Effect of autologous platelet-rich plasma for treatment of recurrent pregnancy loss: a randomized controlled trial.

OBJECTIVE: Recurrent pregnancy loss (RPL) is a fertility problem for which no exact mechanism of abortion or efficient treatment has been described. This study was conducted between 2018 and 2019 to investigate the effectiveness of autologous platelet-rich plasma (PRP) in improving the live birth rate of women with RPL who required in vitro fertilization (IVF). METHODS: A total of 63 patients with at least two previous pregnancy losses and no specific cause detected for the RPL were included and randomly assigned into two groups (PRP and control). Intrauterine infusion of 0.5 mL of autologous PRP was performed 48 hours before embryo transfer in the PRP group. Women in the control group received standard treatment. RESULTS: Forty patients completed the study. The baseline and cycle characteristics of the participants did not differ significantly between the PRP and control groups. The clinical pregnancy rate was higher in the PRP group (35% vs. 20%, P=0.288). The live birth rate was 15% in the PRP group, but no live births were recorded in the control group (P=0.231). CONCLUSION: This is the first study to show that intrauterine infusion of PRP in patients with RPL who undergo IVF may increase the chance of live birth.

Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women.

Recurrent implantation failure (RIF) is the repeated failure of good-quality embryos in implantation process following several assisted reproduction cycles. Disruption of the endometrial receptivity is one of the main causes of RIF. Progesterone plays a pivotal role in the endometrial receptivity through the regulation of gene expression pattern by binding to its receptors in the endometrial cells. The aim of this study was to evaluate the expression level of progesterone receptor (PR) and its phosphorylated form in the endometrial stromal cells (eSC) of RIF patients and compare it to the eSC of healthy fertile women as control group. After isolation of the eSC from biopsy samples of RIF patients and healthy fertile women and their characterization, expression levels of PR mRNA, PR protein, and phospho-Ser294 PR protein were evaluated by quantitative real-time PCR and immunofluorescence staining, respectively. The results demonstrated a significant reduction in PR mRNA expression (P < 0.01.) and phospho-Ser294 PR protein (P < 0.05) level in RIF patients compared to the control group. These data for the first time suggest that the expression of PR and its phosphorylated form are impaired in RIF patients. Therefore, designing therapeutic methods for improving PR expression status and its regulation in the endometrium of RIF patients may help in improving the final reproductive outcomes of these cases.

Efficacy of daily GnRH agonist for luteal phase support following GnRH agonist triggered ICSI cycles versus conventional strategy: A Randomized controlled trial.

OBJECTIVE: The use of gonadotropin-releasing hormone agonist (GnRHa) as an alternative for human chronic gonadotropin (hCG) trigger has potential benefits, but the optimal luteal phase support (LPS) following GnRHa trigger remains to be elucidated. We aimed to investigate a new strategy (daily GnRH agonist for LPS following GnRH agonist trigger) as an alternative for the conventional approach to the patients undergoing intracytoplasmic sperm injection (ICSI). METHODS: In this randomized controlled trial study, 44 ICSI patients were randomly assigned into two groups: group 1, patients received standard strategy (hCG trigger [10000 IU] and progesterone bid [400 mg/BD] for LPS); group 2, patients received a dose of GnRHa (0.2 mg) for ovulation trigger and subcutaneous injection of GnRHa bid (0.2 mg) for LPS. RESULTS: The pregnancy, miscarriage, and live birth rates for the patients undergoing LPS following the GnRHa trigger were similar to those of patients undergoing the standard strategy. CONCLUSIONS: We showed that a daily subcutaneous injection of GnRHa for LPS following the GnRHa trigger can be successfully performed as an alternative to the standard strategy, with comparable pregnancy and live birth rates in ICSI patients.

Effect of antioxidant supplementation containing L-carnitine on semen parameters: a prospective interventional study.

OBJECTIVE: One of the remarkable causes of infertility in men is oxidative stress having a reducing effect on their reproductive function. In the present study, we investigated the efficacy of supplementation with antioxidants and L-Carnitine (contained in Androferti) on semen parameters. METHODS: We included 180 infertile male patients diagnosed with idiopathic oligoastenoteratozoospermia (OAT) in this study, and we analyzed the semen sample from 59 patients before and after oral antioxidant treatment, with the commercial name of Androferti (containing 1500 mg of L-Carnitine, 60 mg of vitamin C, 20 mg of coenzyme Q10, 10 mg of vitamin E, 10 mg of zinc, 200 µg of vitamin B9, 50 µg of selenium, 1 µg of vitamin B12). All of the patients received Androferti twice a day for 3 months. RESULTS: There were significant improvements in the sperm concentration (p=0.004) after the antioxidant supplementation. There was also a meaningfully improvement in sperm morphology (p=0.01) after treatment. However, sperm motility was not significantly altered after antioxidant treatment (p=0.2). CONCLUSIONS: Antioxidants supplementation containing 1500 mg L-carnitine can improve the semen quality in infertile men diagnosed with idiopathic OAT. However, further studies are required to determine the antioxidant effects on reproduction function.

Effect of myo-inositol supplementation on ICSI outcomes among poor ovarian responder patients: A randomized controlled trial.

PURPOSE: This study has evaluated the use of myo-inositol supplementation for improving reproductive outcomes in poor responders undergoing intracytoplasmic sperm injection (ICSI). METHODS: One hundred and twelve poor responder patients were included in the study and randomly categorized into two groups using a permuted block randomization method. Group A included 56 patients who received myo-inositol (4 g) and folic acid (400 µg) daily from one month before starting the ICSI cycle continuing until the ovulation triggering day. Group B included 56 patients consuming only folic acid (400 µg) daily for the same period. The outcome measures were the number of retrieved oocytes, embryo quality, Ovarian Sensitivity Index (OSI: number of oocytes retrieved/total Gonadotropins units × 1000), fertilization, implantation, and ongoing pregnancy rates. RESULTS: No significant difference was observed between the two groups regarding the total dose of gonadotropin used, OSI, and the number of total retrieved and mature oocytes. Grad A embryos and fertilization rate were significantly increased in group A. Implantation and pregnancy rates showed statistically insignificant changes. CONCLUSION: Treatment of poor responders with myo-inositol from one month before starting ICSI cycle continuing until ovulation trigger can improve fertilization rate and embryo quality, and may enhance the cumulative pregnancy rate in poor responders.

The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic control and lipid concentrations in patients with gestational diabetes.

OBJECTIVE: This study was performed to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on glucose metabolism and lipid concentrations in gestational diabetes (GDM) patients. METHODS: This randomized double-blind placebo-controlled clinical trial was done among 140 GDM patients. Participants were randomly divided into 4 groups to receive: (1) 1000 mg omega-3 fatty acids containing 360 mg eicosapentaenoic acid and 240 mg docosahexaenoic acid (DHA) twice a day + vitamin D placebo (n = 35); (2) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo (n = 35); (3) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 35), and (4) vitamin D placebo + omega-3 fatty acids placebo (n = 35) for 6 weeks. RESULTS: After 6 weeks of intervention, patients who received combined vitamin D and omega-3 fatty acids supplements compared with vitamin D, omega-3 fatty acids, and placebo had significantly decreased fasting plasma glucose (-7.3 ± 7.8, -6.9 ± 6.6, -4.0 ± 2.5, and +1.0 ± 11.4 mg/dL, respectively, P < .001), serum insulin levels (-1.9 ± 1.9, -1.3 ± 6.3, -0.4 ± 6.3, and +2.6 ± 6.5 µIU/mL, respectively, P = .005), homeostatic model of assessment for insulin resistance (-0.7 ± 0.6, -0.5 ± 1.4, -0.2 ± 1.5, and +0.6 ± 1.5, respectively, P < .001) and increased quantitative insulin sensitivity check index (+0.01 ± 0.01, +0.008 ± 0.02, +0.002 ± 0.02, and -0.005 ± 0.02, respectively, P = .001). In addition, changes in serum triglycerides (-8.2 ± 41.0, +7.6 ± 31.5, +3.6 ± 29.9, and +20.1 ± 29.6 mg/dL, respectively, P = .006) and very low-density lipoprotein cholesterol (-1.6 ± 8.2, +1.5 ± 6.3, +0.8 ± 6.0, and +4.0 ± 5.9 mg/dL, respectively, P = .006) in the vitamin D plus omega-3 fatty acids group were significantly different from the changes in these indicators in the vitamin D, omega-3 fatty acids, and placebo groups. CONCLUSION: Overall, vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM patients had beneficial effects on fasting plasma glucose, serum insulin levels, homeostatic model of assessment for insulin resistance, quantitative insulin sensitivity check index, serum triglycerides, and very low-density lipoprotein cholesterol levels.

Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: This study was conducted to determine the effects of calcium plus vitamin D supplementation on inflammatory factors and biomarkers of oxidative stress among overweight vitamin D-deficient women with polycystic ovary syndrome (PCOS). DESIGN, PATIENTS AND MEASUREMENTS: This randomized double-blind placebo-controlled clinical trial was performed among 104 overweight vitamin D-deficient women diagnosed with PCOS aged 18-40 years. Participants were randomly divided into four groups. Group A received 1000 mg calcium daily and vitamin D placebo weekly (N = 26), group B 50000 IU vitamin D weekly and calcium placebo daily (N = 26), group C 1000 mg calcium daily plus 50000 IU vitamin D weekly (N = 26) and group D calcium placebo daily plus vitamin D placebo weekly (N = 26) for 8 weeks. Fasting blood samples were taken at baseline and 8 weeks after intervention to measure inflammatory factors and biomarkers of oxidative stress. RESULTS: After 8 weeks, individuals taking calcium plus vitamin D supplements had greater decreases in homoeostatic model assessment beta-cell function (HOMA-B) score (-11·1 vs -8·6, -3·4 and 13·7, respectively, P = 0·03), serum high-sensitivity C-reactive protein (hs-CRP) (-948·3 vs 802·3, -383·8 and 618·2 ng/ml, respectively, P = 0·04) and plasma malondialdehyde (MDA) concentrations (-0·6 vs -0·5, -0·1 and 0·6 µmol/l, respectively, P = 0·009), and significant increases in plasma total antioxidant capacity (TAC) (35·2 vs 21·1, 22·5 and -153·8 mmol/l, respectively, P = 0·006) and glutathione (GSH) levels (216·0 vs 3·9, -47·5 and -160·8 µmol/l, respectively, P = 0·001) compared with calcium alone, vitamin D alone and placebo groups. Calcium plus vitamin D cosupplementation did not influence plasma NO and catalase levels. CONCLUSIONS: We found that calcium plus vitamin D cosupplementation for 8 weeks among overweight and vitamin D-deficient women with PCOS had beneficial effects on inflammatory factor and biomarkers of oxidative stress.

Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome.

BACKGROUND & AIMS: Few studies have examined the effects of calcium plus vitamin D supplementation on glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome (PCOS). This study was conducted to determine the effects of calcium plus vitamin D supplementation on glucose metabolism and lipid concentrations among overweight and obese vitamin D deficient women with PCOS. METHODS: This randomized double-blind placebo-controlled clinical trial was conducted among 104 overweight and obese vitamin D deficient women diagnosed with PCOS. Participants were randomly assigned into four groups to receive: 1) 1000 mg/d calcium + vitamin D placebo (n = 26); 2) 50,000 IU/wk vitamin D + calcium placebo (n = 26); 3) 1000 mg calcium/d + 50,000 IU/wk vitamin D (n = 26) and 4) calcium placebo + vitamin D placebo (n = 26) for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks' intervention to measure glucose metabolism and lipid concentrations. RESULTS: Calcium-vitamin D co-supplementation resulted in higher levels of serum calcium (P = 0.002) and vitamin D (P < 0.001) compared with other groups. Co-supplementation, compared with other groups, led to decreased serum insulin levels (P = 0.03), homeostasis model of assessment-insulin resistance (HOMA-IR) score (P = 0.04) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (P = 0.001). Furthermore, a significant decrease in serum triglycerides (P = 0.02) and VLDL-cholesterol levels (P = 0.02) was seen following the administration of calcium plus vitamin D supplements compared with the other groups. Co-supplementation with calcium and vitamin D had no significant effects on FPG, total-, LDL-, HDL-, and non-HDL-cholesterol levels. CONCLUSIONS: In conclusion, calcium plus vitamin D supplementation for eight weeks among vitamin D deficient women with PCOS had beneficial effects on serum insulin levels, HOMA-IR, QUICKI, serum triglycerides and VLDL-cholesterol levels, but it did not affect FPG and other lipid profiles. Clinical registration numberwww.irct.ir: IRCT201309275623N10.

Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women.

To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 107 CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P > 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3.

Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial.

BACKGROUND: To our knowledge, there is no study that has examined the effects of vitamin D supplementation on metabolic status in gestational diabetes mellitus (GDM). OBJECTIVE: This study was designed to assess the effects of vitamin D supplementation on metabolic profiles, high-sensitivity C-reactive protein, and biomarkers of oxidative stress in pregnant women with GDM. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted in 54 women with GDM. Subjects were randomly assigned to receive either vitamin D supplements or placebo. Individuals in the vitamin D group (n = 27) received capsules containing 50,000 IU vitamin D3 2 times during the study (at baseline and at day 21 of the intervention) and those in the placebo group (n = 27) received 2 placebos at the same times. Fasting blood samples were collected at baseline and after 6 wk of the intervention to quantify relevant variables. RESULTS: Cholecalciferol supplementation resulted in increased serum 25-hydroxyvitamin D concentrations compared with placebo (+18.5 ± 20.4 compared with +0.5 ± 6.1 ng/mL; P < 0.001). Furthermore, intake of vitamin D supplements led to a significant decrease in concentrations of fasting plasma glucose (-17.1 ± 14.8 compared with -0.9 ± 16.6 mg/dL; P < 0.001) and serum insulin (-3.08 ± 6.62 compared with +1.34 ± 6.51 µIU/mL; P = 0.01) and homeostasis model of assessment-insulin resistance (-1.28 ± 1.41 compared with +0.34 ± 1.79; P < 0.001) and a significant increase in the Quantitative Insulin Sensitivity Check Index (+0.03 ± 0.03 compared with -0.001 ± 0.02; P = 0.003) compared with placebo. A significant reduction in concentrations of total (-11.0 ± 23.5 compared with +9.5 ± 36.5 mg/dL; P = 0.01) and low-density lipoprotein (LDL) (-10.8 ± 22.4 compared with +10.4 ± 28.0 mg/dL; P = 0.003) cholesterol was also seen after vitamin D supplementation. CONCLUSIONS: Vitamin D supplementation in pregnant women with GDM had beneficial effects on glycemia and total and LDL-cholesterol concentrations but did not affect inflammation and oxidative stress. This trial was registered at www.irct.ir as IRCT201305115623N7.