Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause inflammatory response and maintenance of the inflammation state in adipocytes by augmented production of inflammatory cytokines, monocyte chemoattractant proteins, and recruitment of the immune cell. Therefore, the PCOS can be related to a low-grade inflammation state and inflammatory markers. Investigating the inflammatory processes and mediators that contribute to the commencement and development of PCOS can be a critical step for better understanding the pathophysiology of the disease and its treatment through inhibition or control of related pathways. In the present review, we discuss the pathophysiological roles of chronic low-grade inflammation mediators including inflammasome-related cytokines, interleukin-1ß (IL-1ß), and IL-18 in PCOS development.

Prevalence and Risk Factors of Prenatal and Postnatal Depressive Symptoms in Babol Pregnancy Mental Health Registry: A Cross-Sectional Study.

BACKGROUND: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mother, fetus, and child. The aim of study was to examine the prevalence and risk factors of prenatal and postnatal depressive symptoms. MATERIALS AND METHODS: This was a cross-sectional and hospital-based survey of 2305 pregnant women and post-partum women (18-48 years) that was registered in the Babol Pregnancy Mental Health Registry (BPMHR) database from June 2020 to March 2021. Two questionnaires, including demographics and depression, were analyzed in this study. Also, the Edinburg Postnatal Depression Scale (EPDS) was used to assess the depressive symptoms. Independent t test and the analysis of variance were used to compare the means. Multiple logistic regressions were used to determine risk factors for depressive symptoms. RESULTS: According to the EPDS scale, the prevalence of depressive symptoms was 19.8% in the pregnant woman group in comparison with the postpartum period (11.6%). Risk factors for antenatal depressive symptoms were parity (women with parity ≥ 4 vs. 1 parity, ß=1.808, P=0.020), two groups of gestational age (gestational age ≤12 weeks vs. 28 weeks, ß=1.562 P=0.030) as well as (gestational age 21-27 weeks vs. 28 weeks (ß=1.586, P=0.033), and high-risk pregnancy (high-risk vs. low-risk pregnancy, ß=1.457, P=0.003). For postnatal depressive symptoms, none of the factors were a significant risk. CONCLUSION: Prenatal and postnatal depressive symptoms should be screened, particularly for women in the first and second trimesters, with high parity, and those with a high-risk pregnancy, as recommended by the present study.

Pharmacotherapy or Psychotherapy? Selective Treatment Depression in The Infertile Women with Recurrent Pregnancy Loss: A Triple-Arm Randomized Controlled Trial.

BACKGROUND: Recurrent pregnancy loss (RPL) and infertility are associated with significant psychiatric complications.
The study aimed to investigate the effectiveness of cognitive behavioral therapy (CBT) and sertraline
in the treatment of in depression, anxiety, and infertility stress of depressed infertile women with RPL in comparison
with usual care.
Materials and Methods: A triple-arm randomized controlled trial was carried out on the 60 depressed infertile
women with RPL, a population of Infertility Center of Babol city, Iran, who were randomly assigned into three
groups: pharmacotherapy with sertraline (n=20), psychotherapy with CBT (n=20), and a usual care as control
group (n=20). The participants of psychotherapy received CBT sessions (90 minutes each) over 10 weeks. The
participants in the pharmacotherapy group took 50 mg/day sertraline daily for 22 weeks. Outcomes were assessed
using the Beck Depression Inventory (BDI-II), fertility problem inventory (FPI), and State-Trait Anxiety
Inventory Form Y (STAI-Y) at the beginning of the trial, 10-weeks post-trial, and three months of follow-up.
Using statistical package for the social sciences (SPSS) software, data were analyzed.
Results: CBT considerably reduced the depression symptoms more than sertraline with a moderate effect size
at the post-trial (g=0.11, 95% CI: -0.03 to -0.50). Sertraline showed reduced the scores of state-anxiety more
considerably in comparison with control group by a large effect size of post-trial (g=-1.04, 95% CI: -1.70 to
-0.38). CBT reduced the total scores of FPI more considerably than sertraline, with a large, small size at follow
up-trial [95% CI=-0.03(-0.65, -0.58)]. Both CBT and sertraline were superior to the control group in reducing
depression and infertility stress.
Conclusion: Depression and infertility stress diminished under CBT and sertraline in depressed infertile women with
RPL, with a significant advantage of CBT. Sertraline was superior to CBT in reduction of anxiety (registration number:
IRCT201304045931N3).

Decreased Frequency of CD8+HLA-G+ T Cell in the Peripheral Blood of Primary Unexplained Infertile Females.

Most of the findings have focused on the importance of CD4+HLA-G+ and CD8+HLA-G+ regulatory T cells (Treg) during pregnancy. It has been demonstrated that these HLA-G+ T cell subsets could induce maternal immune tolerance against semi-allogenic conceptus during pregnancy. There are only a few experiments regarding the Treg cells in the context of unexplained infertility (UI). Thirty-five participants including 18 primary unexplained infertile and 17 fertile females were enrolled in this study. A total of 3-5 ml blood samples were taken, and peripheral blood mononuclear cells (PBMCs) were separated by using Ficoll. Using a flow cytometer, the frequency of CD4+HLA-G+ and CD8+ HLA-G+ T cells was assessed in the peripheral blood samples of primary unexplained infertile and fertile females. Our results showed that the frequency of CD8+HLA-G+ Treg cells was significantly lower in primary unexplained infertile females than fertile females (P = 0.048). Although the frequency of CD4+HLA-G+ Treg cells in the primary unexplained infertile females was lower than fertile females, the difference was not statistically significant (P = 0.25). Regarding the important role of CD8+HLA-G+ Treg cells during pregnancy and its decrease in females with primary UI, it seems that reduced CD8+ HLA-G+ Treg cells could be a leading immunological factor in the context of infertility. Nevertheless, more researches are needed in this field.

Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome.

This study evaluates serum copper and magnesium and total antioxidant capacity levels in PCOS patients. In this regard, the probable association of copper and magnesium with total antioxidant capacity (TAC) was investigated. In total, 150 women (60 PCOS patients and 90 healthy subjects) participated in this case-control study. PCOS was diagnosed according to the Rotterdam criteria (2003). Serum Cu, Mg, Ca, TAC, insulin levels, and insulin resistance indices were determined. Insulin was measured using ELISA methods. Serum Cu and Mg levels were measured by an atomic absorption spectrophotometer and the Xylidyl Blue method respectively. The correlations between the parameters were analyzed using the Spearman correlation test. Serum Cu level was significantly higher while TAC was significantly lower in the PCOS patients than those in the controls (p = 0.019 and p = 0.002 respectively). No significant difference was detected between the two groups in terms of serum Mg and Ca levels and Ca/Mg ratio. In insulin-resistant PCOS subjects, there was a negative correlation between Mg levels and homeostatic model assessment for insulin resistance (r = - 0.449, p = 0.006) but a positive correlation between Mg levels and quantitative insulin sensitivity check index (r = 0.480, p = 0.003). A negative correlation also existed between Mg levels and TAC in non-insulin-resistant PCOS patients (r = - 0.407, p = 0.04). According to the results, copper and magnesium seem to contribute to oxidative stress and insulin resistance in PCOS patients. Therefore, to prevent long-term metabolic complications in PCOS women, it is recommended that these elements be routinely monitored. Also, significantly lower levels of serum TAC in PCOS patients than in normal women may suggest increased oxidative stress in such patients.

Insulin resistance and adverse metabolic profile in overweight/obese and normal weight of young women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOs) is an endocrine-metabolic disorder. This study intends to determine the comparison of insulin resistance (IR) and metabolic disturbance in overweight/obese and normal-weight of young women with polycystic ovary syndrome. METHODS: Using a comparative cross-sectional study design in 2015, 27 normal weight (183.15) vs. 8.3% (5) in the normal group (P<0.001). 82.4% (62) of the overweight/obese group revealed low insulin sensitivity (QUICKI<0.34) while this value was 17.6 % (13) within their lean counterparts (p<0.001). In the study group, 89.7 % (54) showed elevated fasting insulin concentration (>13µU/ml) vs. 10.3% (7) in the control group (p<0.001). CONCLUSIONS: Overweight/obese PCOs patients revealed higher insulin resistance and lower insulin sensitivity, and also greater TG and LDL cholesterol. Priority of management of insulin resistance and lipid profile should be considered on identifying these potentially major complications.

The Effect of Metformin Treatment on the Serum Levels of Homocysteine, Folic Acid, and Vitamin B12 in Patients with Polycystic Ovary Syndrome.

BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia is a well-known risk factor for cardiovascular disease. Although metformin therapy can increase homocysteine (Hcy) levels, it frequently is used as an oral medicine in women with polycystic ovary syndrome (PCOS), who might be at risk of catching diabetes mellitus. The aim of this study was to investigate the effect of metformin on the levels of serum Hcy, vitamin B12 (vit B12), and folic acid in patients with PCOS. MATERIALS AND METHODS: An interventional study was designed with 18 patients with PCOS at the Fatemehzahra infertility Hospital in Babol, Iran. Metformin treatment (500 mg twice daily) was initiated in all patients for a period of consecutive 6 months. The levels of serum Hcy, vit B12, and folic acid were measured in the participants before and after metformin treatment. RESULTS: The mean vit B12 level showed a significant decrease in patients after 6 months of metformin treatment (P = 0.002). However, there was no significant difference in serum folic acid levels. The mean Hcy levels increased after treatment, but this difference not was statistically significant. When patients were stratified into four subgroups by their insulin sensitivity and body mass index (BMI), relatively similar results were obtained in the subgroups, except that Hcy levels in the overweight/obesity group (BMI > 25 kg/m2) after treatment showed a significant increase (P = 0.01). CONCLUSION: These findings indicate that metformin increases the serum Hcy concentration in patients with PCOS especially in the women with BMI > 25 kg/m2. The possible mechanism for this effect would be the obvious reduction in the levels of vit B12.

Women's satisfaction in early versus delayed postcaesarean feeding: A one-blind randomized controlled trial study.

BACKGROUND: The early postoperative feeding after caesarean section (C- section) has remained controversial. This study was designed to evaluate the safety and efficacy of early versus delayed postcaesarean section oral feeding regarding gastrointestinal complications and patients postoperative satisfaction after C- section. METHODS: This clinical trial study was conducted on 200 pregnant women undergoing planned C-section under spinal anesthesia (Registration Number: IRCT: 138712211760N1). Women were randomly divided in two groups; group A (early feeding group) comprised of 101 patients who were encouraged to take oral fluid. If they tolerated, they continue semi-solid and solid foods starting 2 h after caesarean section. Group B (delayed feeding group) comprised of 99 patients who were given oral fluid 8 h after surgery. After beginning of feeding the patients' tolerance, first flatus, first defecation, beginning of regular diet, the length of hospital stay and also patient satisfaction level were evaluated in each group by visual scale analog (VAS). RESULTS: The mean time of the first passage of flatus was 10.2±1.7 hours for the early oral feeding group versus 10.7±1.6 hours for the delayed feeding group and the difference was significant (P=0.03). Duration to first defecation and length of hospital stay as well as patient satisfaction level did not differ significantly between the two groups. CONCLUSION: The results of this study suggest early postcaesarean feeding. It is well tolerated and helps return normal feeding habits.

Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet.

BACKGROUND: This study was designed to investigate the effect of metformin and flutamide alone or in combination with anthropometric indices and laboratory tests of obese/overweight PCOS women under hypocaloric diet. METHODS: This single blind clinical trial was performed on 120 PCOS women. At the beginning, hypocaloric diet was recommended for the patients. After one month while they were on the diet, the patients were randomly divided in 4 groups; metformin (500 mg, 3/day), flutamide (250 mg, 2/day), combined, metformin (500 mg, 3/day) with flutamide (250 mg, 2/day) and finally placebo group. The patients were treated for 6 months. Anthropometric indices and laboratory tests (fasting and glucose-stimulated insulin levels, lipid profile and androgens) were measured. A one-way ANOVA (Post Hoc) and paired t-test were performed to analyze data. A p ≤ 0.05 was considered statistically significant. RESULTS: After treatment, reduction in weight, BMI, hip circumference was significantly greater in the metformin group in comparison to other groups (p<0.05). In addition, the fasting insulin was significantly greater in metformin group and flutamide group in comparison to metformin+flutamide and placebo groups after treatment (p<0.05). Within groups, insulin level showed significant changes (before and after treatment) in metformin+flutamide group and LDL reduction was significant in flutamide group before and after treatment. Post hoc tukey and two-tailed with p≤0.05 were used to define statistical significance. CONCLUSION: Using combination of metformin and flutamide improves anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet.