IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia.

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 wk of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the Reduced Uterine Perfusion Pressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized that IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted intraperitoneal mini-osmotic pumps infusing recombinant rat IL-33 (1 µg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14 to 19. We found that IL-33 supplementation in RUPP rats reduces maternal blood pressure and improves the uterine artery resistance index (UARI). In addition to physiological improvements, we found decreased circulating and placental cytolytic Natural Killer cells (cNKs) and decreased circulating, placental, and renal TH17s in IL-33-treated RUPP rats. cNK cell cytotoxic activity also decreased in IL-33-supplemented RUPP rats. Furthermore, renal ROS and placental preproendothelin-1 (PPET-1) decreased in RUPP rats treated with IL-33. These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, renal ROS, and PPET-1 expression. These data suggest that IL-33 may have therapeutic potential in managing PE.NEW & NOTEWORTHY Though decreased IL-33 signaling has been clinically associated with PE, the mechanisms linking this signaling pathway to overall disease pathophysiology are not well understood. This study provides compelling evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction observed in response to placental ischemia, such as in PE. Data presented in this study submit the IL-33 signaling pathway as a possible therapeutic target for the treatment of PE.

Study on the clinical value of Vitamin D in recurrent spontaneous abortion: Revisiting the Importance of Vitamin D.

OBJECTIVE: This study explores the possible pathogenesis of recurrent spontaneous abortion (RSA) caused by vitamin D (VD), provides evidence-based bases for prevention and treatment of RSA, improves female reproductive health. METHODS: This study randomly selected 305 patients without spontaneous abortion (SA0), 216 patients with a spontaneous abortion (SA1) and 200 patients with RSA from 1421 women of childbearing age who visited the RSA specialty clinic of Hangzhou First People's Hospital from January 2021 to June 2023 to conduct a prospective clinical study. Then, we collected the data of clinical diagnosis and treatment, conducted intervention and follow-up, and finally executed statistical analysis. RESULTS: (1) RSA patients were significantly older than the other two groups. (2) The rates of VD deficiency in SA1 and RSA patients were significantly higher than those in SA0. (3) When BMI < 20  or > 24 kg/m2 , there were abnormal increase in VD and increased number of spontaneous abortions. (4) The bilateral S/D of the VD-sufficient, VD-insufficient and VD-deficient groups gradually increased with statistical significance (p ≤ .018). (5) Among the 65 cases undergoing embryo chromosome examinations, chromosomal abnormalities accounted for 55.38% and 69.05% in RSA patients. (6) Among 186 patients with abnormal ACA, there was a certain negative correlation between ACA and VD, which was stronger among RSA patients. Moreover, ACA significantly decreased (p < .001) after effectively supplementing VD, and the miscarriage rate of re-pregnancy also decreased. CONCLUSION: The rate of VD deficiency is higher in RSA patients. VD deficiency may be related to the age of women of childbearing age and too low or high BMI, and may cause abnormal plasma antiphospholipid antibodies, increased uterine artery resistance and abnormal chromosomal division during fertilization, leading to spontaneous abortion and even RSA. The improvement of VD deficiency may reduce the risk of RSA occurrence.

Efficacy of Traditional Chinese Herbs combined with bioelectrical stimulation on patients with kidney deficiency and blood stasis type thin endometrium: a retrospective observational study.

OBJECTIVE: This study aimed to investigate the efficacy of Traditional Chinese Herbs (TCH) combined with bioelectrical stimulation (BES) on patients with kidney deficiency and blood stasis type thin endometrium. PATIENTS AND METHODS: A retrospective observational study was conducted on 83 patients diagnosed with thin endometrium, treated in our hospital from August 2019 to August 2021. The clinical data of the patients were reviewed, and 60 eligible patients were categorized into two groups based on the treatment they received: the TCH-BES group (n=30, patients received Femoston, TCH and BES treatment) and the control group (n=30, patients received Femoston only). The endometrial thickness (EMT), uterine artery resistance index (RI) and pulsatility index (PI), serum reproductive hormone levels, traditional Chinese medicine (TCM) syndrome scores, and clinical pregnancy outcomes between the two groups were compared. Continuous data were described as mean ± standard deviation (X- ± S). Student's t-test was used for comparison between the two groups and paired-sample t-test was used for comparison within the same group before and after the treatment. RESULTS: A total of 60 patients with thin endometrium, aged 20-35 years (average, 31.67±3.19 years), were included in this study. After the treatment, the EMT, E2 and progesterone (P) levels of the TCH-BES group were higher than that of the control group (p<0.001, p<0.05 and p<0.001, respectively), the PI, RI level and TCM syndrome scores of the TCH-BES group were lower than those of the control group (p<0.001). The clinical efficacy and pregnancy rate in the TCH-BES group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: TCH combined with EBS has a satisfactory efficacy on patients with kidney deficiency and blood stasis type thin endometrium, and improves EMT, E2 and P levels, reduces PI, RI and TCM syndrome, and eventually leads to a favorable clinical pregnancy outcome.

Cesarean Scar Pregnancies Treated by Uterine Artery Chemotherapy Embolization Combined With Ultrasound-Guided Dilation and Curettage: A Retrospective Study.

OBJECTIVES: To explore the effect of cesarean scar pregnancy (CSP) treatment by comparing uterine artery chemotherapy embolization (UACE) combined with dilation and curettage (D&C) with or without ultrasound guidance. METHODS: CSP patients treated with UACE combined with D&C from January 2013 to December 2020 at Shuguang Hospital, affiliated to Shanghai University of Traditional Chinese Medicine were included in this retrospective study. The patients were divided into groups A and B according to whether D&C was guided by ultrasound. RESULTS: Forty-eight patients with CSP diagnosed by transvaginal ultrasound were included in this study, whose gestational age was <8 weeks. There were no significant differences in the basic clinical characteristics of the two groups. The success rates of the 2 groups were no significant difference, 100% (27/27) in group A and 85.7% (18/21) in group B. The maximal intraoperative blood loss of group A was 100 mL and that of group B was 150 mL. There was no uterine perforation during the operation. Ultrasound guidance can shorten the D&C operation time, reduce intraoperative bleeding during D&C, and decrease the residual rate of trophoblastic tissue after D&C. CONCLUSIONS: Ultrasound guidance can improve the safety and efficiency of UACE combined with D&C in the treatment of CSP and reduce its complications. We believe it is an optimal treatment for CSP patients who do not plan to have children in the future.

The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia.

Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (ß 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (ß 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (ß 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (ß - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (ß - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (ß - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (ß - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (ß - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1.

Successful laparoscopic surgical removal of a caesarean scar pregnancy (CSP) using temporary uterine artery ligation.

STUDY OBJECTIVE: To demonstrate a laparoscopic technique to remove a scar pregnancy. DESIGN: Stepwise demonstration of the surgical technique. SETTING: Santa Croce and Carle Hospital, Cuneo. INTERVENTION: Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial-pregnancy interface. (4) Double layer suture on the anterior uterine wall. CONCLUSION: Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively.

Enhanced Sp1/YY1 Expression Directs CBS Transcription to Mediate VEGF-Stimulated Pregnancy-Dependent H2S Production in Human Uterine Artery Endothelial Cells.

[Figure: see text].

Melatonin alters bovine uterine artery hemodynamics, vaginal temperatures, and fetal morphometrics during late gestational nutrient restriction in a season-dependent manner.

The objectives were to examine melatonin-mediated changes in temporal uterine blood flow (UBF), vaginal temperatures (VTs), and fetal morphometrics in 54 commercial Brangus heifers (Fall, n = 29; Summer, n = 25) during compromised pregnancy. At day 160 of gestation, heifers were assigned to one of the four treatments consisting of adequately fed (ADQ-CON; 100% National Research Council [NRC]; n = 13), global nutrient restricted (RES-CON; 60% NRC; n =13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). In the morning (0500 hours; AM) and afternoon (1300 hours; PM) of day 220 of gestation, UBF was determined via Doppler ultrasonography, while temperature data loggers attached to progesterone-free controlled internal drug releases were used to record VTs. At day 240 of gestation, heifers underwent cesarean sections for fetal removal and morphometrics determination. The UBF and VT data were analyzed using repeated measures of analysis of variance (ANOVA), while the morphometrics was analyzed using the MIXED procedure of SAS. Seasons were analyzed separately. In Fall, a nutrition by treatment interaction was observed, where the RES-CON heifers exhibited reduced total UBF compared with ADQ-CON (5.67 ± 0.68 vs. 7.97 ± 0.54 L/min; P = 0.039). In Summer, MEL heifers exhibited increased total UBF compared with the CON counterparts (8.16 ± 0.73 vs. 6.00 ± 0.70 L/min; P = 0.048). Moreover, there was a nutrition by treatment by time interaction in VT for Fall and Summer heifers (P ≤ 0.005). In Fall, all groups had decreased VT in the morning compared with the afternoon (P < 0.05). Whereas, in Summer, VT increased for ADQ-CON and RES-CON (P < 0.0001) from morning to afternoon, the ADQ-MEL and RES-MEL remained constant throughout the day (P = 0.648). Furthermore, the RES-MEL-PM exhibited decreased VT compared with ADQ-CON-PM (38.91 ± 0.09 vs. 39.26 ± 0.09 °C; P = 0.018). Lastly, in Fall, a main effect of nutrition was observed on fetal weights, where the RES dams had fetuses with decreased body weight when compared with ADQ (24.08 ± 0.62 vs. 26.57 ± 0.64 kg; P = 0.0087). In Summer, a nutrition by treatment interaction was observed on fetal weights where the RES-CON dams had fetuses with reduced weight when compared with ADQ-CON and RES-MEL (P < 0.05). In summary, nutrient restriction decreased UBF and melatonin supplementation increased UBF depending on the season. Additionally, melatonin appeared to decrease VT and rescue fetal weights when supplemented in the Summer.

Melatonin ameliorates hypertension in hypertensive pregnant mice and suppresses the hypertension-induced decrease in Ca2+-activated K+ channels in uterine arteries.

Decreased secretion of melatonin was reported to be associated with an enhanced risk of hypertension and diabetes. However, the effect of melatonin on gestational hypertension (GH) and the underlying mechanism remain unclear. A GH mouse model was established via electrical stimulation. The hypertensive phenotypes were indicated by systolic blood pressure (SBP) and urinary protein levels. Uterine artery (UtA) endothelial function was detected by relaxation, peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI). Protein expression levels were determined using immunochemistry and Western blots. Pregnancy outcomes were indicated by the fetal live ratio, fetal weight and placental weight. Melatonin supplementation ameliorated hypertensive phenotypes in the mice with GH and enhanced UtA endothelial response to acetylcholine. The BKCa potassium channel was involved in the effect of melatonin on UtA endothelial function, and melatonin promoted BKCa potassium channel expression and function in UtAs. Finally, melatonin improved pregnancy outcomes in pregnant mice. In conclusion, melatonin ameliorates hypertension in hypertensive pregnant mice and suppresses hypertension-induced decreases in Ca2+-activated K+ channels in uterine arteries.

Laparoscopic Uterine Artery Occlusion Combined with Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for Adenomyosis: A Video Case Report.

OBJECTIVE: Adenomyosis usually causes dysmenorrhea and anemia. Clinically, it is difficult to be treated with medicine or by traditional surgery, however, hysterectomy is always performed for radical treatment. In this article, we introduce a new method that could control the dysmenorrhea and the anemia through laparoscopic uterine artery occlusion (LUAO) combined with uterine-sparing pelvic plexus block and partial adenomyomectomy for uterus preservation. DESIGN: Surgical video article. Local institutional review board approval for the video reproduction was obtained. SETTING: A 42-year-old patient, who had a history of a previous cesarean delivery, was admitted to our department with complaints of progressive dysmenorrhea for more than 5 years and aggravated with anemia for 1 year. The patient had failed treatment with traditional Chinese medicine and gonadotropin-releasing hormone and had to take painkillers for nearly half a year. The patient had no desire for another pregnancy. After careful consideration, the patient strongly rejected hysterectomy and demanded the preservation of the uterus, insisting on the integrity of the organs. A gynecologic examination showed that the uterus was hard and enlarged similar to one that is more than 8 gestational weeks, without tender nodules in the rectouterine pouch. The visual analog scale pain score was 7, and her hemoglobin was 93 g/L (after correction). The preoperative magnetic resonance imaging implied that there was 1 lesion in the posterior wall and the maximum diameter of the lesion was 7.8 cm. INTERVENTIONS: We performed laparoscopic partial adenomyomectomy combined with occlusion of uterine artery to limit the amount of intraoperative bleeding, dissected the uterine branch of pelvic plexus nerve, and performed electrocoagulation blocking to relieve the dysmenorrhea. The specific operation procedures are as follows (Video): Firstly, we opened the peritoneum through Cheng's triangle, which contained the external iliac blood vessels, the round ligament, and the infundibulopelvic ligament (Fig. 1). Secondly, we separated the lateral rectal space and exposed the ureter, the internal iliac artery, the uterine artery, and the deep uterine vein. Thirdly, we found that the pelvic plexus was located on the outside of the sacral ligament and was approximately 2 to 3 cm below the ureter, going against the sacral ligament and passing through below the deep uterine vein (Supplemental Video 1). Fourthly, we separated the 4 layers of the paracervix [1]. The first layer included the internal iliac artery and the uterine artery. The second layer was the ureter. The third layer was the deep uterine vein. The last layer was the pelvic plexus, which involved the forward-going bladder branch, the inward-going uterine branch, and the downward-going rectal branch (Supplemental Video 2). These anatomic structures are similar to the complex architecture of an overpass called the Cheng's Cross [2] (Fig. 2). In this operation, only the uterine artery and the uterine branch would be blocked. Finally, we performed the partial adenomyomectomy. The endometrium, the myometrial tissues, and the serosa were repaired in some layers with continuous suture, depending on the depth of incision. The operation time was 92 minutes, and the intraoperative hemorrhage was approximately 50 mL. The patient was able to get out of bed on the first day after the operation and urinate after removing the catheter. On the second day after the surgery, the patient had exhaustion and defecation. From the third day after the surgery, gonadotropin-releasing hormone (Goserelin Acetate Sustained-Release Depot,3.6mg each, subcutaneous injection, name of the enterprise: AstraZeneca UK Limited) was used every 4 weeks, with a total of 3 times. Menstruation began on the 67th day after withdrawal of the drug. The results of postoperative condition of the patient followed up at 6 months after surgery were collected as follows: dysmenorrhea was significantly relieved (visual analog scale score was 2), hemoglobin was 123 g/L, and uterine volume was reduced to 43% of preoperative volume. The comparison of the patient's preoperative and postoperative magnetic resonance imaging showed that the uterus was approximately the same size as that of a woman of the same age, and the incision healed well (Fig. 3). CONCLUSION: Adenomyosis is a common gynecologic disease, mainly occurring in women of childbearing age. Adenomyosis is defined as endometrial glands and stroma that invade the myometrium and is surrounded by chronical inflammation in the endometrium [3]. Secondary dysmenorrhea and menorrhagia are the most common chief complaints in patients with adenomyosis, among which dysmenorrhea is the most unbearable symptom [2]. In the past, we had always treated adenomyosis by hysterectomy [4]. With the continuous pursuit of quality of life, it is difficult to meet clinical needs through drugs and traditional surgical methods. Uterine sparing surgery is a current trend in the treatment of adenomyosis, which enables women to maintain fertility and avoid the effects of hysterectomy on sexual function and mental discomfort. Dysmenorrhea can be divided into peripheral dysmenorrhea and central dysmenorrhea. According to our previous studies on dysmenorrhea, the uterine branch nerve has a controlling effect on dysmenorrhea [2]. The purpose of pelvic plexus uterine branch ablation is to further relieve dysmenorrhea by blocking nerve conduction pathways. Therefore, we selectively blocked the uterine branch nerve to alleviate the dysmenorrhea of adenomyosis. The uterine artery controls 90% of uterine blood flow. According to our team research, LUAO is an effective method to treat symptomatic uterine myomas and adenomyosis. We investigated the morphologic change and apoptosis occurring in myomal and adjacent myometrial tissues after LUAO. We concluded that apoptosis through mitochondrial pathways may lead to reduction of the volume of myoma and myometrium and eventually relief of symptoms [5,6]. We speculated "single organ shock uterine" to explain uterine artery occlusion (UAO) mechanism, which was different from uterine artery embolization. The single organ shock theory of UAO can still inhibit the growth of myomas effectively. It is difficult to completely remove adenomyosis lesions during surgery, especially for diffuse adenomyosis. Therefore, in our team, we performed UAO combined with resection of focal lesions in key areas for patients with diffuse adenomyosis, instead of pursuing radical resection [7,8]. The purpose of UAO is to reduce the amount of bleeding during surgery and further atrophy of residual and scattered adenomyosis lesions in utero [5,6]. The intraoperative blocking of the uterine artery can reduce intraoperative bleeding and operation time, improve operation quality, and decrease recurrence rate. In our team, this technique has been used in clinic for more than 10 years. Our previous studies have shown that LUAO combined with pelvic plexus uterine branch nerve block and resection of most of the adenomyosis has achieved satisfactory clinical efficacy as a treatment for adenomyosis [2,3]. With this procedure, we can help patients with adenomyosis retain their uterus and relieve the anxiety caused by hysterectomy. In conclusion, UAO and uterine branch ablation in uterine sparing laparoscopic treatment is a safe and effective method, which may be considered as a good choice for symptomatic adenomyosis.

Maternal folate, one-carbon metabolism and pregnancy outcomes.

Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 µg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 µg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.

Effect of Bushen Huoxue recipe on women with thin endometrial ovulation disorder and a rat model of thin endometrium resulted from kidney deficiency-related blood stasis.

To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.

Pregnancy outcome treated with stage-by-stage acupuncture and moxibustion therapy based on the chong channel being sea of blood theory in repeated IVF-ET failure patients: A randomized controlled trial.

INTRODUCTION: Acupuncture and moxibustion has become a commonly used adjuvant treatment method to improve the success rate of in vitro fertilization-embryo transfer (IVF-ET). However, There is still insufficient evidence that acupuncture treatment can improve the local microenvironment of endometrium, the endometrial receptivity, and the pregnancy outcome of patients, which is worthy of further study. METHOD/DESIGN: To investigate the effect of Stage by Stage Acupuncture and Moxibustion Therapy on endometrial receptivity and Pregnancy Outcome based on the theory of "Chong channel being sea of blood," we will conduct a multicenter randomized controlled trial. Inclusion criteria are as follows: infertile women under 45 years of age who received IVF-ET or Intracytoplasmic sperm injection cycles. The study will only be applied to women who have failed repeated implantation, that is, women who have failed 3 or more embryo transplants in the past (existing frozen embryos do not require the retrieval of eggs). Those who are not prepared to receive IVF-ET or are at risk of pregnancy, have a serious medical condition, or are egg donors will be excluded. Subjects will be randomly assigned to either the acupuncture group (IVF-ET plus stage-by-stage acupuncture and moxibustion therapy based on the "Chong channel being sea of blood" theory) or the control group (IVF-ET only). The trial required a total sample size of 246 women to compare endometrial receptivity between the 2 groups. The acupuncture group will receive acupuncture and moxibustion treatment 3 times a week starting from the third day of menstruation in the ovary stimulation cycle. One menstrual cycle was one course of treatment, and a total of 3 menstrual cycles were treated. The main outcome indicator was clinical pregnancy rate. Secondary outcome indicators were the three-dimensional volume blood flow parameters (vascularization index, flow index, and vascularization flow index) of the endometrium, endometrial thickness, endometrial volume, uterine artery PI, RI, and S/D during the "implantation window period" (20-24 days after menstruation in the ovary stimulation cycle). DISCUSSION: This study will provide important evidence for the use of Stage by Stage Acupuncture and Moxibustion Therapy Based on the "Chong Channel Being Sea of Blood" Theory in IVF. TRIAL REGISTRATION: http://www.chictr.org.cn/edit.aspx?pid=28811&htm=4 ID: ChiCTR1800017191 (07/17/2018).

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

KEY POINTS: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. ABSTRACT: Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PaO2 and SaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

Pre­eclampsia (PE) is a multisystem disorder that typically affects 2%­5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Globally, 76 000 women and 500 000 babies die each year from this disorder. Furthermore, women in low­resource countries are at a higher risk of developing PE compared with those in high­resource countries. Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two­stage process. The first stage is caused by shallow invasion of the trophoblast, resulting in inadequate remodeling of the spiral arteries. This is presumed to lead to the second stage, which involves the maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in the clinical features of the disorder. Accurate prediction and uniform prevention continue to elude us. The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an "at risk" group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly. PE has been previously defined as the onset of hypertension accompanied by significant proteinuria after 20 weeks of gestation. Recently, the definition of PE has been broadened. Now the internationally agreed definition of PE is the one proposed by the International Society for the Study of Hypertension in Pregnancy (ISSHP). According to the ISSHP, PE is defined as systolic blood pressure at ≥140 mm Hg and/or diastolic blood pressure at ≥90 mm Hg on at least two occasions measured 4 hours apart in previously normotensive women and is accompanied by one or more of the following new­onset conditions at or after 20 weeks of gestation: 1.Proteinuria (i.e. ≥30 mg/mol protein:creatinine ratio; ≥300 mg/24 hour; or ≥2 + dipstick); 2.Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine ≥90 µmol/L; 1 mg/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase >40 IU/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or hematological complications (thrombocytopenia­platelet count <150 000/µL, disseminated intravascular coagulation, hemolysis); or 3.Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth). It is well established that a number of maternal risk factors are associated with the development of PE: advanced maternal age; nulliparity; previous history of PE; short and long interpregnancy interval; use of assisted reproductive technologies; family history of PE; obesity; Afro­Caribbean and South Asian racial origin; co­morbid medical conditions including hyperglycemia in pregnancy; pre­existing chronic hypertension; renal disease; and autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome. These risk factors have been described by various professional organizations for the identification of women at risk of PE; however, this approach to screening is inadequate for effective prediction of PE. PE can be subclassified into: 1.Early­onset PE (with delivery at <34+0 weeks of gestation); 2.Preterm PE (with delivery at <37+0 weeks of gestation); 3.Late­onset PE (with delivery at ≥34+0 weeks of gestation); 4.Term PE (with delivery at ≥37+0 weeks of gestation). These subclassifications are not mutually exclusive. Early­onset PE is associated with a much higher risk of short­ and long­term maternal and perinatal morbidity and mortality. Obstetricians managing women with preterm PE are faced with the challenge of balancing the need to achieve fetal maturation in utero with the risks to the mother and fetus of continuing the pregnancy longer. These risks include progression to eclampsia, development of placental abruption and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. On the other hand, preterm delivery is associated with higher infant mortality rates and increased morbidity resulting from small for gestational age (SGA), thrombocytopenia, bronchopulmonary dysplasia, cerebral palsy, and an increased risk of various chronic diseases in adult life, particularly type 2 diabetes, cardiovascular disease, and obesity. Women who have experienced PE may also face additional health problems in later life, as the condition is associated with an increased risk of death from future cardiovascular disease, hypertension, stroke, renal impairment, metabolic syndrome, and diabetes. The life expectancy of women who developed preterm PE is reduced on average by 10 years. There is also significant impact on the infants in the long term, such as increased risks of insulin resistance, diabetes mellitus, coronary artery disease, and hypertension in infants born to pre­eclamptic women. The International Federation of Gynecology and Obstetrics (FIGO) brought together international experts to discuss and evaluate current knowledge on PE and develop a document to frame the issues and suggest key actions to address the health burden posed by PE. FIGO's objectives, as outlined in this document, are: (1) To raise awareness of the links between PE and poor maternal and perinatal outcomes, as well as to the future health risks to mother and offspring, and demand a clearly defined global health agenda to tackle this issue; and (2) To create a consensus document that provides guidance for the first­trimester screening and prevention of preterm PE, and to disseminate and encourage its use. Based on high­quality evidence, the document outlines current global standards for the first­trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of pre­eclampsia in singleton pregnancy.1 It provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings. Suggestions are provided for a variety of different regional and resource settings based on their financial, human, and infrastructure resources, as well as for research priorities to bridge the current knowledge and evidence gap. To deal with the issue of PE, FIGO recommends the following: Public health focus: There should be greater international attention given to PE and to the links between maternal health and noncommunicable diseases (NCDs) on the Sustainable Developmental Goals agenda. Public health measures to increase awareness, access, affordability, and acceptance of preconception counselling, and prenatal and postnatal services for women of reproductive age should be prioritized. Greater efforts are required to raise awareness of the benefits of early prenatal visits targeted at reproductive­aged women, particularly in low­resource countries. Universal screening: All pregnant women should be screened for preterm PE during early pregnancy by the first­trimester combined test with maternal risk factors and biomarkers as a one­step procedure. The risk calculator is available free of charge at https://fetalmedicine.org/research/assess/preeclampsia. FIGO encourages all countries and its member associations to adopt and promote strategies to ensure this. The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI). Where it is not possible to measure PLGF and/or UTPI, the baseline screening test should be a combination of maternal risk factors with MAP, and not maternal risk factors alone. If maternal serum pregnancy­associated plasma protein A (PAPP­A) is measured for routine first­trimester screening for fetal aneuploidies, the result can be included for PE risk assessment. Variations to the full combined test would lead to a reduction in the performance screening. A woman is considered high risk when the risk is 1 in 100 or more based on the first­trimester combined test with maternal risk factors, MAP, PLGF, and UTPI. Contingent screening: Where resources are limited, routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of PLGF and UTPI for a subgroup of the population (selected on the basis of the risk derived from screening by maternal factors and MAP) can be considered. Prophylactic measures: Following first­trimester screening for preterm PE, women identified at high risk should receive aspirin prophylaxis commencing at 11­14+6 weeks of gestation at a dose of ~150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed. Low­dose aspirin should not be prescribed to all pregnant women. In women with low calcium intake (<800 mg/d), either calcium replacement (≤1 g elemental calcium/d) or calcium supplementation (1.5­2 g elemental calcium/d) may reduce the burden of both early­ and late­onset PE.

Effect of chronic melatonin supplementation during mid to late gestation on maternal uterine artery blood flow and subsequent development of male offspring in beef cattle.

The objective of the current study was to examine the effects of supplemental melatonin implants on uterine artery blood flow from mid to late gestation in beef cattle and subsequent development of their male offspring. Commercial beef heifers (n = 32) and cows (n = 25) were bred via artificial insemination and assigned to 1 of 2 groups supplemented with melatonin implants (MEL) or without (CON) at day 180, 210, and 240 of gestation. Uterine artery blood flow was determined using color Doppler ultrasonography. A subset of 12 crossbred heifers (n = 6 MEL; n = 6 CON) underwent Cesarean sections on day 243 ± 2 of gestation to allow for placentome collection. Maternal and fetal serum were collected to analyze melatonin concentrations. The remaining cattle were allowed to calve and at weaning (195 ± 2 d of age), bull calves (n = 15) were castrated and testicular tissue harvested for seminiferous tubule analysis. Heifer uterine artery blood flow was increased (P = 0.009) at day 240 of gestation in MEL compared with CON heifers. Cow uterine artery blood flow was increased (P = 0.003) in MEL compared with CON cows irrespective of gestational day. Maternal and fetal concentrations of melatonin were increased (P < 0.05) in MEL compared with CON heifers. The percent of placentome capillary area per mm2 was decreased (P = 0.019) in MEL compared with CON heifers, while cotyledonary ANGPT1 mRNA tended to increase (P = 0.095) in MEL compared with CON heifers. At weaning, body weight of male offspring and their scrotal circumference were increased (P < 0.05) in calves born to MEL compared with CON dams, while seminiferous tubule diameter and area were not different (P > 0.40) between treatments. In summary, melatonin supplementation increased uterine artery blood flow in mid to late gestating cattle, but this was not accompanied by an increase in fetal weight. Alterations in postnatal development of bulls, including increased body weight and scrotal circumference, warrants future investigations related to attainment of puberty and subsequent fertility of offspring born to melatonin supplemented dams.

An effect of maternal nifedipine therapy on fetoplacental blood flow: a prospective study.

PURPOSE: The aim of this study is to assess the effects of maternal nifedipine administration on placental and fetal blood flow. METHODS: A total of 29 patients with preterm labor diagnosis admitted to the tertiary care center, Zeynep Kamil Hospital, were evaluated. Before and 24-48 h after administration of oral nifedipine, Doppler ultrasound scan was carried out to measure fetal middle cerebral artery, ductus venosus, umbilical artery, and maternal uterine artery blood flow. RESULTS: After 24 and 48 h of therapy, there were no changes in mean PI and RI in the umbilical arteries and ductus venosus (p > 0.05). Fetal middle cerebral artery and maternal uterine artery PI and RI values showed a significant reduction 24-48 h after oral nifedipine therapy (p < 0.05). CONCLUSIONS: Our study showed that 24 and 48 h after oral nifedipine therapy, there is a significant increase in fetal MCA and maternal uterine artery blood flow, while fetal umbilical artery and ductus venosus Doppler values do not change.

[PRE-ECLAMPSIA: A NEW TEST FOR AN OLD DISEASE].

INTRODUCTION: In the western world, pre-eclampsia, diagnosed in 3-5% of pregnant women, is a major cause of maternal and fetal morbidity and mortality. Once pre-eclampsia is diagnosed, the only effective treatment is delivery. There are known historical risk factors for the development of pre-eclampsia, however only 30% of the women who will develop pre-eclampsia are identified based on their presence. Recently, new first trimester algorithms for the prediction of pre-eclampsia were developed, based on the observation that pregnant women who develop pre-eclampsia have imbalanced placental angiogenic factors and that failure of the trophoblastic migration may change the flow in the uterine arteries. These algorithms include maternal history and demographics, biochemical and clinical markers (mean arterial pressure, uterine artery flow PLGF, PAPP-A, PP-13). The combination of early diagnosis of a high risk group together with promising evidence that simple preventive measures, such as low-dose aspirin and calcium supplements may prevent pre-eclampsia or change its appearance leads to the idea that we are on the verge of a new era regarding detection and prevention of pre-eclampsia.

Decreasing the Uterine Blood Flow with Electroacupuncture: Bidermatomal and Monodermatomal Applications.

BACKGROUND: Previously we demonstrated a uterine fibroma case in which the decrease in the uterine artery blood flow was obtained with bidermatomal electroacupuncture (EA). A prospective study was conducted to validate the efficacy of bidermatomal and monodermatomal EA applications. METHODS: Ten healthy women participated 3 times for 3 steps of the study. Each woman enrolled into a bidermatomal sham control group application, a bidermatomal 80 Hz EA and as a last step, a monodermatomal EA with 80 Hz. Color Doppler ultrasonographic recordings were made to detect baseline blood flow parameters by a pulsatility index (PI), volume flow, area and diameter of each uterine artery and after stimulations. RESULTS: Doppler ultrasonographic recordings demonstrated statistically significant decreases of the blood flow both with bidermatomal (p = 0.03 for the left side PI and p = 0.04 for the right side PI) and monodermatomal EA (p = 0.006 for the left PI and p = 0.002 for the right side PI). The sham control group did not show a significant change in blood flow parameters. CONCLUSIONS: The present study validates the efficacy of the bidermatomal but also the monodermatomal EA with 80 Hz on decreasing the blood flow to the uterus.

[Impact of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow on dysmenorrhea patients of cold stagnation and blood stasis syndrome with Dingkun Dan].

This research apply Dingkun Dan to treat patients with dysmenorrhea of cold stagnation and blood stasis syndrome. This study observed its effectiveness and safety of the treatment of the disease and its influence on the serum prostaglandin F2α, endothefin, pulsatility index and resistant index of uterine artery blood, to explore the possible mechanism of effect of Dingkun Dan in the treatment of dysmenorrhea and provide scientific basis for clinical application. The 75 patients with dysmenorrhea of cold stagnation and blood stasis who met the inclusion criteria, were divided into treatment group (n=37) and control group (n=38) by using random number remainder grouping method. In the treatment group patients were treated with Dingkun Dan, the other group were given Fuke Zaizao Jiaonang. Two groups have same time to take the medicine, three days prior to the menstruation for ten days. Medication for three menstrual cycles was seen as a course of treatment. To observe and compare the two groups of patients before and after treatment VAS score, syndrome integral, serum levels of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow and related safety index changes. Finally makes statistical analysis. It has been identified that, Treatment group and control group can reduce pain symptom of dysmenorrhea patients and improve the syndromes scores, compare with control group, effect of the treatment group is more significant(P<0.01). VAS pain curative effect: the treatment group and control group total effective rate respectively were, 97.22%, 69.44%, markedly effective rate were 83.33%, 30.56%, comparison between two groups, treatment group is better than that of control group(P＜0.01). Syndromes curative effect: the treatment group and control group total effective rate respectively were 97.22%, 94.44%, markedly effective rate was 66.67%, 2.78%, respectively. The comparison between two groups, the total effective rate has no obvious difference, but markedly effective rate of treatment group is better than that of control group(P＜0.01). The treatment group can significantly reduce the patients' serum level of prostaglandin F2α(P<0.01), but no obvious difference was found in the control group before and after treatment. Both groups can significantly reduce the serum level of endothelin(P<0.01), comparison between two groups, the treatment group is more significant(P<0.01).Both treatment group and control group were significantly lower left and right pulsation index and resistance index of uterus artery blood flow(P<0.01). Between groups to compare the effect, the treatment group is more significant(P<0.01). Both treatment group and control group in the security check before and after treatment found no significant anomalies. Dingkun Dan in treating dysmenorrhea with cold stagnation and blood stasis syndrome seems to have remarkable clinical curative effect and safety, which may be achieved by significantly reducing the serum level of prostaglandin F2αand endothefin of the patients, and reducing the pulsation index and resistance index of uterine artery blood flow of the patients, to improve uterine artery condition of blood, and correcting local tissue ischemia to relieve pain.