Effects of autologous platelet-rich plasma on endometrial expansion in patients undergoing frozen-thawed embryo transfer: A double-blind RCT

Background: Adequate endometrial growth is principal for implantation and pregnancy. Thin endometrium is associated with lower pregnancy rate in assisted reproductive technology. Some frozen-thawed embryo transfer cycles are cancelled due to inadequate endometrial growth. Objective: To assess the effectiveness of autologous platelet-rich plasma (PRP) intrauterine infusion for the treatment of thin endometrium. Materials and Methods: A total of 72 patients who had a history of cancelled frozen-thawed embryo transfer cycle due to the thin endometrium (< 7mm) were assessed for the eligibility to enter the study between 2016 and 2017. Twelve patients were excluded for different reasons, and 60 included patients were randomly assigned to PRP or sham-catheter groups in a double-blind manner. Hormone replacement therapy was administered for endometrial preparation in all participants. PRP intrauterine infusion or sham-catheter was performed on day 11-12 due to the thin endometrium and it was repeated after 48 hr if necessary. Results: Endometrial thickness increased at 48 hr after the first intervention in both groups. All participants needed second intervention due to an inadequate endometrial expansion. After second intervention, endometrial thickness was 7.21 ± 0.18 and 5.76 ± 0.97 mm in the PRP group and sham-catheter group, respectively. There was a significant difference between the two groups. (p < 0.001). Embryo transfer was done for all patients in PRP group and just in six cases in the sham-catheter group. Chemical pregnancy was reported in twelve cases in the PRP group and two cases in the sham-catheter group. Conclusion: According to this trial, PRP was effective in endometrial expansion in patients with refractory thin endometrium

Comparison In Vitro Fertilization Outcomes between DouStim and Minimal Stimulation Protocols in Poor Ovarian Responders: A Randomized Clinical Trial

Background: Various protocols have been approved to improve the response rate leading to successful fertilizationin poor ovarian responders (PORs). The application of double ovarian stimulation (DuoStim) in the follicular andluteal phases of the same ovarian cycle has been shown as an intriguing option to achieve more oocyte retrievals inthe shortest time. The aim of the current study, is to compare the outcomes of different protocols, minimal stimulation(MS) and Duostim.Materials and Methods: This randomized clinical trial was performed on 42 in vitro fertilization (IVF) candidateswith POR diagnosis. Patients were classified into two equal groups and treated with the DuoStim protocol and MSprotocol. The IVF outcomes, including retrieved follicles, oocytes, metaphase II (MII) oocytes and embryos, werecompared between these groups.Results: The patients’ characteristics including age, anti-mullerian hormone (AMH), follicle-stimulating hormone(FSH), luteinizing hormone (LH), and antral follicle count (AFC) were collected and compared. It showed there wasno significant difference between the two groups' baseline characteristics (P>0.05). We observed that the DuoStimprotocol resulted in a significantly higher score in comparison with the MS protocols, including the number of follicles(6.23 ± 2.93 vs. 1.77 ± 1.66, P<0.001), retrieved oocytes (3.86 ± 2.57 vs. 1.68 ± 1.58, P=0.002), MII oocytes (3.36 ±2.42 vs. 1.27 ± 1.27, P=0.001) and obtained embryos (2.04 ± 1.64 vs. 0.77 ± 0.86, P=0.003).Conclusion: The DuoStim protocol is a favourable and time saving plan that is associated with more oocytes in a singlestimulation cycle. The DuoStim protocol significantly can result in more frequent MII oocytes and embryos. We figuredthat the higher number of oocytes and embryos might have led to a higher rate of pregnancy (registration number:IRCT20200804048303N1)

Free polyethylenimine enhances substrate-mediated gene delivery on titanium substrates modified with RGD-functionalized poly(acrylic acid) brushes

Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PAA) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Previously, we described a simple method to graft PAA brushes to Ti and further demonstrated conjugation of cell adhesion peptides (i.e., RGD) to the PAA brushes to improve biocompatibility. The objective of this work was to investigate the ability of Ti substrates modified with PAA-RGD brushes (PAA-RGD) to immobilize complexes composed of branched polyethyleneimine and DNA plasmids (bPEI-DNA) and support SMD in NIH/3T3 fibroblasts. Transfection in NIH/3T3 cells cultured on bPEI-DNA complexes immobilized onto PAA-RGD substrates was measured and compared to transfection in cells cultured on control surfaces with immobilized complexes including Flat Ti, PAA brushes modified with a control peptide (RGE), and unmodified PAA. Transfection was two-fold higher in cells cultured on PAA-RGD compared to those cultured on all control substrates. While DNA immobilization measured with radiolabeled DNA indicated that all substrates (PAA-RGD, unmodified PAA, Flat Ti) contained nearly equivalent amounts of loaded DNA, ellipsometric measurements showed that more total mass (i.e., DNA and bPEI, both complexed and free) was immobilized to PAA and PAA-RGD compared to Flat Ti. The increase in adsorbed mass may be attributed to free bPEI, which has been shown to improve transfection. Further transfection investigations showed that removing free bPEI from the immobilized complexes decreased SMD transfection and negated any differences in transfection success between cells cultured on PAA-RGD and on control substrates, suggesting that free bPEI may be beneficial for SMD in cells cultured on bPEI-DNA complexes immobilized on PAA-RGD grafted to Ti. This work demonstrates that substrate modification with PAA-RGD is a feasible method to enhance SMD outcomes on Ti and may be used for future applications such as tissue engineering, gene therapy, and diagnostics. © 2019 Mantz, Rosenthal, Farris, Kozisek, Bittrich, Nazari, Schubert, Schubert, Stamm, Uhlmann and Pannier

Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes

Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PAA) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Previously, we described a simple method to graft PAA brushes to Ti and further demonstrated conjugation of cell adhesion peptides (i.e., RGD) to the PAA brushes to improve biocompatibility. The objective of this work was to investigate the ability of Ti substrates modified with PAA-RGD brushes (PAA-RGD) to immobilize complexes composed of branched polyethyleneimine and DNA plasmids (bPEI-DNA) and support SMD in NIH/3T3 fibroblasts. Transfection in NIH/3T3 cells cultured on bPEI-DNA complexes immobilized onto PAA-RGD substrates was measured and compared to transfection in cells cultured on control surfaces with immobilized complexes including Flat Ti, PAA brushes modified with a control peptide (RGE), and unmodified PAA. Transfection was two-fold higher in cells cultured on PAA-RGD compared to those cultured on all control substrates. While DNA immobilization measured with radiolabeled DNA indicated that all substrates (PAA-RGD, unmodified PAA, Flat Ti) contained nearly equivalent amounts of loaded DNA, ellipsometric measurements showed that more total mass (i.e., DNA and bPEI, both complexed and free) was immobilized to PAA and PAA-RGD compared to Flat Ti. The increase in adsorbed mass may be attributed to free bPEI, which has been shown to improve transfection. Further transfection investigations showed that removing free bPEI from the immobilized complexes decreased SMD transfection and negated any differences in transfection success between cells cultured on PAA-RGD and on control substrates, suggesting that free bPEI may be beneficial for SMD in cells cultured on bPEI-DNA complexes immobilized on PAA-RGD grafted to Ti. This work demonstrates that substrate modification with PAA-RGD is a feasible method to enhance SMD outcomes on Ti and may be used for future applications such as tissue engineering, gene therapy, and diagnostics

The effect of testosterone gel on fertility outcomes in women with a poor response in in vitro fertilization cycles: A pilot randomized clinical trial

Background: In this study, the effect of testosterone gel administration during ovulation induction on the fertility rate was examined in women with a poor ovarian response in in vitro fertilization (IVF) cycles. Materials and Methods: The current study is a single-blinded, randomized clinical trial. Patients who met inclusion (Bologna) criteria were placed in the antagonist cycle group. The patients were randomly divided into two groups each included 25 participants treated with a placebo (lubricant gel, the controls) and testosterone gel (intervention). Fertility outcomes were compared between two study groups. Results: The mean ± standard deviation (SD) age of intervention (41.04 ± 3.77) versus control group (39.69 ± 3.29) was not statistically different. The two studied groups were not statistically different in terms of follicle-stimulating hormone; antral follicle count, IVF, anti-Mullerian hormone, and the duration of infertility. The mean ± SD of oocyte 2.48 ± 1.64 versus 1.17 ± 1.27 and embryo 1.60 ± 1.58 versus 0.39 ± 0.58 in intervention group was significantly higher than control group (P < 0.01). The rate of pregnancy 16% versus 0% and embryo of quality A–B was significantly higher in intervention group than control (60% versus 17.4%, P < 0.05). Conclusion: The results of the current study showed that the testosterone gel has a significant impact on the fertility rate in women with a poor response in the IVF cycles. Further, randomized clinical trials with larger sample sized are recommended

A Potential Therapeutic Role of Myoinositol in the Metabolic and Cardiovascular Profile of PCOS Iranian Women Aged between 30 and 40 Years

Introduction. Polycystic ovary syndrome (PCOS) is a common disorder in reproductive age. This pilot study investigated the effects of myoinositol (MI) treatment on metabolic and cardiovascular profile in PCOS women over 30 years of age. Methods. Between 2015 and 2016, 50 women with diagnosis of PCOS by the Rotterdam Criteria were included in the study. All women received MI 2 g plus 200 μg of folic acid (Inofolic, Health Parsian, Iran; twice daily) for 3 months. Baseline and 3-month serum samples were taken after an overnight fast to evaluate the insulin resistance index (HOMA-IR), fasting glucose, and the levels of triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, systolic blood pressure, and diastolic blood pressure. Participants’ weight was measured before and after treatment and body mass index (BMI) was calculated. Results. The data showed a significant improvement in the serum level of insulin sensitivity and a reduction of cholesterol, LDL, and homocysteine after three months of treatment. Furthermore, blood pressure was significantly reduced in the treated patients. Three participants became pregnant during treatment. Conclusion. Results showed that supplementation with MI and folic acid in PCOS patients over 30 years of age could decrease the risk of cardiovascular problems by normalizing the metabolic profile

Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes

Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PM) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Previously, we described a simple method to graft PM brushes to Ti and further demonstrated conjugation of cell adhesion peptides (i.e., RGD) to the PM brushes to improve biocompatibility. The objective of this work was to investigate the ability of Ti substrates modified with PM-RGD brushes (PM-RGD) to immobilize complexes composed of branched polyethyleneimine and DNA plasmids (bPEI-DNA) and support SMD in NIH/3T3 fibroblasts. Transfection in NIH/3T3 cells cultured on bPEI-DNA complexes immobilized onto PM-RGD substrates was measured and compared to transfection in cells cultured on control surfaces with immobilized complexes including Flat Ti, PM brushes modified with a control peptide (RGE), and unmodified PM. Transfection was two-fold higher in cells cultured on PM-RGD compared to those cultured on all control substrates. While DNA immobilization measured with radiolabeled DNA indicated that all substrates (PM-RGD, unmodified PM, Flat Ti) contained nearly equivalent amounts of loaded DNA, ellipsometric measurements showed that more total mass (i.e., DNA and bPEI, both complexed and free) was immobilized to PM and PM-RGD compared to Flat Ti. The increase in adsorbed mass may be attributed to free bPEI, which has been shown to improve transfection. Further transfection investigations showed that removing free bPEI from the immobilized complexes decreased SMD transfection and negated any differences in transfection success between cells cultured on PM-RGD and on control substrates, suggesting that free bPEI may be beneficial for SMD in cells cultured on bPEI-DNA complexes immobilized on PM-RGD grafted to Ti. This work demonstrates that substrate modification with PM-RGD is a feasible method to enhance SMD outcomes on Ti and may be used for future applications such as tissue engineering, gene therapy, and diagnostics.Funding Agencies|Nebraska Research Initiative,; University of Nebraska-Lincoln Tobacco Settlement Funds; National Institutes of Health [1 DP2 EB025760-01]; Leibniz Institute of Polymer Research Dresden; National Science Foundation (CAREER) [CBET1254415]; Center for Nanohybrid Functional Materials [NSF EPS-1004094]; J.A. Woollam Company; USDA CSREES-Nebraska [NEB-21-146]</p

Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes

Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PM) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Previously, we described a simple method to graft PM brushes to Ti and further demonstrated conjugation of cell adhesion peptides (i.e., RGD) to the PM brushes to improve biocompatibility. The objective of this work was to investigate the ability of Ti substrates modified with PM-RGD brushes (PM-RGD) to immobilize complexes composed of branched polyethyleneimine and DNA plasmids (bPEI-DNA) and support SMD in NIH/3T3 fibroblasts. Transfection in NIH/3T3 cells cultured on bPEI-DNA complexes immobilized onto PM-RGD substrates was measured and compared to transfection in cells cultured on control surfaces with immobilized complexes including Flat Ti, PM brushes modified with a control peptide (RGE), and unmodified PM. Transfection was two-fold higher in cells cultured on PM-RGD compared to those cultured on all control substrates. While DNA immobilization measured with radiolabeled DNA indicated that all substrates (PM-RGD, unmodified PM, Flat Ti) contained nearly equivalent amounts of loaded DNA, ellipsometric measurements showed that more total mass (i.e., DNA and bPEI, both complexed and free) was immobilized to PM and PM-RGD compared to Flat Ti. The increase in adsorbed mass may be attributed to free bPEI, which has been shown to improve transfection. Further transfection investigations showed that removing free bPEI from the immobilized complexes decreased SMD transfection and negated any differences in transfection success between cells cultured on PM-RGD and on control substrates, suggesting that free bPEI may be beneficial for SMD in cells cultured on bPEI-DNA complexes immobilized on PM-RGD grafted to Ti. This work demonstrates that substrate modification with PM-RGD is a feasible method to enhance SMD outcomes on Ti and may be used for future applications such as tissue engineering, gene therapy, and diagnostics.Funding Agencies|Nebraska Research Initiative,; University of Nebraska-Lincoln Tobacco Settlement Funds; National Institutes of Health [1 DP2 EB025760-01]; Leibniz Institute of Polymer Research Dresden; National Science Foundation (CAREER) [CBET1254415]; Center for Nanohybrid Functional Materials [NSF EPS-1004094]; J.A. Woollam Company; USDA CSREES-Nebraska [NEB-21-146]</p