Hyponatraemia reversibly affects human myometrial contractility. An in vitro pilot study.

BACKGROUND: In a previous study we found a significant correlation between dystocia and hyponatraemia that developed during labour. The present study examined a possible causal relationship. In vitro studies often use area under the curve (AUC) determined by frequency and force of contractions as a measure of myometrial contractility. However, a phase portrait plot of isometric contraction, obtained by plotting the first derivate of contraction against force of contraction, could indicate that bi-or multiphasic contractions might be less effective compared to the smooth contractions. MATERIAL AND METHODS: Myometrial biopsies were obtained from 17 women undergoing elective caesarean section at term. Each biopsy was divided into 8 strips and mounted isometrically in a force transducer. Seven biopsies were used in the first part of the study when half of the strips were immersed in the hyponatraemic study solution S containing Na+ 120 mmol/L and observed for 1 hour, followed by 1 hour in normonatraemic control solution C containing Na+ 136 mmol/L, then again in S for 1 hour, and finally 1 hour in C. The other half of the strips were studied in reverse order, C-S-C-S. The remaining ten biopsies were included in the second part of the study. Response to increasing doses of oxytocin (OT) in solutions S and C was studied. In the first part of the study we calculated AUC, and created phase portrait plots of two different contractions from the same strip, one smooth and one biphasic. In both parts of the study we registered frequency and force of contractions, and described appearance of the contractions. RESULTS: First part of the study: Mean (median) contractions per hour in C: 8.7 (7.6), in S 14,3 (13). Mean (SD) difference between groups 5.6 (4.2), p = 0.018. Force of contractions in C: 11.8 (10.2) mN, in S: 10.8 (9.2) mN, p = 0.09, AUC increased in S; p = 0.018. Bi-/multiphasic contractions increased from 8% in C to 18% in S, p = 0.001. All changes were reversible in C. Second part of the study: Frequency after OT 1.65 x 10-9 M in C:3.4 (2.9), in S: 3.8 (3.2), difference between groups: p = 0.48. After OT 1.65 x 10-7 M in C: 7.8 (8.9), increase from previous OT administration: p = 0.09, in S: 8.7 (9.0), p = 0.04, difference between groups, p = 0.32. Only at the highest dose of OT dose was there an increase in force of contraction in S, p = 0.05, difference between groups, p = 0.33. Initial response to OT was more frequently bi/multiphasic in S, reaching significance at the highest dose of OT(1.65 x 10-7 M), p = 0.015. when almost all contractions were bi/multiphasic. CONCLUSION: Hyponatraemia reversibly increased frequency of contractions and appearance of bi-or multiphasic contractions, that could reduce myometrial contractility. This could explain the correlation of hyponatraemia and instrumental delivery previously observed. Contractions in the hyponatraemic solution more frequently showed initial multiphasic contractions when OT was added in increasing doses. Longer lasting labours carry the risk both of hyponatraemia and OT administration, and their negative interaction could be significant. Further studies should address this possibility.

A functional role for AMPK in female fertility and endometrial regeneration.

Adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved heterotrimeric complex that acts as an intracellular energy sensor. Based on recent observations of AMPK expression in all structures of the female reproductive system, we hypothesized that AMPK is functionally required for maintaining fertility in the female. This hypothesis was tested by conditionally ablating the two catalytic alpha subunits of AMPK, Prkaa1 and Prkaa2, using Pgr-cre mice. After confirming the presence of PRKAA1, PRKAA2 and the active phospho-PRKAA1/2 in the gravid uterus by immunohistochemistry, control (Prkaa1/2 fl/fl ) and double conditional knockout mice (Prkaa1/2 d/d ) were placed into a six-month breeding trial. While the first litter size was comparable between Prkaa1/2 fl/fl and Prkaa1/2 d/d female mice (P = 0.8619), the size of all subsequent litters was dramatically reduced in Prkaa1/2 d/d female mice (P = 0.0015). All Prkaa1/2 d/d female mice experienced premature reproductive senescence or dystocia by the fourth parity. This phenotype manifested despite no difference in estrous cycle length, ovarian histology in young and old nulliparous or multiparous animals, mid-gestation serum progesterone levels or uterine expression of Esr1 or Pgr between Prkaa1/2 fl/fl and Prkaa1/2 d/d female mice suggesting that the hypothalamic-pituitary-ovary axis remained unaffected by PRKAA1/2 deficiency. However, an evaluation of uterine histology from multiparous animals identified extensive endometrial fibrosis and disorganized stromal-glandular architecture indicative of endometritis, a condition that causes subfertility or infertility in most mammals. Interestingly, Prkaa1/2 d/d female mice failed to undergo artificial decidualization. Collectively, these findings suggest that AMPK plays an essential role in endometrial regeneration following parturition and tissue remodeling that accompanies decidualization.

Laminin and Collagen IV: Two Polypeptides as Marker of Dystocic Labor.

Collagen IV and Laminin are localized in cells and tissue of numerous human organs including the uterus, where these polypeptides control either age changes, or uterus growth in pregnancy, or ripening and dilatation in labor. Authors examined the polypeptides distribution of collagen IV and Laminin in the human pregnant uterus, in normal and dystocic labor, to clarify their physiologic role, by distribution and/or their changes in prolonged dystocic labor. We collected lower uterine segment (LUS) fragments during cesarean section (CS); these biopsies were treated with basic morphological staining for the observation of microscopic- anatomic details. Other samples were processed with immunohistochemical staining for collagen IV and for membrane bound Laminin. All morphological and immunochemical results were analyzed with quantitative analysis of images and statistical analysis of data. Both Collagen IV and Laminin show changes in the pregnant uterus before 4 hours of full cervical dilatation in patients after 4 hours. All the three types of the human uterine cells, mucosal, submucosal and smooth muscular cells, are more reduced in LUS after 4 hours of cervical dilatation in dystocic labor. The connective tissues (including fibroblast) show the most evident changes in the dystocic LUS, collagen IV and laminin changes during cervical dilatation in prolonged dystocic labor, with a decreased elasticity with increased roughness and dryness. The LUS anatomical modifications during labor can be the cause of pathological changes in protracted dystocic labor. In the dystocic labor that lasts more than 4 hours from the complete cervical ripening and dilatation, the laminin and collagen IV concentration reduces in the LUS tissue. In dystocic labor, delivery should be completed before the 3 hours of full dilation, to avoid a reduction of laminin and collagen IV and a worsening of LUS healing for the next pregnancy.

Normal first stage of preterm labor.

OBJECTIVE: To compare first-stage labor patterns in women in preterm labor to those in labor at term. STUDY DESIGN: We performed a retrospective cohort study of consecutive women admitted from 2004 to 2008 with viable (≥ 24 weeks) vertex singleton gestations who reached the second stage of labor. Labor curves for preterm and term labor were created using a repeated-measures analysis with polynomial modeling. Interval-censored regression was used to estimate and compare median time of progression of labor. Multivariable analyses were performed to adjust for smoking, obesity (body mass index ≥ 30), induction, and nulliparity. The adjusted model was stratified by parity and induction of labor. RESULTS: Of 5,612 consecutive births, 224 were preterm (<37 weeks) and 5,388 were term (≥ 37 weeks). Preterm first-stage labor progressed significantly faster than term labor (median time 4 to 10 cm: 3.3 hours versus 4.5 hours, p < 0.01). When stratified by parity, preterm labor progressed significantly more rapidly than term labor in both nulliparous and multiparous women (median time 4 to 10 cm: 3.7 hours versus 4.9 hours [p = 0.04] in nulliparous women and 2.5 hours versus 4.3 hours [p = 0.01] in multiparous women). CONCLUSION: Women in preterm labor progress more rapidly through the first stage of labor than women at term.

Distócia de ombro / Shoulder dystocia

A Distócia de Ombro é definida, de acordo com os Colégios Americano e Britânico de Obstetrícia e Ginecologia, como parto que necessita de manobras obstétricas adicionais, após falência da tração da cabeça fetal para liberar os ombros. Apesar de sua baixa incidência, é uma complicação com importante morbidade para o recém nascido e que pode levar a intercorrências maternas, sendo entretanto passível de ser evitada. Esse artigo de revisão se propõe a sumarizar a epidemiologia, fisiopatologia, conduta e complicações, enfocando os fatores de risco e as manobras mais utilizadas, dada a importância de ambos na prevenção dessa complicação. (AU)

The Shoulder Dystocia is defined, according to British and American Colleges of Obstetrics and Gynecology, as delivery which requires additional obstetric maneuvers after failure of traction of the fetal head to release the shoulders. Despite its low incidence, it is a complication with significant morbidity for the newborn and wich can lead to maternal complications. Despite of this, is able to be avoided. This review aims to summarize the epidemiology, pathophysiology, management and complications, focusing on risk factors and the most commonly used maneuvers, due to the importance of both in preventing this complication. (AU)

Retrospective review of predisposing factors and surgical outcomes in obstetric fistula patients at a single teaching hospital in Western Kenya.

OBJECTIVE: We examined success rates and complications of obstetric fistula (OF) surgical repairs in association with patient and fistula characteristics, including sociocultural and socioeconomic determinants of health. A better understanding of these associations will help guide surgical management and prevent predisposing factors. METHODS: We reviewed the medical records of 86 patients who underwent OF repair at Moi Teaching and Referral Hospital in Kenya between 1999 and 2007. RESULTS: Women with OF presented for repair with a variety of concurrent conditions. Seventy-eight percent had laboured for at least 24 hours; 29% had undergone previous unsuccessful surgery. Of the women who presented at postoperative follow-up, 54% still complained of incontinence. Persistent incontinence was associated with larger, more complicated fistulas and having had previous failed attempts at surgical repair. CONCLUSION: The association of factors such as duration of labour with OF reflects the limited availability of obstetrical care in Western Kenya. There is a significant difference in postoperative success of fistula repair between women with large fistulas or those who had previous failed surgery and other patients. This reflects the importance of primary and secondary prevention.

Prepartal concentration of estradiol-17beta in heifers with stillborn calves.

This study was conducted to investigate hormonal imbalances preceding stillbirths and dystocia in primiparous heifers. The study was conducted between 2003 and 2004 on a German dairy farm, including 433 heifers. Starting 3 wk before calving, a weekly blood sample was collected. At calving, another blood sample was obtained, and the calving ease (grade 0 = unassisted to grade 2 = heavy pull with mechanical calf puller), sex, birth weight, as well as vitality status (stillborn, alive) of the calf were recorded. The blood serum was analyzed for estradiol-17beta and progesterone concentration. At parturition, the measured estradiol-17beta concentration was greater in heifers delivering bulls than in those with female calves and was increasing with greater birth weight of the calf and increasing calving difficulty score. Already 2 wk before calving, the serum estradiol-17beta concentration was significantly smaller in heifers with stillborn than live calves. On the other hand, the progesterone concentration was greater 2 wk before calving in heifers with stillborn calves, but it was unaffected by the birth weight or sex of the calf or the calving difficulty score. Stillborn and live calves did not differ in birth weight or pregnancy duration. The smaller estradiol-17beta concentrations of the heifers with stillborn calves could indicate an abnormality of the placenta or an abnormality of hormonal signals from the calf to the placenta in the weeks before the calving.

Impact of calving ease on functional longevity and herd amortization costs in Basque Holsteins using survival analysis.

The aim of this study was to analyze the impact of calving ease (CE) on functional longevity of Basque Holsteins, using a Weibull proportional hazards model. The data considered for the analysis were 53,353 calving records from 25,810 Holstein cows distributed across 781 herds and sired by 746 bulls. The effects included in the statistical model were age at first calving, stage of lactation, interaction between year and season of calving, 305-d adjusted milk yield, CE, herd, and sire. Calving ease was considered as a time-dependent covariate and, as was the case for the rest of covariates included in the model, had a significant effect on functional longevity. Calvings needing assistance or surgery increased culling risk by 18%, when compared with unassisted calvings. The effect of CE on length of productive life in primiparous and multiparous cows was also investigated. A second analysis was performed replacing the CE effect with the interaction between parity and CE to evaluate the effect of CE in primiparous and multiparous cows. An increase in calving difficulty had a greater impact on culling during first lactations than in subsequent ones. Therefore, difficult calvings, mainly at first parities, had a high impact on herd amortization costs, increasing them by 10% in relation to easy calvings. Therefore, calving difficulty should be avoided as much as possible, especially in primiparous cows, to avoid reduction of profitability.

Effect of disease on reproduction in the dairy cow: a meta-analysis.

Effects on reproduction of dystocia, stillbirth, abortion, milk fever, retained placenta, metritis, cystic ovaries, anestrus, ketosis, displaced abomasum, locomotor disorders, and mastitis were reviewed. Papers were considered if they provided quantitative estimates of diseases on days to first estrus, days to first service, conception rate at first service, days from first service to conception, days to conception or days open, calving interval, conception rates at various days post partum (dpp), and number of services per conception or per cow. Only papers in English in peer-reviewed journals were selected for analysis of post 1960 data from intensive dairy regions. Seventy papers fulfilled the selection criteria. Summary estimates of disease effects were calculated according to meta-analysis methods, and study designs were described in detail to identify possible heterogeneity of the results. Stillbirth, milk fever, displaced abomasum and mastitis had no effect on reproduction. Clinical ketosis, dystocia and retained placenta were associated with 2 to 3 more days to first service and with a 4 to 10% lower conception rate at first service, resulting in 6 to 12 more days to conception. Locomotor disorders were associated with an average increase of 12 d to conception, with wide variation depending on lesions and stage of occurrence. Metritis was associated with 7 more days to first service, 20% lower conception rate at first service, resulting in 19 more days to conception. Cystic ovaries were associated with 6 to 11 more days to first service and with 20 to 30 more days to conception. Anestrus was associated with 26 more days to first service and with an 18% lower conception rate at first service, resulting in 41 more days to conception. Abortion was associated with 70 to 80 more days to conception.

Relationships of peri-partum, plasma concentrations of progesterone, oestrogens and 13,14-dihydro-15-ketoprostaglandin F2alpha in heifers and of anatomical measurements of dam and calf with difficulty of calving in early-bred Hereford x Friesian heifers.

Plasma concentrations of progesterone, oestradiol-17beta, oestrone, oestrone sulphate and PGFM have been measured daily during the first peri-partum period of 45 Hereford x Friesian heifers bred at 11 months of age. Anatomical measurements of dam and calf were also recorded. Twelve of the calvings were scored easy, 33 difficult. Each of five models (fitted by linear logistic regression) relating difficulty of calving to the hormonal and anatomical measurements, predicts with at least 94% accuracy the calving score (easy or difficult) among the calvings. The models predict that increases of progesterone concentration on the day before calving, of oestrone sulphate concentration on the day after calving and of heifer heart girth decrease the odds of difficult calving, whereas increases of heifer body length and of calf head circumference increase the odds of difficult calving.

Plasma beta-endorphin around parturition and its relationship to cortisol level and resumption of pituitary and ovarian functions in dairy cows.

The objectives were to evaluate the concentrations of beta-endorphin in peripheral circulation around parturition and to investigate their relationship to the concentrations of cortisol and postpartum resumption of pituitary and ovarian functions in dairy cows. Subjects were 21 Holstein-Friesian cows in late pregnancy. Blood samples were collected from these animals from day 270 in pregnancy until the first ovulation after calving. Average immunoreactive (IR) beta-endorphin concentrations in cows with dystocia (n = 8) in periparturient period (from day 270 of pregnancy until 24 h after calving) were slightly higher than those in cows with normal calving (n = 13) in the same period although the difference was not significant. During the periparturient period, the peak level of IR beta-endorphin was seen at the time of rupture in cows with normal calving and it was observed at the time of parturition in cows with dystocia. The trend of IR beta-endorphin secretion appeared to be concomitant with cortisol secretion in the periparturient period but not in postpartum period (from 24 h after calving until the first ovulation). Average IR beta-endorphin concentrations in cows with dystocia in the postpartum period were not significantly different from those in cows with normal calving. There was no significant association between average IR beta-endorphin concentrations in early postpartum period (from 24 h until 7 days after calving) and the responsiveness of luteinising hormone (LH) to exogenous GnRH administered on day 7 postpartum. However, a negative correlation (r = -0.593; n = 21; P = 0.004) was observed between average IR beta-endorphin concentrations and LH concentrations during the period from day 1 until the first ovulation in the 21 cows. In addition, a positive correlation (r = 0.498; n = 21; P = 0.020) was seen between the beta-endorphin concentrations and time to the first ovulation after calving. The results from this study suggest that beta-endorphin may release into peripheral blood differently from cortisol and that it may be involved in regulating LH secretion and thus the resumption of ovarian cyclicity in postpartum dairy cows.

Cellular and molecular bases for dystocia.

In this review I have briefly outlined some of the cellular and molecular reasons for dystocia. I have described the myogenic, that may control the normal progression of labor and explain inadequate uterine contractility associated with dystocia. I have placed particular emphasis on our studies of gap junctions and their regulation. These studies show that there are specific physiologic mechanisms for regulating structural and functional coupling between myometrial cells during labor. The integration of these control mechanisms probably operates to ensure appropriate activation and maintenance of synchronous contractility of the myometrium and effective delivery.