Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study.

OBJECTIVE: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantation failure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluate the endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrial expressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) in patients with RIF compared to control subjects. MATERIALS AND METHODS: This case-control study was carried out between June 2021-July 2022. Subjects included 17 patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referred to the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopy and Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulation in all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The student's t test, chi-square, Mann-Whitney U, and analysis of covariance (ANCOVA) were used for data analyses. RESULTS: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions of miR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased in patients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrial miR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF. CONCLUSION: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can be reliable, novel biomarkers for diagnosis of RIF.

Astaxanthin ameliorates inflammation, oxidative stress, and reproductive outcomes in endometriosis patients undergoing assisted reproduction: A randomized, triple-blind placebo-controlled clinical trial.

Purpose: In a randomized, triple-blind, placebo-controlled clinical trial (RCT) including 50 infertile women with endometriosis candidate for assisted reproductive techniques (ART), we studied the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes. Methods: Before and after 12 weeks of AST treatment (6 mg per day), blood serum and follicular fluid (FF) samples were collected from 50 infertile women with endometriosis stage III/IV undergoing ART. Pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and total antioxidant capacity [TAC]) were measured in the serum and FF. ART outcomes were also compared between the groups. Results: Increased serum levels of TAC (398.661 ± 57.686 vs. 364.746 ± 51.569; P = 0.004) and SOD (13.458 ± 7.276 vs. 9.040 ± 5.155; P = 0.010) were observed after AST therapy in the treatment group. Furthermore, serum MDA (14.619 ± 2.505 vs. 15.939 ± 1.512; P = 0.031) decreased significantly following antioxidant treatment. In addition, significantly lower serum levels of IL-1ß (4.515 ± 0.907 vs. 6.8760 ± 0.8478; P = 0.000), IL-6 (5.516 ± 0.646 vs. 5.0543 ± 0.709; P = 0.024) and TNF-α (2.520 ± 0.525 vs. 2.968 ± 0.548; P = 0.038) were observed after AST treatment. In addition, AST supplementation led to an improved number of oocytes retrieved (14.60 ± 7.79 vs. 9.84 ± 6.44; P = 0.043), number of mature (MII) oocytes (10.48 ± 6.665 vs. 6.72 ± 4.3; P = 0.041), and high-quality embryos (4.52 ± 2.41 vs. 2.72 ± 2.40; P = 0.024). Conclusion: AST pretreatment can modulate inflammation and OS in endometriosis-induced infertile patients. ART outcomes also improved after 12 weeks of AST therapy. Our results suggest that AST can be a potential therapeutic target for infertile patients with endometriosis undergoing ART.

Association between the food security status and dietary patterns with polycystic ovary syndrome (PCOS) in overweight and obese Iranian women: a case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS), as one of the significant endocrine disorders, is common among women worldwide. Food insecurity (FI) and unhealthy dietary patterns can negatively affect reproductive health. The effects of the lifestyle modifications, especially dietary components, on PCOS are contradictory. The aim was the assessment of association between PCOS with food security status and dietary patterns among overweight or obese women. METHODS: This case-control study was performed on 240 overweight and obese women with and without PCOS (ratio 1:1) referred to the infertility clinic of Arash Hospital, Tehran, Iran. The general and socioeconomic characteristics, anthropometrics (weight, height, body mass index (BMI), waist circumference, hip circumference), physical activity, food security status, and dietary intakes (or patterns) were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was < 0.05. RESULTS: The prevalence of FI was 60% in women with PCOS and 30% in healthy women. PCOS risk was positively related to FI, quasi-western dietary patterns, low economic levels, waist circumference, and menstrual age and negatively with physical activity and healthy dietary patterns, even after controlling the potential confounders (P <  0.05). PCOS women had a higher intake of saturated fats, monounsaturated fats, oleic acid, fluorine, sucrose, and caffeine and a lower intake of vitamins A, B5, B6, B12, C, and D, potassium, proteins, carbohydrates, cholesterols, docosahexaenoic acid, potassium, carotenes, lutein, beta-cryptoxanthin, lycopene, calcium, iron, thiamine, riboflavin, niacin, tetra- and dihydrofolate, biotin, phosphorus, magnesium, zinc, copper, fiber (total, insoluble, and crude), glucose, galactose, fructose, and lactose compared to the healthy women (P <  0.05). CONCLUSIONS: FI, quasi-western dietary patterns, low economic levels, and waist circumference were significantly associated with the higher risk of PCOS. The lifestyle changes, especially dietary patterns, may be an essential strategy for reducing PCOS. Further studies are warranted to confirm these findings and to identify the underlying mechanisms.

Altered TH1, TH2, TH17 balance in assisted reproductive technology conceived mice.

AIM AND PURPOSE: The higher prevalence rate of different diseases may accentuate the possible alteration of the immune system in individuals conceived through the assisted reproductive technologies (ART). The present study was conducted to evaluate the TH1, TH2, TH17 balance in intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) - conceived mice in comparison to naturally conceived offspring. METHODS: Mice (6-8 weeks) were divided into three groups (IVF- conceived, ICSI- conceived and naturally conceived). They were subjected to subcutaneous immunization witMycobacterium bovis Bacille Calmette-Guérin (BCG). The blood samples were taken and the sera were separated. Then the spleens were surgically removed at the time the mice were sacrificed. Serum levels of IFN-γ, IL-17A and IL-4 were detected by ELISA. Then the proportion of TCD4 cells possessing the T-bet+, GATA3+, and ROR-γt + were measured using FACS caliber flow cytometer. RESULTS: In comparison with naturally conceived mice, intracellular expression of T-bet and serum levels of IFN-γ were significantly decreased in ART- conceived mice. Moreover, ART- conceived offspring showed marked increase in IL-4 and IL-17A. CONCLUSION: It is concluded that compared to naturally conceived male mice, ART- conceived counterparts exhibit less efficient immune responses against BCG through further promotion of humoral and inflammatory related immune response characteristics.

Evaluation of prooxidant-antioxidant balance in in vitro fertilization-conceived mice.

OBJECTIVE: Concerns about the safety of assisted reproductive technology (ART) have been raised, as some studies have shown elevated incidence rates of childhood cancer, asthma, allergies, and other diseases in ART-conceived babies. Findings regarding the health of ART-conceived babies are controversial. The present study was conducted to evaluate the prooxidant-antioxidant balance (PAB) in in vitro fertilization (IVF)-conceived mice in comparison to naturally conceived offspring. METHODS: Mice (6-8 weeks) were divided into two groups (IVF-conceived and naturally conceived) matched by sex, age, weight, and litter size. A 1-mL blood sample was taken and the sera were separated. The oxidant-antioxidant balance was evaluated using a fast and reliable PAB assay. The results were expressed as mean±standard deviation. RESULTS: The mean PAB values (HK units) in the IVF-conceived and naturally conceived groups were 59.70±22.30 and 54.70±18.22, respectively (p=0.82). CONCLUSION: Since free radicals contribute to several pathological conditions and antioxidants play an important protective role against oxidative stress, evaluating the oxidant-antioxidant balance is very important. Although the results of this study showed that the quality of the defense mechanism against free radicals was not significantly different between the IVF-conceived and naturally conceived mice, other parameters of metabolic dysfunction need to be measured.

Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome.

PURPOSE: To investigate associations between gene expression pattern of apoptotic biomarkers in cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of oocytes and embryos. METHODS: 40 intracytoplasmic sperm injection patients, of whom 20 were PCOS and 20 were healthy women, were included in this study. Serum hormone levels were measured using Radioimmunoassay for each patient. The expression of survivin, caspase-3, and caspase-7 in 200 cumulus complexes surrounding mature oocytes (100 in PCOS versus 100 in control groups) collected individually at pick up was examined by real-time polymerase chain reaction (real-time PCR). RESULTS: The expression levels of survivin were significantly lower in PCOS patients than those of normal women while caspase-3 and caspase-7 expression levels were higher in PCOS patients (p < 0.05). There was a statistically significant correlation between the levels of these genes and embryo quality. CONCLUSIONS: This study reveals that the measurement of survivin, caspase-3, caspase-7 levels in cumulus cells of PCOS patients could be used as genetic biomarkers for oocyte and embryo selection under an ART program. However, further prospective studies are required to elucidate this issue.

Ovarian tissue culture in the presence of VEGF and fetuin stimulates follicle growth and steroidogenesis.

Ovarian tissue cryopreservation together with follicle culture provides a promising technique for fertility preservation in cancer patients. The study aimed to evaluate follicle parameters in a culture medium supplemented with VEGFA165 and/or fetuin. Vitrified-warmed ovarian cortical pieces were divided randomly into four culture groups consisting of basic culture medium (control), and the basic culture medium supplemented with VEGFA165, fetuin or both. After six days of culture, we evaluated the following: percentage of resting, primary and secondary growing follicles; survival rate; steroid hormones production; levels of reactive oxygen species, lipid peroxidation and total antioxidant capacity; and developmental and antioxidant gene expression. The addition of VEGFA165 alone or in combination with fetuin to the culture medium caused resting follicle activation and increased the number of growing follicles. In the VEGFA165 group, we found a significant increase in the concentrations of 17ß-estradiol at day 6 and progesterone from 4th day of the culture period. In the VEGFA165 + fetuin group, the concentration of 17ß-estradiol rose at day 4 of the culture period. The levels of BMP15, GDF9 and INHB mRNAs were increased in all treated groups. In the fetuin and fetuin + VEGFA165 groups, we observed a high level of total antioxidant capacity and expression of SOD1 and CAT genes, low reactive oxygen species and lipid peroxidation levels and increased number of viable follicles. In conclusion, the present study provides useful evidence that supplementation of culture medium with VEGFA165 + fetuin leads to primordial follicle activation and development and increased percentage of healthy secondary growing follicles.

Effect of bacterial vaginosis on premature rupture of membranes and related complications in pregnant women with a gestational age of 37-42 weeks.

BACKGROUND: The most serious outcome of term, premature rupture of membrane and chorioamnionitis is often associated with adverse maternal and infant outcomes related to infection. This study was undertaken to determine the prevalence of bacterial vaginosis (BV) at 37-42 gestational weeks and its relationship to premature rupture of membranes. METHOD: During an analytical descriptive prospective study, 425 pregnant women with a gestational age of 37-42 weeks were studied for prevalence of BV. Then, 304 women on the basis of having BV or not were followed up until 48 h after delivery for premature rupture of membranes. RESULT: The rate of BV in this population was 30.5%. No significant association was found between BV and premature rupture of membranes (odds ratio 1.6, 95% CI 0.9-2.8). CONCLUSION: BV is a common vaginitis in term pregnancy, but we could not find any relationship between BV and premature rupture of membranes at term.