Long non-coding RNAs and female infertility: What do we know?

Ten percent of people who are of reproductive age experience infertility. Sometimes the most effective therapies, including technology for assisted reproduction, may lead to unsuccessful implantation. Because of the anticipated epigenetic alterations of in vitro as well as in vitro fertilization growth of embryos, these fertility techniques have also been linked to unfavorable pregnancy outcomes linked to infertility. In this regard, a variety of non-coding RNAs such as long noncoding RNAs (lncRNAs) act as epigenetic regulators in the various physiological and pathophysiological events such as infertility. LncRNAs have been made up of cytoplasmic and nuclear nucleotides; RNA polymerase II transcribes these, which are lengthier than 200 nt. LncRNAs perform critical roles in a number of biological procedures like nuclear transport, X chromosome inactivation, apoptosis, stem cell pluripotency, as well as genomic imprinting. A significant amount of lncRNAs were linked into a variety of biological procedures as high throughput sequencing technology advances, including the development of the testes, preserving spermatogonial stem cells' capacity for differentiation along with self-renewal, and controlling spermatocyte meiosis. All of them point to possible utility of lncRNAs to be biomarkers and treatment aims for female infertility. Herein, we summarize various lncRNAs that are involved in female infertility.

The effects of selenium supplementation on glycemic control, serum lipoproteins and biomarkers of oxidative stress in infertile women diagnosed with polycystic ovary syndrome undergoing in vitro fertilization: A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study aimed to evaluate the effects of selenium consumption on metabolic profile among infertile females diagnosed with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 40 infertile females with PCOS aged between 18 and 40 years. Patients were randomly allocated to two groups of intervention to receive selenium supplements (200 µg/day) or placebo (starch). Fasting blood samples were taken at baseline and after 8 weeks of intervention. RESULTS: Selenium administration significantly decreased fasting glucose (P = 0.03), homeostasis model assessment for insulin resistance (P = 0.007) and fasting insulin levels (P = 0.006), and elevated quantitative insulin sensitivity check index (P < 0.001). In addition, selenium supplementation significantly reduced malondialdehyde (MDA) levels (P = 0.006). We did not observe any significant effect of selenium supplementation on pregnancy rate, lipid profiles, total antioxidant capacity (TAC) and total glutathione (GSH) levels. CONCLUSIONS: Overall, our study demonstrated that selenium supplementation for 8 weeks in infertile women with polycystic ovary syndrome undergoing IVF had beneficial effects on glycemic control and MDA levels, but did not affect pregnancy rate, lipid profiles, TAC and GSH levels. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered at www.irct.ir as http://www.irct.ir: IRCT201701025623N100.

Effects of assisted reproduction techniques on breastfeeding outcomes.

AIM: The aim of this study was to compare the breastfeeding outcome between those who conceived via assisted reproduction techniques (ART) and those who had spontaneous conception. METHODS: This case-control study was conducted during a 2-year period between 2014 and 2016 in a tertiary healthcare center in Tehran, capital of Iran. We included a total number of 80 women with ATR conception and 81 women with spontaneous conception. The two study groups were matched regarding the age, parity and the gestational age. Those with contraindication of breastfeeding and history of psychiatric disorders were excluded. The breastfeeding outcome was measured using a structured-based interview and the results were compared between the two study groups. RESULTS: The exclusive breastfeeding was significantly higher in spontaneous conception (p < .001). The duration of the breastfeeding was significantly higher in those with spontaneous conception (p < .001). In the same way, the exclusive breastfeeding within the first week was significantly higher in the spontaneous conception group (p = .002). The ATR conception was associated with higher bad feeling during the breastfeeding (p < .001), higher breastfeeding dysfunction (p < .001) and higher experience with difficult breastfeeding (p < .001). The return of the work after 3 months was significantly higher in spontaneous conception (p = .004). CONCLUSIONS: The results of this study demonstrate that ATR conception is associated with worse breastfeeding outcome determined by lower rate of exclusive breastfeeding and higher rate of breastfeeding dysfunction and bad feeling during breastfeeding.

Sexual Function Before and After Mid-Urethral Sling Procedure for Stress Urinary Incontinence.

PURPOSE: We aimed to assess the effect of TOT procedure on sexual function and quality of life in sexually active patients. MATERIALS AND METHODS: Forty-one patients with SUI aged 18-70 years participated in this study during 2015-2019. Sexual function was evaluated by Female Sexual Function Index (FSFI), Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory Questionnaire (UDI-6) prior to TOT surgery and six months after surgery. RESULTS: The mean IIQ-7 and UDI-6 scores were significant lower after surgery (P < 0.001). The mean FSFI score was 22.69 ± 5.48 prior to surgery and 29.79 ± 4.12 in the sixth month after surgery (P < 0.001). We found significant changes in all FSFI domains except for pain. Two patients complained of new dyspareunia after surgery. There was also a direct significant correlation between education and sexual function improvement in terms of desire (P = 0.031). CONCLUSION: TOT can significantly enhance sexual function with low rate of complications in patients with SUI.

Cesarean scar pregnancy treatment: a case series.

BACKGROUND: Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. This study reports two women with cesarean scar pregnancy who were successfully treated with systemic methotrexate administration, and two other women who needed local re-administration of methotrexate after systemic injection. CASE PRESENTATION: Four Iranian pregnant women aged 29-34 years who were between 5  to 7 gestational weeks with cesarean scar pregnancy diagnosis are described. After a single dose of systemic methotrexate injection, the level of serum beta-human chorionic gonadotropin decreased in two of the women, while fetal activity was observed in the other two women. In the latter patients, methotrexate was injected under transvaginal ultrasound guidance into the gestational sac. As a result, the serum beta-human chorionic gonadotropin level first increased and then decreased in these patients. During the follow-up period, all the patients were stable and no complications were observed. Serum beta-human chorionic gonadotropin levels reached the non-pregnancy range from 4 to 9 weeks after treatment. CONCLUSION: When diagnosed at early gestation, cesarean scar pregnancy can be treated successfully with methotrexate administration alone. The clinicians should be aware that the beta-human chorionic gonadotropin level may initially increase after methotrexate injection in some patients. However, the final outcome will be promising if the patients remain stable.

Comparing the effect of sitagliptin and metformin on the oocyte and embryo quality in classic PCOS patients undergoing ICSI.

BACKGROUND: Insulin resistance plays a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, there is a growing interest in the use of insulin sensitizer drugs in the treatment of PCOS. Research in recent years has shown that sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS patients. AIMS: We aimed to compare the effects of metformin and sitagliptin on PCOS individuals undergoing ICSI. METHODS: Sixty PCOS patients were divided into 3 groups: metformin, sitagliptin, and placebo group. Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of oocyte aspiration. The serum levels of total testosterone, estradiol, and fasting insulin along with the total number of retrieved, normal and abnormal MII, and fertilized oocytes, the number of transferred embryos (grades I, II and III), and biochemical and clinical pregnancy rates as well as the ovarian hyperstimulation syndrome (OHSS) were evaluated. RESULTS: There was a significant reduction in the serum levels of Insulin and total testosterone in the treated groups compared with the placebo. The number of mature and normal MII oocytes increased significantly in the treated groups compared with the placebo. Moreover, the number of immature oocytes decreased significantly and the number of grade I embryos increases significantly in the sitagliptin group compared with the placebo group. CONCLUSION: We conclude that sitagliptin can improve the maturation of oocytes and embryos' quality more effectively than metformin, in PCOS patients undergoing ICSI. TRIAL REGISTRATION: Trial registration is NCT04268563 ( https://clinicaltrials.gov ).

Effect of Zingiber officinale Roscoe rhizome (ginger) capsule on postpartum pain: Double-blind randomized clinical trial.

BACKGROUND: Postpartum pain contributes to increased irritability and excessive stress in the mother and consequently may inhibit successful breastfeeding, reduce a mother's ability to take care of her baby, and cause an imperfect mother-baby interaction. Evidence suggests the positive effect of ginger on reduction in uterus-associated pain. The objective of this study is to investigate the effect of ginger capsules on postpartum pain. MATERIALS AND METHODS: The present double-blinded, randomized, placebo-controlled trial was conducted in Mahdiyeh Educational Hospital, Tehran. One hundred and twenty-eight mothers having moderate-to-severe pain following vaginal delivery were included. The participants were divided into two groups (A and B). Interventions were performed every 8 h in 24 h. In the first intervention (2 h after the delivery), Group A received 500 mg of placebo capsules (containing chickpea flour) and Group B received 500 mg of Zintoma (ginger rhizome) capsules. In the second and third interventions, Group A received 250 mg placebo capsules and Group B received 250 mg Zintoma capsules. All participants received 250 mg capsules of mefenamic acid in each intervention in addition to ginger or placebo capsules. The pain severity was measured before and half an hour, an hour, and 2 h after each intervention. Statistical analysis was performed using the SPSS software version. 22. The Chi-square, Fisher's, and t tests and the GEE model were applied to assess the pain severity. RESULTS: The average pain severity was not statistically significant between the groups in the beginning of the intervention (P = 0.623). The mean score of pain significantly decreased within the duration of intervention in both groups (P < 0.001); however, the pain severity was significantly lower in the intervention group as compared to the control group at any point after the intervention (P = 0.006). CONCLUSION: Ginger can be used as an effective remedy for postpartum pain relief.

Sitagliptin/Metformin: A New Medical Treatment in Polycystic Ovary Syndrome.

Metformin has long been used in the treatment of polycystic ovarian syndrome (PCOS). Recently, sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS. We suggest that a combination of sitagliptin and metformin can be more effective than either treatment alone in improving different aspects of PCOS.

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization.

This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF). Thirty-six women candidate for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 18/group) were randomly assigned into intervention groups to take either 200 µg/day of selenium or placebo for 8 weeks. RT-PCR findings indicated that selenium supplementation downregulated gene expression of interleukin-1 (IL-1) (P < 0.004) and tumor necrosis factor alpha (TNF-α) (P = 0.02) in lymphocytes of patients with PCOS compared with the placebo. In addition, selenium supplementation upregulated gene expression of vascular endothelial growth factor (VEGF) (P = 0.001) in lymphocytes of patients with PCOS compared with the placebo. Selenium supplementation had no significant effect on clinical symptoms and gene expression of IL-8 (P = 0.10) and transforming growth factor beta (TGF-ß) (P = 0.63). Overall, our findings documented that selenium supplementation for 8 weeks to infertile women candidate for IVF improved IL-1, TNF-α, and VEGF gene expression, though selenium had no effect on clinical symptoms and, IL-8 and TGF-ß gene expression. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N23.

The Effects of Chromium Supplementation on Gene Expression of Insulin, Lipid, and Inflammatory Markers in Infertile Women With Polycystic Ovary Syndrome Candidate for in vitro Fertilization: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Purpose: This study was performed to determine the effects of chromium supplementation on the gene expression of insulin, lipid, and inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF). Methods: Forty women, aged 18-40 years, who had been selected for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 20/group) were randomly assigned into intervention groups to take either 200 µg/day of chromium or placebo for 8 weeks. Inflammatory markers were measured at baseline and end of the trial. Genes related to insulin, lipid, and inflammation were expressed in peripheral blood mononuclear cells (PBMCs), using RT-PCR method. Results: Chromium supplementation led to a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (-1.4 ± 1.5 vs. + 0.2 ± 2.2 mg/L, p = 0.01) compared with the placebo. RT-PCR findings indicated that chromium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p = 0.01), glucose transporter 1 (GLUT-1) (p = 0.001) and low-density lipoprotein receptor (LDLR) (p = 0.01), as well as downregulated gene expression of interleukin-1 (IL-1) (p = 0.004) in PBMCs of patients with PCOS compared with the placebo. Chromium supplementation had no significant effect on gene expression of IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß) and vascular endothelial growth factor (VEGF). Conclusion: Overall, our findings demonstrated that infertile women with PCOS, who were candidate for IVF benefited from chromium supplementation for 8 weeks in terms of lowering hs-CRP and improving gene expression of PPAR-γ, GLUT-1, LDLR, and IL-1, though chromium had no effect on the gene expression of IL-8, TNF-α, TGF-ß, and VEGF. Clinical Trial Registration Number: http://www.irct.ir:IRCT20170513033941N32.

The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization.

BACKGROUND: Vitamin D deficiency in women diagnosed with polycystic ovary syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be related to its impact on metabolic abnormalities in these patients. It is hypothesized that vitamin D supplementation influences metabolic profile of these patients and indirectly might affect fertility and the outcomes. Therefore, this study was conducted to determine the effects of vitamin D supplementation on the levels of anti-Müllerian hormone (AMH), metabolic profiles, and gene expression of insulin and lipid metabolism in infertile women with PCOS who were candidate for in vitro fertilization (IVF). METHODS: This study was a randomized, double-blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40 years, diagnosed with PCOS and was candidate for IVF. Participants were randomly assigned into two intervention groups for receiving either 50,000 IU vitamin D or placebo (n = 20 each group) every other week for 8 weeks. Gene expression for insulin and lipid metabolism was conducted using peripheral blood mononuclear cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS: Vitamin D supplementation led to a significant reduction in serum AMH (- 0.7 ± 1.2 vs. - 0.1 ± 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 ± 1.6 vs. -0.3 ± 0.9 µIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (- 0.3 ± 0.3 vs. -0.1 ± 0.2, P = 0.008), and a significant increase in quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. + 0.001 ± 0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D supplementation there was a significant decrease in serum total- (- 5.1 ± 12.6 vs. + 2.9 ± 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 ± 10.3 vs. + 2.5 ± 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION: Overall, the findings of this trial supported that 50,000 IU vitamin D supplementation every other week for 8 weeks had beneficial effects on insulin metabolism, and lipid profile of infertile women with PCOS who are candidate for IVF. These benefits might not be evident upon having sufficient vitamin D levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT20170513033941N27).

The Influences of Chromium Supplementation on Glycemic Control, Markers of Cardio-Metabolic Risk, and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized, Double-Blind, Placebo-Controlled Trial.

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18-40 years old. Individuals were randomly allocated into two groups to take either 200 µg/day of chromium (n = 20) or placebo (n = 20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (- 2.3 ± 5.7 vs. + 0.9 ± 3.1 mg/dL, P = 0.03), insulin levels (- 1.4 ± 2.1 vs. + 0.4 ± 1.7 µIU/mL, P = 0.004), homeostatic model of assessment for insulin resistance (- 0.3 ± 0.5 vs. + 0.1 ± 0.4, P = 0.005), and a significant increase in quantitative insulin sensitivity check index (+ 0.004 ± 0.008 vs. - 0.001 ± 0.008, P = 0.03). In addition, chromium supplementation significantly decreased serum triglycerides (- 19.2 ± 33.8 vs. + 8.3 ± 21.7 mg/dL, P = 0.004), VLDL- (- 3.8 ± 6.8 vs. + 1.7 ± 4.3 mg/dL, P = 0.004) and total cholesterol concentrations (- 15.3 ± 26.2 vs. - 0.6 ± 15.9 mg/dL, P = 0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+ 153.9 ± 46.1 vs. - 7.8 ± 43.9 mmol/L, P < 0.001) and a significant reduction in malondialdehyde values (-0.3 ± 0.3 vs. + 0.1 ± 0.2 µmol/L, P = 0.001) compared with the placebo. Overall, our study supported that chromium administration for 8 weeks to infertile PCOS women candidate for IVF had beneficial impacts on glycemic control, few variables of cardio-metabolic risk, and oxidative stress.

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid in Infertile Polycystic Ovary Syndrome Women Candidate for In Vitro Fertilization: a Randomized, Double-Blind, Placebo-Controlled Trial.

This study was conducted to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid in infertile women with polycystic ovary syndrome (PCOS) candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was conducted among 40 infertile women with PCOS candidate for IVF. Subjects were randomly allocated into two groups to intake either 200-µg selenium (n = 20) or placebo (n = 20) per day for 8 weeks. Gene expression levels related to insulin and lipid were quantified in lymphocytes of women with PCOS candidate for IVF with RT-PCR method. Results of RT-PCR demonstrated that after the 8-week intervention, compared with the placebo, selenium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (1.06 ± 0.15-fold increase vs. 0.94 ± 0.18-fold reduction, P = 0.02) and glucose transporter 1 (GLUT-1) (1.07 ± 0.20-fold increase vs. 0.87 ± 0.18-fold reduction, P = 0.003) in lymphocytes of women with PCOS candidate for IVF. In addition, compared with the placebo, selenium supplementation downregulated gene expression of low-density lipoprotein receptor (LDLR) (0.88 ± 0.17-fold reduction vs. 1.05 ± 0.22-fold increase, P = 0.01) in lymphocytes of women with PCOS candidate for IVF. We did not observe any significant effect of selenium supplementation on gene expression levels of lipoprotein(a) [LP(a)] in lymphocytes of women with PCOS candidate for IVF. Overall, selenium supplementation for 8 weeks in lymphocytes of women with infertile PCOS candidate for IVF significantly increased gene expression levels of PPAR-γ and GLUT-1 and significantly decreased gene expression levels of LDLR, but did not affect LP(a). CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir : IRCT201704245623N113.

Periodontal health in mothers of preterm and term infants.

OBJECTIVE: Recent studies have suggested that chronic periodontitis may induce an inflammatory response which can cause premature delivery. This study was designed to assess the association between periodontal health and preterm labor in Iranian female population. MATERIALS AND METHODS: In this case-control study, 201 pregnant women without systemic disease or other risk factors for preterm labor were chosen. The control group (n = 99) had term labor (infants > or =37 weeks) and the case group (n = 102) had preterm labor (infants < 37 weeks). Bleeding index, pocket depth and debris index were measured. RESULTS: The data of bleeding index (cases, 0.64 +/- 0.38; controls, 0.57 +/- 0.35), probing depth (cases, 2.80 +/- 0.30; controls, 1.63 +/- 0.23) and debris index (cases, 1.38 +/- 0.67; controls, 0.81 +/- 0.38) revealed a statistically significant difference between the two groups (p < 0.05). CONCLUSION: According to the findings of this study, there is a noticeable relationship between periodontal health and duration of pregnancy; periodontal disease could be a risk factor for preterm labor. Oral hygiene is strongly recommended to be included in prenatal care.