Advanced maternal age (AMA) and pregnancy: a feasible but problematic event.

This narrative review aimed to summarize all adverse outcomes of pregnancy in advanced maternal age (AMA) to assess the age of the mother as a potentially crucial risk factor. AMA refers to women older than 35 years. While expectations and the role of women in society have undergone significant changes today, the biology of aging remains unchanged. Various pathologic changes occur in the human body with age, including chronic noncommunicable diseases, as well as notable changes in reproductive organs, that significantly affect fertility. Despite substantial advancements in technology and medicine, pregnancy in AMA remains a formidable challenge. Although there are some advantages to postponing childbirth, they primarily relate to maternal maturity and economic stability. However, regrettably, there are also many adverse aspects of pregnancy at advanced ages. These include complications affecting both the mother and the fetus. Pregnants in AMA were more prone to suffer from gestational diabetes mellitus, preeclampsia, and eclampsia during pregnancy compared to younger women. In addition, miscarriages and ectopic pregnancies were more prevalent. Delivery was more frequently completed via cesarean section, and postpartum complications and maternal mortality were also higher. Unfortunately, there were also complications concerning the fetus, such as chromosomal abnormalities, premature birth, low birth weight, admission to the neonatal intensive care unit, and stillbirth.

Fortifying the foundation: assessing the role of uterine ligament integrity in uterine prolapse and beyond.

BACKGROUND: Pelvic floor stability is influenced by various biomechanical, anatomical, and physiological factors. Understanding these dynamics is crucial for improving the treatment of pelvic organ prolapse (POP) and related conditions. OBJECTIVE: To analyze the key factors affecting pelvic floor integrity and explore both non-surgical and surgical interventions to enhance stability and treatment outcomes. METHODS: This review draws from biomechanical research to assess the role of the uterosacral ligament in pelvic support, while also examining the potential of both traditional and emerging therapeutic approaches, including non-surgical interventions like vitamin C supplementation. RESULTS: - The uterosacral ligament demonstrates superior strength and stiffness, making it essential for structural support of pelvic organs. - Non-surgical interventions, such as vitamin C supplementation, show potential in improving ligament integrity and preventing pelvic floor disorders. - Emerging surgical techniques, including tendon-based procedures and injectable fibrous hydrogel composites, offer promising improvements in outcomes for patients with pelvic organ prolapse. - Additional factors such as muscle strength and neural deficiencies contribute to the complexity of pelvic floor biomechanics, indicating the need for multifaceted treatment approaches. CONCLUSION: This analysis provides a comprehensive framework for understanding and managing pelvic floor stability by integrating biomechanical, physiological, and anatomical insights. The findings highlight the potential for personalized treatment strategies to improve patient outcomes in pelvic floor disorders.

The impact of epigallocatechin gallate, vitamin D, and D-chiro-inositol on early surgical outcomes of laparoscopic myomectomy: a pilot study.

PURPOSE: A prospective investigation to assess the impact of 3 months of treatment with epigallocatechin gallate (EGCG), vitamin D and D-chiro-inositol (DCI) in the treatment of uterine fibroids (UF) with laparoscopic myomectomy as evidenced by surgical outcomes and effect on liver function. METHODS: Non-pregnant or lactating women aged between 30 and 40 years were scheduled for laparoscopic myomectomy to treat symptoms or looking to conceive. After enrollment, patients were assigned to either (1) intervention group, assuming a total of 300 mg EGCG, 50 µg vitamin D, and 50 mg DCI divided in 2 pills per day for 3 months, or (2) control group, including untreated women scheduled to undergo laparoscopic myomectomy after 3 months. RESULTS: 91 patients completed the study. The comparison of the surgical outcomes between the intervention (n = 44) and the control (n = 47) groups revealed that the treatment significantly reduces the duration of surgery (41.93 ± 7.56 min vs 56.32 ± 10.63 min, p < 0.001). Moreover, the treatment also reduced blood loss during surgery (149.09 ± 25.40 mL vs 168.41 ± 21.34 mL, p < 0.001), resulting in treated patients having higher Hb levels at discharge 11.27 ± 0.82 mL vs 10.56 ± 0.82 mL, p < 0.01). The surgery induced an increase in AST and in total bilirubin regardless of the assigned group, and the treatment induced no change in liver function. CONCLUSIONS: Our data suggest that EGCG plus vitamin D, and DCI could represent a safe option for women with UF scheduled for laparoscopic myomectomy, improving surgical outcomes without affecting liver functionality.

PCOS and vitamin D: a clinical appraisal.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine-reproductive disease linked not just to infertility but also to serious comorbidities. There is a reported association between low vitamin D levels and multiple health conditions including PCOS. This narrative review aims to analyze the role of vitamin D in PCOS development, use of the vitamin D in the treatment of PCOS, and the molecular basis of these observations. METHODS: A Medline and PubMed research was performed, during the years 1990-2023, using a combination of keywords on such topic. According to the author's evaluation and target, papers were identified and included for a narrative review. RESULTS: There are associations between lower levels of vitamin D and PCOS, as well as with insulin resistance, metabolic syndrome, hyperandrogenemia, metabolic and endocrine disorders as well as the onset of oxidative stress and pro-inflammatory milieu, in PCOS women. CONCLUSION: Vitamin D has a role in pathologic changes linked to PCOS. Molecular and clinical investigations which give new information about the role of vitamin D in the development of PCOS and related endocrine and metabolic disturbance are further needed.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

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.

Electro-Metabolic Coupling of Cumulus-Oocyte Complex.

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.

Reflections on Postpartum Hysterectomy as a Possible Complication of Cesarean Myomectomy: A Long Debate.

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.

Cesarean Myomectomy: Reflections on Clinical and Surgical Controversies between a New Trans-Decidual Technique vs. Traditional Method.

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.

From 3D to 2D-4K laparoscopic sacral colpopexy: are we addicted to technology?

OBJECTIVE: A study analyzing perioperative outcomes related to a sudden switch from 3D to 2D-4K technology for laparoscopic sacral colpopexy by expert pelvic surgeons: are we addicted to technology? MATERIAL AND METHODS: After a sudden transition from 3D to 2D-4K laparoscopic technology, a total of 115 consecutive pelvic prolapse patients who underwent sacral colpopexy from June 2020 to September 2021 were retrospectively assessed from our database. Perioperative parameters, operative times (OT), and intraoperative difficulty scales were assessed. One-year follow-ups were analyzed for the study. Primary endpoints were OT; secondary endpoint was the evaluation of complications linked to this procedure. RESULTS: We found statistical differences in OT and intraoperative difficulty scales between medians of the last 3D procedures and the first ten 2D-4K surgeries, without differences between operators. Only after more than 20 surgeries, we observed no significant differences between 3D and 2D-4K sacral colpopexy. We observed no statistical differences in terms of anatomic failure, PGI-I, and intra-postoperative complications. CONCLUSION: The transition of urogynecology from an exclusive vaginal approach to 2D-3D-4K laparoscopy significantly increased the level of technology necessary for surgical treatment of prolapse. This could, as a result, lead to pelvic surgeons becoming increasingly dependent on technology.

Laparoscopic posterior vaginal plication plus sacral colpopexy for severe posterior vaginal prolapse: A randomized clinical trial.

AIM: A randomized clinical trial proposing a new laparoscopic prosthetic and fascial approach to severe posterior vaginal prolapse. The primary endpoint was to evaluate the objective and subjective outcomes of our laparoscopic posterior plication (LPP) combined to "two-mesh" sacral colpopexy (laparoscopic sacral colpopexy [LSC]) in severe posterior vaginal prolapse, with a 1-year follow-up. The secondary endpoint was to evaluate the safety of this surgical procedure. METHODS: This is single-center prospective randomized double-blinded clinical trial. A total of 130 consecutive patients with anterior and/or apical pelvic organ prolapse (POP) (POP-Q stage ≥II) and severe posterior vaginal prolapse (posterior POP-Q stage ≥III) were prospectively assessed for inclusion into the study from November 2018 to January 2020. Patients underwent "two-meshes" LSC and were randomized in Group A (LSC plus LPP) and Group A (LSC alone). Of the 130 included subjects, 8 were excluded, not meeting inclusion criteria. Cure rate was evaluated objectively, using POP-Q study, and subjectively using PGI-I, POPDI-6, and FSDS questionnaires. Complications were assessed intra-, peri-, and postoperatively. Twelve-month follow-ups were analyzed for the study. RESULTS: We found in LSC plus LPP Group a significant improvement of Ap and genital hiatus POP-Q points. Our subjective study showed, at 12 months, a statistical difference in PGI-I successful outcomes rate in favor of LPP. Also the FSDS resulted significantly much more improved in Group A. We observed no statistical differences in terms of postoperative complications. CONCLUSIONS: Our LPP approach to LSC could be considered an effective and safe technique to POP patients with severe posterior prolapse.

Myomectomy in adult women of reproductive age: a propensity score-matched study for pregnancy rates.

PURPOSE: To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. MATERIALS AND METHODS: 40 years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. RESULTS: 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. CONCLUSION: Patients aged over 40 years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.

Uterine Aging and Reproduction: Dealing with a Puzzle Biologic Topic.

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.

Prolonged Dystocic Labor in Neuraxial Analgesia and the Role of Enkephalin Neurotransmitters: An Experimental Study.

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.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Comprehensive Multidisciplinary Update.

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.

Local anesthesia for Altis® single incision sling in women with stress urinary incontinence.

OBJECTIVE: Local anesthesia for single incision slings has shown a good objective and subjective cure rate in women with stress urinary incontinence. The aim of the present study was to verify the efficacy and safety of local anesthesia during Altis® single incision placement. MATERIAL AND METHODS: One hundred sixty-six consecutive patients (83 patients for each group: local resp. spinal anesthesia) were selected from our database for this retrospective study among women who underwent an Altis® implantation for SUI from September 2016 to June 2021, after unsuccessful previous conservative treatment. Primary endpoints were objective and subjective cure rates; secondary endpoint was the evaluation of complications linked to this procedure. RESULTS: A total of 155 included patients completed our 12 months follow-up. Baseline characteristics were similar between the groups. Operative time (percentage difference of 50%; p < 0.05) and the Intraoperative Difficulty Scale resulted lower in spinal patients. No differences were found between populations in terms of objective (cough stress test and urodynamics) and subjective (PGI-I and FSDS questionnaires) cure rate and postoperative complications. CONCLUSION: Local anesthesia for Altis® implantation could be considered a safe alternative to spinal anesthesia and an effective opportunity to avoid general anesthesia, increasing the possibility of outpatient implantation of this sling system.

Prevalence of Intrauterine Adhesions after Myomectomy: A Prospective Multicenter Observational Study.

OBJECTIVES: The aim of this study was to evaluate intrauterine adhesion formation after laparoscopic and laparotomic myomectomy. DESIGN: This is a prospective, multicenter, observational study (ClinicalTrials.gov ID: NCT04030273). METHODS: We included patients after laparotomic and laparoscopic myomectomy. All patients underwent postsurgical diagnostic hysteroscopy, after 3 months. The intrauterine adhesion rate and associated factors were investigated. RESULTS: Between January 2020 and December 2020, 38 and 24 consecutive patients underwent laparoscopic and laparotomic myomectomy, respectively. All diagnostic hysteroscopies were performed in the office setting without complications. Intrauterine adhesions were identified in 19.4% of women (95% CI: of 9-29%). Factors univariately associated (p < 0.2) with the presence of intrauterine adhesions after myomectomy were previous uterine surgery, the surgical approach (laparoscopic or laparotomic), the number of removed fibroids, the type and diameter of the largest myoma, and the opening of the uterine cavity. In the multivariable analysis, only the opening of the uterine cavity (odds ratio [OR] 51.99; 95% confidence interval [CI]: 4.53-596.28) and the laparotomic approach (OR, 16.19; 95% CI: 1.66-158.35) were independently associated with the identification of intrauterine adhesions after myomectomy. LIMITATIONS: One of the main limitations of our study is that we used uterine manipulator only in the laparoscopic group; in addition, we did not perform a preoperative hysteroscopy to evaluate the rate of intrauterine adhesions potentially present even before the myomectomy. CONCLUSIONS: The prevalence of intrauterine adhesions after 3 months from surgery was significantly associated with the opening of the uterine cavity and the laparotomic approach.

Laparoscopic ventral rectopexy plus sacral colpopexy: continuous locked suture for mesh fixation. A randomized clinical trial.

PURPOSE: Laparoscopic ventral rectopexy (LVR) plus sacral colpopexy (LSC) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to rectal-mesh fixation during LVR with continuous locked suture. METHODS: This is a prospective randomized double-blinded clinical trial enrolling 80 patients with severe POP and obstructed defecation syndrome (ODS) from November 2016 to January 2021. Patients underwent a "two-meshes" LSC plus LVR and were randomized, regarding rectal mesh fixation, in Group A (extracorporeal interrupted 0 delayed absorbable sutures) and Group B ("U-shaped" running locked 0 delayed absorbable suture). Our primary endpoints were the operative times (OT); the secondary endpoints were the incidence of anatomical failures, vaginal mesh erosions and surgical complications. RESULTS: A total of 75 patients completed the study. Baseline characteristics were similar between the groups. Overall OT (156 vs 138 min; p < 0.05; treatment reduction of 11.5%) and LVR mesh fixation time (29 vs 16 min; p < 0.05; treatment reduction of 44%), resulted in significantly lower in Group B. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. PGI-I, FSDS and Wexner questionnaires resulted significantly improved after surgery, without statistical differences between the studied surgical procedures. CONCLUSION: Laparoscopic continuous locked 0 absorbable suture for LVR mesh fixation guaranteed a faster and effective alternative to multiple interrupted sutures. The significant OT reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LVR. CLINICAL TRIAL REGISTRATION: NCT05254860 (13/02/2017).

Molecular Insights in Uterine Leiomyosarcoma: A Systematic Review.

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.

Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal.

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.

Dystocic Labor and Adrenergic and Noradrenergic Neurotransmitters: A Morphological Experimental Study.

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.