysis, no significant associations were noted for primary outcomes (clinical pregnancy: adjusted OR=0.89, 95% CI: 0.29-2.75; (≥2 excellent quality embryos at day 3: adjusted OR=0.54, 95% CI: 0.21-1.42, with group 1 set as reference category); similarly, no differences were noted with respect to secondary outcomes, except from the increased odds of ≥2 poor-quality embryos at day 3 occurring in group 2 (adjusted OR= 11.69, 95%CI: 1.29-106.19). The addition of low-dose hCG to a short GnRH agonist protocol for IVF does not improve the number of top-quality embryos and clinical pregnancy rates.

Early versus delayed oxytocin infusion following amniotomy for induction of labor: a meta-analysis of randomized controlled trials.

BACKGROUND: Oxytocin infusion prior to confirmation of delay in labor is discouraged by the World Health Organization. However, evidence from the Cochrane library seems to support early amniotomy and oxytocin to reduce the rates of cesarean sections (CS). OBJECTIVES: To investigate differences in mode of delivery among parturient receiving early versus delayed oxytocin infusion following amniotomy as a mean for augmentation of labor. SEARCH STRATEGY: We searched Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials and Google Scholar databases from inception till February 2020. Selection criteria: Randomized controlled trials. DATA COLLECTION AND ANALYSIS: Data were collected using a modified Cochrane data collection form for intervention reviews. Meta-analysis was performed using the meta function in RStudio. MAIN RESULTS: Five studies were included that involved 1.232 parturient. The meta-analysis did not reveal significant differences in the mode of delivery among women that were randomized to receive immediate oxytocin infusion and those that received delayed oxytocin infusion (operative vaginal delivery OR 1.14, 95% CI 0.48, 2.69) and CS OR 0.81, 95% CI 0.53, 1.25)). The interval from amniotomy to delivery was significantly smaller in the immediate oxytocin infusion group; however, prediction intervals were not significant. CONCLUSIONS: The results of our meta-analysis suggest that there is no difference in the mode of delivery and interval from amniotomy to delivery when oxytocin is delayed for at least one hour following amniotomy. Taking in mind this information as well as current recommendations drawn from the WHO physicians should consider withholding oxytocin infusion at least until protracted labor is confirmed.

Past, Present, and Future of Gonadotropin Use in Controlled Ovarian Stimulation During Assisted Reproductive Techniques.

A variety of protocols have evaluated the use of several forms of gonadotropins in controlled ovarian stimulation (COS). We aim to review the evolving trends on the use of gonadotropins human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) over time and their combinations in COS for patients who undergo assisted reproductive techniques (ART) protocols. A meticulous search of three electronic databases was performed for articles published in the field up to September 2020. The administration of hCG seems a promising alternative to conventional modalities for COS related to the enhancement of LH activity. The use of gonadotropins was associated with significantly elevated pregnancy rates that ranged from 20.8% to 46.2%. However, the currently available outcomes with regards to oocytes retrieved, number of embryos are still conflicting. A potential beneficial effect was observed by the majority of the studies in terms of the number of embryos and implantation rates, which is, however, highly affected by the type of protocol used (gonadotropin-releasing hormone [GnRH] agonist or antagonist). Further studies are warranted to elucidate the exact pathways of action of gonadotropins in controlled ovarian stimulation to attain the optimal effect.

The Role of FSHR SNPs and AMH in Follicular Fluid and Serum in Ovarian Response during COS: A Pilot Study.

BACKGROUND: Several studies have investigated on the polymorphism Ser680Asn of FSHR and its use as a predictive indicator of response to an IVF/ICSI protocol. Furthermore, measurement of AMH in serum and follicular fluid is a useful prognostic indicator for the outcome of an assisted reproduction attempt. The purpose of this study is to examine the FSH receptor Ser680Asn polymorphism in combination with AMH levels in both serum and follicular fluid, on the day of oocyte collection. MATERIALS AND METHODS: A total of 32 women who underwent IVF/ICSI were included. Women were grouped into 2 groups: those who received rFSH (n = 11) and those who received hMG (n = 21). Serum AMH was measured on day 3 of the cycle, and AMH in the follicular fluid on the day of oocyte retrieval; the same day peripheral blood was collected for the genotyping of Ser680Asn. RESULTS: No statistical significant difference was found between serum AMH and follicular fluid AMH regarding the FSH receptor genotype for the Ser680Asn polymorphism. Regarding the sAMH/ffAMH ratio in the 3 genotypes, the value was lower in Asn/Asn women than Ser/Ser and Ser/Asn, but no statistical difference was obtained. Women who carry the Ser allele have a higher number of follicles, retrieved oocytes, and mature oocytes than women who do not contain the Ser allele. Women with AMH < 2.22 ng/ml presented lower AMH follicular fluid levels and lower serum AMH/follicular fluid AMH ratio in a statistically significant manner. Concerning the genotype for the polymorphism Ser680Asn of FSHR in relation to AMH levels, no statistically significant differences were found. CONCLUSIONS: The identification of polymorphisms, such as Ser680Asn of FSHR, along with the determination of endocrine markers in the follicular fluid, such as AMH, could lead at some point, to the personalized therapy setting per woman.

Mechanical bowel preparation before gynecologic laparoscopic procedures: Is it time to abandon this practice?

AIM: To examine the influence of mechanical bowel preparation on surgical field visualization and patients' quality of life during benign gynecologic laparoscopic procedures. METHODS: A single blind, randomized, controlled trial was undertaken with laparoscopic gynecologic surgical patients to one of the following three groups: liquid diet on the preoperative day; mechanical bowel preparation with oral polyethylene glycol (PEG) solution; minimal residue diet for 3 days. Primary outcomes included assessment of the condition of small and large bowel and the overall quality of the surgical field. Additional measures included assessment of patients' preoperative symptoms, tolerance of the preparation method and compliance to the protocol, postoperative symptoms and bowel function. RESULTS: One hundred forty-four patients were randomized as follows: 49 to liquid diet, 47 to mechanical bowel preparation, and 48 to minimal residue diet. Most characteristics were similar across groups. The intraoperative surgical view and the condition of large and small bowel were equal or inferior at the patients who received mechanical bowel preparation compared with the other groups. The 4-point Likert scale scoring for small bowel (2.51 vs. 2.72 vs. 2.81, p = 0.04), large bowel (2.26 vs. 2.38 vs. 2.48, p = 0.32) and overall operative field quality (2.34 vs. 2.67 vs. 2.67, p = 0.03) demonstrated no advantage from the use of preoperative mechanical bowel preparation over liquid diet and minimal residue diet, respectively. Preoperative discomfort was significantly greater in the mechanical bowel preparation group. CONCLUSION: Mechanical bowel preparation before gynecologic laparoscopic operations for benign pathology could be safely abandoned. CLINICAL TRIAL REGISTRATION: ISRCTN registry, https://doi.org/10.1186/ISRCTN59502124 (No 59502124).

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.

The Relevance of Notch Signaling in Cancer Progression.

The Notch signaling pathway controls normal embryonic development and tissue homeostasis of many cell types. It regulates cell proliferation, fate, differentiation, and cell death by short-range signaling between nearby cells that come in contact. The Notch pathway has also been critically involved in the pathobiology of a variety of malignancies, regulating cancer initiation and development, as well as early stages of cancer progression, by adjusting conserved cellular programs. Fibroblasts, an essential for tumor growth component of stroma, have also been affected by Notch regulation. Sequencing Notch gene mutations have been identified in a number of human tumors, revealing information on the progression of specific cancer types, such as ovarian cancer and melanoma, immune-associated tumors such as myeloid neoplasms, but especially in lymphocytic leukemia. Activation of the Notch can be either oncogenic or it may contain growth-suppressive functions, acting as a tumor suppressor in other hematopoietic cells, hepatocytes, skin, and pancreatic epithelium.

Evaluation of the efficacy of cervical pessary combined with vaginal progesterone in women with a short cervix and additional risk factors for preterm delivery.

OBJECTIVE: The aim of this study was to examine the efficacy of a combined management with cervical pessary and vaginal progesterone of women with a singleton pregnancy and a short cervix in both low and high risk-cases based on their previous obstetrical history and maternal factors. STUDY DESIGN: This was a prospective cohort study of women with a singleton pregnancy and a sonographically detected mid-trimester cervical length ≤ 25 mm. The high-risk group consisted of women with a history of a previous spontaneous preterm birth (PB), or a second-trimester miscarriage, or a loop electrosurgical excision procedure of the cervix (LEEP) while the low-risk group of women without such a history. All women were managed with cervical pessary and daily vaginal administration of 200 mg of progesterone. The primary outcome measure was spontaneous delivery before 34 weeks (238 days) of gestation. RESULTS: One hundred ninety-six cases with a CL ≤ 25 mm were detected during the study period. Fifty-two women declined to participate in the study. The remaining 144 women were divided into two groups based on the presence (n = 44) or absence (n = 100) of specific risk factors for PB. The rate of PTB < 34 weeks was similar in both low and high-risk pregnancies while a significantly higher rate of sPTB < 37 weeks was found in women with high-risk pregnancies (p = .005). CONCLUSION: The combined treatment of cervical pessary and vaginal progesterone has a similar influence on preterm delivery rate < 34 weeks, in both low and high-risk women, with a mid-trimester short cervix.