Effects of Prophylactic Oxytocin on Bleeding Outcomes in Women Undergoing Dilation and Evacuation: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether routine use of intravenous oxytocin decreases the frequency of interventions to control excess blood loss during dilation and evacuation (D&E). METHODS: In this multisite, randomized, double-blind, placebo-controlled trial, women undergoing D&E at 18-24 weeks of gestation received 30 units of oxytocin in 500 mL of intravenous fluid or 500 mL of intravenous fluid alone initiated on speculum placement. The primary outcome was the frequency of interventions to control excess bleeding. A sample size of 75 patients per group was needed to detect a 15% decrease in intervention from 20% to 5% with 80% power and two-sided alpha 0.05. Secondary outcomes included measured blood loss, complications, procedure duration, postoperative pain, and patient satisfaction. RESULTS: From November 2014 to February 2018, we screened 337 women and randomized 160 to receive prophylactic oxytocin (n=82) or placebo (n=78). Demographic characteristics were similar between groups. The frequency of interventions for bleeding, our primary outcome, was 7.3% in the oxytocin group vs 16.7% in the placebo group, difference of 9.4% (95% CI -21.0% to 1.9%). Interventions primarily included uterine massage and uterotonic administration. Among our secondary outcomes, median measured blood loss was lower in the oxytocin group at 152 (interquartile range 98-235) mL vs 317 (interquartile range 168-464) mL (95% CI 71.6-181.5). Frequency of hemorrhage, defined as blood loss of 500 mL or more and 1,000 mL or more, was lower in the oxytocin group at 3.7% vs 21.8%, difference of 18% (95% CI -29 to -6.9%) and 1.2% vs 10.3%, difference of 9.0% (95% CI -17 to -0.7%), respectively. Procedures were shorter in the oxytocin group at a median of 11.0 (interquartile range 8.0-14.0) vs 13.5 (interquartile range 10.0-19.0) minutes in the placebo group (95% CI 1.0-4.0). We found no differences in the frequency of nonhemorrhage complications, pain scores, or satisfaction scores between groups. CONCLUSION: Prophylactic use of oxytocin during D&E at 18-24 weeks of gestation did not decrease the frequency of interventions to control bleeding. However, oxytocin did decrease blood loss and frequency of hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02083809.

Humoral hypercalcemia caused by uterine corpus carcinosarcoma consisting of squamous cell carcinoma in its epithelial component.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome primarily caused by a tumor-producing parathyroid hormone-related protein (PTH-rP). We describe the first reported case of a uterine carcinosarcoma causing HHM. A 70-year-old patient was transferred to our hospital for a uterine tumor accompanied by impaired consciousness. The laboratory tests indicated anemia, malnutrition, elevated serum calcium and elevated PTH-rP. Emergency surgery, including abdominal hysterectomy and bilateral salpingo-oophorectomy, was performed due to uncontrollable uterine bleeding. The pathological diagnosis was carcinosarcoma consisting of pure squamous cell carcinoma in its epithelial component. Postoperatively, chemotherapy with paclitaxel and carboplatin was performed. The patient had recurrent tumors at the para-aortic lymph nodes 11 months after the initial surgery and underwent a pelvic and para-aortic lymphadenectomy, which removed all of the recurrent tumors.

Changing practice: physiological cord clamping.

Every baby deserves the best start to life. Receiving the full quota of blood from the placenta directly after birth has profound short and long-term benefits for the baby; these have been extensively researched and documented. This article discusses a student midwife's experience of participating in reviewing third stage guidelines to incorporate this growing evidence base into clinical practice within a large London NHS Trust. A new local guideline (unpublished) recommends every baby (where clinically possible) has the opportunity to benefit from 'physiological cord clamping'. The aim of the article is to inspire midwives and student midwives to become involved with similar activities within their own trusts.

Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats.

OBJECTIVES: To determine the effect of leonurine hydrochloride (LH) on abnormal bleeding induced by medical abortion. STUDY DESIGN: Rats had incomplete abortions induced in early pregnancy using mifepristone in combination with misoprostol. After abortion, rats were treated with LH for 7 days, and the duration and volume of uterine bleeding were observed. Approximately 30min after the last treatment, the animals were killed and the uterine shape was observed. The sinistro-uteri were suspended in organ baths to record the contraction curves, including the frequency and tension for 10min; the dextro-uteri were fixed with formaldehyde for pathologic evaluation. In addition, blood samples were collected from the femoral artery for the measurement of estradiol (E2) and progesterone (P) levels by radioimmunoassay. RESULTS: In in vivo experiments, compared with the model group, LH treatment markedly reduced the volume of bleeding and intrauterine residual, and significantly shortened the duration of bleeding. From the contraction curve, LH notably reinforced the frequency and tension of uterine contractions. LH remarkably elevated the serum estradiol level in rats, but had no obvious effect on progesterone level. CONCLUSIONS: LH has an inhibitory effect on bleeding caused by incomplete abortion; the mechanism may be related to up-regulation of the E2 level, leading to an increase in uterine contractions and evacuation of intrauterine residuum.

Up-regulation of Fas/FasL activation contribute to the apoptosis enhancement of RU486 by Gong-Qing Decoction, a traditional Chinese prescription.

AIM OF THE STUDY: To elucidate the mechanisms of Gong Qing Decoction(GQD) on human trephocytes and decidual cells in vivo based upon the effective practice of alleviating uterine bleeding in RU486 medical abortion. MATERIALS AND METHODS: 90 intrauterine pregnancy women within 7 weeks, presenting for elective termination of pregnancy, were divided into the GQD-RU486 group, the RU486 group and the vacuum aspiration group. Duration of uterine bleeding was recorded and volume of uterine bleeding was measured by the method of alkaline hematin photometric. Ultramicrostructure of trephocytes and decidual cells were observed with transmission electron microscope (TEM), and apoptosis rate (AR) was assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. At the same time, immunohistochemical staining was performed and integral optical density was analyzed to evaluate the protein expression of Fas, FasL, Caspase-8 and Caspase-3 in both trephocytes and decidual cells preliminarily. RESULTS: In comparison with the RU486 group and the vacuum aspiration group, both the duration and volume of uterine bleeding decreased significantly in the GQD-RU486 group. At the same time, both trephocytes and decidual cells in the GQD-RU486 group showed typical character of apoptotic ultramicrostructure and displayed up-regulated apoptosis rate. Synchronously, the integral optical density showed increased protein expression of Fas, FasL, Caspase-8 and Caspase-3 in both trephocytes and decidual cells in the GQD-RU486 group compared with other groups. CONCLUSION: These data suggest that GQD can alleviate uterine bleeding effectively in RU486 medical abortion by way of apoptosis induction. The apoptosis enhancement of RU486 by GQD may be attributable to the activation of Fas and FasL.

Policies for care during the third stage of labour: a survey of maternity units in Syria.

BACKGROUND: Care for women during the third stage aims to reduce the risk of major haemorrhage, but is very variable. The current World Health Organisation (WHO) recommendation is that care should include administration of a uterotonic (oxytocin, if it is available) soon after birth of the baby, delayed cord clamping, and delivery of the placenta by controlled cord traction. METHODS: To ascertain care policies used during the third stage of labour in maternity units in Syria, we conducted a survey of 69 maternity units in obstetric and general public hospitals. A brief questionnaire was administered by face to face interview or telephone with senior obstetricians and midwives. Outcome measures were the use of prophylactic uterotonic drugs, timing of cord clamping, use of controlled cord traction, and treatment for postpartum haemorrhage. Obstetricians were asked about both vaginal and caesarean births, midwives only about vaginal births. RESULTS: Responses were obtained for 66 (96%) hospitals: a midwife and an obstetrician were interviewed in 40; an obstetrician only in 20; a midwife only in 6. Responses were similar, although midwives were more likely to report that the umbilical cord was clamped after 1-3 minutes or after cessation of pulsation (2/40 obstetricians and 9/40 midwives). Responses have therefore been combined.One hospital reported never using a prophylactic uterotonic drug. The uterotonic was Syntometrine(R) (oxytocin and ergometrine) in two thirds of hospitals; given after delivery of the placenta in 60 (91%) for vaginal births, and in 47 (78%) for caesarean births. Cord clamping was within 20 seconds at 42 hospitals 64%) for vaginal births and 45 (75%) for caesarean births. Controlled cord traction was never used in a quarter (17/66) of hospitals for vaginal births and a half (32/60) for caesarean births.68% of respondents (45/66) thought there was a need for more randomised trials of interventions during the third stage of labour. CONCLUSION: Most maternity units report using Syntometrine(R), usually given after delivery of the placenta, clamping the cord within 20 seconds, and using controlled cord traction.

Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci.

OBJECTIVE: To compare the efficacy of a fibrin preparation supplemented with tranexamic acid (Adhexil) with that of established devices, and to determine whether its effect is limited to the site of application. DESIGN: Rabbit uterine horns were abraded in nonbleeding and bleeding variants of an established adhesions model. In a separate study, a sidewall excision with approximation of the abraded cecum was added. Animals randomly received Adhexil at both, neither, or either loci. SETTING: Laboratory study. ANIMAL(S): Seventy-two female New Zealand White rabbits (Oryctolagus cuniculus). INTERVENTION(S): Adhexil, Seprafilm or SprayGel and Interceed. MAIN OUTCOME MEASURE(S): The extent of adhesions was evaluated 13 to 16 days after surgery. RESULT(S): Adhexil reduced adhesions (15 +/- 7%; 15 +/- 4%) compared with controls (74 +/- 13%; 78 +/- 9%) in the bleeding and nonbleeding models, respectively. The reductions resulting from the use of Seprafilm (39 +/- 17%; 34 +/- 14%) or SprayGel (61 +/- 18%; 43 +/- 14%) (n = 4) were not statistically significant. In the bleeding model, Interceed (48 +/- 15%) reduced adhesions only modestly. CONCLUSION(S): In the combined uterine and sidewall model, Adhexil reduced selectively the extent and incidence of adhesions. The absolute and relative performance of Adhexil in an established adhesions model and in the presence of bleeding justifies its further investigation.

The effect of guided imagery on the third stage of labor: a pilot study.

OBJECTIVE: The purpose of this pilot study was to test the effects of guided imagery on blood loss during the third stage of labor. DESIGN AND SETTING: This was a three-group randomized controlled trial. Recruitment was conducted from a university nurse-midwifery practice. SUBJECTS: Sixty (60) women between pregnancy weeks 36 and 38 participated. INTERVENTIONS: The women were randomized into experimental, placebo, and control groups. OUTCOME MEASURES: Intrauterine pressure catheters were used to measure uterine contraction frequency and intensity. Blood loss was measured. Analysis of variance was used to compare the three groups on continuous variables. RESULTS: Complete data were collected on 41 subjects. No significant differences were found among the groups on demographic or potentially confounding variables. CONCLUSIONS: Blood loss was nominally lower in the experimental group, but conclusions cannot be drawn due to the sample size.

[Pregnancy and venous thromboembolism. North-American and European guidelines. American College of Chest Physicians]. / Grossesse et maladie thromboembolique veineuse. A propos des recommandations nord-américaines eteuropéennes.

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Haemorrhage in pregnancy: information given to women in Chiradzulu (Malawi).

Advising women on haemorrhage in pregnancy could be viewed as an integral aspect of maternal health care in Malawi. The WHO (1999) confirmed that haemorrhage in pregnancy was not only a direct reason for maternal mortality but also a major cause of maternal death. The question on the nature of information that midwives and traditional birth attendants (referred to as TBA's) in the Chiradzulu district in Malawi gave with regard to haemorrhage in pregnancy, therefore arose. Research available focused on the women's knowledge about the complications of pregnancy but not on the nature of information women received from midwives and TBA's. This study explored and described the nature of information that was given to rural women in the Chiradzulu district by the midwives and TBA's regarding haemorrhage in pregnancy. The findings revealed that although both the midwives and TBA's included important information about haemorrhage in pregnancy, there were deficiencies in some critical areas. Examples of these deficiencies were the definition of haemorrhage in pregnancy; the predisposing factors for antepartum and postpartum haemorrhage and deficiencies in the nature of information on the management and referral of haemorrhaging patients.

[Effects of herb therapy for benefiting qi and removing blood stasis on ultrastructure of vascular endothelial cells and vascular smooth muscle cells of uterine endometrium in rabbits with copper intrauterine device].

OBJECTIVE: To observe the effects of herb therapy for benefiting qi and removing blood stasis on ultrastructure of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) of uterine endometrium in rabbits with copper intrauterine device. METHODS: Fifty-six rabbits were randomly divided into seven groups, which were normal control group, sham-operation group, untreated group, indomethacin-treated group and low-, medium- and high-dose Gonghuan Zhixueling Recipe (GHZXLR)-treated groups. The rabbits in the last five groups were operated with copper IUD insertion and then orally given distilled water, indomethacin and low-, medium- and high-dose GHZXLR respectively for at least one week. Rabbits in the normal control group and sham-operation group were given distilled water orally. The ultrastructure of VECs and VSMCs of uterine endometrium in rabbits was observed by transmission electron microscopy. RESULTS: The morphological changes of VSMCs revealed intracellular edema, organelle disintegration and decrease of organelle amount, or cell atrophy and vacuolar degeneration of mitochondria in the untreated group, and the amount of collagen fibers also increased outside the VSMCs. Local interstitial edema in subendothelial substance and vacuolar degeneration of mitochondria in VECs were both observed. The ultrastructural damages to the mitochondria, Golgi bodies and myofilament of VECs and VSMCs and the intercellular substance in GHZXLR-treated groups were slighter than those in the untreated group, while these damages had no significant differences as compared with those in the indomethacin-treated group. CONCLUSION: The Chinese herb therapy for benefiting qi for removing blood stasis has the protective effect on VECs of uterine endometrium in the rabbits with copper intrauterine device. It appears to be a good treatment for menorrhagia induced by copper IUD insertion.

[Effects of sanqi qiancao recipe on hemorheological parameters of rabbits with copper intrauterine device].

OBJECTIVE: To explore the mechanism of Sanqi Qiancao Recipe (SQR) in treating metrorrhagia caused by copper intrauterine device (IUD) in rabbits and to provide experimental evidence for preventing and treating this disease. METHODS: Fifty-six rabbits were randomly divided into seven groups, which were normal control group, sham-operation group, untreated group, indomethacin-treated group, low-dose SQR-treated group, medium-dose SQR-treated group and high-dose SQR-treated group. Copper IUD insertion was operated in rabbits of the last five groups. Rabbits in the last four groups were treated orally with indomethacin and low-, medium- and high-dose SQR respectively for a week. Rabbits in the untreated group, normal control group and sham-operation group were given distilled water orally. Hematocrit, blood viscosity at low, medium and high shear rate, plasma viscosity and blood sedimentation were examined after treatment. RESULTS: The hematocrit, blood viscosity at low, medium and high shear rate and plasma viscosity were higher in the untreated group than those in the normal control group with significant differences (P<0.01) while those indexes in low-, medium- and high-dose SQR-treated groups were significantly lower than those in the untreated group (P<0.05 or P<0.01). CONCLUSION: SQR can lead to a decrease in blood viscosity and improve the blood flow, which may be one of the mechanisms of SQR in treating metrorrhagia after copper IUD insertion.

Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery.

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery / 华中科技大学学报（医学）（英德文版）

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

Complete abortion of a nonviable cervical pregnancy following methotrexate treatment.

Cervical pregnancy is an uncommon ectopic pregnancy that accounts for approximately <1% of extrauterine gestations. This condition is associated with an extremely high risk of massive hemorrhage and previously often required hysterectomy. Current early ultrasonographic diagnosis and medical management in conjunction with other conservative measures, which include uterine artery embolization and intracervical balloon tamponade, have enabled conservation of the uterus. A young nulliparous patient ultrasonographically diagnosed with a cervical pregnancy and early fetal demise at 11 and 4/7 weeks gestation was managed with high-dose methotrexate and folinic acid rescue treatment. On the second day after treatment was initiated she spontaneously passed an intact gestational sac accompanied by minimal hemorrhage. Treatment was continued, with decreasing serum beta subunit of human chorionic gonadotropin levels and subsiding hemorrhage. Subsequent surgical measures were not required. This case suggests that complete abortion of a cervical pregnancy not necessitating surgical measures can occur.

[Pros and cons of magnesium sulfate as a tocolytic]. / Za i protiv magnezieviiat sulfat kato tokolitichno sredstvo.

Magnesium sulphate (MgSO4) is with a proved effectiveness in cases of praeclampsia/eclampsia, but its use as a tocolytic is discussed in the last few years. That is why we had for an object to study its effect as a tocolytic in cases of abortions and premature labours. The study is prospective and if is made in I-st obstetric clinic of High Medical School--Pleven. Treatment with Cormagnesin was carried out to pregnant women for suppressing the uterine activity. Cormagnesin 200 (1 amp-10 ml) contains 1000 mg MgSO4, and Cormagnesin 400 (1 amp-10 ml) contains 2000 mg MgSO4. The medicine was administered in dosage of 4 or 5 g for 30 min, and after that if there were any uterine contractions the infusion was carried on with additional 5 g MgSO4 for 6 to 12 h. The total dosage was from 4 to 60 g MgSO4. The authors reported on very good effect in cases with pains and increased uterine tone--18 (36.73%), as well as in cases with pains and irregular uterine contractions 5 (10.21%), while the treatment was without any effect in cases with uterine contractions on 15-20 min, increased uterine tone, bleeding and Pelvic score 1-3 points in spite of high dosages of MgSO4 and longer duration of treatment. The authors made the conclusion, that the subjective complaints should not be accepted as an indication for administration of MgSO4, and MgSO4 should be administered in cases with increased uterine tone and irregular uterine contractions. Every genital bleeding and suspicion for placental abruption should be defined more precisely, because lately diagnosed placental abruption and unjustified expectation for suppression of uterine activity by MgSO4, may lead to increase of perinatal morbidity and mortality. In spite of the controversial data about MgSO4 as a tocolytic, its administration is justified and necessary.

Prevention of bone loss with tibolone in postmenopausal women: results of two randomized, double-blind, placebo-controlled, dose-finding studies.

Tibolone, a novel compound with tissue-specific effects, has been found to have antiresorptive properties in bone. To confirm the efficacy of tibolone and determine its minimum effective dose for prevention of bone loss in early postmenopausal women, two randomized, double-blind, placebo-controlled, dose-finding studies were performed. Seven hundred seventy healthy women postmenopausal within 1-4 yr, with normal bone density for their age, were treated for 2 yr with 0.3, 0.625, 1.25, or 2.5 mg tibolone daily or placebo. All subjects took supplemental calcium carbonate (500 mg daily). Bone mineral density (BMD) of the lumbar spine and right proximal femur was measured by dual-energy x-ray absorptiometry for up to 2 yr. At each dose level, except the lowest (0.3 mg), tibolone produced a progressive increase in lumbar spine and total hip BMD over the 2-yr treatment period; at 0.3 mg, total hip density was maintained. However, only the doses 1.25 mg and 2.5 mg produced a progressive increase in femoral neck BMD. The differences in mean percent change from baseline in spine and total hip density were significant (P < 0.05) for all tibolone dose groups compared with placebo at all time points. Tibolone was well tolerated, with a similar overall incidence of adverse events compared with placebo. Tibolone 1.25 mg per day is recommended because it shows a positive and statistically significant change in BMD of spine and femoral neck.

Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo studies.

Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle. This disturbance in the angiogenic process may be caused by an imbalance of pro- and antioxidant processes in the endometrium of Norplant users. The aim of this study is to investigate the effect of vitamin E on the endometrial angiogenic activity and to assess the efficacy of vitamin E supplementation in treating endometrial bleeding in Norplant users. Subjects for this study were selected from Norplant users with an exposure of at least 3 months, with endometrial bleeding and recruited on the basis of fully informed consent. TBA reaction was used to measure degradation products of lipid peroxidation. The endometrial angiogenic response was assayed according to Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from endometrial biopsies were incubated in vitro with vitamin E or placebo before angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or placebo for 10 days/month were given to the subjects with double blind randomisation. The results showed that the blood levels of TBA-reactive substances were significantly higher in Norplant users than in controls. In the endometrium from Norplant users with bleeding problems, in vitro supplementation of vitamin E resulted in a significantly higher angiogenic score than placebo. Although a highly significant reduction of bleeding days in both groups, vitamin E and placebo, was seen during the 2 months of the study, the number of bleeding days was significantly lower in women treated with vitamin E than with placebo.