Increased expression of one isoform of leucine-rich alpha-2-glycoprotein in peritoneal fluid of women with uterine leiomyomas

Objective  To compare the peritoneal fluid (PF) proteome of women with and without uterine leiomyomas. Study design  PF samples were collected at laparoscopy from 14 women with uterine leiomyomas and 14 patients without leiomyomas who underwent tubal sterilization. PF samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by computerised analysis. Protein spots with aberrant expression in PF of women with leiomyomas were identified by liquid chromatography tandem mass spectrometry. Results  One isoform of leucine-rich alpha-2-glycoprotein (LRGm), one immunoglobulin light chain, and one unidentified protein (pI: 5.62; M _r: 51.1 kDa) had significantly higher expression in PF of women with leiomyomas. Two isoforms of fibrinogen gamma chain had decreased expression in PF of women with uterine leiomyomas. Following Bonferroni correction for multiple comparisons, the aberrant expressions of LRGm and of one isoform of fibrinogen gamma chain was confirmed. The expression of these molecules was not affected by the phase of the menstrual cycle. Conclusions  Uterine leiomyomas are associated with changes in proteins present within the peritoneal fluid. The physiopathological relevance of the increased expression of LRGm in PF of women with uterine leiomyomas remains unclear.     

Proteomic analysis and characterisation of human cervico-vaginal fluid proteins

AIM: Cervico-vaginal fluid (CVF) may provide insight into the biochemical pathways of human reproduction and parturition. The aim of this study was to establish a 2-D electrophoretic map of human CVF in healthy, pregnant women at term. METHODS: CVF was collected, concentrated and processed by routine 2-D polyacrylamide gel electrophoresis using pH 4-7-immobilised pH gradient strips and 8-16% gradient polyacrylamide gels. Imaged gels were analysed, yielding more than 400 proteins. A total of 157 proteins were common to all gels with a subgroup of the most abundant proteins being excised and characterised either by MALDI or by electrospray ion-trap mass spectrometry. RESULTS: Twenty-one proteins were successfully identified, yielding 15 different proteins. These included blood transport proteins (albumin and transthyretin); a structural protein (beta-actin); proteins involved in fatty acid metabolism (fatty acid-binding protein and acetyl-CoA-binding protein); a calcium-binding protein (annexin III); an anti-inflammatory cytokine (interleukin-1 receptor antagonist); proteinase inhibitors (alpha-1-antitrypsin, monocyte/neutrophil elastase inhibitor, squamous cell carcinoma antigen-1 and cystatin A); and enzymes involved in oxidative stress defence (thioredoxin, peroxiredoxin 2, glutathione S-transferase P and copper,zinc superoxide dismutase). CONCLUSION: CVF is a complex body fluid consisting of both endogenous and environmental proteins. The putative role of some of these proteins in the human reproductive tract is discussed.     

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Purpose

Asthenozoospermia is a common cause of human male infertility characterized by reduced sperm motility. The molecular mechanism that impairs sperm motility is not fully understood. This study proposed to identify novel biomarkers by focusing on sperm tail proteomic analysis of asthenozoospermic patients.

Methods

Sperm were isolated from normozoospermic and asthenozoospermic semen samples. Tail fractions were obtained by sonication followed by Percoll gradient. The proteins were extracted by solubilization and subjected to two-dimensional gel electrophoresis (2-DE); then, the spots were analyzed using Image Master 2D Platinum software. The significantly increased/decreased amounts of proteins in the two groups were exploited by matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry.

Results

Three hundred ninety protein spots were detected in both groups. Twenty-one protein spots that had significantly altered amounts (p < 0.05) were excised and exploited using MALDI-TOF-TOF mass spectrometry. They led to the identification of the following 14 unique proteins: Tubulin beta 2B; glutathione S-transferase Mu 3; keratin, type II cytoskeletal 1; outer dense fiber protein 2; voltage-dependent anion-selective channel protein 2; A-kinase anchor protein 4; cytochrome c oxidase subunit 6B; sperm protein associated with the nucleus on the X chromosome B; phospholipid hydroperoxide glutathione peroxidase-mitochondrial; isoaspartyl peptidase/L-asparaginase; heat shock-related 70 kDa protein 2; stress-70 protein, mitochondrial; glyceraldehyde-3-phosphate dehydrogenase, testis-specific and clusterin.

Conclusion

Fourteen proteins present in different amounts in asthenozoospermic sperm tail samples were identified, four of which are reported here for the first time. These proteins might be used as markers for the better diagnosis of sperm dysfunctions, targets for male contraceptive development, and to predict embryo quality.     

The relation between amniotic fluid surfactant concentration in preterm labour and histological evidence of chorioamnionitis

Summary Concentration of amniotic fluid disaturated phosphatidylcholine (DSPC), factors related to cervical ripening, and histopathological evidence of chorioamnionitis were studied in 38 patients in preterm labour with intact membranes; all of them delivered spontaneously before 37 weeks. There was no correlation between the amniotic fluid DSPC level and gestational age at the time of amniocentesis. However, a significant inverse correlation was found between the amniotic fluid DSPC level and the interval between the onset of labour and delivery. The amniotic fluid DSPC level in cases with onset-delivery interval of <48h was significantly higher than that in cases with an onsetdelivery interval of 48h or more. The gestational age in the former group was significantly lower than in the latter (28.6 vs 32.0 weeks). The amniotic fluid DSPC level in the patients with chorioamnionitis was significantly higher than that in the patients without chorioamnionitis, although the gestational age did not differ between the two groups. All 3 infants with RDS were associated with cervical incompetence. Patients in preterm labour with chorioamnionitis may be refractory to tocolysis and have higher amniotic fluid surfactant levels.     

Two-dimensional gel electrophoresis in peritoneal fluid samples identifies differential protein regulation in patients suffering from peritoneal or ovarian endometriosis

Endometriosis is determined by local and systemic proinflammatory dysregulation and therefore differential protein expression in peritoneal fluid (PF). Of highest interest is lesion formation and the establishment and persistence of endometriosis. In this study we analyzed well-characterized PF samples of patients with ovarian or peritoneal endometriosis and compared them to control samples. We found 11 proteins differentially regulated, of which some might play a key role in the pathogenesis of endometriosis.     

Association between lactate in vaginal fluid and time to spontaneous onset of labour for women with suspected prelabour rupture of the membranes

OBJECTIVES: To assess whether lactate determination in vaginal fluid is associated with, and can predict, onset of labour for women with suspected prelabour rupture of the membranes (PROM). DESIGN: Prospective observational study. SETTING: Labour ward at Soder Hospital, Stockholm, Sweden. POPULATION: Women with suspected PROM after 34 weeks of gestation, who later had spontaneous onset of labour (n = 179). METHODS: All women underwent a speculum examination and a test for determining lactate concentration in vaginal fluid. We used logistic regression to estimate the association between lactate concentration in vaginal fluid and time to onset of labour. MAIN OUTCOME MEASURES: Time from examination to onset of labour (cervix > or =4 cm), within 24 hours and 48 hours. RESULTS: The median time interval between examination and spontaneous onset of labour was 8.4 hours for women with 'high' lactate (> or =4.5 mmol/l) and 54 hours for those with 'low' lactate concentrations (<4.5 mmol/l). Among 86 women with high lactate concentrations, 76 (88%) had started labour within 24 hours compared with 20 of 93 (22%) women with low lactate concentrations (OR 27.7, 95% CI 12.2-63.3). After checking for the effect of visible amniotic fluid, the corresponding odds were still substantially increased (OR 13.5, 95% CI 5.3-34.3). CONCLUSIONS: High lactate concentration (> or =4.5 mmol/l) in vaginal fluid can be used to predict whether a woman with suspected PROM will commence spontaneous onset of labour within 24 or 48 hours.     

Lipidomics analysis of follicular fluid by ESI-MS reveals potential biomarkers for ovarian endometriosis

PurposeThe aim of the present study was to analyze the lipid profile of follicular fluid from patients with endometriosis and endometrioma who underwent in vitro fertilization treatment (IVF).MethodsThe control group (n = 10) was composed of women with tubal factor or minimal male factor infertility who had positive pregnancy outcomes after IVF. The endometriosis group consisted of women with endometriosis diagnosed by videolaparoscopy (n = 10), and from the same patients, the endometriomas fluids were collected, which composed the endometrioma group (n = 10). From the follicular fluid and endometriomas, lipids were extracted by the Bligh and Dyer method, and the samples were analyzed by tandem mass spectrometry.ResultsWe observed phosphatidylglycerol phosphate, phosphatidylcholine, phosphatidylserine, and phosphatidylnositol bisphosphate in the control group. In the endometriosis group, sphingolipids and phosphatidylcholines were more abundant, while in the endometrioma group, sphingolipids and phosphatidylcholines with different m/z from the endometriosis group were found in high abundance.ConclusionThis analysis demonstrated that there is a differential representation of these lipids according to their respective groups. In addition, the lipids found are involved in important mechanisms related to endometriosis progress in the ovary. Thus, the metabolomic approach for the study of lipids may be helpful in potential biomarker discovery.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0592-1) contains supplementary material, which is available to authorized users.     

PGE2 gel for enhancement of priming and induction of labour at term in patients with unfavorable cervix

Fifty women (25 nulliparae and 25 multiparae) with unfavourable cervix at term were enrolled in a clinical experiment to evaluate the safety and efficacy of the intracervical application of 0.5 mg PGE₂ gel for cervical softening and eventual induction of labour; duration of pregnancy (38–42 wk) was confirmed by ultrasonic records. Global analysis revealed 48 (96%) vaginal deliveries, 43 (86%) being spontaneous labour and 5 (10%) instrumentally assisted deliveries (forceps). Caesarean section was required in 2 cases (4%). Three patients, having registered no Bishop score (above 5) progress after the first treatment, went into labour upon the second application of PGE₂ gel. Mean induction-delivery time was 11 h 50 min for nulliparae and 7 h 50 min for multiparae. Mean ROM/amniotomy-delivery time was 5 h 59 min for nulliparae and 3 h 11 min for multiparae. Four neonates with initial Apgar scores below 7 registered immediately higher values after adequate reanimation manouvres.     

Prediction of time to spontaneous onset of labour with lactate concentration in vaginal fluid in women with suspected preterm prelabour rupture of the membranes

Objective  To assess whether lactate determination in vaginal fluid is associated with and can predict onset of labour for women with suspected preterm prelabour rupture of membranes (PPROMs).
Design  Prospective observational study.
Setting  Labour ward at South General Hospital, Stockholm, Sweden.
Population/participants  Women with suspected PPROMs at 20–36 completed weeks of gestation ( n = 81).
Methods  All women underwent a speculum examination and a test for determining lactate concentration in vaginal fluid. We used logistic regression to estimate the association between lactate concentration in vaginal fluid and time to onset of labour.
Main outcome measure  Time from examination to spontaneous onset of labour (cervix ≥4 cm).
Results  The median time between examination and onset of labour was 13.6 hours for those with a high (≥4.5 mmol/l) lactate concentration and 1152 hours (i.e. 48 days) for those with a low (<4.5 mmol/l) lactate concentration. For a lactate threshold of 4.5 mmol/l, the likelihood ratio for positive test (LR+) was 12.6, and LR− was 0.14 for the outcome of spontaneous onset of labour within 48 hours.
Conclusions  A high lactate concentration in vaginal fluid is strongly associated with whether a woman with suspected PPROM will commence onset of labour within 48 hours. If confirmed, use of lactate ('LAC test') as a predictive test for onset of preterm labour may be an attractive tool in bedside obstetrics.     

Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells

Purpose

The purpose of this study is to study lipid metabolism in oocytes and embryos that is a neglected parameter in human IVF.

Methods

We have tested the total carnitine content (TC) in the follicular fluid of 278 patients (217 non pregnant, 61 pregnant) undergoing IVF.

Results

The follicular fluid TC is neither correlated with the circulating estradiol content in serum nor with the outcome the IVF attempt. Carnitine, through the carnitine shuttle, is a major partner in lipid beta oxidation, metabolic pathway involved in the acquisition of oocyte competence. The expression of carnitine synthesis enzymes and lipid beta oxidation was studied in cumulus cells collected at the time of ovum retrieval and in oocyte. Surprisingly the expression for carnitine synthesis is not detectable in oocytes whereas the enzymes involved in lipid beta oxidation are rather strongly expressed.

Conclusions

The addition of carnitine in oocyte maturation and embryo culture media should not be overlooked.     

Induction of labour with prostaglandin E2 vaginal gel in women with one previous caesarean section

ObjectiveTo study the outcome of induction of labour with prostaglandin E2 (PGE2) vaginal gel in those with one previous caesarean section.DesignOne year prospective comparative study.SettingA tertiary care Armed Forces Hospital, Muscat.PopulationForty-six women with one previous caesarean section (CS) underwent PGE2 vaginal gel induction (study group). Hundred women with previous CS had gone into spontaneous onset of labour (control group).Main outcome measuresPrimary outcome measures are mode of delivery and uterine rupture. Others are neonatal outcome, indications for caesarean section, and complications like, postpartum haemorrhage and infectious morbidity.ResultsOverall rate of vaginal delivery after caesarean section (VBAC) was 65.21% and 79% in the study and control groups, respectively. There were 7 cases of neonatal intensive care unit (NICU) admissions (7%) in the control group; however, none in the study group. Caesarean section done for foetal distress was 5/16 CS in the study group (31.25%) and 10/21 CS in the control group (47.61%). There were no cases of uterine rupture in both control and study groups.ConclusionInduction of labour with prostaglandin E2 vaginal gel in women with one previous caesarean section does not significantly increase the risk of caesarean section rate or ruptured uterus and does not adversely affect immediate neonatal outcome.     

Optimal timing of labour induction in contemporary clinical practice

Induction of labour (IoL) is generally conducted when maternal and foetal risks of remaining pregnant outweigh the risks of delivery. With emerging literature around non-medically indicated IoL, contemporary clinical practice has seen an increase in IoL at 39 weeks’ gestation. This review highlights recent evidence on the most common indications for IoL including gestational diabetes, hypertensive disorders of pregnancy, intrahepatic cholestasis of pregnancy, and post-term pregnancies. It also summarizes the evidence related to the timing of IoL for other common conditions based on recent literature reviews.     

Women's perceptions of social support during labour: Development,reliability and validity of the Birth Companion Support Questionnaire

Objective

to develop and test the reliability and validity of a research instrument to measure women's perceptions of social support provided during labour by at least one lay birth companion.

Design

a cross-sectional study was carried out from April 2009 to February 2010.

Setting

non-tertiary hospital in the outer western region of Brisbane, Australia.

Participants

six registered midwives and 10 postnatal women reviewed the instrument. The instrument was then completed by 293 inpatient women who had experienced a vaginal birth.

Measurements and findings

the Birth Companion Support Questionnaire (BCSQ) was developed and its reliability and validity were evaluated in this study. An exploratory factor analysis was performed on the final instrument using principal component analysis with an oblique (Promax) rotation. This process suggested two subscales: emotional support and tangible support. The questionnaire was found to be reliable and valid for use in midwifery research.

Key conclusions

the BCSQ is an appropriate instrument to measure women's perceptions of lay birth companion support during labour.

Implications for practice

this is the first rigorous study to develop and test a measure of social support in labour which is critical at a time when policy makers and health planners need to consider the needs of birthing women and their network of support friends and family.     

PGE2 gel for enhancement of priming and induction of labour at term in patients with unfavourable cervix

Fifty women (25 nulliparae and 25 multiparae) with unfavourable cervix at term were enrolled in a clinical experiment to evaluate the safety and efficacy of the intracervical application of 0.5 mg PGE₂ gel for cervical softening and eventual induction of labour; duration of pregnancy (38–42 wk) was confirmed by ultrasonic records. Global analysis revealed 48 (96%) vaginal deliveries, 43 (86%) being spontaneous labour and 5 (10%) instrumentally assisted deliveries (forceps). Caesarean section was required in 2 cases (4%). Three patients, having registered no Bishop score (above 5) progress after the first treatment, went into labour upon the second application of PGE₂ gel. Mean induction-delivery time was 11 h 50 min for nulliparae and 7 h 50 min for multiparae. Mean ROM/amniotomy-delivery time was 5 h 59 min for nulliparae and 3 h 11 min for multiparae. Four neonates with initial Apgar scores below 7 registered immediately higher values after adequate reanimation manouvres.     

Effects of a pushing intervention on pain, fatigue and birthing experiences among Taiwanese women during the second stage of labour

Objectives

to evaluate maternal labour pain, fatigue, duration of the second stage of labour, the women's bearing-down experiences and the newborn infant Apgar scores when spontaneous pushing is used in an upright position.

Design

quasi-experimental study.

Setting

medical centre in Taichung, Taiwan.

Participants

66 women giving birth at the hospital, with 33 primigravidas assigned to each group.

Interventions

during the second stage of labour, the women in the experimental group pushed from an upright position and were given support to push spontaneously; the women in the control group pushed from a supine position and were supported via Valsalva pushing.

Outcome measures

pain scores were recorded at two evaluation time points: at 10 cm of cervical dilation and one hour after the first pain score evaluation. One to four hours after childbirth, the trained nurses collected the fatigue and pushing experience scores.

Findings

the women in the experimental group had a lower pain index (5.67 versus 7.15, p=0.01), lower feelings of fatigue post birth (53.91 versus 69.39, p<0.001), a shorter duration of the second stage of labour (91.0 versus 145.97, p=0.02) and more positive labour experiences (39.88 versus 29.64, p<0.001) compared with the control group. There was no significant difference in the Apgar score for newborn infants during either the first minute (7.70 versus 7.73, p=0.72) or the fifth minute (8.91 versus 8.94, p=0.64).

Key conclusions

the pushing intervention during the second stage of labour lessened pain and fatigue, shortened the pushing time and enhanced the pushing experience.

Implications for practice

pushing interventions can yield increased satisfaction levels for women giving birth.     

The concept of early labour in the experience of maternity in twentieth century Britain

Objective

This paper explores perceptions of time and experience in midwifery with particular reference to the concept of early labour. Health professionals and lay people are used to describing labour in terms of ‘stages’ which correspond to agreed notions of progress based on physiological features. However the understanding of labour which underpins them is not a static entity but is a product of a particular era and set of circumstances which are primarily socially rather than biologically mediated.

Design

The research uses a historical methodology to describe understanding of, and strategies around, the management of early labour. It includes a variety of source material, including midwifery and obstetric textbooks, midwifery casebooks, books of advice to women and the oral testimony of midwives and mothers.

Setting

Twentieth century Britain. The twentieth century was a period of significant philosophical and concrete change in maternity in Britain, with occupational hegemony developing around both midwifery and obstetrics, and with the concomitant institutionalisation of labour and birth.

Participants

Mothers, midwives and doctors.

Findings

The evidence suggests that during the first half of the twentieth century early labour was not seen as a discrete period within the first stage of labour with specific features or associated issues. Instead it was a private and individual experience, which rarely involved the presence of either doctors or midwives. Women, and those around them, made the decision about what early labour meant and how they should respond to it. The development of divisions in labour and notions of what constituted ‘normality’ or ‘abnormality’ as regards the length of each stage, based on time and clinical features, developed as the setting for labour and birth moved from home to hospital in the second half of the twentieth century. Labour became more described and more proscribed, with a rash of textbooks aimed at both midwives and doctors, and with the growing visibility of the entire process of labour through the use of technological surveillance and through the fact that women labouring on a hospital bed were observable in a way that women labouring at home were not.

Key conclusions and implications

To look for historical strategies around the management of entities such as early labour is to assume, ahistorically, that similar beliefs and issues existed in an earlier period, and that there perhaps existed strategies for management which could profitably be rediscovered for use in current maternity care. The evidence suggests that such divisions were not described or managed features of labour before the second half of the twentieth century. The use of history does, however, give insights into breaks and continuities in beliefs and practice over time, and demonstrates that beliefs about stages of labour and their management are, like other aspects of maternity, multi-faceted and complex in both origin and effect.