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Association study of rs2228570 SNP of the VDR gene with spermatogenesis disorders in infertile men in Iranian population
Mehdi Mohebi, Fateme Karami , Mohammad Hossein Modarressi, Seyed Mohammad Akrami ,
Volume 74, Issue 2 (5-2016)
Abstract

Background: Lots of vitamin D functions are mediated by its steroid family receptor (VDR). Vitamin D role in infertility is reported by significant fertility reduction in many male laboratory animals with vitamin D deficiency. The reason for reduced fertility in male VDR-null mouse model has been reported to be reduced sperm count and sperm motility. Vitamin D has effects on sperm motility, sperm-ovum coupling, and acrosome reaction stimulation. As VDR is expressed in human male reproductive system, the aim of the current study was to investigate the role of rs2228570 polymorphism of VDR gene in male infertility.

Methods: Investigation was done as a case-control study on infertile azoospermic or oligospermic men referring to Avicenna Research Institute from March 2014 to April 2015. Rs2228570 single nucleotide polymorphism (SNP) located in exon 1 of VDR gene was chosen according to its role on protein function. Blood sampling was done on cases and control groups and after DNA extraction the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) reaction was designed and performed on 100 normal cases, 100 azoospermic and 100 oigospermic control samples. Distribution of quantitative age variable was done using Student’s t-test and qualitative variables (genotype and allelic frequencies) was done using SPSS, ver. 22 (Chicago, IL, USA).

Results: Chi-square test didn’t show significant difference between two case groups and controls (Azoosperm and control P=0.5 and oligosperm and control P=0.09). Comparing CC genotype frequency with TT and CT genotypes (azoosperm and control P=0.48 OR=0.77, oligosperm and control, P=0.17 OR=0.77) and in comparing between TT genotype with CT and CC genotypes (azoosperm and control P=0.49 OR=3.03, oligosperm and control P=0.19 OR=7.21) the difference between these groups was not significant and didn’t increase the probability of disease and didn’t show protective role against it.

Conclusion: According to the findings, the association between rs2228570 polymorphism of vitamin D receptor gene and infertility was not significant and investigation of other polymorphisms might show a relationship with male infertility.


Effect of the time in administration of clomiphene on follicular growth, endometrium and pregnancy rates in PCOS patients
Mahtab Zeinalzadeh , Yousefreza Yousefnia Pasha , Zinatossadat Bouzari , Mohadese Mahdavi , Mojgan Naeimi Rad,
Volume 74, Issue 12 (3-2017)
Abstract

Background: Clomiphene citrate is very successful in inducing ovulation; there is usually a discrepancy between ovulation and pregnancy rate. If treatment is started early in the cycle this negative effect is reduced. The aim of this study was to investigate the effect of the time of administration of clomiphene citrate on follicular growth, endometrial thickness and ovulation and pregnancy rates in PCOS (Polycystic ovary syndrome) patients.

Methods: This randomized controlled trial study was performed on 115 PCOS (Polycystic ovary syndrome) women in Fateme Zahra Fertility and Infertility Research Health Center in April 2012. Patients randomly divided into two groups. Patients in the early group (No. 55) received 100 milligrams of clomiphene citrate tablet daily starting the next day after finishing medroxyprogesterone acetate tablet for 5 day, whereas the patient in the late group (No. 60) received 100 milligrams of clomiphene citrate tablet daily for 5 day starting on day 3 of the menstrual cycle. Then on follicular growth, endometrial thickness and ovulation and pregnancy rates by SPSS software, version 16 (Armonk, NY, USA) were compared in two groups.

Results: 36.4% of patients of early administration of clomiphene and 60% of patients in the later administration of Clomiphene were able to build dominant follicle. This difference was statistically significant (P<0.011). There was no statistically significant difference between the two groups on age, body mass index, duration of infertility. Findings showed that in the early group 14 (63.6%) and in the late groups 8 (36.4%) women who made dominant follicle, were pregnant. There was significant difference between these two groups (P<0.001). But, in the number of follicles, endometrial thickness and pregnancy rate, there were no significant difference. In the early administration of clomiphene, the pregnancy rate was 25.5%. However in the later administration of clomiphene it was 13.3% (P=0.882).

Conclusion: According to the results of this study, if the dominant follicle was made, with administration of clomiphene citrate in luteal phase the incidence of successful pregnancy is higher.

Hormonal profiling and clusterin gene expression in non-obstructive azoospermic patients
Azar Mardi Mamaghani, Seyed Jalil Hosseini, Elham Moslemi,
Volume 75, Issue 11 (2-2018)
Abstract
Background: Infertility is clinically defined as failure of a couple to conceive after one year of regular sexual intercourse and occurs in both males and females for various reasons. About half of the infertility causes is due to male factors such as azoospermia and the lack of sperm in the ejaculate. Azoosperima is divided into two types: Non-obstructive azoospermia (NOA) and obstructive azoospermia (OA). NOA is a type of male infertility caused by spermatogenesis defects. Therefore, investigating the factors involved in spermatogenesis, including hormones and genes, is one of the important aspects in understanding the mechanism of infertility in men. To this end, we aimed to investigate the expression of the clusterin gene expression and LH, FSH and testosterone hormone levels in the testicular tissue and blood of NOA patients, respectively.
Methods: The study population included 42 NOA infertile men referred to Royan Institute, Tehran, Iran in June 2016 to February 2017. Their blood samples were collected and testosterone, LH and FSH hormones were measured by ELISA. Afterwards, based on the biopsy results the patients were categorized into TESE+ (positive sperm retrieval) and TESE- groups. The genomic RNA was extracted from testicular tissue samples obtained from TESE surgery. After converting to cDNA, the clusterin gene expression was investigated by Real-time PCR technique. The achieved data was analyzed using SPSS software, version 18 (Armonk, NY, USA).
Results: According to Real-time PCR results, the expression level of clusterin gene in TESE+ group was significantly higher than TESE- group (P= 0.035). The mean of FSH and LH hormone levels in the TESE+ group was relatively lower than the TESE- group (P= 0.07 and P= 0.08), but there was no significant difference in the mean of testosterone hormone levels between the two groups (P= 0.66).
Conclusion: Based on the results of this study, the clusterin gene can have a role in spermatogenesis and by evaluating FSH and LH hormones in a larger non-obstructive azoospermic patient’s population significant statistical results can be achieved.

Metabolomics: a bird’s eye view of infertile men: review article
Niloofar Agharezaee , Rezvan Marzbani , Hassan Rezadoost , Saeideh Zamani Koukhaloo, Babak Arjmand , Kambiz Gilany ,
Volume 75, Issue 12 (3-2018)
Abstract
Infertility influences an estimated 20% of couples worldwide. The factors that can affect the fertility potential are equally distributed between men and women. Despite extensive research in male infertility, the etiology in majority of infertile men is unknown. In 2010, there was an opinion published in Nature asking a selection of leading researchers and policy-makers about what their future focuses will be in 2020. Metabolomics was mentioned as the leading omics technology by them. The word metabolomics has been defined almost 20 years ago. However, the clinical metabolomics history goes back to more than 1,000 years ago. The great Persian physician and philosopher Avicenna observed an individual urine changes during illness. Today, the color or smell changes are known to be caused by metabolites deregulation indicating metabolic diseases. Metabolomics approach is a systematic analysis of the unique pattern followed by a specific biochemical pathway that uses a biological material, e.g. spermatozoa or human seminal plasma. For the diagnosis of infertile men, the typical parameters of semen analysis are: sperm motility, sperm morphology, concentration and count. Human seminal plasma is a valuable biological source which was not used in the diagnosis of infertile men, unfortunately. To the best of our knowledge, there is no parameter for analysis of the human seminal plasma. Thus, the need for a novel parameter to diagnose infertile men is urgently needed. We recommend the use of seminal plasma in order to diagnose infertile men according to our previous research. Only a handful studies have used metabolomics approaches in the male infertility. In this study, we summarize the current research and our contribution to the field of male infertility and metabolomics. One of our main contributions has been to use metabolic profiling of seminal plasma from non-obstructive azoospermia to find 36 potentials biomarkers for detection of spermatogenesis. A search in the PubMed using keywords “metabolomics” and “infertility” shows only 59 publications. This demonstrates how newborn the metabolomics in its application for male infertility is. In this review article we have tried to have a comprehensive and specific approach to male infertility from a metabolomics perspective and related techniques.

Evaluation of gene expression of three adrenergic receptors in infertile women with poor ovarian response, candidate for IVF
Farideh Zafari Zangeneh , Mohammad Mehdi Naghizadeh , Maryam Bagheri , Masoumeh Dehghan ,
Volume 78, Issue 3 (6-2020)
Abstract
Background: Most studies show that 9 to 24% of people who are in in vitro fertilization (IVF) cycles are women who respond poorly to ovarian stimulation. Women with poor ovarian response (POR) are a group of infertile patients whose ovarian reserve, ovarian response to medication, and the quality of ovum are declining. Therefore, the number of female cycles, the number of fetuses from the oocyte and the rate of pregnancy in these women is reduced. The purpose of this study was to investigate the expression of three adrenoceptor receptor genes in the cumulus cells of women with poor ovarian response in culture medium.
Methods: This case-control study was conducted in two groups: study (POR) and control (oocyte donor's women) groups. POR diagnosis was performed by ESHRE Bologna criteria. After puncture of the follicles, cumulus-oocyte complex was collected and the cumulus cells (CCs) were isolated by enzyme and are counted with Neobar lamella and then were added in the culture medium. After completing the culture, RNA was extracted from cumulus cells and the RNA concentration was read by the Spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA). Then cDNA synthesized and primers designed for ADR-α1, 2 and ADR-B2 or gene expression by real-time polymerase chain reaction (PCR) technique. The research was done in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, from April to December 2017.
Results: Comparison of the results of ADR-α1, 2 gene expressions in cumulus cells showed a significant decrease, but ADR-B2 was not significant in two groups. Correlation coefficients also showed that there are relationship between three adrenoceptors and their effects on each other.
Conclusion: Our results showed that the decreased expressions of ADR-α1, 2 probably related to activation of the sympathetic system and release of the more neurotransmitter that lead to down-regulation of ADR-α1, 2 in the cell membrane of cumulus in culture medium.

The role of MMP9 C-1562T and MMP2 G1575A genetic variants in male infertility: review article
Rezvan Asgari, Mitra Bakhtiari,
Volume 78, Issue 6 (9-2020)
Abstract
Infertility as a vital process in human reproduction involves many couples worldwide. Although many genetic causes of infertility are known, the genetic basis of infertility in men is largely unknown. Therefore, the identification of genetic biomarkers in this field is important and genetic polymorphisms in key genes of the spermatogenesis pathway can be valuable biomarkers in this field. Gene's polymorphisms with specific genetic background and/or environmental factors can lead to the dysfunction in testicular function or the process of sperm production. Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that play an important role in extracellular matrix remodeling by activating gelatinases, collagenases, and proteolytic enzymes. These enzymes are essential for the regulation of cellular connections in the testis. Extracellular matrix degradation and connective tissue remodeling are important structural changes in germ cell migration that are controlled through important genes, including MMPs and their biological inhibitors. Given the important role of MMPs in the structural and functional characteristics of reproductive organs, genetic polymorphisms in MMP genes are significant because they can influence gene transcription and the biological function of proteins. Studies have shown that matrix metalloproteinases are involved in the degradation of extracellular matrix and play an important role in the process of spermatogenesis and sperm quality. This review article aims to evaluate the role of two common, functional MMP2 G1575A and MMP9 C-1562T polymorphisms in male infertility. The findings indicate that polymorphisms of MMP2 G1575A and MMP9 C-1562T can affect gene transcription, protein level, and enzymatic activity, and also, these variants can be as one of the genetic causes in male infertility among different ethnic populations. Therefore, identifying these molecular changes can help to adopt appropriates therapeutic and diagnostic measures as well as guide therapeutic approaches to intelligent therapies. To achieve a definitive conclusion and confirm the association of these polymorphisms with male infertility, evaluations of gene-gene and gene-environment interactions can be important for larger sample sizes of different ethnicities.
Evaluation of depression and anxiety in couples with infertility and related factors
, Seyedeh Reyhaneh Yousefi Sharami, Setare Nasiri, Shahrzad Aghaamoo, Abbas Ziari,
Volume 78, Issue 8 (11-2020)
Abstract
Background: Infertility is associated with high levels of stress which can pose a tremendous challenge on treatment. These psychological disorders such as depression and anxiety among the barrens are very important and have a crucial role as well. On-time detection and evaluation of such disorders are effective in the successful treatment of infertility. Some variables can interfere and influence on psychological occasions, such as education, age and duration of infertility. This study aims to investigate depression and anxiety on couples with infertility.
Methods: In this study, 60 infertile couples were enrolled. Thirty couples with male factors and 30 couples with female factors. The study is a cross-sectional study carried out in the Amiralmomenin Hospital of Semnan, Iran in 2016-2017. Symptoms of psychological disorders were documented via questioner. Date were entered into SPSS software, version 23 (SPSS Inc., Chicago, IL, USA), P<0.05 was significant.
Results: We figured out that 15% of women and 13% of men had clinical depression. Severe anxiety was found in 30% of women and 6% of men. We found that there is a significant correlation between depression and duration of infertility in women but not in men. Whereas there is not any significant relationship between both of the disorders and level of education in the patients.
Conclusion: This study showed that depression level among half of infertile women and one-third of infertile men were more than healthy men and women. One of the reasons could be family problems and pressure to get pregnant. The psychological burden of infertility can affect the whole life of the infertile couple. Fear of an ambiguous future after infertility treatment failure, expensive treatment and its outcomes can be so annoying for many men and women. Most of these problems are hidden from the eyes of the treatment team. Take a deep look at what infertile women and men say showed that they need the support of their spouses, friends and family, the medical team and insurance services.

The relationship between infertility and abortion with celiac disease in southern Iran: a cross-sectional study
Ramin Niknam, Laleh Mahmoudi,
Volume 78, Issue 9 (12-2020)
Abstract
Background: Celiac disease (CD) is a common disease caused by autoimmunity to the gluten protein. Although some studies have shown an association between infertility and abortion with CD, there are many risk factors that may influence this relationship that should be addressed in the researches. Therefore, we designed this study to evaluate this association with respect to these confounding factors.
Methods: This study was designed to investigate the association between infertility and abortion with CD in women who were referred to the celiac clinic in Fars province, from October 2017 to April 2020. CD was defined as an increase in serum levels of tissue transglutaminase antibodies and histological confirmation of a small bowel specimen, infertility with no pregnancy after 12 months of unprotected sex, and abortion with spontaneous termination of pregnancy before the 20th week.
Results: Out of 711 patients, 98 women with CD were eligible for inclusion. The mean age (SD) was 31.73 (7.52) ranging from 19 to 45 years. 27 (27.6%) and 39 (39.8%) patients had a history of infertility and abortion, respectively. According to Robust Poisson regression models, weight loss with a body mass index of less than 18.5 kg/m2 was significantly associated with infertility (PR=0.779, CI95%=0.640-0.950, P=0.013) and abortion (PR=0.794, CI95%=0.649-0.971, P=0.025), but other variables such as age, ethnicity, education level, gastrointestinal manifestations, tissue transglutaminase antibody level, histological severity, family history of CD, and history of cousin marriage were not significantly associated with infertility or abortion.
Conclusion: In this study, weight loss due to long-term malnutrition was suggested as an important risk factor for fertility problems in CD. There was no significant association between infertility and abortion with other variables such as the level of anti-transglutaminase antibody and histological findings. Therefore, routine use of antibody levels and evaluation of the severity of histological findings as criteria for predicting the risk of abortion or infertility in these patients is not recommended until further research is performed.

Evaluating the relationship between intrauterine insemination outcome and special causes of infertility
Shahideh Jahanian Sadatmahalleh, Firouzeh Ghaffari, Mohammad Reza Akhoond ,
Volume 78, Issue 11 (2-2021)
Abstract
Background: Common treatment for infertile couples is the use of controlled ovulation hyperstimulation (COH) with intrauterine inseminations (IUI). IUI is used in cases such as ovulatory dysfunction, cervical factor infertility, male subfertility, and unexplained infertility. In this study, we evaluated the relationship between IUI outcome and special causes of infertility.
Methods: This was a cross-sectional study and a sampling method was available in this study, from January 2014 to August 2016, 994 cycles in 803 infertile couples referred to Royan Research Institute in Tehran were analyzed. Inclusion criteria were: male factor infertility, combined causes, ovarian disease, and infertility of unknown cause. To evaluate pregnancy, 12-16 days after IUI, it was considered positive if pregnancy test followed by transvaginal ultrasound at week 4 after IUI were positive.
  Data were analyzed using SPSS software, version 20. T-test and chi-square were used to compare the case and control groups. Linear-by-linear test was also used to calculate the relationship between female age and clinical and multiple success rates. P<0.05 was considered significant for the results of these tests.
Results: The success rate of pregnancy in all cycles (16.5%) and live birth rate per cycle (14.5%) were calculated. The mean age in the pregnant group was significantly lower than that of the non-pregnant group (P = 0.01).  Our findings were: Infertility with unknown cause (290 people, 29.2%), male factor (395 people, 39.7%), ovulation disorders (201 people, 20.2%) [which include: decreased ovarian reserve (1 person) 0.5%), polycystic ovary syndrome (188 patients, 93.5%) and hypothalamic amenorrhea (12 patients, 6%)] and a combination of different factors (108 patients, 10.9%). There was also a significant relationship between the cause of infertility and clinical pregnancies (P<0.001). A Significant decrease in pregnancy success rate was observed with increasing infertility duration (OR=0.8, CI=0.8-0.9, P<0.001).
Conclusion: Women’s age, etiology of infertility, duration of infertility, irregular menstruation, semen volume, and gonadotropin dose were important factors in COH+IUI cycles.

Evaluation of demographic information and consequences of in vitro fertilization in pregnant women in 2019-2020
Elham Naghshineh, Minoo Movahedi , Hatav Tehrani , Maryam Hajhashemi , Ferdows Mehrabian, Fatemeh Jahani, Fedyeh Haghollahi,
Volume 79, Issue 12 (3-2022)
Abstract
Background: Assisted reproductive techniques have increased the chances of pregnancy for couples looking for a way to treat their infertility. To increase the effectiveness of these methods, studies are needed to identify the determinants of a successful pregnancy with these techniques.
Methods: The present study is a cross-sectional retrospective study that was performed on 253 couples who were referred for infertility treatment to the infertility clinic of Shahid Beheshti Hospital in Isfahan from April 2019 to March 2020 to evaluate the results of pregnancy in vitro fertilization. Demographic, clinical, and laboratory data from patient records were collected and entered into checklists.
Results: Out of 253 couples, eighty-five (33.6%) became pregnant by IVF. The mean age of women with successful pregnancies was 33.96±5.2 years and in the unsuccessful pregnancies was 35.84±5.07 years. The results of this study showed that women who had a successful pregnancy after IVF were significantly younger than women who did not have a successful pregnancy (P=0.006). In the classification of patients into two groups of positive and negative pregnancies, younger age, adequate vitamin D levels, and higher sperm motility were the determinants of pregnancy in the first period of fertilization (Fresh protocol). Also, the existence of a failed history of infertility treatment in couples has been introduced as a negative factor for IVF fertility. 13(15.9%) abortions occurred and 11(12.9%) infants who were born with this method needed intensive care.
Conclusion: Lower age at the time of fertilization, higher vitamin D levels, and more active sperms were found to have important and prognostic roles in the success of pregnancy by in vitro fertilization technique.
The results of the present study showed that, Increased unsuccessful treatment has been associated with the history of failed treatment. Therefore, to respond to the relationship between previous infertility treatments and success in subsequent pregnancies in the IVF process, It is recommended to conduct studies with larger sample size and at a higher time efficiency.

Success of gonadotropin replacement therapy in men with hypogonadotropin hypogonadism in urology and endocrinology clinics of Golestan Hospital in Ahvaz
Alireza Jahanshahi , Alireza Kheradmand, Mehrnoosh Zakerkish, Homeira Rashidi, Narges Goudarzian Khozani ,
Volume 80, Issue 10 (1-2023)
Abstract
Background: The treatment of male hypogonadotropic hypogonadism leading to infertility in men and caused by gonadotropin is the subject of the current thesis. In this research, particularly, the fertility rate has been noticed. However, changes in the secondary traits of testes size, induction of spermatogenesis, and hormonal activity have also been considered. this project is to investigate the effectiveness of the mentioned treatment in creating fertility in the spouses of patients and comparing it with other researches conducted in other centers of the world.
Methods: In this retrospective and descriptive-analytical study, men with isolated hypogonadotropic hypogonadism based on the normality of other pituitary axes who had a tendency to be fertile were studied. From November 2017 to February 2020, these patients had been referred to the doctor at the endocrinology and urology clinics of Ahvaz for fertility purposes. The initial test was based on clinical examinations and testosterone measurement and sperm count for the patients was recorded after the treatment. The treated patients simultaneously received HMG 75 units every other day (three times a week) and HCG 5000 units every other day. Hormonal evaluation and clinical examinations were assessed again.
Results: This research showed that the size of the testicles increased in 54.8% of these patients. Secondary characteristics (secondary hair growth) were developed in 88.9% of the patients. Spermatogenesis induction occurred in 36 patients, 29 of whom became fathers. Meanwhile, in 67.3% of patients, sexual desire and in 69.4% of them hormonal activity increased. In addition, it was observed that the response time to replacement therapy is more than 12 months in 47.5% of the patients. Moreover, 6.6% of the study samples had used assisted reproductive methods.
Conclusion: The results of this research indicate the timely initiation of treatment to improve infertility and treat hypogonadism among men.According to the results, it seems that the use of HMG and HCG in the treatment of hypogonadotropic hypogonadism disease is effective in creating secondary sexual characteristics and increasing hormonal activity and fertility.

The satisfaction of infertile patients with the quality of medical services in Tehran university of medical sciences hospitals during the year 2020-2021
Batool Hossein Rashidi, Maryam Bagheri., Ashraf Aleyasin, Ladan Kashani, Fatemeh Davari Tanha , Elham Feizabad , Fedyeh Haghollahi,
Volume 81, Issue 1 (4-2023)
Abstract
Background: Patient satisfaction is considered as one of the most important elements of the evaluation of healthcare centers. In this research, the level of satisfaction of infertile patients was evaluated.
Methods: This study is a cross-sectional descriptive study. The research population is infertile patients who referred to the infertility clinic (at least 4 visits) and hospitalized in four hospitals affiliated with the Tehran University of Medical Sciences. The satisfaction questionnaire was valid researcher-made which included 56 questions in 9 areas, and were collected from May 2021 to September 2022. In order to comply with the ethical principles in research, hospitals were named 1-4.The results were analyzed using the chi-square test or Fisher's exact test for qualitative variables and analysis of variance for quantitative variables in SPSS software, version 24 (SPSS Inc., Chicago, IL, US).
Results Three hundred–four infertile women in four hospitals were studied. The mean age of the participants was 33.8 years, with a standard deviation of 5.8 years. The average satisfaction with admission and discharge services, medical services, nutrition, accounting, and insurance services in the number-1 Hospital had the highest score, and the average satisfaction with nursing or midwifery services, diagnostic and therapeutic services (radiology/laboratory), hospital services, charter patient rights, management services, paid expenses in Hospital 4 received the most points. The mean score of satisfaction was the highest among those who visited the infertility clinic of Hospital 3 (161.54±21.41). Average satisfaction with admission and discharge services, medical services, nutrition, accounting, and insurance services in Hospital No. 1 had the highest score, and average satisfaction with nursing or midwifery services, medical diagnostic services (radiology/laboratory), hospital services, respecting the patient's rights, management services, paid expenses in hospital number 4 got the most points. The average of nursing or midwifery services, respecting the patient's rights, and hotelling in all hospitals received the highest score, respectively, and nutrition services and paid expenses received the lowest points (most dissatisfaction) (P<0.05).
Conclusion: The level of satisfaction of women referring to the infertility clinic in 35.9% of cases was considered to be at an appropriate and exceptional level, in 49.3% of cases it was at a partially appropriate level, and in 14.8% at an inappropriate level.

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