Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Analysis of the uterine artery pulsatility index on the day of endometrial transformation and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer.

Objective: The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. Results: The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). Conclusion: In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.

Immediate Effect of Electro-acupuncture on Endometrial Blood Flow in Patients with Recurrent Implantation Failure: A Randomized Controlled Trial.

OBJECTIVE: To investigate the immediate effects of electro-acupuncture (EA) on endometrial blood flow among recurrent implantation failure (RIF) patients. METHODS: Eighty RIF patients, enrolled from March 2022 to December 2022, were randomly allocated into either the EA group (40 cases) or the waiting-list (WL) group (40 cases) by using a random number table. The EA group underwent acupuncture at points of Shenting (GV 24), Baihui (GV 4), Benshen (GB 13), bilateral Zigong (EX-CA 1), Huangshu (KI 16), Sanyinjiao (SP 6) and Xuehai (SP10), and electric acupuncture apparatus was connected to EX-CA 1, KI 16, SP 6, and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound, while the WL group received no intervention. The primary outcome measured was the endometrial volume blood flow. The secondary outcomes included the bilateral uterine artery index, endometrial volume, endometrial blood flow type, vascular distribution index (VIMV) for endometrial and ovary, clinical pregnancy rate, and embryo implantation rate. RESULTS: In the EA group, there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA (P<0.05). Both the endometrial blood flow type and VIMV for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment (P<0.05). Conversely, no significant disparities were observed in vascular index, flow index, vascular blood flow index, uterine arterial blood flow indices, endometrial volume, clinical pregnancy rate and embryo implantation rate between the two groups after treatment (P>0.05). Besides, no adverse events related to EA were observed. CONCLUSIONS: EA can promptly ameliorate VIMV for the endometrial and right ovary, and endometrial blood flow type. Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes. (Trial registration No. ChiCTR2200057377).

Cell Chirality of Micropatterned Endometrial Microvascular Endothelial Cells.

Chirality is an intrinsic cellular property that describes cell polarization biases along the left-right axis, apicobasal axis, or front-rear axes. Cell chirality plays a significant role in the arrangement of organs in the body as well as in the orientation of organelles, cytoskeletons, and cells. Vascular networks within the endometrium, the mucosal inner lining of the uterus, commonly display spiral architectures that rapidly form across the menstrual cycle. Herein, the role of endometrial-relevant extracellular matrix stiffness, composition, and soluble signals on endometrial endothelial cell chirality is systematically examined using a high-throughput microarray. Endometrial endothelial cells display marked patterns of chirality as individual cells and as cohorts in response to substrate stiffness and environmental cues. Vascular networks formed from endometrial endothelial cells also display shifts in chirality as a function of exogenous hormones. Changes in cellular-scale chirality correlate with changes in vascular network parameters, suggesting a critical role for cellular chirality in directing endometrial vessel network organization.

An investigation of endometrial vascularity in normally menstruating women and those in other physiological states using 3D ultrasound imaging.

OBJECTIVES: This study aimed to determine the normal vasculature indices of the endometrium and to correlate them with those in various physiological states. METHODS: Women undergoing ultrasound at the Feto-Maternal Center, Qatar in 2020-2021 as part of their gynecologic evaluation were enrolled into the study. They were divided into those with normal menses and no additional pathology, those following spontaneous miscarriage, postpartum and menopausal. Three-dimensional (3D) evaluation of the endometrial vasculature was done and the parameters quantified included vascularization index (VI), flow index (FI), vascularization flow index (VFI), endometrial thickness, endometrial volume and uterine volume. JASP, an open-source statistical analysis software, was used for analysis and an independent t-test to compare the vascularity indices. A multivariate regression analysis was also done to look at the factors affecting the endometrial vascular indices within the luteal phase. RESULTS: A total of 461 women were studied: 122 in the follicular phase, 199 in the luteal phase, 90 after a spontaneous miscarriage, 29 postpartum, and 16 menopausal. The vascularity indices were highest after miscarriage and lowest postnatally. There were no significant effects of age, gravida, para, or abortions on VI and VFI. However, there was a significant positive effect of age on FI (P = 0.019) There was a significant increase in endometrial volume and thickness in the luteal phase as compared to follicular phase (P < 0.01), but there was no difference in the vascularity indices. The uterine and endometrial volume in the postnatal group were nearly double that of the luteal group (P value <0.01 and 0.014, respectively). There was a significant decrease in flow index in the postnatal group compared to the luteal group (P < 0.01), suggesting low flow intensity in the postnatal group. CONCLUSIONS: Endometrial vascular indices measured using 3D Doppler can be used to determine normal vascular indices and vary with physiological states such as after miscarriages, postnatally and in the menopausal states.

Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

The influence of radical trachelectomy on endometrial thickness in in vitro fertilization-embryo transfer.

AIM: Both morbidity and mortality rates of cervical cancer are increasing, especially in reproductive-aged women. Radical trachelectomy (RT) is an effective fertility-preserving surgery for early-stage cervical cancer. This study aimed to determine the influence of RT on endometrial thickness during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Forty-four patients had undergone RT, and 23 women undergoing IVF-ET treatment (105 ET cycles) were included. Endometrial thickness during hormone replacement therapy (HRT) was retrospectively evaluated and compared between patients with and without RT. RESULTS: Eleven patients (50 ET cycles) in the RT group and 12 (52 ET cycles) in the control group were investigated. Compared with the control group, higher ET cancellation rates were observed in patients in the RT group (1 of 52 cycles [control group] vs. 8 of 50 cycles [RT group], p < 0.01). Endometrial thinning was not affected by patient age at first IVF-ET treatment, history of artificial abortion, preservation of uterine arteries during RT, or postoperative chemotherapy (p = 0.27, 1, 1, and 1, respectively). CONCLUSIONS: Our data revealed that RT influenced endometrial thickness in IVF-ET. This was not affected by the background of the patients or perioperative management in this study. We could not reveal the underlying mechanism, but it is postulated that the transient postoperative uterine blood flow status and postoperative infections may have some effect on the endometrium. To resolve these issues, accumulation of evidences are required. We recommend informing patients about the impact of RT on IVF-ET before starting assisted reproductive technology (ART).

Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET).@*METHODS@#Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births.@*RESULTS@#Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05).@*CONCLUSIONS@#Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

Pregnancy prediction via ultrasound-detected endometrial blood for hormone replacement therapy-frozen embryo transfer: a prospective observational study.

BACKGROUND: This study aimed to assess the predictive value of endometrial blood flow branches on pregnancy outcomes after hormone replacement therapy-frozen embryo transfer (HRT-FET). METHODS: This prospective observational study involved 292 reproductive-aged women who underwent endometrial receptivity assessment in a tertiary care academic medical center in southwest China using power Doppler ultrasonography during HRT-FET. Three-dimensional power Doppler ultrasound was performed on the day of endometrial transformation and the day before embryo transfer. The endometrial blood flow branches of the endometrial and subendometrial regions were compared in the non-pregnant and pregnant groups at the two time points mentioned above. RESULTS: The endometrial blood flow branches were higher in pregnant patients than in non-pregnant patients on the day of endometrial transformation (P = 0.009) and the day before embryo transfer (P = 0.001). Changes in endometrial blood flow pattern and endometrial blood flow branches at the two time points did not differ among the pregnancy outcome samples. After adjusting for age, antral follicles, and embryos transferred, the endometrial blood flow branches on the day before embryo transfer was the independent factor influencing the chance of clinical pregnancy, with an odds ratio of 3.001 (95% confidence interval: 1.448 - 6.219, P = 0.003). CONCLUSIONS: Endometrial blood flow perfusion during the peri-transplantation period of the HRT-FET cycle is a good indicator of pregnancy outcomes, suggesting that valuation of endometrial branches via power Doppler ultrasound is a simple and effective approach for achieving indicator measurements.

Terapia manual para la mejora del flujo sanguíneo de las arterias uterinas en el área vascular endometrial/subendometrial en mujeres infértiles mediante ultrasonografía tridimensional: estudio piloto / Manual therapy for the improvement of blood flow of the uterus arteries in the endometrial/subendometrial vascular area in infertilized women through three-dimensional ultrasonography: Pilot study

Objetivo Evaluar cuantitativamente el efecto de la técnica manual de fisioterapia sobre el volumen endometrial y los valores del histograma en participantes infértiles. Métodos Estudio piloto, analítico, intervencionista, con grupo control, desarrollado en la Clínica Juana Crespo sobre 34 participantes infértiles. Se midió el volumen endometrial y subendometrial del útero, los índices de vascularización (IV%), el índice de flujo de vascularicación (IVF%) y el índice de flujo (IF%) mediante ultrasonografía Doppler 3D, después de aplicar la técnica manual de movilización de tejidos blandos de las fosas ilíacas. Resultados En el grupo experimental la comparación de los volúmenes endometriales totales antes (M=41,09) y después de la aplicación de la técnica fisioterápica (M=47,29) presentó diferencias estadísticamente significativas, z=–3,946 (p<0,001), r=–0,73, al igual que el estudio de los histogramas, alcanzando diferencias significativas en el índice de flujo (IF%) entre los registros pre (M=35,22) y post (M=37,62), z=–2,849 (p<0,005), r=–52. El índice de flujo de vascularización (IFV%) y el índice de vascularización (IV%) no tuvieron diferencias significativas entre el tiempo pre y post. Los histogramas IV%, IF%, IFV% indican p<0,005. Conclusiones La técnica de fisioterapia aumenta los volúmenes endometriales totales y el IF% endometrial después de su aplicación, aunque no varían las variables IV% e IFV% (AU)

Objective To quantitatively assess the effect of physical therapy manual technique on endometrial volume and histogram values in infertile participants. Methods Pilot, analytical, interventional study, with a control group, developed at the Juana Crespo Clinic on 34 infertile participants. The endometrial and subendometrial volume of the uterus, Vascularization Indices (VI%), Vascularization Flow Index (VFI%) and Flow Index (IF%) were measured by 3D Doppler Ultrasonography, after applying the manual mobilization technique in soft tissue of the iliac fossa. Results In the experimental group, the comparison of the total endometrial volumes before (M=41.09) and after the application of the physiotherapy technique (M=47.29) presented statistically significant differences, z=-3.946 (p<0.001), r=-, 73, like the study of histograms, reaching significant differences in the flow index (IF%) between the pre (M=35.22) and post (M=37.62) records, z=-2.849 (p<0.005), r=- 52. The vascularization flow index (IFV%) and the vascularization index (IV%) did not have significant differences between the pre and post time. Histograms IV%, IF%, IFV% indicate p<0.005. Conclusions The physiotherapy technique increases the total endometrial volumes and the endometrial IF% after its application, although the IV% and IFV% variables do not vary (AU)

Comparison of uterine, endometrial and subendometrial blood flows in predicting pregnancy outcomes between fresh and frozen-thawed embryo transfer after GnRH antagonist protocol: a retrospective cohort study.

This retrospective cohort study aimed to compare endometrial receptivity and pregnancy rate between fresh embryo transfer (ET) and frozen-thawed ET after gonadotrophin-releasing hormone (GnRH) antagonist protocol in normal ovarian responders. The patients were divided into two groups: the fresh ET group and the frozen-thawed ET group. Uterine artery resistance index (RI) and endometrial thickness were lower in the frozen-thawed ET group. The proportion of detectable endometrial-subendometrial flow was significantly higher in the frozen-thawed ET group. There was no significant difference in miscarriage rate between the two groups. Frozen-thawed ET group had a significantly higher CPR (56.0% vs. 48.1%), implantation rate (32.2% vs. 26.4%), and LBR (45.4% vs. 36.5%) than the fresh ET group. In GnRH antagonist protocol, elective frozen-thawed ET should be ideally taken, as this could improve embryo implantation rate, clinical pregnancy rate, and live birth rate, thus presenting an effective strategy to enhance the embryo utilization rate.IMPACT STATEMENTWhat is already known on this subject? The clinical pregnancy rate following fresh embryo transfer (ET) was lower than frozen-thawed ET after GnRH antagonist protocol. IVF success depends on embryo quality, embryo-endometrium interaction and endometrial receptivity. A good blood supply toward the endometrium is generally considered a requirement for implantation.What do the results of this study add? Uterine artery RI and endometrial thickness were significantly lower in the frozen-thawed ET group. The proportion of detectable endometrial-subendometrial flow was significantly higher in the frozen-thawed ET group. Frozen-thawed ET group had a significantly higher clinical pregnancy rate, implantation rate and live birth rate than the fresh ET group after GnRH antagonist protocol.What are the implications of these findings for clinical practice and/or further research? In GnRH antagonist protocol, elective frozen-thawed ET should be ideally taken, as this could improve embryo implantation rate, clinical pregnancy rate and live birth rate, thus presenting an effective strategy to enhance the embryo utilization rate.

Predictive Value of Endometrial Receptivity for Pregnancy Outcomes of In-vitro Fertilization Embryo Transfer for Patients of Different Ages.

Context: In recent years, the number of women with unexplained infertility has increased, and clinicians consider poor endometrial receptivity (ER) to be one of the main reasons. ER can have great predictive value for in-vitro fertilization embryo transfer (IVF-ET)-induced pregnancy. Objective: The study intended to investigate the predictive value of ER-endometrial thickness (EMT) and type and hemodynamic parameters-using color-doppler ultrasound on the pregnancy outcome of IVF-ET for women of different ages. Design: The research team performed a prospective controlled study. Setting: The study took place at the Department of Reproductive Medicine at Hebei Reproductive Hospital in Shijiazhuang, China. Participants: Participants were 841 infertile patients undergoing IVF-ET treatment at the hospital between March 01, 2018 and December 30, 2018. The research team divided participants into two groups: (1) participants diagnosed as having a clinical pregnancy after IVF-ET became the pregnancy group, with 439 participants, and (2) participants who didn't become pregnant became the nonpregnancy group, with 402 participants. Outcome Measures: The research team: (1) measured EMT, (2) determined endometrium types, (3) classified the intimal and subintimal blood flow, and (4) determined the hemodynamic parameters of the endometrium and subendometrium. The team also measured: (1) the systolic blood flow velocity (VS), (2) diastolic blood flow velocity (VD), and (3) average blood flow velocity (VM) three times and recorded the average value. Results: Statistically significant differences existed in the pregnancy and implantation rates among the different age groups for the groups with EMTs of <8 mm and 8-13 mm (P < .05). The results were similar in the endometrial Type A and endometrial Type B groups as well as between the endometrial blood flow Type 1 and Type 2 groups (P < .05). The distribution of endometrial blood flow types was significantly different between the groups (P = .002). In addition, statistically significant differences existed in the implantation rates between the <30 years and 30-34 groups in different blood-flow-type groups (P < .05). Based on the results of the ROC curve, high-quality embryos (0.566, 95%CI: 0.527-0.605) and endometrial blood flow types (0.554, 95%CI: 0.515-0.593) could not predict clinical pregnancy. Conclusions: The pregnancy and implantation rates increased between the <30 and 30-34 age groups and them decreased between the age groups as age increased. EMT, endometrial type, and blood flow type can be valuable parameters in predicting the implantation and pregnancy rates of patients of different ages.

Endometrial microstimulation effects on endometrial receptivity assessed by transvaginal color Doppler sonography.

OBJECTIVE: This study investigated the effect of endometrial microstimulation (EM) on endometrial receptivity using transvaginal color Doppler sonography (TVCDS). METHOD: Women of childbearing age who were preparing to conceive (n = 90) were randomly divided into the EM group (n = 30), who were examined by EM on days 3-5 of the menstrual cycle, and the control group (n = 60). TVCDS was conducted during the implantation window phase, and endometrial thickness, endometrial pattern, endometrial movement, blood flow type, and uterine and spiral arterial hemodynamic parameter measurements were made. The groups were compared to identify differences. RESULTS: Endometrial thickness (0.97 ± 0.18 cm and 0.95 ± 0.17 cm), endometrial movement (type 1: 46.7% and 51.7%; type 2: 30.0% and 28.3%; type 3: 6.7% and 5.0%; type 5: 16.7% and 15.0%), and hemodynamic parameters of the uterine (pulsatility index [PI]: 2.46 ± 0.50 and 2.41 ± 0.48; resistance index [RI]: 0.85 ± 0.05 and 0.84 ± 0.05) and spiral (PI: 1.11 ± 0.32 and 1.19 ± 0.33; RI: 0.48 ± 0.11 and 0.51 ± 0.08) arteries did not differ significantly between groups (P > 0.05). However, the endometrial pattern (a trilaminar pattern: 80.0% and 58.3%; P = 0.041) and blood flow type (type I: 16.7% and 43.3%; type II: 63.3% and 40.0%; type III 20.0% and 16.7%; P = 0.038) differed significantly between groups. CONCLUSION: Endometrial microstimulation did not alter endometrial pathological staging, endometrial thickness, or movement, nor did it affect uterine and spiral arterial blood flow parameters. However, it may be able to abrade abnormal endometrial tissue, optimizing the endometrial pattern. Endometrial microstimulation may support local spiral artery regeneration and increase endometrial blood supply in new cycles.

Assessment of uterine receptivity by endometrial and sub-endometrial blood flow using SlowflowHD in hormone prepared frozen embryo transfer cycles: a pilot study.

PURPOSE: Utilizing SlowflowHD as a measurement of endometrial and sub-endometrial blood flow in women with infertility undergoing frozen embryo transfer (FET) cycles and correlation with pregnancy outcomes. METHODS: A prospective pilot study of 99 women undergoing hormone replacement FET cycles. Ultrasounds were performed with Voluson E8 at 3-time points: day 15, day of transfer, and 11 days post transfer (T + 11). SlowflowHD Doppler blood flow indices in the endometrium and sub-endometrium were compared in women who achieved pregnancy with those who did not. RESULTS: Using SlowflowHD, both pregnant and non-pregnant women had similar trends with decreased endometrial blood flow day of transfer compared with day 15. However, there was a borderline significantly lower mean percentage decrease of endometrial blood flow in women achieving a pregnancy (28.3% vs 42.9%). Significantly higher numbers of pregnant women had a 20% or less decrease in blood flow (21 vs 9) with increases in mean percentage blood flow on T + 11 (pregnant 39.59% vs non-pregnant 25.20%). The RI and S/D ratio in the spiral arteries was also significantly higher on transfer day in women who had a live birth RI (0.68 vs 0.65) and S/D (3.91 vs 3.17). CONCLUSION: There are blood flow changes both in pregnant and non-pregnant patients with decreases in blood flow after progesterone replacement. Pregnancy and live births were associated with a lower mean percentage drop in blood flow from day 15 to the day of transfer and elevated RI and S/D ratio on transfer day.

Reduced Hemoglobin Signal and Improved Detection of Endogenous Proteins in Blood-Rich Tissues for MALDI Mass Spectrometry Imaging.

Mass spectrometry imaging provides a powerful approach for the direct analysis and spatial visualization of molecules in tissue sections. Using matrix-assisted laser desorption/ionization mass spectrometry, intact protein imaging has been widely investigated for biomarker analysis and diagnosis in a variety of tissue types and diseases. However, blood-rich or highly vascular tissues present a challenge in molecular imaging due to the high ionization efficiency of hemoglobin, which leads to ion suppression of endogenous proteins. Here, we describe a protocol to selectively reduce hemoglobin signal in blood-rich tissues that can easily be integrated into mass spectrometry imaging workflows.

Comparative study of endometrial & subendometrial angiogenesis in unexplained infertile versus normal fertile women.

Background & objectives: Local angiogenesis in endometrium has been shown to be an essential pre-requisite for endometrial receptivity needed for implantation and gestation. Recently, numerous diagnostic gears have been projected to 'measure' or 'estimate' the endometrial receptivity relying upon angiogenic factors helping throughout implantation. This study evaluated the endometrial and subendometrial blood flow and the local endometrial gland vascular endothelial growth factor (EG-VEGF) expression as markers of local angiogenesis. Methods: The present study was done to give quantitative assessment of endometrial thickness (ET), endometrial blood flow and subendometrial blood flow colour Doppler indices with endometrial vascular zones. Endometrial biopsy was taken and with VEGF stained and scored with immunohistochemistry. Results: The mean ET for fertile women was 9.41 mm, while in unexplained infertile women it was around 7.90 mm. Upon comparison of ET with EG-VEGF which is considered as a gold standard with correlation coefficient, the present study suggested a positive correlation of EG-VEGF with ET, endometrial pulsatility index (PI), and subendometrial PI also the vascular zones were considered as significant. However, a strong negative correlation was seen with subendometrial resistivity index and PI. Interpretation & conclusions: The present study suggests that uterine ultrasound, uterine colour Doppler and EG-VEGF are parameters which can be used as markers of local angiogenesis for endometrial receptivity in the evaluation of women with unexplained infertility.

Minimally invasive adenomyomectomy via a laparoscopic-assisted approach compared to a laparoscopic or laparotomic approach.

OBJECTIVE: The present study assessed the safety and benefits of laparoscopic-assisted adenomyomectomy compared to laparoscopic or laparotomic adenomyomectomy. MATERIALS AND METHODS: This study was a retrospective comparative study. A total of 277 patients underwent adenomyomectomy between January 2016 and January 2019 at the Department of Obstetrics and Gynaecology, Ulsan University Hospital, including 25 with laparoscopic-assisted adenomyomectomy, 82 with laparoscopic adenomyomectomy, and 170 with laparotomic adenomyomectomy. Laparoscopic-assisted adenomyomectomy consisted of a laparoscopic uterine artery procedure to reduce blood loss and a minimal incisional for laparotomic adenomyomectomy. An additional laparoscopic surgery was performed for possible pelvic pathology. RESULTS: Data on patient demographics, surgical indications, operative times, estimated blood loss (EBL), short-term complications, and postoperative hospital stays were compared. The laparoscopic-assisted surgery (LAS) and laparotomic groups were comparable in average EBL (208.0 ± 128.8 vs. 193.6 ± 193.0 ml, p = 0.11), weight of removed mass (85.5 ± 71.7 vs. 108.2 ± 91.9 g, p = 0.39), and postoperative hospital days (HDs) (4.5 ± 1.0 vs. 4.7 ± 0.8 days, p = 0.27). These values were lower in the laparoscopic group (EBL 119.5 ± 79.6 ml, mass weight 39.3 ± 25.9 g, HD 3.6 ± 0.8 days). Additional procedures, including myomectomy and combined severe endometriosis surgery, were more frequently performed in the LAS group than the laparotomic group. The mean operating time was longer in the LAS group (179.8 ± 36.6 min) than the other groups (laparoscopy 99.9 ± 40.6 min, p < 0.00; laparotomy 133.0 ± 41.1 min, p < 0.00). The three groups did not differ significantly in transfusion rates, hemoglobin changes, or perioperative complications. However, febrile morbidity was lower in the laparoscopic group than the LAS and laparotomic groups. CONCLUSION: LAS adenomyomectomy allows for maximal debulking of adenomyosis via extracorporeal and intracorporeal procedures while retaining the advantages of the laparoscopic approach. Additional pelvic surgery for benign uterine and adnexal pathology may easily be performed with this approach.

G-CSF and IL-6 may be involved in formation of endometriosis lesions by increasing the expression of angiogenic factors in neutrophils.

Evidence accumulated in recent years has revealed that neutrophils are involved in the initial establishment of endometriosis, which is well-known as a chronic inflammatory disease. So far, why and how neutrophils promote the formation of early endometriosis are still unclear. In this study, using a mouse model of endometriosis, we demonstrated that endometriosis mice (EMs mice) had a significantly increased number of neutrophils in peritoneal fluids and lesions, and increased levels of granulocyte colony-stimulating factor (G-CSF) and IL-6 in serum and peritoneal fluids compared to the control group. In the neutrophils and uterine fragments co-injection experiment, neutrophils regulated by G-CSF and IL-6 had a similar effect to neutrophils from EMs mice, increasing the number, area, weight and microvessel density (MVD) of endometriotic lesions. Blocking the effect of G-CSF and IL-6 in EMs mice resulted in a decrease in the number, area and weight of endometriotic lesions. Following the depletion of neutrophils in vivo using a anti-Ly6G antibody, the MVD in the lesions of mice treated with neutrophils from EMs mice and neutrophils from pG/pI6 mice were significantly reduced. Neutrophils from EMs mice and neutrophils from pG/pI6 mice altered the expression levels of Mmp9, Bv8 and Trail genes compared to the neutrophils from PBS-treated mice. IL-6 together with G-CSF induced a higher expression of phospho-STAT3 and STAT3 in neutrophils. These findings suggest that neutrophils modulated by G-CSF and IL-6 through the STAT3 pathway alter the expression levels of the angiogenesis-related genes Mmp9, Bv8 and Trail, and may promote the establishment of early endometriosis.

Peri-estrus ovarian, uterine, and hormonal variables determine the uterine luminal fluid metabolome in beef heifers.

In cattle, uterine luminal fluid (ULF) is the main source of molecules that support embryo development and survival during the peri-implantation period. Our overarching hypothesis is that peri-estrus changes in uterine function, including ULF accumulation and absorption, are uneven among individuals, and affect ULF composition and fertility. Our objectives were (1) to characterize temporal and spatial changes in ULF volume, endometrial and luteal blood perfusion, endometrial and luteal size, and circulating progesterone concentrations during the peri-estrus period in beef heifers and (2) to associate such changes with the metabolite composition in the ULF, 4 days after estrus (d 0). Fourteen Bos indicus heifer that presented a PGF2α responsive CL received 500 µg PGF2α analog i.m. and were examined daily by rectal B-mode and pulse-wave color-Doppler ultrasonography until the fifth day after estrus (d 5). The composition of the ULF was analyzed by targeted mass spectrometry on d 4. Multivariate analyses clustered heifers according to ovarian, uterine, and hormonal variables in clusters A (n = 5) and B (n = 8 heifers). Concentrations of Pro, Ala, Leu, Gly, Val, Lys, Ile, Phe, Asp, Orn, Tyr, Arg, Trp, Suc, Cit, ADMA, the sum of essential Amino Acids (AA), sum of nonessential AA, sum of aromatic AA, and total AA were greater in cluster A (FDR ≤ 0.05). ULF volume dynamics and uterine, ovarian, and hormonal variables during the peri-estrus period presented a concerted variation among heifers within clusters, which was associated with the ULF composition 4 days after estrus.