Does Maternal Vitamin D Level Affect the Ovarian Reserve of Female Newborn Infants?

OBJECTIVE: To evaluate whether maternal vitamin D levels affect cord blood Anti Müllerian Hormone (AMH) levels, reflecting ovarian reserve, in female offspring. METHODS: Cord blood AMH from healthy pregnant women delivering term female infants were compared in groups with different maternal vitamin D levels. RESULTS: Maternal age, weight gain during pregnancy, usage of vitamin D supplements, newborn birth weight, and 5th-min Apgar scores were significantly higher in the normal vitamin D level group (All p < 0.05). AMH levels were similar among all groups (p = 0.6). There was no significant correlation between newborn AMH and maternal vitamin D levels (rho = 0.006, p = 0.9). The stepwise regression analysis showed that the maternal age and birth weight had lower AMH levels, whereas the maternal vitamin D level did not. (p = 0.03, p = 0.04, p = 0.5, respectively). CONCLUSION: Maternal vitamin D levels did not have a significant effect on AMH, a reflection of ovarian reserve.

Does Follicle-Stimulating Hormone Receptor Polymorphism Status Affect In vitro Fertilization-Intracytoplasmic Sperm Injection Results and Live Birth Rate? A Retrospective Study.

Background: Follicle-stimulating hormone (FSH) plays a key role in fertility and shows its effect through the FSH receptor (FSHR), which is localized in cells. Aims: The aim of this study was to examine pregnancy outcomes and responses to controlled ovarian stimulation according to FSHR polymorphism types. Study Setting and Design: The study was retrospective, and included patients who applied to the University of Health Sciences Tepecik Training and Research Hospital in vitro fertilization (IVF) Unit during 2018 and 2019. Materials and Methods: Patients who underwent IVF-intracytoplasmic sperm injection and at the same time studied FSHR gene polymorphism in the genetic unit of our hospital were included in the study. Statistical Analysis: The Kruskal-Wallis test was used for multiple comparisons of continuous variables. The Chi-square test was used for categorical variables between groups. Results: A total of 143 patients who met our criteria were included in the study. 14% (n = 20) of the patients are also homozygous natural (Asn/Asn) type; 44.7% (n = 64) of the heterozygous mutant (Asn/Ser) type; 41.3% (n = 59) of them were homozygous mutant (Ser/Ser) type. There was no statistically significant difference between the groups in terms of pregnancy rate per started cycle, ongoing pregnancy per started cycle, ongoing pregnancy per embryo transfer and live birth per embryo transfer. A significant difference was observed between peak E2 and peak progesterone levels between Asn/Ser and Ser/Ser groups, and the levels of these hormones were lower in the Ser/Ser group (P = 0.018 and P = 0.016, respectively). Ovarian responses were classified as poor (≤3 oocytes), normal (4-20 oocytes) and hyperresponse (≥20 oocytes) according to the oocyte count. Accordingly, the number of patients with poor response was higher in the Ser/Ser group (P = 0.011). Conclusions: Ser/Ser polymorphism is characterised by a poor ovarian response. Despite this, polymorphisms in the FSHR gene do not seem to affect the results of pregnancy per started cycle, ongoing pregnancy per started cycle, ongoing pregnancy per embryo transfer and live birth per embryo transfer.

Can the difference of Doppler indexes at the different points of the umbilical artery predict to the umbilical cord length?

Background: The aim of the study is to investigate whether the Doppler indexes which measured at different points of the umbilical cord (UC) are related to the cord length.Materials and methods: In this prospective study, umbilical artery (UA) Doppler indexes were measured at the fetal and placental insertion, free loop (FL) and intra-abdominal (IA) portion at 37-42 weeks of gestation in low-risk singleton pregnancies. After birth, the UC was measured. The difference of Doppler indexes of different points was evaluated by nonparametric Kruskal-Wallis test or analysis of variance (ANOVA) test and significant values have been adjusted by the Bonferroni correction for multiply tests. The correlation of between UC length and change of Doppler indexes which measured at different points of the UC was evaluated using Spearman's rank correlation test.Results: The data of 74 participants were analyzed in this study. Mean UC length was 58 cm (min: 38 cm and max: 84 cm). There was no difference between characteristics of two groups that UC length <58 cm and ≥58 cm and different percentiles. UA systole/diastole (S/D) rate, resistance index (RI), and pulsatility index (PI) were higher at the IA portion than other measurement points (p = .003, <.001, and <.001, respectively). The mean differences (delta values) of UA blood velocity between the fetal and placental ends (PEs) were correlated UC length (c = 0.32, p = .04).Conclusions: The differences of UA blood velocities between the fetal and PEs may be a useful marker for UC length prediction during antenatal period.

Vitamin D deficiency in pregnancy may affect fetal thymus development.

OBJECTIVES: The aim of our study was to evaluate the association of vitamin D deficiency (VDD) during pregnancy with thymus size in full-term fetuses. MATERIAL AND METHODS: In this prospective study, we evaluated mid-pregnancy serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations. The fetal thymus size was measured by ultrasound in the third trimester. Neonatal 25(OH)D3 levels were evaluated by umbilical cord blood sampling. Correlation of maternal and neonatal vitamin D levels and association between thymus size and both, maternal and neonatal vitamin D concentrations were investigated. RESULTS: Serum 25(OH) D3 concentrations were within the normal range in 48 (29.8%) mothers and 10 (13.1%) new-borns. A strong correlation between mid-pregnancy maternal and neonatal 25(OH)D3 concentration (r = 0.8, p < 0.001) was found. A significant linear correlation was observed between both, maternal and neonatal 25(OH)D3 concentrations and thymus perimeter length (r = 0.45, p = 0.04 and r = 0.43, p < 0.01, respectively). Both, maternal and fetal VDDs were associated with decreased thymus perimeter (p = 0.04, p = 0.03). CONCLUSIONS: Vitamin D deficiency during pregnancy may be associated with smaller fetal thymus. Our data suggest that VDD in pregnancy may lead to systemic inflammatory response in the fetus.

Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps.

BACKGROUND: The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium. METHODS: Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry. RESULTS: The percentage of COX-2-positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase. CONCLUSIONS: Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

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 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.

Thyroid antibodies in euthyroid and subclinical hypothyroidic pregnant women with autoimmune hypothyroidism: effects on hematological parameters and postpartum hemorrhage.

OBJECTIVES: The aim of the study was to investigate the relationship between thyroid antibodies and hematological parameters in euthyroid or subclinical hypothyroidic (S H) pregnant women with autoimmune hypothyroidism and to verity whether these pregnant women are affected by a higher rate of postpartum hemorrhage. MATERIAL AND METHODS: Thirty-six out hyroid and 21 S H pregnant women with autoimmune thyroid disease and 52 healthy pregnant women were evaluated. The relationship between thyroid hormones, thyroid antibodies level, the dosage of Levotroxin (LT4) and hematological parameters and the amount of postpartum bleeding was investigated. RESULTS: The mean platelet volume (MPV), was significantly higher in the SH group than in the euthyroid group and in the euthyroid group than healthy group (p<0.001). Hemoglobin (Hb) was significantly lower in both the SH group and the euthyroid group than control group (p<0.001). Other hematological parameters and the amount of postpartum bleeding did not differ between the groups. The correlation between Hb and fT3, FT4 was significant and positive, whereas between Hb and T SH was significant and negative (r=0.3 p<0.01, r=0.2 p=0.01, and r = -0.18 p=0.04, respectively). There was a significant and negative correlation between the PLT count and FT4, PT and FT3 (r = -0.2 p=0.01, r = -0.3 p<0.01, and r = -0.3 p<0.01, respectively). CONCLUSION: It has been described that being thyroid antibody-positive (TAb+) may be a risk factor for anemia and high MPV. However euthyroid and SH pregnant women with thyroid antibodies do not differ in terms of other coagulation parameters and postpartum hemorrhage from healthy controls.

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

ObjectiveTo 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 methodsThis 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.ResultsLow 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).ConclusionsVitamin D deficiency may contribute to an increased risk for future cardiovascular diseases and a risk of thrombotic complications in pregnant women with GDM.

Fetal programming of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS.

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.

The impact of intrahepatic cholestasis of pregnancy on fetal cardiac and peripheral circulation.

OBJECTIVE: The aim of this study was to evaluate changes in fetal cardiac and peripheral circulation in pregnancies complicated with intrahepatic cholestasis. MATERIAL AND METHODS: The Doppler examination results of 22 pregnant subjects complicated with intrahepatic cholestasis of pregnancy (ICP) and 44 healthy controls were compared. The parameters of fetal cardiac circulation were pulmonary artery and aortic (Ao) peak systolic velocity (PSV), pulmonary vein (Pv), peak velocity index (PVI) and pulsatility index (PI), mitral valve (MV) and tricuspid valve (TV), early diastole (E)- and atrial contraction (A)-wave peak velocity ratio (E/A), and isthmus aortic peak systolic velocity (IAo PSV). The parameters of fetal peripheral circulation were middle cerebral artery (MCA) and umbilical artery (UA) PI, resistance index (RI), systolic/diastolic (S/D) ratio. Fetal obstetric Doppler monitoring was conducted weekly before 36 weeks and biweekly after that, and the results were compared with the normal reference values for gestational age. RESULTS: The Doppler parameters of fetal cardiac and peripheral circulation did not significantly differ between the two groups. S/D ratio readings in the ICP group were significantly above 2 SD before 35 weeks of gestation. Women with ICP had increased risks of preterm delivery, neonatal unit admission, and meconium-stained amniotic fluid compared with those in the controls. CONCLUSION: Fetuses of pregnant women with ICP showed no differences in the evaluation of cardiac and peripheral Doppler measurements compared with fetuses of healthy mothers. The Doppler investigation of the umbilical artery may be useful in monitoring of pregnancies complicated by early onset intrahepatic cholestasis.

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.

The effect of place of residence and lifestyle on vitamin D deficiency in pregnancy: Comparison of eastern and western parts of Turkey.

OBJECTIVE: The aim of this study was to determine the prevalence and the predictive factors of vitamin D deficiency in pregnancy and the compliance with "The National Vitamin D Support Program" at Turkey's easternmost and westernmost provinces. MATERIAL AND METHODS: Lifestyles of women at 24-28 weeks of pregnancy were assessed using a questionnaire form, and serum 25-hydroxyvitamin D3 (25(OH)D3) levels were measured. RESULTS: Vitamin D deficiency (≤20 ng/mL) in pregnant women had a prevalence of 27.8% in Izmir and 76.3% in Erzurum. The compliance of "The National Vitamin D Support Program" was 8% in Izmir and 32.6% in Erzurum. Clothing style, fish consumption, seaside holiday duration, and 1200 IU/day vitamin D replacement had an effect on 25(OH)D3 levels in pregnant subjects in Izmir, whereas only holiday duration and 1200 IU/day vitamin D replacement affected 25(OH)D3 levels in Erzurum. However, when a threshold for 25(OH)D3 level was considered ≥32 ng/mL, lifestyles did not affect 25(OH)D3 level. CONCLUSION: The effect of lifestyle on 25(OH)D3 level in pregnancy is limited, especially in cold regions. We recommended increasing the compliance with "The National Vitamin D Support Program" at the follow-up of all pregnant women, irrespective of region and season.