Effect of different squatting exercises on menstrual aspects, pelvic mechanics and uterine circulation in primary dysmenorrhoea: a randomised controlled trial.

This was a randomised trial aimed to determine squatting exercises' effects on menstruation, pelvic mechanics, and uterine circulation in primary dysmenorrhoea. A total of 120 females with primary dysmenorrhoea were assigned into group (A), receiving yoga protocol, or groups (B, C & D), receiving yoga protocol added to modified wall squat, sumo squat, or deep squat, respectively. Menstrual pain and distress, pelvic inclination, and uterine circulation were measured before and after interventions using a pain scale, a questionnaire, palpation metre, and Doppler ultrasonography, respectively. There was a significant reduction in pain intensity in groups B & C (effect size = 3.97 & 5.89, respectively), compared to group A (effect size = 3.68), and in group C (effect size = 5.89) compared to group D (effect size = 3.94), pain subscale in the groups B, C & D (effect size = 1.69, 3.3 & 3.41, respectively), compared to group A (effect size= 2.47), water retention subscale in group D effect size 0.90 compared to group A (effect size =0.41) and in the questionnaire total scores in the groups C &D (effect size = 2.3 & 2.46, respectively) when compared to group A (effect size =1.94). Adding squatting exercises to yoga is more effective than yoga alone in reducing menstrual pain and distress.IMPACT STATEMENTWhat is already known on this subject? Physical exercises positively affect primary dysmenorrhoea in terms of decreased pain and distress, possibly through altering faulty posture. Squatting exercises affect lumbopelvic mechanics.What do the results of this study add? This study explores the effect of squatting exercises on pelvic inclination, menstrual aspects, and circulation.What are the implications of these findings for clinical practice and/or further research? Squatting exercises can be utilised to affect pelvic mechanics leading to decreased menstrual pain and distress, because of decreased pelvic congestion.

[Influence of complex rehabilitation programs on the uterine blood flow in patients of different age after plastic surgery for rectocele]. / Vliyanie reabilitatsionnykh kompleksnykh programm na pokazateli matochnogo krovotoka po dannym 3D-ekhodopplerografii u patsientok raznykh vozrastnykh grupp posle plasticheskoi operatsii po povodu rektotsele.

OBJECTIVE: To develop the optimized complex programs, including general magnetotherapy, fractional microablative therapy with a CO2 laser, electromyostimulation with biofeedback of the pelvic floor muscles, and a special exercise therapy complex in late rehabilitation programs for women of different age after reconstructive plastic surgery for rectocele. MATERIAL AND METHODS: There were 200 women of childbearing, peri- and menopausal age with rectocele grade II-III and 20 healthy women of comparable age. All patients were divided into 4 groups by 50 womes: main group, two comparison groups and control group. Surgical treatment of rectocele was followed by long-term postoperative rehabilitation including symptomatic therapy, general magnetotherapy, and electromyostimulation with biofeedback of the pelvic floor muscles, intra-vaginal fractional microablative therapy with a CO2 laser and special complex of therapeutic physical education. RESULTS: General magnetotherapy in early (1 day) postoperative period and complex rehabilitation in long-term postoperative period (within a month after surgery) including 2 procedures of intra-vaginal microablative fractional therapy with carbon dioxide laser, electromyostimulation with biological connection of the pelvic floor muscles and special complex of therapeutic physical education ensured more significant improvement of uterine blood flow regardless age and baseline disorders in the uterine arteries in patients with rectocele. In our opinion, this is primarily due to vasoactive effects of general magnetotherapy, recovery of circulation via relief of spasm in the arteries and arterioles, improved vein contractility and venous outflow. These processes combined with electrical stimulation and therapeutic exercises of pelvic floor muscle followed by their reinforcement, as well as fractional microablative therapy ensured significant vascular effect.

[Effect of warming acupuncture on uterine blood perfusion in patients with failed high-quality freeze-thawed embryo transfer].

OBJECTIVE: To observe the effect of warming acupuncture on uterine blood perfusion in the patients with failed high-quality freeze-thawed embryo transfer (FET) and explore its effect mechanism on the improvement of clinical pregnancy rate after re-tranfer. METHODS: A total of 72 patients of failed high-quality FET were randomized into an observation group and a control group, 36 cases in each one. In the observation group, after the menstrual period ended, warming acupuncture started at the acupoints located on the abdomen, e.g. Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3) and Qugu (CV 2) and those on the lumbar sacral region, e.g. Shenshu (BL 23), Mingmen (GV 4) and Yaoyangguan (GV 3), 50 min in each treatment, once daily, at the interval of 1 day after 4-day treatment. The treatment was discontinued till the patients were at the ovulatory stage. In the control group, nuangong yunzi capsules were taken orally and continuously after the end of menstrual period, 3 capsules each time, three times a day and stopped at the ovulatory stage. The treatment of one menstrual cycle was taken as one course and the treatment for 3 menstrual cycles was required. Before and after treatment, the uterine artery pulsation index (PI), endometrial thickness, endometrial type, uterine blood perfusion, the recovery time of sufficient uterine blood flow, the endomentrial receptivity (ER) during the implantation window period and the clinical pregnancy rate were observed in the two groups. RESULTS: After treatment, the endometrial thickness was increased and PI decreased obviously in the two groups (P<0.05) and PI in the observation group was lower than that in the control group (P<0.05). After treatment, the proportion of type a and type A of endometrium was increased markedly in the two groups (P<0.05) and the proportion in the observation group was higher than the control group (P<0.05). After treatment, the case proportion of sufficient uterine blood flow was increased obviously in the two groups (P<0.05) and the value in the observation group was higher than the control group [83.3% (30/36) vs 69.4% (25/36), P<0.05]. After treatment, the proportion of ER during the implantation window period was increased remarkably in the two groups (P<0.05) and the value in the observation group was higher than the control group [72.2% (26/36) vs 50.0% (18/36), P<0.05]. The recovery time of sufficient uterine blood flow in the observation group was shorter than the control group (P<0.05) and the clinical pregnancy rate was higher than the control group [47.2% (17/36) vs 33.3% (12/36), P<0.05]. CONCLUSION: Warming acupuncture enhances uterine blood perfusion and improves uterine endometrial receptivity so that the clinical pregnancy rate is increased after re-transfer in the patients with failed high-quality freeze-thawed embryo transfer.

Comparison of the immediate analgesic effect of perpendicular needling and transverse needling at SP6 in patients with primary dysmenorrhea: Study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture has been widely used to treat primary dysmenorrhea (PD) with satisfactory outcomes. Sanyinjiao (SP6) is the most commonly used acupoint for PD. Different needling techniques may influence the effect of SP6, and its underlying mechanism needs to be explored. This randomized controlled parallel trial is designed to evaluate the immediate analgesic effect and hemodynamic responses in uterine arterial blood flow of perpendicular needling and transverse needling at SP6 in patients with PD of cold-dampness stagnation pattern using color doppler ultrasonography. METHODS: Forty-eight patients who meet inclusion criteria will be randomized in a ratio of 1:1 to either perpendicular needling or transverse needling groups. Every participant will receive 1 session of acupuncture treatment for 10 minutes at bilateral SP6. In the perpendicular needling group, needles will be inserted vertically 1 to 1.2 cun and will be manipulated to achieve needling sensation. In transverse needling group, the needles will be inserted transversely 1 to 1.2 cun toward the abdomen without any manipulation to avoid needling sensation. Color doppler ultrasonography will be performed before, during, and after needling. The primary outcome measure is visual analog scale for pain. The secondary outcome measures include the uterine artery blood flow changes by measuring pulsatility index, resistance index values, and ratio of systolic peak and diastolic peak, the Hamilton anxiety scale, blood pressure, and heart rate. Adverse events in both groups also will be recorded. DISCUSSION: This trial will be the first study protocol designed to explore the influence of needling techniques on the analgesia effect of solo acupoint and its hemodynamic responses for PD. It will promote more widespread awareness of the benefits of using suitable needling techniques in acupuncture clinical setting and provide a further explanation of the underlying hemodynamic mechanism. TRIAL REGISTRATION: This study protocol was registered at the Chinese clinical trial registry (ChiCTR1900026051).

L-(+)-Ergothioneine Significantly Improves the Clinical Characteristics of Preeclampsia in the Reduced Uterine Perfusion Pressure Rat Model.

Preeclampsia is a multifactorial hypertensive disorder of pregnancy founded on abnormal placentation, and the resultant placental ischemic microenvironment is thought to play a crucial role in its pathophysiology. Placental ischemia because of fluctuations in the delivery of oxygen results in oxidative stress, and recent evidence suggests that mitochondrial dysfunction may be a prime mediator. However, large clinical trials of therapeutic antioxidants such as vitamins C and E for the treatment of preeclampsia have been disappointing. L-(+)-ergothioneine (ERG)-an unusual amino acid betaine derived from histidine-has important cytoprotective and antioxidant properties under conditions of high oxidative stress. In this study, we investigated the potential therapeutic effects of administration of ERG in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. ERG (25 mg/kg per day) was administered to rats on gestational day 11. On gestational day 14, RUPP surgery was performed, and on gestational day 19, blood pressure (mean arterial pressure) and fetal growth were measured. Production of mitochondria-specific H2O2 was analyzed in vivo in kidney samples. ERG ameliorated the hypertension (129±3 versus 115±4 mm Hg; P=0.01; n=8) and significantly increased pup weight in RUPP rats. ERG also significantly decreased circulating levels of antiangiogenic sFlt-1 (soluble fms-like tyrosine kinase-1) in RUPP rats (1367±245 pg/mL; P=0.04). Mitochondria-specific H2O2 (0.022±0.003 versus 0.029±0.001; MitoP/B ratio, n=3; P=0.05) was also significantly decreased in kidney tissue in RUPP rats treated with ERG. These data support the potential use of ERG for the treatment of preeclampsia.

Spinal glycinergic and gamma-aminobutyric acid-ergic neurons inhibit the micturition reflex after electrical stimulation of the perineum in rats with pelvic venous congestion.

OBJECTIVES: To examine whether electrical stimulation of the perineum inhibited urinary frequency in rats with pelvic venous congestion, and whether electrical stimulation influences spinal glycinergic/gamma-aminobutyric acid-ergic neurons. METHODS: Bilateral common iliac veins and bilateral uterine veins were ligated to create pelvic venous congestion rats. At 4 weeks after ligation, cystometry was carried out before and after electrical stimulation with/without intrathecal injection of strychnine (a glycine receptor antagonist) and/or bicuculline (a gamma-aminobutyric acid type A receptor antagonist). In addition, measurement of amino acid levels in the lumbosacral cord was carried out with/without electrical stimulation, and cystometry was carried out after oral administration of glycine. RESULTS: Continuous cystometry showed that the interval between bladder contractions was shorter in pelvic venous congestion rats than in sham rats. Electrical stimulation did not change cystometric parameters in sham rats, but the interval between bladder contractions was increased by electrical stimulation in pelvic venous congestion rats. Electrical stimulation increased the levels of glutamic acid, glycine, gamma-aminobutyric acid, and taurine in the lumbosacral cord of pelvic venous congestion rats. Intrathecal strychnine abolished the effects of electrical stimulation in pelvic venous congestion rats, and intrathecal administration of both strychnine and bicuculline shortened the interval between bladder contractions more than before electrical stimulation. Oral administration of glycine (3%) to pelvic venous congestion rats increased bladder capacity. CONCLUSIONS: Electrical stimulation of the perineum inhibits urinary frequency mainly through activation of spinal glycinergic neurons, and partly through activation of gamma-aminobutyric acid-ergic neurons in a rat model of pelvic venous congestion.

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.

PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Alterations in uteroplacental hemodynamics during melatonin supplementation in sheep and cattle.

Compromised placental function can result in fetal growth restriction which is associated with greater risk of neonatal morbidity and mortality. Large increases in transplacental nutrient and waste exchange, which support the exponential increase in fetal growth during the last half of gestation, are dependent primarily on the rapid growth and vascularization of the uteroplacenta. The amplitude of melatonin secretion has been associated with improved oxidative status and altered cardiovascular function in several mammalian species; however, melatonin mediated alterations of uteroplacental capacity in sheep and cattle are lacking. Therefore, our laboratories are examining uteroplacental blood flow and fetal development during maternal melatonin supplementation. Using a mid- to late-gestation ovine model of intrauterine growth restriction, we examined uteroplacental blood flow and fetal growth during supplementation with 5 mg/d of dietary melatonin. Maternal nutrient restriction decreased uterine arterial blood flow, while melatonin supplementation increased umbilical arterial blood flow compared with non-supplemented controls. Although melatonin treatment did not rescue fetal weight in nutrient restricted ewes; we observed disproportionate fetal size and fetal organ development. Elevated fetal concentrations of melatonin may result in altered blood flow distribution during important time points of development. These melatonin specific responses on umbilical arterial hemodynamics and fetal development may be partially mediated through vascular melatonin receptors. Recently, we examined the effects of supplementing Holstein heifers with 20 mg/d of dietary melatonin during the last third of gestation. Uterine arterial blood flow was increased by 25% and total serum antioxidant capacity was increased by 43% in melatonin supplemented heifers vs. non-supplemented controls. In addition, peripheral concentrations of progesterone were decreased in melatonin supplemented heifers vs. non-supplemented controls. Using an in vitro model, melatonin treatment increased the activity of cytochrome P450 2C, a progesterone inactivating enzyme, which was blocked by treatment with the melatonin receptor antagonist, luzindole. Elucidating the consequences of specific hormonal supplements on the continual plasticity of placental function will allow us to determine important endogenous mediators of offspring growth and development.

One year symptom severity and health-related quality of life changes among Black African patients undergoing uterine fibroid embolisation.

BACKGROUND: The main aim in the treatment of symptomatic fibroids by various modalities including uterine fibroid embolisation (UFE) is to alleviate symptoms and ultimately improve the quality of life. The efficacy of this modality of treatment in Black African women with significant fibroid burden and large uterine volumes is not clear. The main objective of the study was to examine potential changes in symptom severity among Black African patients 1 year following UFE for symptomatic uterine fibroids in a resource-constrained setting, rated using a validated questionnaire (UFS-QOL). Secondary outcomes examined were changes in quality of life and potential associations with age, parity, uterine volume and fibroid number prior to UFE. Additional interventions after UFE were also recorded. METHODS: A prospective before and after study of Black African patients undergoing UFE was undertaken. Participants underwent pelvic MR imaging prior to UFE and completed the UFS-QOL, a validated condition-specific questionnaire at baseline and at 1 year. Ninety five participants were recruited and data from 80 completing 1 year of follow up were available for analysis of changes in the symptom severity scores. RESULTS: The mean reduction in symptom severity score was 29.6 [95% CI 23.6 to 35.6, P < 0.001] and the mean improvement in HRQOL score was 35.7 [95% CI 28.4 to 42.9, P < 0.001]. A greater number of fibroids identified prior to UFE was associated with a more substantial improvement in symptom severity score (rs = 0.28, n = 80, P = 0.013) and participants of higher parity reported a greater improvement in HRQOL score (r = 0.336, P = 0.002). Major and minor surgical interventions were needed in 5 (6.3%) and 10 (12.5%) participants respectively. CONCLUSIONS: UFE is associated with clinically useful and statistically significant symptom relief in Black African patients. Symptom improvement following UFE is not compromised by a large fibroid burden and the rate of subsequent intervention is within an acceptable range. UFE is a safe alternative and efforts are needed to widen access to this non-surgical treatment modality.

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

BACKGROUND: The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. METHODS/DESIGN: This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. DISCUSSION: Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. TRIAL REGISTRATION: ClinicalTrials NCT02591186 registered on October 7, 2015.

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.

A randomized controlled study of the efficacy of 4 weeks of supplementation with ω-3 polyunsaturated fatty acids in cases of unexplained oligohydramnios.

OBJECTIVE: To investigate the effect of ω-3 fatty acids on amniotic fluid volume and uterine artery blood flow after 4 weeks of treatment. STUDY DESIGN: A randomized clinical trial was conducted on 140 participants with unexplained oligohydramnios at Woman's Health Hospital, Assiut University, Egypt. Participants were randomly assigned to ω-3 plus capsules or placebo. Categorical variables were analyzed by means of the χ2 test, whereas continuous variables were analyzed by means of the independent-sample T-test between the two groups. RESULTS: One hundred and forty women were recruited. There was significant improvement in the amniotic fluid index (AFI) in the ω-3 plus group in comparison with the placebo group (P=0.001). Moreover, there were significant decreases in the systolic/diastolic ratio (P=0.01), resistance index (P=0.041) and pulsatility index (P=0.002) of the uterine arteries in the ω-3 plus group when comparing baseline values with those after 4 weeks. CONCLUSION: The results suggest that ω-3 fatty acids may have a role in the increase in AFI in cases of unexplained oligohydramnios. This effect may be secondary to the increase in uterine blood flow.

Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy.

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

Dietary melatonin alters uterine artery hemodynamics in pregnant Holstein heifers.

The objective was to examine uterine artery hemodynamics and maternal serum profiles in pregnant heifers supplemented with dietary melatonin (MEL) or no supplementation (CON). In addition, melatonin receptor-mediated responses in steroid metabolism were examined using a bovine endometrial epithelial culture system. Twenty singleton pregnant Holstein heifers were supplemented with 20 mg of melatonin (n = 10) or no melatonin supplementation (control; n = 10) from days 190 to 262 of gestation. Maternal measurements were recorded on days 180 (baseline), 210, 240, and 262 of gestation. Total uterine blood flow was increased by 25% in the MEL-treated heifers compared with the CON. Concentrations of progesterone were decreased in MEL vs CON heifers. Total serum antioxidant capacity was increased by 43% in MEL-treated heifers when compared with CON. Activity of cytochrome P450 1A, 2C, and superoxide dismutase was increased in bovine endometrial epithelial cells treated with melatonin, whereas the melatonin receptor antagonist, luzindole, negated the increase in cytochrome P450 2C activity. Moreover, estradiol or progesterone treatment altered bovine uterine melatonin receptor expression, which could potentiate the melatonin-mediated responses during late gestation. The observed increase in total uterine blood flow during melatonin supplementation could be related to its antioxidant properties. Compromised pregnancies are typically accompanied by increased oxidative stress; therefore, melatonin could serve as a therapeutic supplementation strategy. This could lead to further fetal programming implications in conjunction with offspring growth and development postnatally.

Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling.

Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia.

Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. RESULTS: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

[Effect of drug-spreading moxibustion for primary dysmenorrheal with cold-damp stagnation and its uterine artery blood flow].

OBJECTIVE: To observe the effect difference between drug-spreading moxibustion and the oral administration of meloxicam for primary dysmenorrheal with cold stagnation and to explore its mechanism. METHODS: A total of 101 patients with primary dysmenorrheal were randomly assigned into a drug-moxibustion group(52 cases) and a western medication group(49 cases). Drug-spreading moxibustion was used on the lumbosacral acupoints area and then around lower abdominal five days before menstruation until the 3rd day of menstruation,once three days,while western medicine meloxicam was prescribed one day before menstruation,7.5 mg at a time,once a day and continuously for three days. The clinical effects after one course,namely three menstrual cycles,were compared between the two groups. Meanwhile,the resistance index(RI) and the pulsatility index (PI) of uterine artery and arcus arteriarum were examined through color Doppler ultrasound before and after treatment. RESULTS: After one-course treatment,the effective rate was 92.3%(48/52) in the drug-spreading moxibustion group,which was better than 67.3%(33/49) in the western medication group(P<0.05). Also,all the RI and PI in the drug-spreading moxibustion group were obviously decreased than those before treatment(all P<0.05),and the ones were superior to those of the western medication group(all P<0.05),which showed no apparent decrease after treatment(all P>0.05). CONCLUSIONS: Drug-spreading moxibustion can improve the symptoms of primary dysmenorrheal with cold-damp stagnation,and the effect is better than that of meloxicam. The mechanism may be related to improve the blood supply to the uterus.

Arginine supplementation between 41 and 146 days of pregnancy reduces uterine blood flow in dairy heifers.

We hypothesized that arginine (Arg) supplementation during early pregnancy could foster placental vascularization. The objective of this study was to evaluate the effects of Arg supplementation on uterine artery hemodynamics between 40 and 140 days of gestation. At 41 days of gestation, 17 Holstein heifers (448 ± 73.9 kg) were surgically fitted with a catheter in the peritoneal cavity. After surgery, nine heifers received a daily intraperitoneal infusion of 40 mg of Arg/kg of body weight (BW; ARG), whereas the remaining eight heifers received a daily intraperitoneal infusion of saline solution at equivalent volumes as ARG heifers relative to BW (CTRL). Daily infusions took place every 12 hours until heifers reached 146 days of pregnancy. At 41, 62, 83, 104, 125, and 146 days of pregnancy, all heifers were body weighed, bled, and uterine blood flow volume (FV) and other hemodynamics were determined using Doppler ultrasonography. The measurements included heart rate, FV, pulsatility index, and resistance index. Plasma concentrations of amino acids (AAs), nitric oxide, glucose, insulin growth factor, progesterone (P4), growth hormone, and prolactin were analyzed. In a second experiment, we evaluated Arg metabolism when infused either intravenously or intraperitoneally. Overall, FV did not differ between the treatments, but it increased (P < 0.001) with pregnancy day. Uterine blood FV evolved differently between the treatments, with CTRL heifers having a greater (P < 0.05) FV (1104 ± 65.42 mL/min) at 146 days of pregnancy than in ARG heifers (806 ± 65.32 mL/min). Pulsatility index and resistance index decreased throughout pregnancy but did not differ between the treatments. Heart rate was decreased (P < 0.05) in ARG (74 ± 1.4 beats/min) compared with CTRL heifers (81 ± 1.5 beats/min). Plasma concentrations of Arg tended (P < 0.09) to be greater in ARG than those in CTRL heifers, but carnitine, valine, isoleucine, leucine, phenylalanine, and tryptophan were lower (P < 0.05) in ARG than those in CTRL heifers. The proportion of essential AAs (with respect to total AAs) in plasma was greater (P < 0.05) in CTRL (73 ± 2.4%) than that in ARG heifers (65 ± 2.3%). No differences between the treatments were found in plasma prolactin (P = 0.43), insulin growth factor (P = 0.97), glucose (P = 0.45), growth hormone (P = 0.39), or nitric oxide (P = 0.89) concentrations. However, plasma P4 concentration was greater (P < 0.05) in ARG than in CTRL heifers. Contrary to our hypothesis, Arg supplementation did not increase blood flow to the uterus but did change other parameters that could influence placental and fetal growth such as heart rate, maternal concentration of plasma AAs, or P4 synthesis. Furthermore, infusion sites (blood vs. peritoneum) of Arg render different metabolic responses.

[Dynamics of the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis under effect of contrast massage].

The objective of the present work was to study the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis before and after a course of contrast massage. Three types of functional changes in the microcirulation system were distinguished based on the results of laser-assisted Doppler flowmetry. All of them were characterized by high coefficients of correlation with the results of dopplerometry of uterine blood flow and underwent dynamic changes in the course of the treatment. The study has demonstrated the high therapeutic effectiveness of the contrast massage technique as a tool for inducing hemodynamic changes in the small pelvis basin in the women suffering from chronic endometritis.