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ObjectivesThe safety of cesarean myomectomy has been proven by previous studies. Our study aimed to reveal the long-term perinatal, obstetric, and surgical outcomes of cesarean myomectomy (CM) by comparing different CM techniques.Material and methodsThis retrospective multicentric case–control study involved 7 hospitals and included 226 singleton pregnancies that underwent repeated cesarean section (CS) between 2015 and 2020. Among these pregnancies, 113 of 226 cases had CM (Group A), and 113 had only CS (Group B). Of the 113 cases in which CM was performed, 58 underwent endometrial myomectomy (EM) (Subgroup A1) and 55 underwent serosal myomectomy (SM) (Subgroup A2). The groups were compared in terms of obstetric, perinatal, and surgical outcomes, and fibroid recurrence, myomectomy scar healing rate, and adhesion formation were noted.ResultsThere was no significant difference between the groups in terms of maternal age, body mass index, gravidity, parity, and fibroid diameter in previous CS (p > 0.05). In the perinatal and obstetric evaluation of the groups, there was no significant difference between the groups in terms of neonatal weight, Apgar score, fetal growth restriction, preterm premature rupture of membranes, preterm delivery, hypertension in pregnancy, and diabetes mellitus (p > 0.05). The fibroid recurrence rate was 28.3%, and the myomectomy scar good healing rate was 99.1%. There was no difference between the groups in terms of CS duration, preoperative and postoperative hemoglobin levels, perioperative blood transfusion rates, febrile morbidity, and prolonged hospitalization (p > 0.05). In terms of adhesion formation, although the adhesion rate of the SM group was higher than that of the EM group, no statistically significant difference was detected between the groups.ConclusionThis study showed that in pregnancies following CM, obstetrical, perinatal, and surgical outcomes were unaffected. Obstetricians can safely use CM, either the trans-endometrial or serosal technique, as it is a safe and effective method with long-term results.

Human Papillomavirus (HPV) infection represents a global health concern. HPV infects the mucosa, particularly in the uterine cervix, where it may establish a persistent infection, exposing women to a risk of developing cancer. The available treatments include surgery or topic solutions, while a systemic treatment is still unavailable. In recent years, natural molecules such as epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12, and hyaluronic acid (HA) gained importance as innovative therapies for HPV. We enrolled 163 women with a positive HPV DNA test or previous history of HPV infections, and a PAP test indicating LSIL/AGUS/ASCUS cytology. The patients in the treatment group (n = 86) received an oral combination of EGCG 200 mg, FA 400 µg, vitamin B12 1 mg, and HA 50 mg (1 cps/day) for 3 months (T1), while the control group (n = 77) underwent standard clinical surveillance. Both groups repeated a PAP test and an HPV DNA test after 3 (T1) months, and another PAP test after 6 months (T2) as a follow up. The treatment group experienced a significant reduction in HPV positivity at T1 compared to the control group. Moreover, the treatment group exhibited an improvement in cervical lesions either at T1 (p < 0.0001) or T2 (p < 0.00001).

Background: To investigate whether fetal adrenal gland volume (AGV) and fetal zone volume (FZV), important components of the fetal adrenal gland, differ between women who have term and preterm births, and to determine whether these two parameters can be used to predict premature birth. Methods: A total of 238 pregnant women at 24–28 weeks of gestation were included in this case-control study. The fetal AGV and FZV were ultrasonographically evaluated, and corrected AGV (cAGV) and corrected FZV (cFZV) were assessed with adjustments for estimated birth weight. Receiver operating characteristic (ROC) curves were used to assess the ability of AGV, FZV, cAGV, and cFZV to predict preterm birth. Results: Ultrasound exams on 220 term fetuses and 18 preterm fetuses showed that preterm fetuses exhibited higher AGV (p = 0.039), FZV (p = 0.001), cAGV (p = 0.001), and cFVZ (p = 0.001) compared to term fetuses. Conclusions: These results demonstrated that term and preterm fetuses differ in their AGV and FZV within this study population. The data generated by 3D sonography between 24 and 28 weeks of gestation may be beneficial for predicting premature birth. However, larger prospective studies with a larger sample size of preterm births are needed to validate these findings.

Asynclitism, a misalignment of the fetal head with respect to the plane of passage through the birth canal, represents a significant obstetric challenge. High degrees of asynclitism are associated with labor dystocia, difficult operative delivery, and cesarean delivery. Despite its clinical relevance, the diagnosis of asynclitism and its influence on the outcome of labor remain matters of debate. This study analyzes the role of the degree of asynclitism (AD) in assessing labor progress and predicting labor outcome, focusing on its ability to predict intrapartum cesarean delivery (ICD) versus non-cesarean delivery. The study also aims to assess the performance of the AIDA (Artificial Intelligence Dystocia Algorithm) algorithm in integrating AD with other ultrasound parameters for predicting labor outcome. This retrospective study involved 135 full-term nulliparous patients with singleton fetuses in cephalic presentation undergoing neuraxial analgesia. Data were collected at three Italian hospitals between January 2014 and December 2020. In addition to routine digital vaginal examination, all patients underwent intrapartum ultrasound (IU) during protracted second stage of labor (greater than three hours). Four geometric parameters were measured using standard 3.5 MHz transabdominal ultrasound probes: head-to-symphysis distance (HSD), degree of asynclitism (AD), angle of progression (AoP), and midline angle (MLA). The AIDA algorithm, a machine learning-based decision support system, was used to classify patients into five classes (from 0 to 4) based on the values of the four geometric parameters and to predict labor outcome (ICD or non-ICD). Six machine learning algorithms were used: MLP (multi-layer perceptron), RF (random forest), SVM (support vector machine), XGBoost, LR (logistic regression), and DT (decision tree). Pearson’s correlation was used to investigate the relationship between AD and the other parameters. A degree of asynclitism greater than 70 mm was found to be significantly associated with an increased rate of cesarean deliveries. Pearson’s correlation analysis showed a weak to very weak correlation between AD and AoP (PC = 0.36, p < 0.001), AD and HSD (PC = 0.18, p < 0.05), and AD and MLA (PC = 0.14). The AIDA algorithm demonstrated high accuracy in predicting labor outcome, particularly for AIDA classes 0 and 4, with 100% agreement with physician-practiced labor outcome in two cases (RF and SVM algorithms) and slightly lower agreement with MLP. For AIDA class 3, the RF algorithm performed best, with an accuracy of 92%. AD, in combination with HSD, MLA, and AoP, plays a significant role in predicting labor dystocia and labor outcome. The AIDA algorithm, based on these four geometric parameters, has proven to be a promising decision support tool for predicting labor outcome and may help reduce the need for unnecessary cesarean deliveries, while improving maternal-fetal outcomes. Future studies with larger cohorts are needed to further validate these findings and refine the cut-off thresholds for AD and other parameters in the AIDA algorithm.

The uterus is a highly innervated organ, and during labor, this innervation is at its highest level. Oxytocinergic fibers play an important role in labor and delivery and, in particular, the Lower Uterine Segment, cervix, and fundus are all controlled by motor neurofibers. Oxytocin is a neurohormone that acts on receptors located on the membrane of the smooth cells of the myometrium. During the stages of labor and delivery, its binding causes myofibers to contract, which enables the fundus of the uterus to act as a mediator. The aim of this study was to investigate the presence of oxytocinergic fibers in prolonged and non-prolonged dystocic delivery in a cohort of 90 patients, evaluated during the first and second stages of labor. Myometrial tissue samples were collected and evaluated by electron microscopy, in order to quantify differences in neurofibers concentrations between the investigated and control cohorts of patients. The authors of this experiment showed that the concentration of oxytocinergic fibers differs between non-prolonged and prolonged dystocic delivery. In particular, in prolonged dystocic delivery, compared to non-prolonged dystocic delivery, there is a lower amount of oxytocin fiber. The increase in oxytocin appeared to be ineffective in patients who experienced prolonged dystocic delivery, since the dystocic labor ended as a result of the altered presence of oxytocinergic fibers detected in this group of patients.

Background: One of the most popular surgical procedures is the cesarean section (CS), and one of the most prevalent side effects of this procedure is wound and scar issues. The aim of this prospective, short-term, placebo-controlled study was to evaluate the safety and effectiveness of a silicone-based medical device (Lecoxen cream, Ekuberg Pharma, Carpignano Salentino, Italy) in healing wounds and scars derived from cesarean sections in nulliparous women. Methods: Seventy-four nulliparous women, ranging in age from 18 to 45, and underwent CSs, were divided in two groups of treatment (Lecoxen cream or Vaseline). The quality of scar was examined using the Vancouver scar scale after 28 days, while wound healing was evaluated using the Redness, Edema, Ecchymosis, Discharge, and Approximation (REEDA) scale on the 14th day following CS. Results: The treatment with Lecoxen cream determined a statistically significant improvement (p < 0.001) of the wound healing state, in terms of redness, edema, ecchymoses and discharge. Even about Vancouver Scar Scale (VSS) score there was a significative improvement in the observed group in terms of vascularization, pigmentation, flexibility and height (p < 0.001). No adverse effects were reported from the use of Lecoxen cream in participants. Conclusions: Lecoxen cream proved to be a safe and efficient treatment for wounds from CSs, making it a valuable topical to accelerate the healing process and reduce the visibility of scars. Clinical Trial Registration: The study was registered with the ISRCTN registry (https://www.isrctn.com/), registration number: ISRCTN51125312.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women’s mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles’ activation, which could cause an aberrant mechano-sensitive pacemaker activation–deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Introduction: Intrapartum ultrasound (IU) is used in the delivery ward; even if IU monitors the labouring women, it could be perceived as a discomfort and even as an“ obstetric violence”, because it is a young technique, not often well ''accepted''. A group of clinicians aimed at obtain an informed consent from patients, prior to perform a translabial ultrasound (TU). The aim of this study was to evaluate the acceptance of both translabial and transabdominal IU. Methods: In this study, performed at the University Hospital of Bari (Unit of Obstetrics and Gynecology), were enrolled 103 patients in the first or second stage of labor in singleton cephalic presentation. A statistical frequency and an association analysis were performed. As a significant result, we consider the peace of mind/satisfaction and the” obstetric violence”. IU was performed both transabdominal and translabial to determine the presentation, head positions, angle of progression and head perineum distance. During the first and second stage of labor, the ASIUG questionnaires (Apulia study intrapartum ultrasonography group) were administered. Results: 74 (71, 84%) patients underwent IU and 29 had a vaginal examination (28, 15%). Significant less “violence” has been experienced with a IU (73 out 74/98, 65%) and only one person (1 /1, 35%) recorded that. On the contrary, 10 patients (10/29) perceived that “violence” (34, 48%) while 19 (65, 52%) did not respond on a similar way, after a vaginal examination (VE). More patients felt satisfaction (71 out 74/95, 95%) with the use of IU and only 3 (3/4, 05%) felt unease. A different picture was evident in the vaginal examination group. Only 17 patients (17 out 29/58, 62%) felt comfort while 12 (41, 38%) felt unease. Conclusions: In our study, IU use is well accepted by most of patients, because it could reassure women about their fetal condition. Moreover, they can see the fetus on the screen, while the obstetrician is performing the US and this is important for a visual feedback, in comparison with the classical VE.

Cervical and ovarian cancer are two aggressive neoplasms for women, still with high mortality and morbidity. Among the molecules and compounds that have anticancer activity, it was studied the JG-98, a heat shock protein 70 (HSP70) inhibitor. It demonstrated inhibitory effects on the growth of neoplastic cells, mediated by the induction of apoptosis, with anti-proliferation activity on neoplastic cells via the apoptotic pathway. The authors investigated the antiproliferative effects of JG-98 on human cervical cancer HeLa and ovarian cancer SKOV-3, examined by a standard XTT assay. Apoptotic effects and oxidative status were also evaluated by flow cytometry, ELISA, and total oxidant status assays in HeLa cells, respectively. The IC50 values of JG-98 in HeLa and SKOV-3 cells were recorded as 1.79 and 2.96 μM, respectively. Flow cytometry results showed that JG-98 treatment remarkably increased the proportion of apoptotic cells at IC50 concentration. The JG-98 treatment significantly increased the proteins Bax, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels, all indicators of cellular apoptosis. These findings show that JG-98 significantly decreased cell proliferation and increased apoptosis in HeLa cells, suggesting that JG-98 has a promising anti-tumor effect in cervical and ovarian cancers. [Med-Science 2023; 12(1.000): 20-5]

The position of the fetal head during engagement and progression in the birth canal is the primary cause of dystocic labor and arrest of progression, often due to malposition and malrotation. The authors performed an investigation on pregnant women in labor, who all underwent vaginal digital examination by obstetricians and midwives as well as intrapartum ultrasonography to collect four “geometric parameters”, measured in all the women. All parameters were measured using artificial intelligence and machine learning algorithms, called AIDA (artificial intelligence dystocia algorithm), which incorporates a human-in-the-loop approach, that is, to use AI (artificial intelligence) algorithms that prioritize the physician’s decision and explainable artificial intelligence (XAI). The AIDA was structured into five classes. After a number of “geometric parameters” were collected, the data obtained from the AIDA analysis were entered into a red, yellow, or green zone, linked to the analysis of the progress of labor. Using the AIDA analysis, we were able to identify five reference classes for patients in labor, each of which had a certain sort of birth outcome. A 100% cesarean birth prediction was made in two of these five classes. The use of artificial intelligence, through the evaluation of certain obstetric parameters in specific decision-making algorithms, allows physicians to systematically understand how the results of the algorithms can be explained. This approach can be useful in evaluating the progress of labor and predicting the labor outcome, including spontaneous, whether operative VD (vaginal delivery) should be attempted, or if ICD (intrapartum cesarean delivery) is preferable or necessary.

Uterine fibroids are common benign tumors found in fertile women. Numerous obstetrical issues, such as dystocia during labor, fetal hypotrophy, a ruptured amniotic sac, early labor, low-birth-weight newborns, etc., are associated with fibrous pregnant uteri. Cesarean myomectomy is not a common procedure because of the possibility of postpartum hysterectomy or a potentially lethal hemorrhage. For the chosen topic, we present two instances of emergency postpartum hysterectomies following cesarean myomectomy. After a cesarean myomectomy, two women experienced a perioperative hemorrhage that required a postpartum hysterectomy without a salpingo-oophorectomy. A postpartum hysterectomy was required in every instance due to the failure of additional hemostatic techniques to control the bleeding after the cesarean myomectomy. In every case, the location and number of fibroids—rather than their size—were the primary factors leading to the postpartum hysterectomy. In order to ensure that the patient is safe and that the advantages outweigh the dangers, the current trends in cesarean myomectomy include aiming to conduct the procedure either electively or when it offers an opportunity. The treatment is still up for debate because it is unknown how dangerous a second hysterectomy is for people who have had a cesarean myomectomy.

Up to 70–80% of women of reproductive age may be affected with the most common uterine tumors, known as fibroids or myomas. These benign tumors are the second most prevalent cause of surgery among premenopausal women. Predictions show that the occurrence of myomas in pregnancy will increase, and that the risk of having myomas during pregnancy increases with advanced maternal age. Although most women with fibroids do not experience any symptoms during pregnancy, up to 30% of women experience problems during pregnancy, childbirth, and the puerperium. The viability of myoma excision during cesarean surgery (CS) is a contentious issue raised by the rising incidence of myomas in pregnancy and CS rates. A new surgical procedure for removing fibroids using a trans-endometrial approach, which involves making an incision through the decidua itself, has put into doubt the long-standing practice of cesarean myomectomy (CM) with a trans-serosal approach. Some authors have recently advocated for this last approach, highlighting its advantages and potential uses in real-world situations. The purpose of this paper is to critique the present approach to cesarean myomectomy by analyzing the clinical and surgical distinctions between the two approaches and providing illustrations of the CM methods.

Uterine aging is the process of the senescence of uterine tissue, observed in all middle-aged mammals. Since the aging-related changes in the uterus are associated with infertility and poor pregnancy outcomes, with a lack of studies discussing uterine aging, authors reviewed uterine aging and its consequences on reproduction. MEDLINE, Scopus, and PubMed searches during the years 1990–2023 were performed using a combination of keywords and terms on such topics. According to the author’s evaluation, articles were identified, selected, and included in this narrative review. The aging process has an unfavorable impact on the uterus of mammals. There are different and selected molecular pathways related to uterine aging in humans and animals. Uterine aging impairs the function of the uterine myometrium, neurofibers of the human uterus, and human endometrium. These biological pathways modulate oxidative stress, anti-inflammatory response, inflammation, mitochondrial function, DNA damage repair, etc. All these dysregulations have a role in poorer reproductive performance and pregnancy outcomes in older mammals. The most recent data suggest that uterine aging is accompanied by genetic, epigenetic, metabolic, and immunological changes. Uterine aging has a negative impact on the reproductive performance in mammalian species, but it could be potentially modulated by pharmacological agents, such as quercetin and dasatinib.

Objective: The transvaginal natural orifice transluminal endoscopic surgery (vNOTES) is a kind of natural orifice transluminal endoscopic surgery in which the abdominal cavity is reached by using the natural orifices, such as the stomach, rectum, esophagus, and bladder. In comparison to traditional laparoscopic and robotic surgery, there are potential advantages of the vNOTES. This narrative review shows the use of vNOTES in contemporary gynecologic endoscopic surgery. Mechanism: MEDLINE, Scopus, and PubMed searches on these themes were conducted from 1990 to 2023 using a mix of keywords. Papers and articles were identified and included in this narrative review after the authors’ revision and evaluation. Findings in Brief: The vNOTES procedures allow a short surgery time, as well as estimated blood loss and postoperative pain. These procedures are safe and feasible in contemporary endoscopic gynecology surgery. Conclusions: The vNOTES procedures are beneficial for the patients, and to be added to other minimally invasive procedures, such as conventional laparoscopy and robotic surgery. However, further studies about the long-term outcomes of vNOTES procedures are still needed.

Nowadays it is quite common to encounter pregnants over 35 years with uterine fibroids (UFs), requiring cesarean section (CS). Large UFs may cause severe complications during delivery, as bleeding and hemorrhage, during vaginal or cesarean delivery. Frequently, the caesarean myomectomy (CM) is recommended, but generally obstetricians are reluctant to perform CM, since literature data do not agree on its surgical recommendation. CM is jet particularly controversial, due to increased risk of perioperative hemorrhage and cesarean hysterectomy, and UFs are often left in situ during cesarean section (CS). CM investigations are generally directed to myomectomy associated issues, whereas CS complications without CM are largely underreported. The risks of leaving UF for an interval myomectomy is underestimated and large UFs, left in uterus during CS, might cause significant early and late postoperative complications, even necessitating a relaparotomy and/or a subsequent hysterectomy. CM would be mandatory in some instances, whatever the UF diameter, to avoid further damage or complications. UFs management prior to CS should include a full counselling on pro and cons on the possible consequences of surgical decisioning. To illustrate what was discussed above, authors performed a narrative review with an expert opinion, reporting a case of a 31-year-old woman with a large UF who underwent a CS without myomectomy. Nine hours after CS, puerpera was submitted, for a massive postoperative hemorrhage and hemorrhagic shock, to an emergency relaparotomy with total hysterectomy without salpingo-oophorectomy.

Objective This multi-center study aims to determine the efficiency and safety of endometrial myomectomy (EM) for the removal of uterine fibroids during cesarean section (CS). Methods Retrospective review of 360 women diagnosed for fibroids during pregnancy. They all delivered by CS between 2014 and 2019. The study groups included 118 women who only underwent EM, 120 women who only had subserosal myomectomy by traditional technique and 122 women with fibroids who decided to avoid cesarean myomectomy, as control group. They were analyzed and compared the surgical outcomes. Results The EM, subserosal myomectomy and control groups were statistically (p > 0.05) similar for to age, body mass index (BMI), gravidity, parity, gestational age at delivery, indications for CS, number of excised fibroids, size of the largest myoma. Postoperative hemoglobin values and ? (?) hemoglobin concentrations were lower in SM group (10.39gr/dl vs 9.98 gr/dl vs 10.19 – 1.44 gr/dl vs 1.90 gr/dl vs 1.35; p = 0.047, p = 0.021; respectively) Hybrid fibroids were significantly more frequent in the EM group than subserosal myomectomy and control groups (respectively, 33.1% vs 23.3% vs 27.0%, p = 0.002). Surgery time was significantly longer in the subserosal myomectomy group than EM and control groups (respectively, 46.53 min vs 37.88 min vs 33.86 min, p = 0.001). Myomectomy took significantly longer time in the subserosal myomectomy than EM group (13.75 min vs 8.17 min, p = 0.001). Conclusions Endometrial myomectomy is a feasible choice for treatment of fibroids during CS, and, basing on our results could be an alternative to traditional cesarean subserosal myomectomy.

Background and Objectives: The uterine smooth muscle tumors of uncertain malignant potential (STUMP) are tumors with pathological characteristics similar to leiomyosarcoma, but that do not satisfy histological criteria for leiomyoma. These are problematic lesions with intermediate morphologic features; thus, diagnosis and treatment are difficult. This narrative review aims to review data in the literature about STUMPs, particularly focusing on management and therapeutic options and strategies for women who desire to preserve fertility. Material and Methods: authors searched for “uterine smooth muscle tumor of uncertain malignant potential” in PubMed and Scopus databases, from 2000 to March 2023. Pertinent articles were obtained in full-text format and screened for additional references. Only articles in English language were included. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: The median age was 43 years old. Symptoms are similar to those of leiomyomas, with a mean diameter of 8.0 cm. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard care for women if fertility desire is satisfied. Myomectomy alone can be considered for young patients. Although these tumors have not a high malignant potential, several studies described recurrence and metastases. Conclusions: STUMPs are complex uterine smooth muscle tumors, with a rare but reasoned clinical–diagnostic management. Considering the high clinical and histological complexity of these tumors, high level of expertise is mandatory.

Background: To explore the predictive value of endometrial receptivity and pregnancy outcomes using pipelle biopsy examination during the luteal phase of the menstruation cycle in infertile women. We also compare the importance of this factor with other potential causes of infertility. Methods: This retrospective study included 279 women with repeated implantation failures. All patients were examined and treated at the Intersono in vitro fertilization (IVF) center. To determine the cause of the implantation failure, an implantation window (IW) was defined for all patients included in this retrospective cohort. Examinations were performed by three-fold aspiration biopsies of the endometrium during the luteal phase of the cycle as this period is when the endometrium is most receptive for implantation. Analysis of the tissue was done by scanning electron microscopy of endometrial tissues and, based on results obtained, an endometrial preparation protocol was individualized for the next attempt. Statistical analyses were performed using Microsoft Excel (Office 365) and RStudio software v. 1.4.1106. Results: According to the results obtained, 206 women included in this study displayed a unique IW (74%), and 73 women had a standard IW period (26%). Patient characteristics, screening indicators, previous IVF treatment details, IVF cycle characteristics, as well as number, quality, and stage of embryos transferred were comparable between the two groups. Clinical pregnancy rates of 59.2% (95% confidence interval (CI) 52.5–65.8) versus 57.5% (95% CI 46.1–68.6) (p = 0.80), and live birth rates of 50.7% (95% CI 43.9–57.6) versus 47.9% (95% CI 36.6–59.4) (p = 0.49) in the unique and standard IW groups, respectively, did not show significant differences. Conclusions: Unique IW is one of the underlying causes of implantation failures. The personalization of an endometrial preparation protocol is a method to improve IVF outcomes.

Background: Novel coronavirus disease 2019 (COVID-19) outbreak negatively impacted on the mental wellbeing of infertile couples, because of the World Health Organization’s recommendation to stop all fertility treatments. This study aims to investigate the level of depression and hopelessness during the COVID-19 outbreak, in women with primary and secondary infertility. Methods: A 16-item online questionnaire was applied to a total of 220 women with primary and secondary infertility in June 2020. Participants’ knowledge and concerns about COVID-19 pandemic stop of treatments and follow-up preferences were evaluated. In addition, the Beck Depression Inventory (BDI) and the Beck Hopelessness Scale (BHS) were adapted to Turkish and applied to each participant. Total scores of inventories between women were calculated. The correlation between depression and hopelessness levels of the groups was evaluated. Results: The BDI and BHS mean scores of 220 infertile women who completed our questionnaire were 14.63 ± 9.123 and 5.43 ± 5.026 and Cronbach’s α-values were 0.853 and 0.904, respectively. It was found that 142 women with secondary infertility had higher mean depression and hopelessness scores (15.92 ± 9.758, 11.81 ± 6.501; P = 0.001) VS 78 women with primary infertility (6.51 ± 5.262, 3.78 ± 3.670; P = 0.000). A strong positive correlation was detected between depression and hopelessness levels for each group (r = 0.625, P = 0.000 and r = 0.740, P = 0.000). Conclusions: Total depression and hopelessness scores of both groups were in a strong positive correlation with primary and secondary infertility during the COVID-19 outbreak. Particularly, women with secondary infertility had mild depression and low levels of hopelessness.

Background: The various techniques for performing a Cesarean Section (CS) have a long history. There are numerous surgical variations based on personal or local tradition, but these are not based on evidence and often have different outcomes on maternal and newborn health. Many modifications of the CS technique have been utilized in order to improve outcome with variable results both positive and negative. Several CS laparotomic methods have been developed but no consensus has been reached on the most optimal approach as related to safety and morbidity. Methods: The minimalistic approach of the Stark Cesarean Section (SCS) is compared to other methods thorugh an evaluation of the studies published in the last 20 years comparing this technique with others, the systematic reviews and the personal experience of the authors. Results and discussion: The abdominal incision done at the Stark Cesarean Section differs from the Pfannenstiel incision by its location being above the arcuate line eliminating the need to separate the fascia from the recti muscles. The muscle separations being away from the pubic bone and the iliohypogastric and ilioinguinal nerves eliminates the risk of damage. This unique surgical approach is a logical, fast and simple one that eliminates unnecessary operative steps saving time and reducing complications. After fifteen years of experience and thousands of SCS performed at our departments, we may conclude that this method has several advantages over other surgical methods as related to short and long-term outcomes, including chronic/neuropathic pain and quality of life.

The investigation studied the enkephalinergic neuro fibers (En) contained in the Lower Uterine Segment (LUS) during the prolonged dystocic labor (PDL) with Labor Neuraxial Analgesia (LNA). PDL is generally caused by fetal head malpositions in the Occiput Posterior Position (OPP), Persistent Occiput Posterior Position (POPP), in a transverse position (OTP), and asynclitism (A), and it is detected by Intrapartum Ultrasonography (IU). The En were detected in the LUS samples picked up during cesarean section (CS) of 38 patients undergoing urgent CS in PDL, compared to 37 patients submitted to elective CS. Results were statistically evaluated to understand the differences in En morphological analysis by scanning electron microscopy (SEM) and by fluorescence microscopy (FM). The LUS samples analysis showed an important reduction in En in LUS of CS for the PDL group, in comparison with the elective CS group. The LUS overdistension, by fetal head malpositions (OPP, OTP, A) and malrotations, lead to dystocia, modification of vascularization, and En reduction. The En reduction in PDL suggests that drugs used during the LNA, usually local anesthetics and opioids, cannot control the “dystocic pain”, that differs from normal labor pain. The IU administration in labor and the consequent diagnosis of dystocia suggest stopping the numerous and ineffective top-up drug administration during LNA, and to shift the labor to operative vaginal delivery or CS.

Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types.

IntroductionIt is not known whether appendectomy for acute appendicitis (AA) increases the Cesarean section (CS) rate and whether CS increases the likelihood of AA and appendectomy in the early puerperium. In this study, delivery type and delivery outcomes and appendectomy during pregnancy and puerperium were analyzed.MethodsThis cross-sectional retrospective study was performed on 11,513 women, delivered during 2015–2020. Inclusion criteria were patients undergoing appendectomy for AA during pregnancy and the first 6 weeks after delivery. Evaluating parameters were age, parity, gestational week at birth, delivery type, and babies' birth weight.ResultsThirty-two patients underwent appendectomy: 12 during pregnancy (2 in the first trimester, 6 in the second trimester, 4 in the third trimester) and 20 women during puerperium. 58.2% of pregnant women and 65% of puerperal women were submitted to CS.DiscussionHalf of the women who underwent appendectomy for AA during pregnancy may require urgent CS. The cause of acute abdomen in the postpartum period, especially in the first week, could be AA, especially in women delivered by CS.

Asynclitism, the most feared malposition of the fetal head during labor, still represents to date an unresolved field of interest, remaining one of the most common causes of prolonged or obstructed labor, dystocia, assisted delivery, and cesarean section. Traditionally asynclitism is diagnosed by vaginal examination, which is, however, burdened by a high grade of bias. On the contrary, the recent scientific evidence highly suggests the use of intrapartum ultrasonography, which would be more accurate and reliable when compared to the vaginal examination for malposition assessment. The early detection and characterization of asynclitism by intrapartum ultrasound would become a valid tool for intrapartum evaluation. In this way, it will be possible for physicians to opt for the safest way of delivery according to an accurate definition of the fetal head position and station, avoiding unnecessary operative procedures and medication while improving fetal and maternal outcomes. This review re-evaluated the literature of the last 30 years on asynclitism, focusing on the progressive imposition of ultrasound as an intrapartum diagnostic tool. All the evidence emerging from the literature is presented and evaluated from our point of view, describing the most employed technique and considering the future implication of the progressive worldwide consolidation of asynclitism and ultrasound.

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes’ maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy.

Oocyte maturation abnormalities (OMAS) are a poorly understood area of reproductive medicine. Much remains to be understood about how OMAS occur. However, current knowledge has provided some insight into the mechanistic and genetic origins of this syndrome. In this study, current classifications of OMAS syndromes are discussed and areas of inadequacy are highlighted. We explain why empty follicle syndrome, dysmorphic oocytes, some types of premature ovarian insufficiency and resistant ovary syndrome can cause OMAS. We discuss live births in different types of OMAS and when subjects can be offered treatment with autologous oocytes. As such, we present this review of the mechanism and understanding of OMAS to better lead the clinician in understanding this difficult-to-treat diagnosis.

The authors reviewed uterine fibroid (UF) morcellation and its potential consequences, notably a hypothetical spread and dissemination of occult uterine leiomyosarcoma (LMS) tissue, evaluating the effect of laparoscopic versus open myomectomies with and without morcellation on patients’ outcomes, as well as related medical-legal issues. MEDLINE and PubMed search was performed for the years 1990–2021, using a combination of keywords on this topic. Relevant articles were identified and included in this narrative review. There is an individual risk, for all patients, for LMS diagnosis after myomectomy. However, the risk for occult LMS diagnosis during a laparoscopic myomectomy is generally reduced when the guidelines of scientific societies are followed, with an overall benefit from the laparoscopic approach with morcellation in appropriate cases. Gynecological societies do not ban morcellation and laparoscopic hysterectomy/myomectomy per se, but recommend their use on the basis of the patients’ clinical characteristics. It is suggested for gynecologists to provide detailed information to patients when obtaining an informed consent for open or laparoscopic hysterectomy/myomectomy. A detailed preoperative assessment of patients and the risk benefit ratio of laparoscopic morcellation of uterine mass could overcome the “a priori” banning of the morcellation technique.

Authors investigated the catecholaminergic neurotransmitters (chNs) quantitative modifications in pregnant uterine Lower Uterine Segment (LUS) during prolonged labor (PL) with the fetus in an occiput-posterior position (OPP), in occiput transverse position (OTP) and in fetal head asynclitism, all diagnosed by Intrapartum Ultrasonography (IU). The chNs neurotransmitters, particularly adrenaline (or epinephrine-A) and noradrenaline (or norepinephrine-N), were evaluated in LUS fragments sampled during CS of 34 patients undergoing urgent cesarean section (CS) in PL, compared to chNs fibers in the LUS of 36 women submitted to elective CS. All results were statistically analyzed to understand the differences in neurotransmitters morphological analysis by scanning electronic microscopy examination (SEM). The LUS fragments analysis revealed a reduction of A and N fibers in LUS during PL, compared with the expression of A and N fibers in LUS during elective CS. The PL for OPP, the OTP and asynclitism, all positions causing dystocia in labor lead to a reduction in neurotransmitters in LUS, with a uterine vascularization modification and a reduction in the contractility of smooth uterine cells. The A and N neurotransmitters reduction observed in PL negatively interferes with uterine contraction during labor.

Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990–2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.

Authors evaluated the impact of laparoscopic intracapsular myomectomy (LIM) in women 40 years of age and over with desire of future fertility compared with medical management of symptomatic fibroids, by a prospective cohort study in University affiliated Hospitals. This study includes a cohort of women 40 years of age and older with symptomatic intramural fibroids with desire of future fertility. Women with symptomatic fibroid uterus were offered to undergo LIM or medical management. They were encouraged to attempt conception either spontaneously or by assisted reproductive technology (ART) according to their individual preference. All women were followed for 2 years. Fibroid characteristics, pre- and post-surgical variables, including surgical complications, days of hospitalization, pregnancy rate, and obstetrical outcomes were collected. A total of 100 patient were included in the analysis. Fifty patients were assigned to the LIM group and 50 to the medical treatment group (MT). Groups were similar regarding age (43.5 ± 2.4 and 43.5 ± 2.4, p = 0.99), body mass index (23.8 ± 3.1 and 24.2 ± 3.1, p = 0.54), parity (0.46 ± 0.09 and 0.58 ± 0.09, p = 0.37), fibroid number (1.38 ± 0.6 and 1.46 ± 0.6, p = 0.53), and fibroid size (5.92 ± 1.62 cm vs. 5.94 ± 1.49 cm, p = 0.949). Of the patients who underwent LIM, 62% conceived within the study period compared with 56% in the control group (p = 0.54). Pregnancy was achieved by ART in 44% of the patients of the LIM group and 30% in control group. There was no significant difference in pregnancy rates among the two groups regarding spontaneous pregnancy rate (p = 0.332), nor in pregnancies obtained by ART with own eggs (p = 0.146) and oocyte or embryo donation (p = 0.821). The take home baby rate was 65% (20/31) in the LIM group and 61% (17/28) in the control group (p = 0.7851). Both groups had similar rate of miscarriage (p = 0.748). Patients 40 years old and over with symptomatic fibroid uterus who undergo LIM have similar subsequent fertility and obstetrical outcomes than women treated with medical management. LIM has no detrimental impact on future fertility in women 40 years old and over.

This retrospective cohort study focused on colposcopic accuracy for the diagnosis of cervical premalignant lesions using cytology and histology, as well as HPV data not included in current cervical screening practices in Kazakhstan. Colposcopy performance was assessed using the modified Reid index in women aged 18–63 years. In total, 1,129 colposcopic-HPV-cytology triple samples and 94 histology findings were collected. The sensitivity of colposcopy was 81.6% with specificity 72.6% for LSIL but fell to 56.6% with specificity 88.3% for CIN2+ vs. 89.6% and 74.5% for cytology at CIN2+, respectively. The ORs for high-grade lesion occurrence within each colposcopy group at viral load rising vs. ORs for HPV-negative women were 3.4; 5.3; and 39.7, respectively (p

Background: Uterine fibroids (UFs) are the most common female benign tumors linked to significant morbidity. There are large literature data connecting UFs with infertility and adverse pregnancy outcome. In this research, authors reviewed literature on UFs, analyzing their relationship with infertility, influence of different therapeutic approaches of UFs on fertility and the possible mechanisms related to UFs and infertility. Methods: MEDLINE and PubMed search, during the years 1990–2020 was performed using a combination of keywords on such topic. Peer-reviewed, systematic review, meta-analysis and prospective trials, examining relationship between UFs and infertility were included in this investigation. According to authors evaluation, additional articles were also identified from the retrieved papers references and included in this narrative review. Results: UFs, especially the submucous and intramural types, with related treatments are linked to impairment of fertility and adverse pregnancy outcome, but many data are conflicting. Molecular mechanisms investigations could explain relationship between UFs and infertility. Conclusion: UFs are linked to infertility and interventions improve fertility. However, many studies conflict in the final results, so further investigations on UFs and infertility should clarify the exact role of molecular mechanisms of this association.

Abstract Background The cause of contamination and dissemination of leiomyoma tissue particles and cells in the peritoneal cavity during myomectomy is a challenging issue for both clinicians and researchers. Therefore, the article by Huang et al. recently published in your journal is the subject of this letter. Main body We comment on the role of laparoscopic condition in xenograft implantation and also highlighted the shortcomings of this study. The surgical technique of intramural fibroid enucleation, cell spillage during morcellation and postsurgical hormonal impact on the development of parasitic myomas become evident, while the contribution of CO2 insufflation, the fibroid’s nature, mutations and pseudocapsule impacts on angiogenesis are not clear. In addition, an exploration of the exact origin of implanted fragments harvested from the fibroid tissue and their nature might play a significant role in the implantation and the angiogenesis induction ability of xenografts. Conclusion Taking into account the current literature in the scope of this study, we suggest that the factors involved in development of parasitic myomas can be classified as confirmed and doubtful contributions.

This article describes a Protocol for a study to determine a scope of Human Papillomavirus (HPV) infection and evaluate cervical cancer prevention measures in the western Kazakhstan. Introduction — ICO (Institut Catala d’Oncologia) working group in 2015 informed that cervical cancer in Kazakhstan ranked as the 1st most frequent cancer among 15-44 aged women. Aim — comprehensive analysis of the HPV infection across the female population to predict further trends in the cervical cancer morbidity and outline the circle of urgent preventive measures. The most important tasks are the following: to analyze a set of clinical, laboratory and socio-demographic data for identification the region-specific risk factors of the disease; to present a comparative analysis of diagnostic screening tools practiced in the region for the development corrective recommendations for existing screening strategy. Methods — This study constitutes a mix of three different types: interview+cross-sectional study for general female population and interview+case-control study for women with the first time diagnosed cervical cancer, where women of the general sample of the same age with detected HPV infection but not affected by the disease serve as a control for those with the disease. Anticipated Results — A high feasibility and pithiness of this study is expected. Obtaining a wide body of information relatively HPV scope and a quality of the screening process during a patient’s single visit is the main strength of the research. Conclusion — Successful implementation of challenges announced in the research can lead to changing a general vector or/and constituent parts of the existing screening program.

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.

Myomas are the most common benign tumors of the genital organs in women of childbearing age, causing significant morbidity and impairing their quality of life. In our investigation, we have reviewed the epidemiological data related to the development of myomas in order to homogenize the current data. Therefore, a MEDLINE and PubMed search, for the years 1990-2013, was conducted using a combination of keywords, such as "myoma," "leiomyoma," "fibroids," "myomectomy," "lifestyle," "cigarette," "alcohol," "vitamins," "diet," and "hysterectomy". Randomized controlled studies were selected based upon the authors’ estimation. Peer-reviewed articles examining myomas were sorted by their relevance and included in this research. Additional articles were also identified from the references of the retrieved papers and included according to authors’ estimation. Many epidemiologic factors are linked to the development of myomas; however, many are not yet fully understood. These factors include age, race, heritage, reproductive factors, sex hormones, obesity, lifestyle (diet, caffeine and alcohol consumption, smoking, physical activity and stress), environmental and other influences, such as hypertension and infection. Some of the epidemiological data is conflicting. Thus, more research is needed to understand all the risk factors that contribute to myoma formation and how they exactly influence their onset and growth.