Research Performance in Reproductive Biomedicine: A National Scientometrics Study.

Recent achievements in reproductive biomedicine have led to a revolution in infertility treatment. A comprehensive understanding of the current status of reproductive medicine is necessary for the development of a forward-looking plan by health policymakers, based on fundamental requirements. This study is a systematic review of the Scopus database to assess reproductive biomedicine publications within Iran and compared to the rest of the world from 1990 to 2020. The data were categorized by geographical distribution across five continents. National data were assessed in comparison with the world and with neighboring countries. Finally, prominent national research institutes in the field of reproductive biomedicine in Iran were identified, and their contributions to the field highlighted. Of the five continents, the highest number of publications and citations is from Europe (36% publications and 41.5% citations). Corresponding numbers for the other continents are 32 and 33% for America, and 26 and 18.4% for Asia respectively. The remaining publications and citations were from Australia (3.8 and 4.1%) and Africa (2.6 and 3.1%). In a national analysis, the highest-ranking institutes in reproductive biomedicine are in Tehran province (50.9% of all Iranian publications), Shiraz (8.8%), Yazd (7.8%), Isfahan (7.1%), and Tabriz (6.9%). More specifically, Tehran University of Medical Science (15.9%), the Royan Institute (12.2%), Shahid Beheshti Medical University (10.1%), Shahid Sadoughi University of Medical Sciences (6.9%), and Tarbiat Modares University (6.7%) account for more than 50% of all Iranian scientific publications. In recent decades, reproductive biomedical research has grown significantly in Iran. Reviewing publications in this field helps health policy decision makers to monitor the direction of research and adjust investment in the treatment of infertility. In addition, it is necessary to expand and organize inter-organizational and international collaborations to improve the research, gain the benefits of different experiences, and engage in international multicenter studies.

CNFE-SE: a novel approach combining complex network-based feature engineering and stacked ensemble to predict the success of intrauterine insemination and ranking the features.

BACKGROUND: Intrauterine Insemination (IUI) outcome prediction is a challenging issue which the assisted reproductive technology (ART) practitioners are dealing with. Predicting the success or failure of IUI based on the couples' features can assist the physicians to make the appropriate decision for suggesting IUI to the couples or not and/or continuing the treatment or not for them. Many previous studies have been focused on predicting the in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcome using machine learning algorithms. But, to the best of our knowledge, a few studies have been focused on predicting the outcome of IUI. The main aim of this study is to propose an automatic classification and feature scoring method to predict intrauterine insemination (IUI) outcome and ranking the most significant features. METHODS: For this purpose, a novel approach combining complex network-based feature engineering and stacked ensemble (CNFE-SE) is proposed. Three complex networks are extracted considering the patients' data similarities. The feature engineering step is performed on the complex networks. The original feature set and/or the features engineered are fed to the proposed stacked ensemble to classify and predict IUI outcome for couples per IUI treatment cycle. Our study is a retrospective study of a 5-year couples' data undergoing IUI. Data is collected from Reproductive Biomedicine Research Center, Royan Institute describing 11,255 IUI treatment cycles for 8,360 couples. Our dataset includes the couples' demographic characteristics, historical data about the patients' diseases, the clinical diagnosis, the treatment plans and the prescribed drugs during the cycles, semen quality, laboratory tests and the clinical pregnancy outcome. RESULTS: Experimental results show that the proposed method outperforms the compared methods with Area under receiver operating characteristics curve (AUC) of 0.84 ± 0.01, sensitivity of 0.79 ± 0.01, specificity of 0.91 ± 0.01, and accuracy of 0.85 ± 0.01 for the prediction of IUI outcome. CONCLUSIONS: The most important predictors for predicting IUI outcome are semen parameters (sperm motility and concentration) as well as female body mass index (BMI).

Clinical aspects of infertile 47,XYY patients: a retrospective study.

47,XYY syndrome is a sex chromosomal anomaly in men, which may be associated with infertility and has an incidence of 0.1% of male births. The clinical and paraclinical characteristics of men suffering from this anomaly have not been fully described. In this retrospective study, we present 37 cases of 47,XYY infertile men with sperm counts varying from normal to azoospermia, referred to the Genetics Laboratory at the Royan Institute, Iran. Thirteen individuals were mosaic and 24 non-mosaics. Non-mosaic patients were classified as azoospermic (nine cases) and normospermic/oligozoospermic men (15 cases). Two of the non-mosaic and three mosaic patients had secondary infertility. In addition, 13 of them underwent IUI, IVF or ICSI, and in seven cases, there was a biochemical pregnancy. The remaining 14 patients did not have ART. The 47,XYY syndrome is relatively unusual and can be missed clinically because of the lack of symptoms and of diverse phenotypes. Diagnosis of this aneuploidy can provide valuable data for counselling and early management of the patients who undergo fertility evaluation.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. RESULTS: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. CONCLUSIONS: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).

Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a debilitating disease that typically affects a large number of the middle-aged and elderly population. Current treatment strategies have had limited success in these patients. This study aims to investigate the safety of treatment with autologous bone marrow (BM)-derived mesenchymal stem cells (MSCs) transplanted in patients with OA of the knee, ankle, or hip. METHODS: We enrolled 18 patients with different joint involvements (knee, ankle, or hip OA) and one was lost to follow-up. BM samples were taken from the patients, after which BM-derived MSCs were isolated and cultured. Each patient received one MSC injection. Patients were followed with clinical examinations, MRI and laboratory tests at 2, 6, 12, and 30 months post-transplantation. RESULTS: We observed no severe adverse events such as pulmonary embolism, death, or systemic complications. A limited number of patients had very minor localized adverse effects such as rash and erythema. There were no changes in liver function, hematology, or biochemistry analyses before and after cell therapy. There was no evidence of tumor or neoplastic changes in the patients during the 30-month follow-up period. All patients exhibited therapeutic benefits such as increased walking distance, decreased visual analog scale (VAS), and total Western Ontario and McMaster Universities OA Index (WOMAC) scores which were confirmed by MRI. CONCLUSIONS: Our study has shown that injection of MSCs in different OA affected joints is safe and therapeutically beneficial. However, further studies are needed with larger sample sizes and longer follow-up periods to confirm these findings.

Can permeable super oxide dismutase mimetic agents improve the quality of frozen-thawed ram semen?

This study was carried out to assess the effects of MnTBAP, a cell permeable antioxidant, on motility, membrane integrity, capacitation status and in vitro fertilization ability of frozen-thawed ram semen. Fresh semen ejaculates were collected with artificial vagina from five rams, mixed and divided into five equal fractions, and diluted (1:20 v/v) with commercial extender, Bioxell®, containing 0 (control), 50, 100, 150 and 200 µM of MnTBAP. All diluted sperm suspensions were cooled to 5°C for 2h followed by transfer into 0.5 ml French straws before being stored in liquid nitrogen. The results showed that MnTBAP supplementation of extender improved ram semen quality in a dose-dependent manner. Accordingly, the extender supplemented with 150µM MnTBAP resulted in higher sperm motility and improved acrosomal membrane integrity compared to control. However, further supplementation (200µM) with MnTBAP not only did not improve the results but inversely affected motility and membrane integrity. The results of in vitro fertilization (IVF) indicated that the presence of MnTBAP in semen extender has a marginal beneficial effect on developmental competence of inseminated oocytes, though this improvement was not significant. In conclusion, this study demonstrated that semen extender supplemented with MnTBAP can reduce the oxidative stress provoked by freeze/thaw processes. Moreover, beneficial effect of 100 µM of MnTBAP on preservation of spermatozoa in a non-capacitated state post freezing, an important criterion for in vitro or in vivo fertilization, was observed. However, at 150 µM of MnTBAP, the harmful effects of cryopreservation on membrane integrity were decreased. Regarding to importance of non-capacitated spermatozoa during IVF or artificial insemination, the optimum MnTBAP concentration appears to be 100 µM for commercial ram semen extender tested here.