Cables1 links Slit/Robo and Wnt/Frizzled signaling in commissural axon guidance.

During neural circuit formation, axons navigate from one intermediate target to the next, until they reach their final target. At intermediate targets, axons switch from being attracted to being repelled by changing the guidance receptors on the growth cone surface. For smooth navigation of the intermediate target and the continuation of their journey, the switch in receptor expression has to be orchestrated in a precisely timed manner. As an alternative to changes in expression, receptor function could be regulated by phosphorylation of receptors or components of signaling pathways. We identified Cables1 as a linker between floor-plate exit of commissural axons, regulated by Slit/Robo signaling, and the rostral turn of post-crossing axons, regulated by Wnt/Frizzled signaling. Cables1 localizes ß-catenin, phosphorylated at tyrosine 489 by Abelson kinase, to the distal axon, which in turn is necessary for the correct navigation of post-crossing commissural axons in the developing chicken spinal cord.

ATRA regulates myoblast differentiation and fusion through the RARα/Pitx2 signaling pathway, causing abnormal development of PFMs in ARM fetal rats.

Anorectal malformation (ARM) is the most common congenital digestive tract anomaly in newborns, and children with ARM often have varying degrees of underdevelopment of the pelvic floor muscles (PFMs). To explore the effects of RARα and Pitx2 on the development of rat PFMs, we constructed a rat ARM animal model using all-trans retinoic acid (ATRA), and verified the expression of RARα and Pitx2 in the PFMs of fetal rats. Additionally, we used rat myoblasts (L6 cells) to investigate the regulatory roles of RARα and Pitx2 in skeletal muscle myoblast differentiation and their interactions. The results indicated a significant decrease in the expression of RARα and Pitx2 in the PFMs of fetal rats with ARM. ATRA can also decrease the expression of RARα and Pitx2 in the L6 cells, while affecting the differentiation and fusion of L6 cells. Knocking down RARα in L6 cells reduced the expression of Pitx2, MYOD1, MYMK, and decreased myogenic activity in L6 cells. When RARα is activated, the decreased expression of Pitx2, MYOD1, and MYMK and myogenic differentiation can be restored to different extents. At the same time, increasing or inhibiting the expression of Pitx2 can counteract the effects of knocking down RARα and activating RARα respectively. These results indicate that Pitx2 may be downstream of the transcription factor RARα, mediating the effects of ATRA on the development of fetal rat PFMs.

Exosomes isolated from TNF-α-treated bone marrow mesenchymal stem cells ameliorate pelvic floor dysfunction in rats.

Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.

Assessing the efficacy of pelvic floor muscle training and duloxetine on urinary continence recovery following radical prostatectomy: A randomized clinical trial.

BACKGROUND: Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP. METHODS: A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires. RESULTS: From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR. CONCLUSIONS: PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.

Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies.

Epithelial cilia, whether motile or primary, often display an off-center planar localization within the apical cell surface. This form of planar cell polarity (PCP) involves the asymmetric positioning of the ciliary basal body (BB). Using the monociliated epithelium of the embryonic zebrafish floor-plate, we investigated the dynamics and mechanisms of BB polarization by live imaging. BBs were highly motile, making back-and-forth movements along the antero-posterior (AP) axis and contacting both the anterior and posterior membranes. Contacts exclusively occurred at junctional Par3 patches and were often preceded by membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. Later, BBs became less motile and eventually settled at posterior apical junctions enriched in Par3. BB posterior positioning followed Par3 posterior enrichment and was impaired upon Par3 depletion or disorganization of Par3 patches. In the PCP mutant vangl2, BBs were still motile but displayed poorly oriented membrane contacts that correlated with Par3 patch fragmentation and lateral spreading. Thus, we propose an unexpected function for posterior Par3 enrichment in controlling BB positioning downstream of the PCP pathway.

Progressive Changes in the Neuroretinal Rim and Retinal Nerve Fiber Layer in Glaucoma: Impact of Baseline Values and Floor Effects.

PURPOSE: To determine whether more severe baseline damage impedes measurement of minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (RNFLT) change in glaucoma patients because of a floor effect. DESIGN: Prospective, longitudinal cohort study in a hospital-based setting. PARTICIPANTS: The study included patients with open-angle glaucoma and healthy control subjects. Participants had at least 5 years of follow-up with OCT every 6 months. METHODS: Baseline global and sectorial MRW and RNFLT values were classified as within normal limits, borderline, or outside normal limits based on reference normative values. Regression analysis was used to determine the magnitude and significance of MRW and RNFLT change. Additionally, the follow-up period for each participant was divided into 2 equal halves (first and second periods) to determine whether there was attenuation of MRW and RNFLT change with follow-up time. MAIN OUTCOME MEASURES: Rates of global and sectoral MRW and RNFLT changes (slopes). RESULTS: A total of 97 patients with glaucoma (median age, 70.3 years) and 42 healthy subjects (median age, 64.8 years) were followed for a median of 6.9 years and 7.0 years, respectively. The median mean deviation of the visual field in glaucoma patients was -4.30 decibels (dB) (interquartile range, -7.81 to -2.06 dB; range, -20.68 to 1.37 dB). Statistically significant changes in global and sectoral MRW and RNFLT were detected across all baseline classifications; however, there was a tendency for less change with increasing baseline damage. In glaucoma patients, RNFLT slopes, but not MRW slopes, were significantly more positive (less change) in the second period compared with the first. There were also no differences in MRW or RNFLT slopes in the first and second periods in healthy subjects. CONCLUSIONS: Significant MRW and RNFLT changes were detected at all levels of baseline damage. However, an attenuation in the rate of RNFLT change compared with MRW indicates an earlier floor effect in RNFLT measurements globally and in equivalent sectors. Because the axonal component of these measurements should be equivalent, our results suggest important differences in tissue remodeling at the level of the optic nerve head and peripapillary retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Twisted orientation of the muscle bundles in the levator ani functional parts in women: Implications for pelvic floor support mechanism.

This study presents a comprehensive investigation of the anatomical features of the levator ani muscle. The levator ani is a critical component of the pelvic floor; however, its intricate anatomy and functionality are poorly understood. Understanding the precise anatomy of the levator ani is crucial for the accurate diagnosis and effective treatment of pelvic floor disorders. Previous studies have been limited by the lack of comprehensive three-dimensional analyses; to overcome this limitation, we analysed the levator ani muscle using a novel 3D digitised muscle-mapping approach based on layer-by-layer dissection. From this examination, we determined that the levator ani consists of overlapping muscle bundles with varying orientations, particularly in the anteroinferior portion. Our findings revealed distinct muscle bundles directly attached to the rectum (LA-re) and twisted muscle slings surrounding the anterior (LA-a) and posterior (LA-p) aspects of the rectum, which are considered functional parts of the levator ani. These results suggest that these specific muscle bundles of the levator ani are primarily responsible for functional performance. The levator ani plays a crucial role in rectal elevation, lifting the centre of the perineum and narrowing the levator hiatus. The comprehensive anatomical information provided by our study will enhance diagnosis accuracy and facilitate the development of targeted treatment strategies for pelvic floor disorders in clinical practice.

Pelvic floor muscle training as treatment for female sexual dysfunction: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the efficacy of pelvic floor muscle training in treating female sexual dysfunction. DATA SOURCES: A systematic review of databases, including PubMed, Ovid Medline, CINAHL, Embase, BVSalud, Scopus, and Cochrane Library, was performed in July 2021 and updated in May 2023. STUDY ELIGIBILITY CRITERIA: Full-text articles of randomized controlled trials comparing pelvic floor muscle training with no intervention or another conservative treatment were included. At least 1 arm of these trials aimed to improve women's sexual function or treat sexual dysfunction. METHODS: The data for this review were extracted and analyzed by 2 independent reviewers. Data on the characteristics of each intervention were extracted using the Consensus on Exercise Reporting Template. The risk of bias and certainty of evidence were assessed using the Physiotherapy Evidence Database (PEDro) scale and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, respectively. A meta-analysis was conducted considering the posttreatment mean score difference in the Female Sexual Function Index between the control and treatment groups. RESULTS: A total of 21 randomized controlled trials were included in this review. The Consensus on Exercise Reporting Template revealed varying quality of the pelvic floor muscle training protocols. Four studies were included in the meta-analysis showing that pelvic floor muscle training improved arousal (1.49; 95% confidence interval, 0.13-2.85), orgasm (1.55; 95% confidence interval, 0.13-2.96), satisfaction (1.46; 95% confidence interval, 0.14-2.77), pain (0.74; 95% confidence interval, 0.11-1.37), and the Female Sexual Function Index overall score (7.67; 95% confidence interval, 0.77-14.57). Very low certainty of evidence due to the data's high clinical and statistical heterogeneity was found according to the GRADE criteria. No side effects of the interventions were reported. CONCLUSION: This systematic review and meta-analysis showed that pelvic floor muscle training improved female Female Sexual Function Index total score and several subscales; however, the certainty of the evidence is low.

Physician awareness of patients' preferred level of involvement in decision-making at the initial urogynecology visit: a randomized trial.

BACKGROUND: Studies have shown up to a 40% discordance between patients' preferred roles in decision-making before and their perceived roles after their visit. This can negatively affect patients' experiences; interventions to minimize this discordance may significantly improve patient satisfaction. OBJECTIVE: We aimed to determine whether physicians' awareness of patients' preferred involvement in decision-making before their initial urogynecology visit affects patients' perceived level of involvement after their visit. STUDY DESIGN: This randomized controlled trial enrolled adult English-speaking women presenting for their initial visit at an academic urogynecology clinic from June 2022 to September 2022. Before the visit, participants completed the Control Preference Scale to determine the patient's preferred level of decision-making: active, collaborative, or passive. The participants were randomized to either the physician team being aware of their decision-making preference before the visit or usual care. The participants were blinded. After the visit, participants again completed a Control Preference Scale and the Patient Global Impression of Improvement, CollaboRATE, patient satisfaction, and health literacy questionnaires. Fisher exact, logistic regression, and generalized estimating equations were used. Based on a 21% difference in preferred and perceived discordance, we calculated the sample size to be 50 patients in each arm to achieve 80% power. RESULTS: Women (n=100) with a mean age of 52.9 years (standard deviation=15.8) participated in the study. Most participants identified as White (73%) and non-Hispanic (70%). Before the visit, most women preferred an active role (61%) and few preferred a passive role (7%). There was no significant difference between the 2 cohorts in the discordance between their pre- and post-Control Preference Scale responses (27% vs 37%; P=.39) or whether their symptoms were much better or very much better following the visit (18% vs 37%; P=.06). However, when asked whether they were completely satisfied with the visit, those assigned to the physician awareness cohort reported higher satisfaction than those in the treatment as usual cohort (100% vs 90%; P=.03). CONCLUSION: Although there was no significant decrease in discordance between the patient's desired and perceived level of decision-making following physician awareness, it had a significant effect on patient satisfaction. All patients whose physicians were aware of their preferences reported complete satisfaction with their visit. Although patient-centered care does not always entail meeting all of the patients' expectations, the mere understanding of their preferences in decision-making can lead to complete patient satisfaction.

Effect of nonsteroidal anti-inflammatory drugs on pelvic floor muscle regeneration in a preclinical birth injury rat model.

BACKGROUND: Pelvic floor muscle injury is a common consequence of vaginal childbirth. Nonsteroidal anti-inflammatory drugs are widely used postpartum analgesics. Multiple studies have reported negative effects of these drugs on limb muscle regeneration, but their impact on pelvic floor muscle recovery following birth injury has not been explored. OBJECTIVE: Using a validated rat model, we assessed the effects of nonsteroidal anti-inflammatory drug on acute and longer-term pelvic floor muscle recovery following simulated birth injury. STUDY DESIGN: Three-month old Sprague Dawley rats were randomly assigned to the following groups: (1) controls, (2) simulated birth injury, (3) simulated birth injury+nonsteroidal anti-inflammatory drug, or (4) nonsteroidal anti-inflammatory drug. Simulated birth injury was induced using a well-established vaginal balloon distension protocol. Ibuprofen was administered in drinking water (0.2 mg/mL), which was consumed by the animals ad libitum. Animals were euthanized at 1, 3, 5, 7, 10, and 28 days after birth injury/ibuprofen administration. The pubocaudalis portion of the rat levator ani, which, like the human pubococcygeus, undergoes greater parturition-associated strains, was harvested (N=3-9/time point/group). The cross-sectional areas of regenerating (embryonic myosin heavy chain+) and mature myofibers were assessed at the acute and 28-day time points, respectively. The intramuscular collagen content was assessed at the 28-day time point. Myogenesis was evaluated using anti-Pax7 and anti-myogenin antibodies to identify activated and differentiated muscle stem cells, respectively. The overall immune infiltrate was assessed using anti-CD45 antibody. Expression of genes coding for pro- and anti-inflammatory cytokines was assessed by quantitative reverse transcriptase polymerase chain reaction at 3, 5, and 10 days after injury. RESULTS: The pubocaudalis fiber size was significantly smaller in the simulated birth injury+nonsteroidal anti-inflammatory drug compared with the simulated birth injury group at 28 days after injury (P<.0001). The median size of embryonic myosin heavy chain+ fibers was also significantly reduced, with the fiber area distribution enriched with smaller fibers in the simulated birth injury+nonsteroidal anti-inflammatory drug group relative to the simulated birth injury group at 3 days after injury (P<.0001), suggesting a delay in the onset of regeneration in the presence of nonsteroidal anti-inflammatory drugs. By 10 days after injury, the median embryonic myosin heavy chain+ fiber size in the simulated birth injury group decreased from 7 days after injury (P<.0001) with a tight cross-sectional area distribution, indicating nearing completion of this state of regeneration. However, in the simulated birth injury+nonsteroidal anti-inflammatory drug group, the size of embryonic myosin heavy chain+ fibers continued to increase (P<.0001) with expansion of the cross-sectional area distribution, signifying a delay in regeneration in these animals. Nonsteroidal anti-inflammatory drugs decreased the muscle stem cell pool at 7 days after injury (P<.0001) and delayed muscle stem cell differentiation, as indicated by persistently elevated number of myogenin+ cells 7 days after injury (P<.05). In contrast, a proportion of myogenin+ cells returned to baseline by 5 days after injury in the simulated birth injury group. The analysis of expression of genes coding for pro- and anti-inflammatory cytokines demonstrated only transient elevation of Tgfb1 in the simulated birth injury+nonsteroidal anti-inflammatory drug group at 5 but not at 10 days after injury. Consistently with previous studies, nonsteroidal anti-inflammatory drug administration following simulated birth injury resulted in increased deposition of intramuscular collagen relative to uninjured animals. There were no significant differences in any outcomes of interest between the nonsteroidal anti-inflammatory drug group and the unperturbed controls. CONCLUSION: Nonsteroidal anti-inflammatory drugs negatively impacted pelvic floor muscle regeneration in a preclinical simulated birth injury model. This appears to be driven by the negative impact of these drugs on pelvic muscle stem cell function, resulting in delayed temporal progression of pelvic floor muscle regeneration following birth injury. These findings provide impetus to investigate the impact of postpartum nonsteroidal anti-inflammatory drug administration on muscle regeneration in women at high risk for pelvic floor muscle injury.

Pelvic floor injury during vaginal birth is life-altering and preventable: what can we do about it?

Pelvic floor disorders after childbirth have distressing lifelong consequences for women, requiring more than 300,000 women to have surgery annually. This represents approximately 10% of the 3 million women who give birth vaginally each year. Vaginal birth is the largest modifiable risk factor for prolapse, the pelvic floor disorder most strongly associated with birth, and is an important contributor to stress incontinence. These disorders require 10 times as many operations as anal sphincter injuries. Imaging shows that injuries of the levator ani muscle, perineal body, and membrane occur in up to 19% of primiparous women. During birth, the levator muscle and birth canal tissues must stretch to more than 3 times their original length; it is this overstretching that is responsible for the muscle tear visible on imaging rather than compression or neuropathy. The injury is present in 55% of women with prolapse later in life, with an odds ratio of 7.3, compared with women with normal support. In addition, levator damage can affect other aspects of hiatal closure, such as the perineal body and membrane. These injuries are associated with an enlarged urogenital hiatus, now known as antedate prolapse, and with prolapse surgery failure. Risk factors for levator injury are multifactorial and include forceps delivery, occiput posterior birth, older maternal age, long second stage of labor, and birthweight of >4000 g. Delivery with a vacuum device is associated with reduced levator damage. Other steps that might logically reduce injuries include manual rotation from occiput posterior to occiput anterior, slow gradual delivery, perineal massage or compresses, and early induction of labor, but these require study to document protection. In addition, teaching women to avoid pushing against a contracted levator muscle would likely decrease injury risk by decreasing tension on the vulnerable muscle origin. Providing care for women who have experienced difficult deliveries can be enhanced with early recognition, physical therapy, and attention to recovery. It is only right that women be made aware of these risks during pregnancy. Educating women on the long-term pelvic floor sequelae of childbirth should be performed antenatally so that they can be empowered to make informed decisions about management decisions during labor.

Evolution of the human birth canal.

It seems puzzling why humans have evolved such a small and rigid birth canal that entails a relatively complex process of labor compared with the birth canal of our closest relatives, the great apes. This study reviewed insights into the evolution of the human birth canal from recent theoretical and empirical studies and discussed connections to obstetrics, gynecology, and orthopedics. Originating from the evolution of bipedality and the large human brain million years ago, the evolution of the human birth canal has been characterized by complex trade-off dynamics among multiple biological, environmental, and sociocultural factors. The long-held notion that a wider pelvis has not evolved because it would be disadvantageous for bipedal locomotion has not yet been empirically verified. However, recent clinical and biomechanical studies suggest that a larger birth canal would compromise pelvic floor stability and increase the risk of incontinence and pelvic organ prolapse. Several mammals have neonates that are equally large or even larger than human neonates compared to the size of the maternal birth canal. In these species, the pubic symphysis opens widely to allow successful delivery. Biomechanical and developmental constraints imposed by bipedality have hindered this evolutionary solution in humans and led to the comparatively rigid pelvic girdle in pregnant women. Mathematical models have shown why the evolutionary compromise to these antagonistic selective factors inevitably involves a certain rate of fetopelvic disproportion. In addition, these models predict that cesarean deliveries have disrupted the evolutionary equilibrium and led to new and ongoing evolutionary changes. Different forms of assisted birth have existed since the stone age and have become an integral part of human reproduction. Paradoxically, by buffering selection, they may also have hindered the evolution of a larger birth canal. Many of the biological, environmental, and sociocultural factors that have influenced the evolution of the human birth canal vary globally and are subject to ongoing transitions. These differences may have contributed to the global variation in the form of the birth canal and the difficulty of labor, and they likely continue to change human reproductive anatomy.

Soft-tissue dystocia due to paradoxical contraction of the levator ani as a cause of prolonged second stage: concept, diagnosis, and potential treatment.

Smaller pelvic floor dimensions seem to have been an evolutionary need to provide adequate support for the pelvic organs and the fetal head. Pelvic floor dimension and shape contributed to the complexity of human birth. Maternal pushing associated with pelvic floor muscle relaxation is key to vaginal birth. Using transperineal ultrasound, pelvic floor dimensions can be objectively measured in both static and dynamic conditions, such as pelvic floor muscle contraction and pushing. Several studies have evaluated the role of the pelvic floor in labor outcomes. Smaller levator hiatal dimensions seem to be associated with a longer duration of the second stage of labor and a higher risk of cesarean and operative deliveries. Furthermore, smaller levator hiatal dimensions are associated with a higher fetal head station at term of pregnancy, as assessed by transperineal ultrasound. With maternal pushing, most women can relax their pelvic floor, thus increasing their pelvic floor dimensions. Some women contract rather than relax their pelvic floor muscles under pushing, which is associated with a reduction in the anteroposterior diameter of the levator hiatus. This phenomenon is called levator ani muscle coactivation. Coactivation in nulliparous women at term of pregnancy before the onset of labor is associated with a higher fetal head station at term of pregnancy and a longer duration of the second stage of labor. In addition, levator ani muscle coactivation in nulliparous women undergoing induction of labor is associated with a longer duration of the active second stage of labor. Whether we can improve maternal pelvic floor relaxation with consequent improvement in labor outcomes remains a matter of debate. Maternal education, physiotherapy, and visual feedback are promising interventions. In particular, ultrasound visual feedback before the onset of labor can help women increase their levator hiatal dimensions and correct levator ani muscle coactivation in some cases. Ultrasound visual feedback in the second stage of labor was found to help women push more efficiently, thus obtaining a lower fetal head station at ultrasound and a shorter duration of the second stage of labor. The available evidence on the role of any intervention aimed to aid women to better relax their pelvic floor remains limited, and more studies are needed before considering its routine clinical application.

Parturition at term: induction, second and third stages of labor, and optimal management of life-threatening complications-hemorrhage, infection, and uterine rupture.

Childbirth is a defining moment in anyone's life, and it occurs 140 million times per year. Largely a physiologic process, parturition does come with risks; one mother dies every two minutes. These deaths occur mostly among healthy women, and many are considered preventable. For each death, 20 to 30 mothers experience complications that compromise their short- and long-term health. The risk of birth extends to the newborn, and, in 2020, 2.4 million neonates died, 25% in the first day of life. Hence, intrapartum care is an important priority for society. The American Journal of Obstetrics & Gynecology has devoted two special Supplements in 2023 and 2024 to the clinical aspects of labor at term. This article describes the content of the Supplements and highlights new developments in the induction of labor (a comparison of methods, definition of failed induction, new pharmacologic agents), management of the second stage, the value of intrapartum sonography, new concepts on soft tissue dystocia, optimal care during the third stage, and common complications that account for maternal death, such as infection, hemorrhage, and uterine rupture. All articles are available to subscribers and non-subscribers and have supporting video content to enhance dissemination and improve intrapartum care. Our hope is that no mother suffers because of lack of information.

Conservative interventions for female exercise-induced urinary incontinence: a systematic review.

OBJECTIVE: To systematically review and synthesise what is known about the effectiveness of non-pharmaceutical conservative interventions for the management of urinary incontinence (UI) experienced by women during physical exercise. METHODS: A systematic search was performed in the following databases in September 2023: the Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica dataBASE (EMBASE), Scientific Electronic Library Online (SciELO), Latin American and Caribbean Health Sciences Literature (LILACS), and Physiotherapy Evidence Database (PEDro). Studies were deemed eligible if population consisted of females who reported symptoms of UI while participating in physical exercise, and the interventions involved any non-pharmaceutical conservative treatment to manage symptoms during exercise. The primary outcome was severity of UI signs and symptoms. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42022379138). RESULTS: Of the 3429 abstracts screened, 19 studies were retained. Pelvic floor muscle training (PFMT) and intravaginal devices were the most commonly investigated modalities. Only two randomised controlled trials (RCTs), both among volleyball players, compared PFMT with no PFM exercise, showing a reduction in pad weight gain after the intervention in the experimental groups only. PFMT with and without biofeedback randomised among soldiers demonstrated a reduction in the frequency of urine leakage episodes in both groups, while supervised and unsupervised PFMT randomised among athletes from different sports showed pad weight gain reduction in the supervised group only. Seven single-arm studies suggested that PFMT alone or combined with other modalities may reduce UI severity in active women based on questionnaires, bladder diaries, and self-reported symptoms. A single-arm and a crossover study found pessary use beneficial in reducing urine leakage based on questionnaires and pad weight gain, respectively. When comparing pessary, tampon, and no intervention, two repeated-measures studies found tampons may reduce leakage more than pessaries in CrossFit exercisers and women performing aerobic exercises. A vaginal sponge also reduced pad weight gain during aerobic exercises. Other modalities (i.e., an intraurethral device, photobiomodulation, and combined therapies) were investigated using case series or single case studies. While all interventions showed some evidence of effectiveness, the results must be interpreted with caution due to methodological limitations and high risk of bias. In particular, despite a high reliance on pad tests as a primary outcome, we identified inconsistencies in how pad tests were administered and interpreted. CONCLUSION: Only the effectiveness of PFMT to reduce urine leakage during exercise has been evaluated through RCTs, with some evidence of effectiveness. We identified a clear need for higher quality studies, with better reporting on the interventions, and more judicious use and interpretation of outcome measures.

Physiotherapy for continence and muscle function in prostatectomy: a randomised controlled trial.

OBJECTIVE: To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. RESULTS: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. CONCLUSION: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP.

Investigating the role of the pelvic floor muscles in sexual function and sexual response: a systematic review and meta-analysis.

INTRODUCTION: The pelvic floor muscles (PFMs) have been suggested to play a key role in sexual function and response in women. However, syntheses of the evidence thus far have been limited to interventional studies in women with pelvic pain or pelvic floor disorders, and these studies have failed to fully capture the involvement of the PFMs in a broader population. AIM: We sought to appraise the evidence regarding the role of the PFMs in sexual function/response in women without pelvic pain or pelvic floor disorders. More specifically, we examined the following: (1) effects of treatment modalities targeting the PFMs on sexual function/response, (2) associations between PFM function and sexual function/response, and (3) differences in PFM function between women with and those without sexual dysfunction. METHODS: We searched for all available studies in eight electronic databases. We included interventional studies evaluating the effects of PFM modalities on sexual outcomes, as well as observational studies investigating the association between PFM function and sexual outcomes or the differences in PFM function in women with and those without sexual dysfunction. The quality of each study was assessed using the Mixed Methods Appraisal Tool. Estimates were pooled using random-effects meta-analyses whenever possible, or a narrative synthesis of the results was provided. MAIN OUTCOMES: The main outcomes were sexual function (based on a questionnaire)/sexual response (based on physiological test), and PFM function (assessment of the PFM parameters such as strength and tone based on various methods). RESULTS: A total of 33 studies were selected, including 14 interventional and 19 observational studies, most of which (31/33) were deemed of moderate or high quality. Ten out of 14 interventional studies in women with and without sexual dysfunctions showed that PFM modalities had a significant effect on sexual function. Regarding the observational studies, a meta-analysis revealed a significant moderate association between PFM strength and sexual function (r = 0.41; 95% CI, 0.08-066). Of the 7 observational studies performed to assess sexual response, all showed that the PFMs were involved in arousal or orgasm. Conflicting results were found in the 3 studies that evaluated differences in PFM function in women with and those without sexual dysfunction. CLINICAL IMPLICATIONS: Our results highlight the contribution of the PFMs in sexual function/response. STRENGTHS AND LIMITATIONS: One strength of this review is the inclusion of a broad range of study designs and outcomes, allowing a thorough synthesis of evidence. However, interpretations of these data should consider risk of bias in the studies, small sample sizes, and the absence of control/comparison groups. CONCLUSION: The findings of this review support the involvement of the PFMs in sexual function/response in women without pelvic pain or pelvic dysfunction. Well-designed studies should be performed to further investigate PFM modalities as part of the management of sexual dysfunction.

Psychosexological correlates of 372 women with vulvodynia, overactive pelvic floor, postcoital cystitis, and interstitial cystitis.

BACKGROUND: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence. AIM: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms. METHODS: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests. OUTCOMES: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis. RESULTS: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women. CLINICAL IMPLICATIONS: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner. STRENGTHS AND LIMITATIONS: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation. CONCLUSION: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission.

Treatment of women with vaginal laxity: systematic review with meta-analysis.

BACKGROUND: Despite several treatments that have been used for women reporting vaginal laxity (VL), to our knowledge no systematic review is available on the topic so far. AIM: In this study, we sought to summarize the best available evidence about the efficacy and safety of interventions for treating VL, whether conservative or surgical. METHODS: A comprehensive search strategy was performed in Medline, Embase, Scopus, Web of Science, and Cochrane Library for reports of clinical trials published from database inception to September 2022. Studies selected for inclusion were in the English language and were performed to investigate any type of treatment for VL, with or without a comparator, whether nonrandomized studies or randomized controlled trials (RCTs). Case reports and studies without a clear definition of VL were excluded. OUTCOMES: The outcomes were interventions (laser, radiofrequency, surgery, and topical treatment), adverse effects, sexual function, pelvic floor muscle (PFM) strength, and improvement of VL by the VL questionnaire (VLQ). RESULTS: From 816 records, 38 studies remained in the final analysis. Laser and radiofrequency (RF) were the energy-based treatment devices most frequently studied. Pooled data from eight observational studies have shown improved sexual function assessed by a Female Sexual Function Index score mean difference (MD) of 6.51 (95% CI, 5.61-7.42; i2 = 85%, P < .01) before and after intervention, whether by RF (MD, 6.00; 95% CI, 4.26-7.73; i2 = 80%; P < .001) or laser (MD, 6.83; 95% CI, 5.01-8.65; i2 = 92%; P < .01). However, this finding was not shown when only 3 RCTs were included, even when separated by type of intervention (RF or laser). When RF treatment was compared to sham controls, VLQ scores did not improve (MD, 1.01; 95% CI, -0.38 to 2.40; i2 = 94%; P < .001). Patient PFM strength improved after interventions were performed (MD, 4.22; 95% CI, 1.02-7.42; i2 = 77%; P < .001). The ROBINS-I (Risk Of Bias In Nonrandomized Studies of Interventions) tool classified all non-RCTs at serious risk of bias, except for 1 study, and the risk of bias-1 analysis found a low and unclear risk of bias for all RCTs. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) certainty of the evidence was moderate for sexual function and the VLQ questionnaire and low for PFM strength. CLINICAL IMPLICATIONS: Sexual function in women with VL who underwent RF and laser treatment improved in observational studies but not in RCTs. Improvement in PFM strength was observed in women with VL after the intervention. STRENGTHS AND LIMITATIONS: Crucial issues were raised for the understanding of VL, such as lack of standardization of the definition and for the development of future prospective studies. A limitation of the study was that the heterogeneity of the interventions and different follow-up periods did not make it possible to pool all available data. CONCLUSIONS: Vaginal tightening did not improve sensation in women with VL after intervention, whereas RF and laser improved sexual function in women with VL according to data from observational studies, but not from RCTs. PFM strength was improved after intervention in women with VL.

Pain with orgasm in endometriosis: potential etiologic factors and clinical correlates.

BACKGROUND: Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis. AIM: To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization. METHODS: An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100). OUTCOMES: Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no). RESULTS: Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups. CLINICAL IMPLICATIONS: Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis. STRENGTHS AND LIMITATIONS: A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function. CONCLUSION: Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.