Polycystic ovary syndrome and low-grade inflammation with special reference to YKL-40

Objective: To evaluate the plasma level of YKL-40 in a Danish polycystic ovary syndrome (PCOS) population and to investigate whether YKL-40 is associated with CVD risk factors such as waist circumference, body mass index (BMI), insulin resistance (IR), fasting glucose, fasting insulin, blood lipids and CRP.

Design: Cross-sectional study.

Setting: Gynecological clinics at three Danish University Hospitals.

Patients: One hundred seventy-one premenopausal women with PCOS recruited consecutively from April 2010 to February 2012. PCOS was diagnosed according to the Rotterdam criteria.

Main outcome measures: Plasma level of YKL-40 in four phenotypes of PCOS defined by BMI and IR.

Results: No statistically significant difference was observed in the plasma level of YKL-40 across the four BMI/IR-phenotypes. Positive associations were observed between YKL-40 and BMI, total and free testosterone, triglycerides, and CRP. Total and free testosterone were independent predictors of YKL-40.

Conclusion: YKL-40, the marker of low-grade inflammation is not increased in women with PCOS.     

ß-hCG and prediction of therapeutic success in ectopic pregnancies treated with methotrexate,results from a prospective observational study

Objective: To evaluate the diagnostic accuracy of different beta-human chorionic gonadotrophin (ß-hCG) levels measurement, for predicting success of medical treatment in cases diagnosed as tubal ectopic pregnancy (TEP).

Design: Five-year prospective observational study.

Setting: Prenatal Diagnosis Unit, Vall d'Hebron University Hospital – Barcelona.

Patients: TEP cases fulfilling criteria for medical treatment with Methotrexate.

Interventions: ß-hCG levels were measured on d 0, 4 and 7 of treatment. Results were compared by non-parametrical tests. A ROC curve was plotted to define cut-off points. Diagnostic accuracy of the different measurements was evaluated.

Main outcome measure: Failure of treatment defined as need for surgical treatment or persistence of high ß-HCG levels despite treatment.

Results: 126 women were diagnosed as TEP, eligible for medical treatment. There were no differences in parity, age, previous TEP, or adnexal mass size. Success rate was 88%. ß-HCG decreased significantly more, between days 0–7 and 4–7, in the successful cases. LR for success prediction was 6.2 and 7.8 for ß-HCG levels at days 4 and 7 respectively, 4.02 and 2.47 for decrement between days 0–7 (25%) and 4–7 (20%), respectively.

Conclusion: ß-hCG cutoff values have a potential for predicting a successful medical treatment of TEP.     

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors

Purpose: Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice.

Methods: Female mice were injected with sertraline or saline throughout pregnancy. Offspring continued to receive injections on postnatal days 1–14, a time period in mice similar to the third trimester in human pregnancy. Adult offspring underwent behavioral testing, and serotonin receptor mRNA levels were quantified.

Results: Compared to controls, SSRI exposed mice did not have a reduction in social interactions, spatial learning, or exploratory behavior. As adults, sertraline exposed mice had significantly increased mRNA levels of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex.

Conclusion: Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI exposure.     

Why perimenopausal women should consider to use a levonorgestrel intrauterine system

Objective: The use of a levonorgestrel intrauterine system (LNG-IUS) is useful in preventing pregnancy and for the treatment of menstrual disturbances. A smooth or symptom-free transition to and through menopause is possible when LNG-IUS is combined with estrogen therapy. Unfortunately the majority of physicians are generally unaware of this usefulness combined hormonal therapy in the pre-, peri- and postmenopausal women.

Design and method: Based on long-term clinical experience with LNG-IUS in the form of Femilis®, 104 women where followed from the premenopause through the menopausal transition into the postmenopause. These perimenopausal women received supplemental 17 β-estradiol by gel or patch, or orally as estradiol valerate. Patients received one or two separate Femilis insertions at 5 year intervals. Main outcome measures included acceptability and continued use of the combined regimen for the treatment of climacteric symptoms and for prevention of cardiovascular disease, osteoporosis and other adverse effects caused by estrogen deprivation.

Results: The average age at insertion was 48 years (range 28–58) and the total duration of use was 137 months (range 80–161). The Femilis LNG-IUS was well tolerated as the number of removals for LNG-IUS-related reasons was low. The LNG-IUS was well retained in the uterine cavity as no expulsions were observed. Seven women were lost to follow-up. Eighty-six women (82%) opted for replacement of an LNG-IUS at expiry after 5 years and continued with the estrogen therapy.

Conclusion: Intrauterine progestogen delivery for endometrial suppression in combination with estrogen therapy in the symptomatic perimenopausal women is highly practical as it combines the benefits of prevention of endometrial proliferation and treatment of menorrhagia and hyperplasia, if present. In addition, the contraceptive effect of locally administered LNG is highly desirable as many perimenopausal women run considerable risk of unintended pregnancy. For these reasons, the author views this regimen as one of the most effective, safest and best accepted route resulting in high patient compliance. It is important to convey this message to general practitioners as well as women.     

Transcervical Foley’s catheter versus Cook balloon for cervical ripening in stillbirth with a scarred uterus: a randomized controlled trial

Objective: To compare the efficacy and safety of the use of transcervical Foley’s catheter versus Cook cervical ripening balloon in pregnant women with stillbirth, unfavorable cervix and scarred uterus.

Design: Randomized controlled study.

Setting: El Minia University Hospital, El Minia, Egypt.

Patients and methods: Two-hundred pregnant women with stillbirth, unfavorable cervix and scarred uterus were recruited into this study. They were randomized into two groups. In group I (n?=?100), cervical ripening was done using Foley’s catheter. In group II (n?=?100), cervical ripening was done using Cook cervical ripening balloon.

Main outcome measures: Balloon insertion to delivery interval, successful ripening rate, cesarean delivery rate, maternal adverse events and maternal satisfaction.

Results: Time from balloon insertion to expulsion and from balloon insertion to delivery was significantly shorter in Foley’s catheter group. However, the difference between the two groups regarding time from balloon insertion to active labor, time from balloon expulsion to delivery, cervical ripening, cesarean section, instrumental delivery, pain score, need for analgesia, hospital stay and maternal satisfaction was not statistically significant.

Conclusions: Foley’s catheter and Cook cervical ripening balloon are comparable regarding efficacy and safety profile when used to ripen the cervix in pregnant women with stillbirth, unfavorable cervix and scarred uterus. However, Foley’s catheter has a shorter induction to delivery interval and is relatively cheaper device.     

The influence of psychological factors on postpartum weight retention 12 months post-birth

Background

During the first postpartum year 20% of women retain excessive weight from pregnancy (postpartum weight retention; PPWR), which predicts long-term overweight/obesity.

Objective

The aim of this study was to explore the associations between psychological factors (depression, anxiety and stress symptoms and body attitudes) in late gestation and at 12-months postpartum with PPWR one-year post-birth.

Methods

Pregnant women (N = 176) completed questionnaires in early–mid pregnancy (Time 1; mean (SD) = 16.97 (1.35) weeks), late pregnancy (Time 2; mean (SD) = 33.33 (2.05) weeks), and one year postpartum (Time 3; mean (SD) = 53.12 (3.34) weeks). Women provided demographic characteristics, height and pre-pregnancy weight at Time 1. At Times 2 and 3, weight, depressive, anxiety and stress symptoms and body attitudes (salience of weight and shape, attractiveness, feeling fat, and strength and fitness) were assessed in addition to physiological, socio-contextual and lifestyle factors. Gestational weight gain and PPWR were calculated. Hierarchical linear regression models were conducted to explore variance in 12-month PPWR.

Results

Overall, models explained 26–39% variance in PPWR. Gestational weight gain in late pregnancy and low attractiveness at 12 months postpartum were the only variables associated significantly with 12-month PPWR.

Conclusion

While psychological factors did not appear to be important direct contributors to PPWR at 12 months, the overall contribution of all variables suggests that such factors may be implicated in a small and incremental way. Exploration of the interactions between variables will help unpack potential mechanisms of the development of PPWR at 12 months post-birth.     

Elevated periostin in serum and peritoneal washing fluids as potential biomarkers for endometriosis

Background: To identify the level of periostin in serum and peritoneal washing fluids (PWF) from women with and without endometriosis, as well as to explore the potential of periostin as a biomarker of endometriosis.

Methods: Samples were obtained from 184 women with and without endometriosis. Concentrations of periostin in PWF and blood were measured by enzyme-linked immunosorbent assay.

Results: Levels of periostin both in serum and PWF were notably elevated in women with endometriosis in both the proliferative and secretory phase. Combined with dysmenorrhea and infertility, two potential covariates, the serum periostin had a sensitivity of 75.00%, specificity of 65.00%, and area under the curve (AUC) of 0.774, whereas the PWF periostin had a sensitivity of 94.23%, specificity of 90.00%, and AUC of 0.967 for the diagnosis of endometriosis.

Conclusion: Serum and PWF periostin concentrations may be new potential biomarkers for endometriosis, especially when combined with dysmenorrhea and infertility.     

Little beneficial effect of maternal vitamin supplement on metabolic disturbances in the offspring from the obese mother mice

Objective: To examine whether vitamin supplement before and during pregnancy alters the detrimental effect of maternal obesity on the offspring.

Methods: Obese C57BL/6 female mice were randomly divided into four groups and fed with the control, vitamin D, folic acid or multivitamin supplement diet before and during pregnancy. Physiologic and biochemical variables were obtained.

Results: No significant differences were observed in glucose and lipid variables among offspring from each maternal obese group.

Conclusions: Overall, vitamin D, folic acid or multivitamin supplement cannot ameliorate the detrimental effect of maternal obesity on the metabolic disturbances in the offspring.     

Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model

Objective: The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline.

Design: Randomized controlled, animal study.

Animal(s): Female Wistar rats.

Material and methods: A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared.

Results: The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3–5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group.

Conclusion(s): Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.     

Investigation of maternal psychopathological symptoms,dream anxiety and insomnia in preeclampsia

Purpose: The aim of the current study was to investigate the psychopathological symptoms, psycho-emotional state, dream anxiety, and insomnia in healthy, mild and severe preeclamptic postpartum women and their relation to the severity of preeclampsia (PE).

Materials and methods: This observational study included 45 healthy, 41 mild preeclamptic and 44 severe preeclamptic postpartum women. The 90-item Symptom Checklist Revised, Hospital Anxiety and Depression Scale, Insomnia Severity Index, and Van Dream Anxiety Scale (VDAS) were used to evaluate the psychopathological symptoms, psycho-emotional state, insomnia, and dream anxiety of the participants after delivery.

Results: Severe preeclamptic women had higher VDAS scores than mild preeclamptic and healthy postpartum women (p: 0.001). The psychopathological symptoms were more frequent in preeclamptic women than in healthy controls (p: 0.001). Severe preeclamptic women had the highest scores in Hospital Anxiety-Depression Scale and Insomnia Severity Index (p: 0.001, p: 0.001, respectively).

Conclusion: Preeclampsia negatively affects the psycho-emotional state, psychopathological symptoms and sleep patterns. Further, disturbed dreaming was more frequent in PE and also, all of these conditions became worse with the severity of PE. We speculated that the obstetricians should offer their preeclamptic patients an appropriate mental health care at bedside and postpartum period as needed.     

Prognostic value of funisitis and/or chorionic vasculitis compared to histologic chorioamnionitis in full-term infants

Aim: To compare pathological findings in the placenta and cord with the prognosis of full-term infants in cases of neonatal infection and microbial analyses.

Methods: The pathological findings in the placenta and cord and microbial analyses of amniotic fluid and neonatal samples based on culture or polymerase chain reaction (PCR) were observed in 1208 full-term mother–infant pairs at our center. We also collected neonatal clinical infection data, such as the occurrence of septicemia and other infectious diseases.

Results: Neonatal infection and positive identification of microorganisms were more common in the funisitis and/or chorionic vasculitis group than in the histologic chorioamnionitis group.

Conclusion: Funisitis and/or chorionic vasculitis is a valuable pathological marker for assessing the comparison between intrauterine infection and neonatal inflammatory conditions in infants delivered at full-term.     

Maternal hemoglobin at 27–29 weeks’ gestation and severity of pre-eclampsia

Objective: To examine the relationship between maternal hemoglobin concentration (Hb) at 27–29 weeks’ gestation and severity of pre-eclampsia (PE).

Methods: This was a retrospective study of maternal Hb at 27–29 week in 497 pregnancies that developed PE and 497 healthy controls with normal pregnancy outcomes. Multiple regression analysis was used to examine the association between HB and maternal characteristics and severity of PE classified according to gestation at delivery, birth weight and prevalence of abnormal peripartum maternal creatinine, aspartate transaminase and platelet count.

Results: There was no significant difference in median Hb between the PE and control groups. Multiple regression analysis in the PE group showed that significant prediction for Hb was provided by Afro-Caribbean race, gestation at delivery, maternal platelet count <2.5th percentile and birth weight, but not serum creatinine or aspartate transaminase above the 97.5th percentile. Increased Hb was observed in both small and large for gestational age neonates.

Conclusion: In PE, Hb at 27–29 weeks is influenced by birth weight, maternal characteristics and platelet count.     

Treating patients with “thin” endometrium – an ongoing challenge

Objective: To review the literature regarding inadequate growth (“thin”) of the endometrium and to present the hitherto published methods aimed to improve endometrial thickness and the consequent endometrial receptivity.

Materials and methods: A literature review was conducted for all relevant articles assessing the effect of various treatment modalities on “thin” endometrium and the consequent reproductive outcome.

Results: Several treatment modalities have been offered to patients with “thin” endometrium, including hysteroscopic adhesiolysis, hormonal manipulation by estrogen and GnRH-agonist, vasoactive measures such as aspirin, vitamin E, pentoxifylline, l-arginine or sildenafil, intra-uterine infusion of growth factor such as G-CSF and the recent application of regenerative medicine. In spite of the vast diversity of treatment, most of the options accomplish only minor change in the endometrium thickness and subsequent pregnancy rate, and when they fail, patients are usually referred to surrogacy.

Conclusions: “Thin” endometrium is known to adversely affect reproductive performance. Treatment of “thin endometrium” remains a challenge and future large researches are required to further elucidate and optimal management of patients with “thin” endometrium.     

Anti-Mullerian hormone and insulin resistance in polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent disease affecting women of reproductive age. It may be associated with metabolic disorders such as insulin resistance (IR) and obesity. The anti-Mullerian hormone (AMH) levels seem to be higher in patients with PCOS.

Objective: The present study was designed to evaluate the association between AMH and insulin in women with PCOS with and without IR.

Methods: Cross-sectional study, including 86 patients, selected and divided into three groups: Group A: 26 women with PCOS and IR; Group B: 30 women with PCOS and without IR; and Group C: 30 controls without PCOS.

Results: We found significant difference between serum AMH levels in the group of women with PCOS and without IR when compared to the control group, thus showing that PCOS and IR play an important role in elevating the levels of this hormone. When the groups were compared with each other following adjustment for BMI, serum AMH levels were significantly higher in the group of women with PCOS and IR.

Conclusion: AMH levels are significantly higher in patients with PCOS, particularly in those women with PCOS and IR. Nevertheless, larger samples are required to confirm these findings.     

Maternal and umbilical cord copeptin levels in pregnancies complicated by fetal growth restriction

Objective: The aim of this study was to compare maternal and fetal serum copeptin concentrations in pregnancies complicated by isolated fetal growth restriction (FGR), and uncomplicated pregnancies, and to investigate relationships between copeptin levels and clinical parameters.

Methods: Maternal and fetal serum copeptin levels were measured in 21 women with pregnancies complicated by isolated FGR and 20 women with normal pregnancies (control group). Doppler assessment of the uterine and umbilical arteries was performed in each patient.

Results: Maternal serum copeptin levels were significantly higher in women with isolated FGR compared to controls (p?=?0.042). In addition, maternal copeptin levels were inversely correlated with the uterine artery pulsatility and resistance indices and positively correlated with neonatal birth weight. Umbilical vein copeptin levels were significantly increased in neonates with adverse outcomes (p?=?0.001).

Conclusions: Increased maternal copeptin concentration may reflect a response to stress, thus serving as a compensatory mechanism in pregnancies complicated by FGR.     

Micronized progesterone reduces vasoconstriction in the placenta

Objective: To investigate if micronized progesterone (P4) has the ability to attenuate thromboxane mimetic U46619-mediated fetoplacental artery vasoconstriction.

Methods: Paired cotyledons obtained from the same placenta of five-term subjects were analyzed. The fetal artery and maternal intervillous space of one cotyledon was infused with P4 while another cotyledon was infused with control perfusate. After 30?min, a bolus dose of U44619 was administered to both cotyledons.

Results: The change in the measured fetoplacental vascular pressure caused by bolus administration of U46619 was less in the cotyledons infused with P4 (p?=?0.009).

Conclusion: Continuous treatment with P4 significantly attenuates the U46619-mediated fetoplacental vasoconstriction.     

Does preeclampsia involve the pancreas? A report of original research

Objective: To analyze the effect, if any, of pregnancy-related hypertension on the pancreas.

Methods: A database of pregnant women with hyperbilirubinemia was reviewed for cases with serum amylase values. These cases were linked to a computerized obstetric database, and women were analyzed according to the diagnosis of preeclampsia.

Results: A total of 292 consecutive women with hyperbilirubinemia during pregnancy delivered at our institution between 2005 and 2011. Of these, 52 (18%) were diagnosed with preeclampsia, and in only nine was serum amylase abnormally elevated.

Conclusion: Using serum analytes as surrogates for organ injury, it appears preeclampsia infrequently affects the pancreas.     

Umbilical cord care: national survey,literature review and recommendations

Background: The basic principle of umbilical cord (UC) care is to keep it clean and dry, as this provides the fastest and safest UC healing.

Objective: To evaluate Slovenian UC care practice and compare its consistency with current international recommendations.

Methods: A questionnaire covering UC care from birth to complete healing of the umbilical wound was sent to all Slovenian primary-, secondary- and tertiary-level pediatric centers. Three different clinical conditions of the newborn’s umbilicus were defined: healthy umbilicus (HU), umbilicus at risk (UR) and unhealthy umbilicus (UU).

Results: The study revealed a correlation between the clinical condition of the umbilicus, the frequency of UC care and the antiseptic usage in both the outpatient and inpatient UC care groups. HU was treated less frequently than UR and significantly less than UU. In both groups, these two conditions were also indications for UC care with antiseptic. The frequency of antiseptic usage for HU care was significantly lower in the outpatient care group.

Conclusions: Slovenian UC care follows the general international recommendations. Based on these and our experience, we formulated recommendations for adjustments to UC care, depending on the clinical condition of the umbilicus, in order to prevent important complications.     

Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies

Objective: Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both fetuses share the same maternal environment.

Methods: This prospective cohort study involved dichorionic twin pairs, with one co-twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin.

Results: Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly.

Conclusion: Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxidative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.