Função sexual pós-histerectomia: quais os impactos e aspectos técnicos envolvidos? / Sexual function after hysterectomy: what are the impacts and technical aspects involved?

Objetivo: Identificar o impacto da histerectomia para patologias benignas sobre a sexualidade feminina. Métodos: Revisão de literatura com busca na plataforma PubMed, sendo selecionados 23 artigos em português e inglês publicados entre 2016 e 2021. Resultados: Foi descrita, majoritariamente, melhora na função sexual após histerectomia, semelhante às abordagens totais ou supracervicais e independentemente da via de acesso cirúrgico, apesar de impacto ligeiramente menor com a via laparoscópica. Na laparoscopia, houve melhor desfecho sexual no fechamento da cúpula vaginal, quando comparado ao fechamento via vaginal. Ademais, a ooforectomia concomitante apresentou resultados conflitantes e inconclusivos. Conclusão: A histerectomia afeta positivamente a saúde sexual feminina e aspectos técnicos podem interferir na função sexual, porém os dados são limitados. Devido à importância do tema, necessitam-se de mais estudos com metodologias padronizadas para possibilitar análises mais detalhadas.

Objective: To identify the impact of hysterectomy for benign pathologies on female sexuality. Methods: Literature review with search on PubMed platform, being selected 23 articles in Portuguese and English published between 2016 and 2021. Results: Improvement in sexual function after hysterectomy was mostly described, being similar in total or supracervical approaches and independent of the surgical access route, although it had slightly lower impact when laparoscopic. In the laparoscopic approach, there was better sexual outcome in the vaginal dome closure when compared to vaginal closure. In addition, concomitant oophorectomy showed conflicting and inconclusive results. Conclusion: Hysterectomy positively affects female sexual health and technical aspects may interfere with sexual function, but data are limited. Due to the importance of the theme, more studies with standardized methodologies are needed to enable more detailed analyses.

Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis.

This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

Continuous artificial light potentially disrupts central and peripheral reproductive clocks leading to altered uterine physiology and reduced pregnancy success in albino mice.

AIMS: The mechanism behind clock coordination in female reproductive disorders is poorly understood despite the known importance of coordinated and synchronized timing of central and clocks in reproductive organs. We investigated the effect of continuous artificial light (LL) on the central and peripheral reproductive clock gene (Bmal1, Clock, Per1, Per2 and Cry1) and its downstream regulators (Hgf, PR-A and HOXA10) during non-pregnancy and pregnancy phases of female mice. MAIN METHODS: Mice (n = 60) in two sets, were maintained under continuous light (LL) and natural day cycle (LD;12L: 12D) for both non-pregnant and pregnant study. Tissues from hypothalamus-containing SCN, ovary, uterus and serum were collected at different zeitgeber time points (ZT; at 4-h intervals across 24-h periods). KEY FINDINGS: LL exposure desynchronized the expressions of the clock mRNAs (Bmal1, Clock, Per1, Per2 and Cry1) in SCN, ovary, and uterus along with Hgf mRNA rhythm. LL significantly increased the thickness of endometrial tissues. Furthermore, the pregnant study revealed lower serum progesterone level during peri- and post-implantation under LL along with downregulated expression of progesterone receptor (PR) as well as progesterone dependent uterine Homeobox A-10 (Hoxa10) proteins with lowered pregnancy outcomes. SIGNIFICANCE: Our result suggests that LL disrupted the circadian coordination between central and clock genes in reproductive tissue leading to interrupted uterine physiology and altered pregnancy in mice. This led us to propose that duration of light exposure at work-places or home for females is very important in prevention of pregnancy anomalies.

Manipulative Reduction for Abnormal Uterine Inclination in Vaginal Delivery.

OBJECTIVE: To investigate the manipulative reduction in abnormal uterine inclination in vaginal delivery. METHODS: With the independently developed uterine inclination surveyor, 40 primiparas with abnormal uterine inclination were randomly divided into two groups: treatment group (Group A, 20 cases) and control group (Group B, 20 cases). The general condition of the primipara, the labor stages, the changes in uterine inclination after treatment, postpartum hemorrhage at 2 hours, and the general condition of fetuses were observed to study the therapeutic value of manual reduction in abnormal uterine inclination. RESULT: In the control group, one uterine inclination was not corrected with the change in labor process, and the pregnancy was terminated due to stagnation of the active phase. In the first stage of labor, the time spent in the treatment group (393.4 ± 31.3 mins) was significantly lower than that in the control group (440.7 ± 34.9 mins) (P = 0.001). Compared with the control group (49.8 ± 6.5 mins), the treatment group (42.6 ± 7.2 mins) also exhibited a significantly shortened second stage of labor (P = 0.02). Sixteen cases (16/20) in the treatment group returned to normal after manual reduction, and 9 cases (9/20) in the control group returned to normal with the progression of natural labor. Manual reduction could be used as an option to treat abnormal uterine inclination (P = 0.01). There was no significant difference in the third stage of labor (P = 0.2), 2-hour postpartum hemorrhage (P = 0.35), Apgar score (P = 0.64), or body weight (P = 0.76) between the two groups. CONCLUSION: Manual reduction in the treatment of abnormal uterine inclination has obvious effects, shortens the birth process, and is safe for the fetus.

Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice.

Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5-9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

Uterine adhesion: Is luteal phase prior to follicular phase in uterine adhesiolysis?

ABSTRACT: To compare the patients' outcomes of Asherman syndrome who underwent uterine adhesiolysis in luteal phase or follicular phase.A retrospective cohort study.A tertiary hospital in China.Four hundred sixty-four women suffered intrauterine adhesion who underwent monopolar adhesiolysis from March 2014 to March 2017 were analyzed. One hundred seventy-eight patients underwent operations in follicular phase (OFP) and 286 underwent operations in luteal phase (OLP).Hormone therapy was accompanied with an intrauterine device and a second-look hysteroscopy was performed postoperatively.Endometrial thickness in women was analyzed by a transvaginal 3-dimensional ultrasound examination. Re-adhesion was confirmed by a second-look hysteroscopy 3 months after hysteroscopic adhesiolysis. Pregnancy rate was acquired by questionnaires 3 months after a second-look hysteroscopy.OLP has advantages with thicker luteal endometrium (P = .001), higher pregnancy rates (P < .001), and lower re-adhesion rates (P = 0015) compared to these values of OFP.For Asherman syndrome, our study showed that OLP is more feasible than OFP in intrauterine adhesiolysis.

ACE2: a key modulator of the renin-angiotensin system and pregnancy.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.

Ascension of Chlamydia is moderated by uterine peristalsis and the neutrophil response to infection.

Chlamydia trachomatis is a common sexually transmitted infection that is associated with a range of serious reproductive tract sequelae including in women Pelvic Inflammatory Disease (PID), tubal factor infertility, and ectopic pregnancy. Ascension of the pathogen beyond the cervix and into the upper reproductive tract is thought to be necessary for these pathologies. However, Chlamydia trachomatis does not encode a mechanism for movement on its genome, and so the processes that facilitate ascension have not been elucidated. Here, we evaluate the factors that may influence chlamydial ascension in women. We constructed a mathematical model based on a set of stochastic dynamics to elucidate the moderating factors that might influence ascension of infections in the first month of an infection. In the simulations conducted from the stochastic model, 36% of infections ascended, but only 9% had more than 1000 bacteria ascend. The results of the simulations indicated that infectious load and the peristaltic contractions moderate ascension and are inter-related in impact. Smaller initial loads were much more likely to ascend. Ascension was found to be dependent on the neutrophil response. Overall, our results indicate that infectious load, menstrual cycle timing, and the neutrophil response are critical factors in chlamydial ascension in women.

Intrauterine Hyperglycemia Alters the Metabolomic Profile in Fetal Mouse Pancreas in a Gender-Specific Manner.

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.

Down regulatory response of reproductive potentials in stress-induced rats supplemented with clomifene citrate: The fate of infertility.

This study was designed to physiologically investigate the fate of stress related infertility conditions to focus on the regulatory response of reproductive potentials in stress-induced female Wistar rats supplemented with clomifene citrate. 42 apparently healthy female Wistar rats weighing about 120-160 g were used in the study. The animals were randomly distributed into 3 groups after acclimatization for 2 weeks. Group 1 served as the control pregnant rats not induced by restraint, mirrored and intruder stressors, group 2 consisted of rats treated with 0.013 mg/g of clomifene citrate drug and exposed to three different stressors while group 3 represented pregnant rats exposed to different stressors but not treated with clomifene citrate. At the end of 3weeks, the rats were euthanized via cervical dislocation. The uterus and ovary organs were carefully isolated, weighed and examined for histological changes. The reproductive capacities studied were gestation period, mean pup weight, litter size and survival rate respectively. Data collected is expressed in Mean±SEM and one way ANOVA statistics was used for comparison of means while Fisher's LSD was employed for post hoc test and the level of significance is determined at p-value < 0.05. Results from our study revealed that restraint and intruder stressors following supplementation with clomifene citrate produced similar stress response in the gestation length, pub-weights, litter size and percentage of survival. Stress of different nature altered the histoarchitecture of the ovary and the uteri of rats exposed to restraint or intruder stressor. Meanwhile, Clomifene citrate administration produced effect on ovulation and pregnancy outcome of stressed pregnant rats and the survival ratio of the offspring.

Mapping of endometriosis in patients with unilateral endometrioma.

ABSTRACT: To map the distribution of the sites most affected by endometriosis in patients with unilateral ovarian endometriomas.A descriptive case series of 84 patients with unilateral endometriomas undergoing laparoscopy for the treatment of endometriosis. To evaluate the distribution of the sites of endometriosis lesions, the peritoneal compartments were divided into 5 zones: zone 1/the anterior compartment, including the anterior uterine serosa, vesicouterine fold, round ligament, and bladder; zone 2/the lateral compartment, including the left and right ovary, ovarian fossa, tubes, mesosalpinx, uterosacral ligaments, parametrium, and the ureter; zone 3/the posterior compartment, including posterior uterine serosa, the pouch of Douglas, posterior vaginal fornix, and bowel; zone 4 consisting of the abdominal wall; and zone 5 consisting of the diaphragm.Of the 5 zones evaluated, the lateral compartment (zone 2) was the most affected, with 60.7% of the patients having dense adhesions around the left ovarian fossa and 57.1% around the right ovarian fossa. The ovarian endometriomas were more commonly found on the left side (54.8%) compared to the right (45.2%). In the posterior compartment (zone 3), the posterior cul-de-sac was obliterated in 51.2% of the patients. In the anterior compartment (zone 1), there were lesions in the vesicouterine fold in 30.9% of the patients and in the bladder in 19%. Lesions were found in the abdominal wall (zone 4) and diaphragm (zone 5) in 21.4% and 10.7% of patients, respectively.Unilateral endometriomas are important markers of the severity of endometriosis.

Hysteroscopic incision of the incomplete uterine septum using 5-French scissors with marking strategies: a modified hysteroscopic technique.

OBJECTIVE: To demonstrate an easier surgical strategy by using the marking technique for hysteroscopic incision of the uterine septum using 5-French cold scissors. DESIGN: A step-by-step surgical video demonstration. SETTING: Gynecologic department of the affiliated hospital. PATIENT(S): A 33-year-old woman presented with a 4-year history of primary infertility. She previously had undergone transcervical resection of (uterine) septum owing to the presence of a complete uterine septum and double cervices. Postoperative 3-dimensional ultrasound revealed a 1.2-cm residual uterine septum, and the outline of the uterine fundus was flat. A second surgery for resection of the residual septum was recommended before in vitro fertilization and embryo transfer. We used the Campo hysteroscope (4.4-mm outer sheath) and 5-French scissors with our modified marking strategy to incise the incomplete uterine septum. INTERVENTION(S): There were several critical strategies for this approach. After fully exposing 2 fallopian tube ostia, a 3-5-mm mark was made on each side of the uterine fundus where the septum ended, and the marks were parallel to the fallopian tubal ostia. The septum then was incised along the line between the two previously marked points that served as the endpoints. Care was taken to avoid incising myometrial blood vessels during incision, and the 5-French bipolar electrode was used for coagulation when necessary. At the end of the surgery, the distension pressure was gradually decreased to 80 mm Hg to confirm hemostasis of the wound before withdrawing the hysteroscope. MAIN OUTCOME MEASURE(S): Description of a modified hysteroscopic technique. RESULT(S): The overall operation time was 10 minutes, and the estimated blood loss was 5 mL. The residual septum was resected successfully while maintaining optimal hysteroscopic visualization. There were no short-term complications, such as uterine perforation or fluid overload. Hysteroscopic evaluation performed 3 months after surgery revealed that the uterine cavity was nearly normal, with no intrauterine adhesion appreciated. There are several advantages to this innovative and practical hysteroscopic surgical approach. Marking the lateral limits of the uterine septum means that a shorter reference line is obtained to incise the septum effectively rather than using the bilateral ostia as reference points. At the same time, marking the bilateral endpoint of the uterine septum incision at the beginning of the surgery might be helpful when bilateral tubal ostia are invisible because of quick absorption of the distension media, which causes insufficient distention pressure at the end of the surgery. Use of the narrow 5-French scissors allowed for instrumentation without prior cervical dilation. Moreover, with this "see and treat" strategy, a clear visualization of the surgical field was maintained without inserting and withdrawing the hysteroscope. The endometrium sustained minimal damage because of the "cold scissors" technique. CONCLUSION(S): Our hysteroscopic marking strategy allows the surgeon's intraoperative judgment to be efficient and safe during incision of the uterine septum and ensures that the incision is adequate. It is an improved and valid surgical strategy for hysteroscopic incision of the uterine septum.

Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs.

Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10-7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10-7 M). GALR1/GALR2 antagonist and GAL (10-7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.

Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models.

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

Loss of basigin expression in uterine cells leads to subfertility in female mice†.

Basigin (BSG) is a transmembrane glycoprotein involved in cell proliferation, angiogenesis, and tissue remodeling. BSG has been shown to be essential for male and female reproduction although little is known about its role in normal uterine function. To study the potential function of BSG in the female reproductive tract, we generated mice with conditional knockout of Bsg in uterine cells using progesterone receptor-Cre and hypothesized that BSG is required for normal pregnancy in mice. Fertility study data showed that the conditional knockout mice had significantly reduced fertility compared to controls. Ovarian function of the conditional knockout mice appeared normal with no difference in the number of superovulated oocytes collected or in serum progesterone levels between the conditional knockout and the control mice. Uterine tissues collected at various times of gestation showed increased abnormalities in implantation, decidualization, placentation, and parturition in the conditional knockout mice. Uterine cross sections on Day 5 of pregnancy showed implantation failure and abnormal uterine epithelial differentiation in a large proportion of the conditional knockout mice. There was a compromised decidual response to artificial decidualization stimuli and decreased mRNA and protein levels for decidualization genes in the uteri of the conditional knockout mice. We also observed altered protein expression of monocarboxylate transporter 1 (MCT1), as well as impaired angiogenesis in the conditional knockout uteri compared to the controls. These results support that BSG is required for successful pregnancy through its functions in implantation and decidualization.

Bioengineering of the Uterus.

Impairment of uterine structure and function causes infertility, pregnancy loss, and perinatal complications in humans. Some types of uterine impairments such as Asherman's syndrome, also known as uterine synechiae, can be treated medically and surgically in a standard clinical setting, but absolute defects of uterine function or structure cannot be cured by conventional approaches. To overcome such hurdles, partial or whole regeneration and reconstruction of the uterus have recently emerged as new therapeutic strategies. Transplantation of the whole uterus into patients with uterine agenesis results in the successful birth of children. However, it remains an experimental treatment with numerous difficulties such as the need for continuous and long-term use of immunosuppressive drugs until a live birth is achieved. Thus, the generation of the uterus by tissue engineering technologies has become an alternative but indispensable therapeutic strategy to treat patients without a functional or well-structured uterus. For the past 20 years, the bioengineering of the uterus has been studied intensively in animal models, providing the basis for clinical applications. A variety of templates and scaffolds made from natural biomaterials, synthetic materials, or decellularized matrices have been characterized to efficiently generate the uterus in a manner similar to the bioengineering of other organs and tissues. The goal of this review is to provide a comprehensive overview and perspectives of uterine bioengineering focusing on the type, preparation, and characteristics of the currently available scaffolds.

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking.

BACKGROUND: Curcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown. OBJECTIVE: The present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea. METHODS: Observations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis. RESULTS: The results of HE staining and biochemical assays of PGF2α, TXB2 and Ca2+ showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation. CONCLUSION: This study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.

Anisotropic Mechanical Properties of the Human Uterus Measured by Spherical Indentation.

The mechanical function of the uterus is critical for a successful pregnancy. During gestation, uterine tissue grows and stretches to many times its size to accommodate the growing fetus, and it is hypothesized the magnitude of uterine tissue stretch triggers the onset of contractions. To establish rigorous mechanical testing protocols for the human uterus in hopes of predicting tissue stretch during pregnancy, this study measures the anisotropic mechanical properties of the human uterus using optical coherence tomography (OCT), instrumented spherical indentation, and video extensometry. In this work, we perform spherical indentation and digital image correlation to obtain the tissue's force and deformation response to a ramp-hold loading regimen. We translate previously reported fiber architecture, measured via optical coherence tomography, into a constitutive fiber composite material model to describe the equilibrium material behavior during indentation. We use an inverse finite element method integrated with a genetic algorithm (GA) to fit the material model to our experimental data. We report the mechanical properties of human uterine specimens taken across different anatomical locations and layers from one non-pregnant (NP) and one pregnant (PG) patient; both patients had pathological uterine tissue. Compared to NP uterine tissue, PG tissue has a more dispersed fiber distribution and equivalent stiffness material parameters. In both PG and NP uterine tissue, the mechanical properties differ significantly between anatomical locations.

The pathogenesis of abnormal uterine bleeding in myopathic uteri.

It has been suggested that impaired venous drainage and endometrial vascular ectasia (EMVE), secondary to increased intramural pressure, explains abnormal bleeding in fibroid uteri. Striking EMVE with extravasated red blood cells (ecchymosis) has also been seen in uteri with grossly obvious myometrial hyperplasia (MMH), suggesting that increased intramural pressure can cause EMVE in the absence of fibroids. EMVE with MMH may explain the century old association of clinically enlarged uteri with abnormal bleeding, and this same mechanism may be operative in myopathic uteri with grossly obvious adenomyosis. EMVE with associated thrombosis, ecchymosis, and/or stromal breakdown is commonly seen in random sections of hysterectomies for bleeding. EMVE may also be associated with endothelial hyperplasia, consistent with a reaction to endothelial injury due to impaired venous drainage. This further supports the theory that EMVE bleeds when thrombosis occurs, due to Virchow's Triad (stasis, endothelial injury, and hypercoagulability). EMVE may be "the lesion for which surgery was performed" in hysterectomies with otherwise unexplained bleeding.

4D ultrasound as a method to assess uterine peristalsis.

OBJECTIVE: To study uterine peristalsis using step-by-step 4-dimensional (4D) ultrasound assessment video, explore its relationship with progesterone levels in a select in vitro fertilization population, and assess the reproducibility of the technique. DESIGN: Four-dimensional uterine ultrasound and a retrospective analysis of outcomes in relation with progesterone levels. The videos were also analyzed by a senior doctor, junior doctor, and a nurse for their reproducibility. SETTING: Instituto Bernabeu of Alicante is a private clinic. PATIENT(S): The study included 197 consecutive patients undergoing in vitro fertilization (from 2018 to 2019) with a history of recurrent implantation failure (defined as unsuccessful implantation of a total number of ≥3 blastocysts originated from oocyte donation cycles). Because it is known that most failures are attributed to the quality of the embryo, we deemed it important to explore the potential uterine factors explaining the failures in oocyte donation cycles, the use of which decreases the probability of embryo-related factors influencing it. INTERVENTION(S): The participants were evaluated for uterine contractions and serum progesterone levels (10-30 minutes before the embryo transfer procedure). Uterine contractility (UC) was assessed by recording a 6-minute-long video using a 4D mode (Voluson E10; General Electric, Boston, MA), which was performed by a single operator (B.M.). MAIN OUTCOMES MEASURE(S): The contractions were seen like waves going through the endometrial cavity. They were counted on a ×15 accelerated recording video. To define high-frequency UC, we separated uterine peristalsis (contractions per minute [cpm]) into quartiles. The highest quartile defined the hypercontractility group (>1.51 cpm; n = 41), considering the remaining quartiles as the normal contractility group (≤1.51 cpm; n = 156). The Mann-Whitney U test was performed. The intraclass correlation coefficient was used to validate variability. P <.05 was considered significant. SPSS version 21.0 was used for the statistical analysis. The institutional review board's approval was obtained. RESULT(S): Overall, an average of 1.1 cpm was found in the study population. There were no differences between the groups (hypercontractility vs. normal contractility) in terms of patient age and the presence of any uterine factor (adenomyosis, myomas, adhesions, or polyps). An inverse association was observed between UC and progesterone levels. Low progesterone levels (15.9 vs. 19.5 ng/mL; P = .027) were observed in the HUP and NUP group, respectively. The intraclass correlation coefficient to evaluate the interobserver variability was 0.75 (0.63-0.85; P = .000). CONCLUSION(S): Four-dimensional ultrasound assessment provides a dynamic view of uterine contractions, including their directionality and frequency. Even though recurrent implantation failure is yet a title of obscure definition and probably associated with multiple factors, a subgroup of patients with elevated UC associated with "low" progesterone levels may have a potential effect on their outcomes. Four-dimensional scan evaluation of UC constitutes a promising diagnostic tool in clinical practice; however, larger studies confirming our initial results are still pending.