Effect of Lymphadenectomy on Survival in Early-Stage Type II Endometrial Carcinoma and Carcinosarcoma.

PURPOSE: We aimed to investigate whether systematic pelvic and paraaortic lymph node dissection delivers any survival advantage in a subgroup of patients with type II endometrial carcinoma and carcinosarcoma. METHODS: We evaluated 135 patients with clinically early-stage (Stage I-II) type II endometrial carcinoma and carcinosarcoma who underwent systematic pelvic and paraaortic lymph node dissection or who did not undergo any lymph node dissection. RESULTS: Overall survival (OS) and recurrence-free survivals (RFS) were significantly longer in the systematic lymph node dissection group (hazard ratio 0.28, 95% CI 0.13-0.62 p=0.002 for OS and hazard ratio 0.31, 95% CI 0.14-0.69 p=0.004 for RFS). Multivariate analysis showed that lymph node dissection, age, lymph node metastasis, and adjuvant therapy were independent prognostic variables of OS and RFS. CONCLUSIONS: Systematic pelvic and paraaortic lymph node dissection independently and significantly prolongs the survival of patients with early-stage type II endometrial carcinoma and carcinosarcoma.

Association between circulating neuregulin 4 levels and metabolic, aterogenic, and AMH profile of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a metabolic disorder associated with obesity and energy metabolic system disturbances in adipose tissue. Neuregulin 4 (NRG4), which is secreted by adipose tissue, regulates energy metabolism. In the present study, we aimed to evaluate the association between serum NRG4 levels in obese and normal weight PCOS patients. This cross-sectional study was conducted at a tertiary hospital in Turkey from April to August 2017. We included 148 women who were divided into four groups as follows: 40 normal weight and 39 obese PCOS women diagnosed according to the Rotterdam criteria as well as 38 normal weight and 31 obese, age-matched, non-hyperandrogenemic women with a regular menstrual cycle (controls). Levels of serum NRG4, anti-Müllerian hormone (AMH), fasting blood glucose (FBG), insulin, and high-sensitivity C-reactive protein (hs-CRP); lipid and hormone profiles; insulin resistance indices [homeostasis model assessment of insulin resistance (HOMA-IR)];and anthropometric parameters were evaluated. Serum NRG4 levels were elevated in the normal weight PCOS group than in the control group. Moreover, serum NRG4 levels were higher in the obese PCOS group than in the normal weight PCOS and obese control groups (p < .01). Serum NRG4 levels were positively correlated with body mass index (BMI); waist/hip ratio; HOMA-IR; and levels of triglycerides, hs-CRP, FBG, insulin, AMH, and dehydroepiandrosterone sulphate. Multiple regression analyses revealed that serum NRG4 levels were independently associated with BMI. Obesity appears to be the most influential factor for NRG4 secretion in PCOS patients. Management of obesity may be a key factor for resolving PCOS-related metabolic abnormalities and fertility problems. Impact Sstatement What is already known on this subject? PCOS is a dynamic syndrome with different clinical and metabolic features during the reproductive age. PCOS is associated with various metabolic abnormalities, such as insulin resistance (IR), glucose intolerance, dyslipidemia, and obesity (particularly visceral obesity) as well as long-term complications, such as type 2 diabetes and cardiovascular diseases. Neuregulin 4 (NRG4), which is secreted by adipose tissue, regulates energy metabolism. What do the results of this study add? To the best of our knowledge, this was the first study investigating NRG4 levels in PCOS patients with different BMIs. Obesity appears to be the most influential factor for NRG4 secretion in these patients. Managing obesity may be a key factor for resolving PCOS-related metabolic abnormalities. What are the implications of these findings for clinical practice and/or further research? Further research in PCOS is warranted to ameliorate obesity, and our study can provide basis for future studies investigating NRG4 levels in PCOS patients with different phenotypes as well as studies of gene polymorphisms, AMH, and infertility and can contribute to the elucidation of problems related to the pathophysiology of PCOS.

Clinical significance of neuregulin 4 (NRG4) in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is defined as glucose intolerance detected during pregnancy. GDM is increasing worldwide and is associated with adverse maternal and fetal outcomes. Neuregulin 4 (NGR4) is epidermal growth factor like signaling molecule. It plays an important role in cell to cell communication furthermore recent studies indicate that NRG4 may work as a novel adipokine with a possible role in maintaining energy and metabolic homeostasis. The aim of the present study was to assess serum NRG4 levels along with several metabolic parameters in patients diagnosed with gestational diabetic mellitus. MATERIALS AND METHODS: In this prospective cross-sectional study, the study group was composed of 63 women with GDM and 64 healthy pregnant women matched for age, body mass index (BMI) and gestational age. Blood samples were collected at the 24-28th gestational weeks. Serum NRG4, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, glucose levels during 75-gr OGTT, fasting insulin, glycosylated hemoglobin A1c (HbA1c), alanine aminotransferase (ALT) and creatinine levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated. RESULTS: Serum NRG4 values were significantly elevated in the GDM group compared to the control group (p < .001). Multivariate linear regression analyzes revealed that BMI (ß = 0.910, p < .001), glucose 2-h OGTT (ß = 0.866, p < .001) and HOMA-IR (ß = 0.222, p < .001) independently and positively predicted NRG4 levels. CONCLUSIONS: Serum NRG4 levels were associated with metabolic parameters of GDM. The present study can be considered to be a guide for future studies to clarify the pathophysiology of NGR4 in GDM patients.

The effect of labour pain in caesarean delivery on neonatal and maternal outcomes in a term low-risk obstetric population.

Planned caesarean delivery (CD) frequency is increasing in many countries, and elective CD accounts for 50% of preventable causes of neonatal respiratory morbidity. The clearing of fluid in the lungs is important for the establishment of normal gas exchange with inspired air. A defect in this clearance can result in respiratory problems in neonate, but on the other hand patients waiting for the onset of spontaneous labour pain, the increase in emergency CD, together with severe mortality and morbidity are causes of concern and cause anxiety and distrust of obstetricians. In the current study, it was observed that foetal respiratory morbidity was reduced in the group with labour pain. The caesarean applied after the onset of labour pain could be a reason for the significant increase in foetal cord cortisol values in term low-risk neonates. A major advantage of this study was the inclusion of a low-risk patient group, and the increase in foetal cortisol secondary to pain in term neonates was shown objectively. Impact statement What is already known on this subject: The timing of CD is reported to be critical for neonatal morbidity, and elective CD accounts for 50% of preventable causes of neonatal respiratory morbidity. The clearing of fluid in the lungs is important for the establishment of normal gas exchange with inspired air. Cortisol secretion from the foetal adrenal gland is stimulated by stress. What do the results of this study add: Labour pain-related stress in the foetus might be a cause for elevated physiological cortisol, and secondary to that, lower respiratory morbidity. Caesarean delivery commenced after the onset of labour pain could be a reason for the significant increase in foetal cord cortisol values in term neonates. A major advantage of this study was the inclusion of a low-risk patient group, and the increase in foetal cortisol secondary to pain in term neonates was shown objectively. What are the implications of these findings for clinical practice and/or further research: Although it would seem to be rational to perform a caesarean section after the onset of labour pain in cases with a planned caesarean and a history of C-section delivery, with respect to maternal complications, especially in those with a history of more than one caesarean or those who have started active labour; there is a need for further prospective studies.

CXCL12 Promotes Stem Cell Recruitment and Uterine Repair after Injury in Asherman's Syndrome.

Asherman's syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury that adversely affects fertility and pregnancy. We have previously demonstrated that bone marrow-derived mesenchymal stem cells (BMDSCs) contribute to uterine repair after injury and that stem cells supplementation improves fertility. Here, we demonstrate that CXCL12 is the chemokine that mediates stem cell engraftment and functional improvement using a murine model of Asherman's syndrome. After uterine injury, we demonstrate that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4) antagonist, ADM3100, blocked stem cell recruitment. CXCL12 reduced, whereas ADM3100 increased fibrosis. CXCL12 treatment led to improved fertility and litter size, whereas ADM3100 treatment reduced fertility and litter size. ADM3100 prevented optimal spontaneous uterine repair mediated by endogenous CXCL12 production, reducing pregnancies after injury in the absence of supplemental CXCL12 administration; however, ADM3100 treatment could be partially rescued by CXCL12 augmentation. CXCL12 or other CXCR4 receptor agonists may be useful in the treatment of infertility or adverse pregnancy outcomes in Asherman's syndrome and other related uterine disorders.

Cigarette Smoking Affects Uterine Receptivity Markers.

OBJECTIVE: Smoking negatively affects fertility and the rate of other endometrial diseases. To determine the effect of smoking on endometrial physiology, we evaluated 2 endometrial regulatory cytokines and receptivity markers, C-X-C motif chemokine ligand 12 (CXCL12) and fibroblast growth factor 2 (FGF2), both in vitro and in vivo. STUDY DESIGN: The human endometrial stromal cell line (HESC) and primary human endometrial stromal cells were treated with cigarette smoking extract (CSE) or with vehicle control. Twenty female mice were randomly assigned to either cigarette smoke (CS) exposure for 8 weeks or to a nonsmoke (NS) group that received room air. Immunohistochemical analysis of CXCL12 and FGF2 expression was performed in mouse uterine tissue. Human endometrial samples were obtained from both nonsmokers and smokers. Real-time reverse transcription-polymerase chain reaction was performed for all cell cultures and human samples. RESULTS: Compared to controls, CXCL12 and FGF2 mRNA expression were significantly decreased in CSE-exposed HESC and primary cells. In mice, immunohistochemical analysis showed that both CXCL12 and FGF2 protein expression was lower in the CS group compared to controls. Similarly, both CXCL12 and FGF2 expression were decreased in women who smoke compared to nonsmokers. CONCLUSION: Decreased endometrial CXCL12 and FGF2 expression contribute to the impaired endometrial receptivity in women who smoke. Smoking is also associated with decreased rates of endometrial cancer and endometriosis; increased CXCL12 and FGF2 are implicated in both conditions. The changes in the expression of cytokines described here may explain the impact of smoking on all of these diseases. Tobacco has direct effects on normal endometrium that impacts endometrial health and disease.

Mycophenolate mofetil attenuates uterine ischaemia/reperfusion injury in a rat model.

This study evaluated the effect of mycophenolate mofetil (MMF) on uterine tissue preservation following ischaemia/reperfusion (I/R) injury. Uterine I/R injury was induced in rats by clamping the lower abdominal aorta and ovarian arteries for 30 min. Group I/R + V (n = 7) received vehicle alone while Group I/R + M (n = 7) received 20 mg/kg/day MMF. Control groups underwent sham surgery and received vehicle (Group C) or 20 mg/kg/day MMF (Group M) (n = 7 for both). Four hours after detorsion, uterine tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione, malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and serum ischaemia modified albumin (IMA) concentrations were measured. Histopathological analyses were performed. The I/R + M group showed significant reduction in serum IMA and uterine tissue 8-OHdG, MDA and MPO and significant increase in SOD concentrations compared with the I/R + V group, indicating a protective effect against I/R oxidative damage (P = 0.009, P = 0.006, P = 0.002, P = 0.003 and P = 0.009, respectively). Histopathological evaluation revealed MMF treatment resulted in significantly less tissue and cellular damage and apoptosis compared with the I/R + V group. These results indicate MMF is effective in attenuating uterine tissue damage and preventing apoptosis following uterine I/R injury, probably via anti-inflammatory and anti-oxidative action.

Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels, atherogenic and metabolic profile.

OBJECTIVE: To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters. RESULTS: Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels. CONCLUSION: WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.

WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus.

OBJECTIVE: To investigate Wnt1-inducible signaling pathway protein-1 (WISP1) levels and their correlation with metabolic parameters in pregnant women with gestational diabetes mellitus (GDM) and non-GDM healthy pregnant women. MATERIALS AND METHODS: In this prospective cross-sectional study, the study group was composed of 62 women with GDM and 73 healthy pregnant women matched for age, body mass index (BMI) and gestational age. Blood samples were collected at 25-29th gestational week. Serum WISP1, betatrophin, glucose, fasting insulin, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, C reactive protein, alanine aminotransferase and creatinine levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) values was calculated. The level of significance was accepted as p < 0.05. RESULTS: Circulating WISP1 in the GDM group was significantly higher than the control group (p <0.001). Further, WISP1 was positively correlated with BMI, HOMA-IR values and fasting glucose, fasting insulin, triglyceride, betatrophin levels. BMI, HOMA-IR and betatrophin independently and positively predicted WISP1 levels. CONCLUSION: These results demonstrate a relationship between WISP1 and the metabolic parameters of GDM. And, WISP1 might be involved in the pathophysiology of GDM. As a part of this pathophysiological mechanism, the activation of WISP1 and betatrophin might take place through several ways; WISP1 and betatrophin might either use same signaling pathways and potentiate each other or they might also constitute the sequential steps of a common pathway.

Comparison of the long-term effects of single-dose methotrexate and salpingectomy on ovarian reserve in terms of anti-müllerian hormone levels.

The aim of this study was to compare the effects of single-dose methotrexate (MTX) and salpingectomy on ovarian reserve in women with ectopic pregnancy in the late post-treatment period. A total of 181 patients were included in the study; 56 of them received a single-dose of MTX, 45 of them had undergone salpingectomy treatment for ectopic pregnancy in the previous 12-18 months, and 80 healthy women constituted an age-matched control group. The anti-müllerian hormone (AMH), follicle stimulating hormone (FSH) and oestrogen (E2) levels, as well as antral follicle counts (AFC) of the patients were evaluated. The average age was similar in both groups (p = 0.094) and there was no statistically significant difference in the smoking status of the patients (p = 0.949). None of the three groups displayed a significant difference in terms of AFC (p = 0.528), AMH (p = 0.147), FSH (p = 0.393) and E2 levels (p = 0.117). In the treatment of ectopic pregnancy neither the single-dose MTX application nor the salpingectomy had any permanent detrimental effect on the ovarian reserve; serum AMH levels and AFC are unaltered in the long term following single-dose MTX or salpingectomy.

N-acetylcysteine leads to greater ovarian protection than enoxaparin sodium in a rat ovarian torsion model.

This study evaluated the effects of N-acetylcysteine (NAC) and enoxaparin on ovarian tissue preservation, ovarian reserve and oxidative damage following ovarian torsion/detorsion injury. Rats were divided into four groups (n = 6/group): control; ischaemia/reperfusion (I/R); I/R + NAC; I/R + enoxaparin. Twenty-four hours after detorsion, ovarian tissues were collected for histopathological analysis and measurement of tissue 8-OHdG, GSH, MDA, MPO and SOD concentrations, as well as pre- and post-operative circulating AMH concentrations. Administration of NAC resulted in more pre-antral follicles compared with enoxaparin treatment and haemorrhage and follicle cell degeneration were more pronounced in I/R + enoxaparin group than I/R + NAC group. Both NAC and enoxaparin led to a significant reduction in ovarian tissue 8-OHdG (P = 0.004 and P = 0.01, respectively) and MPO (P = 0.013 and P = 0.023, respectively) concentrations compared with I/R group, indicating a protective effect against I/R oxidative damage. Only NAC-treated animals showed a significant increase in GSH and SOD concentrations and decrease in MDA concentrations compared with I/R group (P = 0.007, P = 0.024 and P = 0.026, respectively). These results indicate that NAC is more effective than enoxaparin in minimizing ovarian damage and preserving ovarian reserve following ovarian torsion.

An easy and noninvasive technique for harvesting split thickness skin grafts in rats.

Skin graft studies in rats constitute a valuable adjunct to scientific human experimentations, however the harvesting of split thickness skin graft poses a challenge to the researcher due to the presence of panniculus carnosus tissue in rat skin. This striated muscle tissue renders significant laxity and mobility to the skin layer, greatly interfering with the process of skin graft harvest. In order to fixate the rat skin and limit its flexibility various techniques and modifications have been described, which mostly rely on the use of subdermal implanted templates. These methods are therefore time consuming, with an additional exposure to surgical stress and wounds. A new and simple technique is presented which offers a rapid and reliable alternative to the existing methods of split thickness skin graft harvesting without any additional invasive procedure or extra instruments other than the researchers hands and a dermatome.

Vitamin D deficiency in pregnancy is not associated with diabetes mellitus development in pregnant women at low risk for gestational diabetes.

OBJECTIVE: We aimed to investigate the effect of vitamin D deficiency as a risk factor for the development of gestational diabetes mellitus (GDM) among pregnant women without known risk factors. MATERIALS AND METHODS: The study was conducted on pregnant women who had been under regular follow-up and had low risk for GDM development. The patients were divided into two groups according to the presence of GDM; GDM and no GDM (control) group. Body mass index (BMI), sociodemographic data including level of education and nutritional habits were recorded. Serum 25 (OH) vitamin D3 levels, hemoglobin, hematocrit, and mean corpuscular volume (MCV) values were measured. An oral glucose tolerance test was performed, between 24 and 28 weeks of pregnancy. RESULTS: GDM ratio was calculated as 4.6%. The false positive rate of 50 g oral glucose load screening test was found to be 16.5%. The BMI levels of women diagnosed as having GDM and those with no GDM group at the beginningof the pregnancy period were calculated as 24.3±2.6 and 22.8±1.6 kg/m2 respectively, exhibiting a statistically significant difference between the two groups (p=0.001). Hemoglobin, hematocrit, and MCV values did not show a statistically significant difference between the two groups (p>0.05). The levels of 25 (OH) vitamin D3 of the study groups were found comparable in both groups (p=0.13). CONCLUSION: Plasma levels of vitamin D may not be a contributing factor for the development of GDM in women with a low risk for GDM.

Interpregnancy interval as a risk factor for postmenopausal osteoporosis.

OBJECTIVE: Bone mass loss associated with pregnancy and lactation is usually regained in the postpartum period. However, it is not known whether the bone loss is completely recovered in women with a shortened interpregnancy interval (IPI). The aim of this study was to analyze the effect of IPI and gynecological history on postmenopausal osteoporosis. STUDY DESIGN: The study was conducted among 537 postmenopausal women who were divided into two groups in accordance with the osteoporosis status. Prior to bone densitometry, the patients were questioned about reproductive history. Dual-energy X-ray absorptiometry was used to measure lumbar spinal, femur neck and total femoral bone mineral density. MAIN OUTCOME MEASURE: Association between IPI and postmenopausal osteoporosis was analyzed. RESULTS: The comparison of both groups according to the total duration of breastfeeding did not reveal a considerable variation (p=0.288). In the osteoporosis group the age and duration of menopause were found to be significantly higher (p<0.001) whereas the age of first pregnancy and IPI were notably lower in comparison to the controls group (p<0.001). Multivariate logistic regression analyses revealed that women who have 0-12 months interpregnancy interval have the highest risk for osteoporosis (OR: 4.306; 95% CI, 1.684-11.01). This analysis confirmed that the occurrence of first pregnancy under 27 years of age conveyed a higher risk for osteoporosis, as well. CONCLUSIONS: Shortened IPI may have a detrimental effect on bone mineral density in postmenopausal age.

What is the fate of scientific abstracts? The publication rates of abstracts presented at the 7th National Congress of Gynecology and Obstetrics.

OBJECTIVE: Oral and poster presentations held at national and international congresses are recognized as valuable tools for sharing current scientific data and experience among physicians. However, a large proportion of these works fail to be published in scientific journals. We have designed a study to identify the publication rate of presentations held at the 7th National Congress of Obstetrics and Gynecology in 2009. MATERIALS AND METHODS: A systematic search of databases was performed using author names and key words from the abstract title to locate publications in peer-reviewed journals corresponding to the presentations held at the 7th National Congress of Obstetrics and Gynecology. Information regarding mode of presentation, topic, type of affiliation, name and impact factor of the scientific journal, change in author names and time elapsed between presentation and publication were recorded and analyzed statistically. RESULTS: Of 243 abstracts that were presented at the congress, 45 papers (18.5%) were published in international peer-reviewed journals, whereas 39 (16%) were published in national journals. The mean time to publication was 17±2 months for international and 11±4 months for national journals (p=0.102). The international publication rate of oral presentations was significantly higher than that of poster presentations (50% vs. 16.2%; p<0.03). The manuscripts were published in a total of 21 journals, with four journals accounting for 49% of the publications. The comparison of the publication rates of the universities with other institutions has yielded no significant difference. CONCLUSION: Alltough a significant proportion of the abstracts presented in the 7th National Gynecology and Obstetrics Congress have been succesfully converted to publication overall, only a limited percentage of all abstracts have been published in international peer-reviewed journals. The relatively higher conversion to international publication rate of the oral presentations show that they are of higher interest and clinical relevance.