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.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN: In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. RESULTS: The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. CONCLUSIONS: Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Myo-inositol is a promising treatment for the prevention of ovarian hyperstimulation syndrome (OHSS): an animal study.

PURPOSE: To evaluate the efficacy of myo-inositol (MI) pretreatment in OHSS. METHODS: In this experimental OHSS rat model, 42 immature Wistar albino female rats were divided into 6 groups: (1) the control group, (2) the ovarian stimulation group, (3) the OHSS group, (4) the OHSS + Metformin group, (5) OHSS + MI group, (6) OHSS + Metformin + MI group. OHSS was established after treatment with metformin and myo-inositol for 14 days, in the meanwhile the treatment of metformin and myo-inositol was also continued. All animals were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight and diameter, ovarian VEGF, COX-2 and PEDF expression (immunohistochemistry), serum PEDF and estradiol (E2) levels. RESULTS: Vascular permeability, VEGF and COX-2 expressions were reduced in animals treated with MI and/or metformin. While PEDF expression was increased in the groups taking metformin, there was no difference in PEDF expression in the group taking MI and OHSS group. There was no significant difference in serum PEDF levels between groups. Blood E2 levels were decreased in groups treated with MI or metformin compared to the OHSS group. CONCLUSIONS: Our data demonstrate that myo-inositol is effective in preventing OHSS, similar to metformin. Although the two drugs are thought to act through distinct mechanisms, there is no apparent benefit to co-treatment with both drugs in an animal model of OHSS. Administration of myo-inositol prior to IVF treatment may favor the control of ovulation induction. Further studies are necessary to elucidate the mechanism of action and further support our findings.

Prophylactic vitamin D supplementation in ovarian hyperstimulation syndrome: an animal study.

PURPOSE: To investigate the effect of vitamin D in ovarian hyperstimulation syndrome (OHSS). METHODS: In this animal study, 28 immature female Wistar rats were divided into four groups: group 1 (control); group 2 (ovarian stimulation); group 3 (OHSS group); group 4 (OHSS + vitamin D group). All groups were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight, ovarian diameter, vascular endothelial growth factor (VEGF) expression (immunohistochemistry) in ovarian tissue and pigment epithelium-derived factor (PEDF) level in the serum (ELISA test) with the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: VEGF expression in the vitamin D group was similar to that in the OHSS group. However, the PEDF level was significantly higher in the vitamin D group (p = 0.013). CONCLUSIONS: Prophylactic vitamin D supplementation is not sufficiently effective in preventing OHSS. Vitamin D effectively increases PEDF, which has an opposing effect on VEGF, which plays a key role in OHSS. Thus, the protective effect of Vitamin D on OHSS should be investigated with a vitamin D deficient model in the study group.

Complete blood count parameters may have a role in diagnosis of gestational trophoblastic disease.

OBJECTIVE: The goal of this study was to investigate whether gestational trophoblastic disease (GTD) and healthy pregnancy differ with respect to complete blood count parameters and these parameters can be used both to explain the pathophysiologic mechanisms and differentiate the two conditions from each other. METHODS: The data obtained from 37 women with GTD and 61 healthy pregnancies (control group) regarding platelet (PLT), mean PLT volume (MPV) and PLT distribution width (PDW), and white blood cell (WBC) levels were evaluated. Patients with GTD were further subdivided into two groups composed of 20 partial mole (PM) and 17 complete mole (CM) cases. RESULTS: PDW and WBC were lower in the GTD than the control. There were no differences for PLT and MPV. WBC was lower in PM and both WBC and PDW were lower in CM compared with control. ROC curve analysis revealed an area under curve (AUC) 75.5% for WBC and AUC 69.3% for PDW. A cut-off value was determined 8.19 for WBC with 81.0% sensitivity and 54.1% specificity. While, 15.85 were accepted for PDW, with 87.9% sensitivity and 44.4% specificity. CONCLUSION: Lower WBC in GTD may suggest that molar pregnancy requires a lower inflammatory reaction facilitating trophoblastic invasion. Lower PDW as an indicator of platelet activation in CM may suggest that CM requires less PLT activation than healthy pregnancy that needs stronger trophoblast invasion for normal placental development. Decreased PDW levels especially < 15.85 and WBC levels < 8.19 may alert clinicians for risk of GTD.

Montelukast is effective in preventing of ovarian hyperstimulation syndrome; an experimental study.

OBJECTIVES: To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats. MATERIAL AND METHODS: An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergollne 100 microg/kg/day via oral gavage for 6 days (days 22-27), in addition to those of severe OHSS. All groups were sacrificed on 28th day Body weight, ovarian diameter and weight, vascular permeability vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated. RESULTS: Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression. CONCLUSIONS: The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.

The role of selectins in the first trimester pregnancy loss.

OBJECTIVE: There are no well-defined findings about reasons for first trimester abortion in some pregnancy cases. Selectins are cell adhesion proteins which are important for blastocyst implantation in the decidua. The goal of the study was to investigate the role of selectins in first trimester pregnancy loss by immunohistochemistry. STUDY DESIGN: Decidual and placental tissue samples have been obtained from the women with unwanted pregnancy as the control group (n = 40) and missed abortion (n = 40) as the study group. Immunohistochemistry technique has been used to compare P, L and E-selectin expression of the fibroblast and the decidual cells in uterine decidual stroma; and fibroblasts and mesenchymal cells in placental villous stroma. Immunostaining for P, L, E-Selectin has been evaluated semiquantitatively by HSCORE analysis. RESULTS: Decidual cells, for E and L-selectin showed stronger staining in the study group than controls, and the difference was statistically significant (p = 0.007, p = 0.007). P-selectin showed stronger staining in the control group, but the difference was not as significant as the E and L-selectins (p = 0.04). In the placenta, cytotrophoblasts and syncytiotrophoblasts showed stronger staining for P, E, L-selectins for the control group (p < 0.007, p = 0.001 and p < 0.001, respectively). CONCLUSION: Strong expression of each of the three investigated selectins in healthy pregnancy villi shows their contribution to implantation and strong placentation. There is a need for better understanding of the functions of adhesive molecules in these events to reveal unknown causes for pregnancy loss.

The efficacy of complete blood count parameters in the diagnosis of tubal ectopic pregnancy.

OBJECTIVE: Ectopic pregnancy (EP) is the major cause of maternal morbidity and is responsible for maternal mortality in the first trimester. In order to reduce undesirable results, it is necessary to find rapid and accurate, non-surgical diagnostic tests for ER The goal of the study was to investigate the differences in complete blood count parameters between tubal EPs and healthy pregnancies in be used in the diagnosis of ectopic pregnancy. STUDY DESIGN: White blood cell (WBC), neutrophil, monocyte, lymphocyte, platelet (PLT) counts, mean PLT volume (MPV) and PLT distribution width (PDW) levels in the complete blood count samples have been obtained from subjects with diagnosed tubal EP (n=78; study group) and women with healthy intrauterine gestations (n=79; control group). Statistical comparisons between groups were performed using the t test. RESULTS: PDW levels were found to be significantly higher in the control group than EP (p<0.001). However no differences between the study and control groups with regard to PLT and MPV levels were observed. WBC levels were found to be significantly higher in the EP group as compared to controls (p<0.001). When leukocyte differentials were compared, monocyte counts in the EP group were significantly higher than in controls (p=0.005). No statistically significant differences in neutrophil and lymphocyte values were observed in either group. CONCLUSION: PDW as an indicator of PLT activation is lower in tubal EP than intrauterine pregnancy so, possibly endometrial invasion in the intrauterine pregnancy needs more PLT activation. Monocyte counts are higher in tubal EP, indicating that monocyte activation in the pathophysiology of EP could be effective in the formation of tubal motility and microenvironment regulation.

The association of HLA-G and immune markers in recurrent miscarriages.

OBJECTIVE: To determine role of human leukocyte antigen (HLA)-G, CD8, CD16, CD56, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for recurrent miscarriages in feto-maternal interface. METHOD: Chorion and decidua samples were obtained from 11 women with unwanted pregnancies (healthy pregnancy, HP) and 10 women with missed abortion diagnosis after at least two pregnancy losses (recurrent miscarriage, RM). In addition, endometrial tissues were obtained from 10 non-pregnant women (NonP). The expressions of markers were evaluated using the Western blot analysis. The values obtained between different groups were compared. RESULTS: The highest protein expression of CD56 was found in the HP compared to NonP and RM. Meanwhile, the lowest protein expression of CD16 was observed in the NonP compared to HP and RM. The HLA-G expression exhibited the highest level in HP; however, there was no statistically significant difference between groups. CD8 and IFNγ expressions were lowest in the NonP group; however, TNF-α was highest in the RM group. CONCLUSIONS: The CD56 expression of uterine NK cells may be an indicator of a HP. However, not statistically significant, the increased expression of CD16, CD8, and also significantly increased expression of TNF may be associated with the predominant cytotoxic activity in the maternal immune system in patients with RM. Although there was no change in the expression of HLA-G, this finding may mean that the maternal immune system is unresponsive to HLA-G-mediated immunosuppressive signals originating from the fetus in these cases.

Investigation of the relationship between salivary cortisol, dehydroepiandrosterone sulfate, anxiety, and depression in patients with hyperemesis gravidarum.

BACKGROUND: The aim of this study was to determine the relationship of the salivary levels of dehydroepiandrosterone sulfate (DHEA-S) and cortisol with factors related to depression and anxiety in patients with hyperemesis gravidarum (HG). METHODS: Forty patients with a diagnosis of HG were selected for the study and matched with 40 control patients according to body mass index, parity, and age. Symptoms of depression and anxiety were investigated using the Beck Depression Inventory and Beck Anxiety Inventory for Adults, respectively. Saliva samples were collected in the morning and at night and subjected to enzyme-linked immunosorbent assay for the determination of DHEA-S and cortisol levels. RESULTS: We observed a positive correlation between increased levels of depression and anxiety and increased salivary levels of cortisol and DHEA-S in patients with HG. CONCLUSIONS: Salivary cortisol and DHEA-S levels, as well as mood disorders, should be monitored in patients with HG, although further large, prospective studies are needed to confirm our results.

Changes in distribution patterns of integrins in endometrium in copper T380 intrauterine device users.

Intrauterine contraception is the most cost-effective reversible method of contraception today, but its mechanism of action is not well understood. Our objective was to investigate immunohistochemical distribution patterns of alphav, alpha3, beta1 integrins in women using a copper T380 intrauterine device (IUD) for different periods of time to obtain insight into the role of integrins in intrauterine contraception. Endometrial biopsies were obtained from patients using T Cu380A IUD in follicular and luteal phases and in menopausal women grouped according to the period of time of IUD use (group 1: <3 year, and group 2:>or=3 years). Each group consisted of 10 patients, with a total number of 60 patients. Labelling intensity of all integrins, except for beta1 which increased in the follicular phase, were decreased in women who used IUD for>or=3 years when compared with group 1 in the follicular and luteal phases and in the menopause. We conclude that long-term use of IUD affects integrin expression in endometrium not only in follicular and luteal phases of premenopausal women but also in postmenopausal women. Copper IUD can inhibit binding of integrins to the extracellular matrix and it may cause inhibition of the implantation stage, which is crucial for pregnancy.

Relationship between mean platelet volume and vitamin D deficiency in gestational diabetes mellitus.

OBJECTIVE: To investigate whether vitamin D deficiency is associated with high mean platelet volume (MPV) in pregnancies diagnosed with gestational diabetes mellitus (GDM) compared to healthy pregnancies. SUBJECTS AND METHODS: This study included 200 pregnant women. 25-hydroxyvitamin D3(25(OH)D3) and MPV values were monitored between pregnant women with GDM and normal glucose metabolism. Correlation between 25(OH)D3 and MPV was calculated both in GDM and healthy pregnancies. Both 25(OH)D3 level in different MPV percentile (≤ 50, 50-75, 75-90, ≥ 90 percentile) and MPV value in different 25(OH)D3 level (≤ 10, 10-20, ≥ 20 ng/mL) were calculated. RESULTS: Low 25(OH)D3 level and high MPV were observed both in GDM group (p = 0.007, p = 0.06, respectively) and in glucose metabolism disorders (GMD) group (p = 0.03, p = 0.04, respectively). There was no significant relationship between 25(OH)D3 and MPV in healthy pregnancies. Whereas, it is observed that there is a negative, but statistically insignificant correlation between MPV and 25(OH)D3 pregnant women with GMD (r = 0.1, r = -0.7, respectively). MPV values had significantly higher in vitamin D deficient group than pregnant women with normal 25(OH)D3 level in GMD group (p = 0.04). The optimal 25(OH)D3 cut off point for predicting future cardiovascular risk was 10.4 ng/ mL (area under curve (AUC) = 0.58). CONCLUSIONS: Vitamin D deficiency may contribute to an increased risk for future cardiovascular diseases and a risk of thrombotic complications in pregnant women with GDM.

Mid-pregnancy vitamin D levels and postpartum depression.

OBJECTIVES: Postpartum depression (PPD) is a common disorder that affects 10-15% of postpartum women, and it can have negative effects on both the mother and newborn. Recent studies have suggested that low levels of vitamin D are associated with poor mood and depression. The aim of this prospective study was to evaluate a possible association between PPD and serum levels of 25-hydroxy vitamin D3 (25(OH)D3), a reliable measurement of vitamin D, during mid-pregnancy. STUDY DESIGN: The source population consisted of all pregnant women between 24 and 28 gestational weeks from June 2012 to October 2012 at Bornova Health Research and Application Hospital, Sifa University. In order to better evaluate a possible effect between vitamin D levels and PPD, individuals with characteristics that put them at risk for developing PPD were excluded from the study. Serum 25(OH)D3 levels were evaluated mid-pregnancy in the study group. Serum 25(OH)D3 concentrations ≤20ng/mL (50nmol/L) were classified as a mild deficiency and those ≤10ng/mL (25nmol/L) were classified as a severe deficiency. Pregnant subjects having complications during birth or with the newborn after delivery were excluded from the study. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal PPD 1 week, 6 weeks, and 6 months after delivery. A Pearson correlation was used to measure the strength of the associations between the EPDS scores and vitamin D levels analyzed during the three time periods. A logistic regression analysis was used to determine the independent effects of vitamin D on PPD. RESULTS: Six hundred and eighty-seven pregnant women were included in this study. After excluding women due to PPD risk factors (in two stages), 179 pregnant women were screened for vitamin D levels during mid-pregnancy and in the 6th month postpartum. Eleven percent of our study group had severe vitamin D deficiency and 40.3% had mild vitamin D deficiency. The frequency of PPD was 21.6% at the 1st week, 23.2% at 6th week, and 23.7% at the 6th month. There was a significant relationship between low 25(OH)D3 levels in mid-pregnancy and high EPDS scores, which is indicative of PPD for all three follow-up periods (p=0.003, p=0.004 and p<0.001, respectively). In addition, there was a significant negative correlation between vitamin D levels and EDPS at all three time points (r=-0.2, -0.2, -0.3, respectively). CONCLUSIONS: Vitamin D deficiency in mid-pregnancy may be a factor affecting the development of PPD. More extensive studies are required to be carried out on this subject.

Adnexal torsion with dystrophic calcifications in an adolescent: a chronic entity?

Intermittent pelvic pain caused by ovarian cysts in adolescence may be due to torsion or partial torsion of the ovary. We present a case of 18-year old adolescent with symptomatic left ovarian torsion with calcifications demonstrated by pelvic MRI and ultrasonography prior to surgery. The pathologic investigation demonstrated dystrophic calcifications. We speculated that the pattern of the intermittent pain in the story of the patient and the dystrophic calcifications in pathologic investigation which is thought that it might have been potentially developed as a result of chronic hypoxia due to intermittent partial torsions over a period of two years.