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عضویت

جستجوی مقالات مرتبط با کلیدواژه « recurrent pregnancy loss » در نشریات گروه « پزشکی »

  • Manar Dahash *, Azhar Al-Turaihi, Qays Alkhafaji, Bushra Al Musawi
    Background & Objective

     Consecutive miscarriages are considered recurrent pregnancy loss (RPL), which affects 1-2% of women and may be unpleasant for couples attempting to conceive. Patients and healthcare professionals confront a difficult situation in this regard. The present study was conducted with aim to investigate the potential role of anti-mullerian hormone (AMH) in predicting the rate of live birth in women with RPL who are trying to conceive naturally.

    Materials & Methods

     This cross-sectional study involved 60 pregnant women from Baghdad and Al-Najaf infertility centers (June 2022 - June 2023), recording age, gestational age, miscarriage frequency, fetal outcomes, parity, and number of live births. AMH levels were measured using Minividas Biomeriux 2020 (France), followed by assessments of FSH and Estradiol. Low AMH prompted further tests for autoimmune and genetic disorders. Inclusion criteria were all pregnant women with spontaneous or induced pregnancies and a history of recurrent miscarriage. Exclusions were those with unexplained pregnancy loss and male factor infertility.

    Results

     The mean age of participants was 32.8 years, with 46.7% aged 21-30 years. AMH levels were higher in females aged 21-30 years, those with two abortions, and those with two parities. A significant correlation was observed between age over 40 years and a history of four abortions.

    Conclusion

     AMH emerges as a crucial biomarker that intertwines with various aspects of female reproductive health, including miscarriage history, age, and parity. Future research is needed to deeply investigate the mechanisms behind these associations and offer more comprehensive insights into female fertility dynamics.

    Keywords: Anti-Mullerian Hormone, Predictor, Live Birth, Recurrent Pregnancy Loss}
  • Zahra Panahi, Razieh Akbari, Marjan Ghaemi
    Background

    The research combined different bibliometric techniques to analyze systematically recurrent pregnancy loss (RPL) documents from 1970 to 2023.

    Methods

    Overall, 1287 documents from the Web of Science database associated with recurrent pregnancy loss between 1970 and 2023 were identified for more than 300 journals. The data were analyzed with VOSviewer software.

    Results

    The trend of paying attention to the topic of RPL can be divided into three periods. The number of publications on RPL increased significantly after 2010. Most of the papers were published in Obstetrics and Gynecology and Reproductive Biology areas. Utilizing co-occurrence and co-citation analysis, our study found that the most influential documents mapped the knowledge structure, and projected future research directions. The co-occurrence analysis showed five clusters even though the co-citation analysis designates four.

    Conclusion

    RPL has increased in recent years exponentially and some areas were explained carefully, therefore these results could be used as a research agenda for the future direction by a range of interested beneficiaries.

    Keywords: Recurrent Pregnancy Loss, Bibliometric, Co-Occurrence, Co-Citation, Web Of Science Database}
  • Hamed Akhavizadegan*
    Purpose

    This review presents a clinical approach to genetic issues in male infertility. Unlike other related reviews that discuss different types of genetic diseases (such as Klinefelter and Down syndrome), this review focuses on the clinical features that result from these genetic problems (such as azoospermia and oligospermia).

    Methods

    A narrative review of the clinical literature in PubMed was conducted using keywords related to male infertility, recurrent pregnancy loss, recurrent in vitro fertilization failure, and genetics. The search included articles with English reviews published online after 2020. Headlines were defined based on the available literature, and after a critical review of each manuscript, clinical facts were classified under the corresponding headlines, and a primary draft was written.

    Results

    29 relevant articles were selected from the search. According to the literature, there are clinical genetic approaches for azoospermia, severe oligospermia, severe teratospermia, severe asthenospermia, recurrent miscarriage, and recurrent in vitro fertilization failure.

    Conclusion

    Although many mutations that can affect male fertility and spermogram have been identified, only a few have clinical predictive value.

    Keywords: Male Infertility, Genetics, Recurrent Pregnancy Loss, Recurrent In Vitro Fertilization Failure}
  • مرتضی رئیسی، مهدی یوسفی، جواد احمدیان هریس، شهلا دانایی، محمد توفیقی فرد، پویا بهلولی، لیلی عاقبتی ملکی*
    زمینه

    سقط مکرر بارداری به صورت حداقل دو سقط بالینی متوالی قبل از هفته بیستم بارداری تعریف می شود. در این مطالعه microRNA-1 و microRNA-1229 را در بیماران سقط مکرر قبل و بعد از درمان با لنفوسیت در مقایسه با گروه شاهد بررسی کردیم.

    روش کار

    ابتدا رضایت نامه کتبی و آگاهانه از جامعه هدف این مطالعه که افراد مبتلا به RPL مراجعه کننده به بیمارستان بین المللی ولیعصر بودند، اخذ شدند. طبق پروتکل استاندارد، تعداد 2×107 به صورت زیر جلدی به بیماران تزریق گردید. برای بررسی میزان بیان مولکول های hsa-miR-1 و hsa-miR-1229 از تکنیک Real-time PCR استفاده شد.

    یافته ها

    سطح بیان ژن micro-RNA 1 در زنان RPL قبل از لنفوسیت درمانی 2.030±1.445 و سطح بیان ژن همان micro-RNA پس از لنفوسیت درمانی مادر 1.101±0.4780 بود. همچنین میزان بیان micro-RNA 1229 در این زنان قبل از درمان 0.6296±2.100 و بعد از درمان با لنفوسیت 1.247±0.9631 گزارش شد. این میزان بیان ژن در گروه کنترل برای ژن های micro-RNA 1 و micro-RNA 1229 به ترتیب 0.08334±1.000 و 0.08091±1.000 است.

    نتیجه گیری

    میکرو RNA های hsa-miR-1229 وhsa-miR-1 نقش مهمی در افزایش فاکتورهای التهابی و میزان موفقیت و شکست بارداری را نشان داد. استفاده از درمان لنفوسیت تراپی می تواند عملکرد سلول ها در القای تنظیم سیستم ایمنی از طریق کاهش بیان میکرو RNA های ذکر شده گردد.

    کلید واژگان: لنفوسیت درمانی, میکرو RNA, التهاب, سقط مکرر}
    Mortaza Raeisi, Mehdi Yousefi, Javad Ahmadian Haris, Shahla Danaii, Mohammad Tofighifard, Pouya Bahlouli, leili Aghebati-Maleki*
    Background

    Recurrent pregnancy loss is defined as at least two consecutive clinical pregnancy losses before 20th week of gestation. In this study, we investigated microRNA-1 and microRNA-1229 in recurrent miscarriage patients before and after lymphocyte therapy in comparison to control group.

    Methods

    First, a written and informed consent will be obtained from the target population of this study, who are people with RPL referring to Waliasr International Hospital. According to the standard protocol, the number of 2×107 is injected subcutaneously to patients. Real-time PCR technique will be used to check the expression level of microRNA-1 and microRNA-1229.

    Results

    The gene expression level of micro-RNA 1 in RPL women before of lymphocyte therapy was 2.030±1.445 and the gene expression level of the same micro-RNA after the lymphocyte therapy of the mother was 1.101±0.4780. Also, the expression level of micro-RNA 1229 in these women was reported to be 2.100±0.6296 before treatment and 1.247±0.9631 after treatment with lymphocytes. This level of gene expression in control group, for micro-RNA 1 and micro-RNA 1229 genes is 1.000±0.08334 and 1.000±0.08091, respectively.

    Conclusion

    The results of our study showed a noticeable decrease in the gene expression of microRNAs under study, both microRNAs 1 and 1229, in women with a history of three consecutive injections of the father's subcutaneous lymphocytes.

    Keywords: lymphocyte therapy, MicroRNA, Inflammation, Recurrent Pregnancy Loss}
  • Tooba Farazmand, Raheleh Rahbarian, Mitra Jalali, Amirali Ghahremani, Abdollah Razi, Hasan Namdar Ahmadabad*
    Background

    The objective of this study was to compare the levels of vitamin D in non-pregnant women with a history of recurrent pregnancy loss (RPL) who were seropositive or seronegative for autoantibodies (autoAbs).

    Methods

    The study examined 58 RPL patients with autoAbs (ANA, anti-TPO, or APAs), 34 RPL patients without autoAbs, and 58 healthy women with prior successful pregnancies and without autoantibodies. The levels of 25 (OH) D were measured using the sandwich ELISA technique.

    Results

    Our results showed insufficient serum 25(OH) D levels in study groups, with significantly lower levels observed in RPL patients with or without autoAbs compared to healthy women (P=0.0006).  In addition, RPL patients with autoAbs had significantly lower 25(OH) D levels compared to RPL patients without autoAbs. We also found that serum levels of 25(OH) D in RPL patients with autoAbs were significantly lower than in RPL patients without autoAbs (20.51 ± 1.15 ng/ml Vs. 23.69 ± 0.74 ng/ml, P=0.0356). Further analysis indicated that RPL patients who were positive for ANA, and APAs, except anti-TPO, had significantly lower than 25(OH)D serum levels than RPL patients without autoAbs.

    Conclusion

    These findings suggest that RPL patients, especially those with APAs or ANA, have lower vitamin D levels compared to healthy women. This may indicate a link between maternal immune dysregulation due to vitamin D deficiency and the presence of autoantibodies in RPL.

    Keywords: Vitamin D, Recurrent pregnancy loss, antinuclear antibody, Antiphospholipid antibody, Anti-thyroid peroxidase}
  • فاطمه منتظری، مسعود تجملیان، الهام السادات حسینی، سید مهدی حسینی*

    سقط مکرر حاملگی (RPL) حدود 2 تا 3 درصد از زنانی را که قصد باردار شدن دارند، تحت تاثیر قرار می دهد. در حالی که برخی از عوامل موثر در RPL شناسایی شده اند، علت تقریبا نیمی از موارد ناشناخته باقی مانده است. عوامل ایمونولوژیک به عنوان یکی از علل بالقوه چنین سقط های جنینی مطرح شده است. با این حال، ردیابی عوامل مشترک منجر به RPL دشوار است زیرا هویت ژنومی فردی جنین های سقط شده در یک خانواده مانند سایر خواهران و برادران متفاوت است. عوامل ایمنی دخیل در پاتوژنز سقط جنین عموما ناشی از عملکرد دو عامل است: سیستم ایمنی مادر که به پس زمینه ژنومیک او نسبت داده می شود، و یا منشا جنینی دارند که پس زمینه ژنومی مادر و پدر که ژنوم جنین را تشکیل می دهند، در ایجاد آن دخیل می باشد.

    کلید واژگان: سقط مکرر حاملگی, عوامل ایمونولوژیک, عوامل ژنومی, رابط جنینی-مادری}
    Fateme Montazeri, Masoud Tajamolian, Elham Sadat Hosseini, Seyed Mehdi Hoseini*

    Recurrent pregnancy loss (RPL), which is also known as repeated miscarriage, affects around 2-3% of women who are trying to conceive. While some factors contributing to RPL have been identified, the cause of almost half of all cases remains unknown. Immunological factors have been proposed as one of the potential causes of such miscarriages. However, it is hard to track the common factors leading to RPL since the individual genomic identity of aborted fetuses is different in a family like other siblings. The immunological factors involved in the pathogenesis of miscarriage generally result from either the function of the maternal immune system attributable to her genomic background or the fetal origination established by both maternal and paternal genomic backgrounds that constitute the fetal genome.

    Keywords: Fetal-maternal interface, Genomic factors, Immunologic factors, Recurrent pregnancy loss}
  • Zahra Sadeghi Jam, Zahra Tahmasebi Fard *
    Background
    Hormones such as prolactin, by influencing expression of the endometrial genes, play a pivotalrole in embryo implantation and development. The present study aimed to evaluate serum level of prolactin andits effect on altering expression level of colony-stimulating factor-1 (CSF-1) and colony-stimulating factor-1 receptor(CSF-1R) genes in endometrial tissue during in vitro fertilization (IVF) pregnancy in the infertile womenand recurrent pregnancy loss (RPL), compared to fertile women, who lost their pregnancies at gestational age<20 weeks.
    Materials and Methods
    In this case-control study, 40 infertile women, 40 IVF pregnant women with RPL and 40fertile women who lost their pregnancies at <20 weeks of gestation for unknown reasons were selected. Prolactinserum level was assessed using ELISA technique and expression of CSF-1 and CSF-1R genes was determined inendometrial tissue, using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
    Results
    Mean prolactin level of the infertile group was 24.38 ± 1.43 ng/mL and it had statistically significantrelationship with the fertile group (P<0.001). Expression level of the CSF-1 and CSF-1R genes were higher in thefertile than infertile groups by 2.88 times (P<0.0001) and 2.64 times (P<0.0001), while it was respectively 2.28(P<0.0001) and 1.69 (P<0.0001) times higher compared to the RPL group. Risk factors for pregnancy loss, suchas aging, increased body mass index (BMI), smoking and diabetes caused decreasing changes in gene expression(CSF-1 and CSF-1R) and the differences were statistically significant, except in the infertile group.
    Conclusion
    The present study showed a significant relationship of CSF-1 and CSF-1R expression levels with pregnancyloss. Risk factors such as aging, obesity, smoking and diabetes decreased both genes expression levels.
    Keywords: genes, infertility, Miscarriage, Prolactin, Recurrent Pregnancy Loss}
  • Mohammad Reza Javan, Bahareh Moghimian-Boroujeni, Hossein Ayatollahi, Amirali Ayatollahi, Nafise Amini, Elham Jafaei, Maryam Sheikhi, Narjes Soltani *
    Background &
    Objective
     Recurrent pregnancy loss (RPL) is the occurrence of three or more miscarriages before the 20th week of pregnancy. Thrombophilia factors are one of the common causes of RPL.Materials &
    Methods
     This retrospective study was performed on women with miscarriages. 620 patients’ documents with pregnancy loss were investigated. Based on the number of pregnancy loss, the women were divided into a control group with less than three miscarriages (212) and RPL group (180). Cytogenetics analysis and thrombophilia factors polymorphism tests were performed for all patients.
    Results
     In the analysis, none of the studied polymorphisms (MTHFR 677 C⁄T /Factor V Leiden /Prothrombin G20210A/ ACE I/D/ PAI-1) showed a significant relationship between Control and RPL groups (P-value ˃ 0.05). Cytogenetic analysis showed 2 numerical and 9 structural abnormalities among both groups. Statistical analysis indicated a significant association between the number of abortions and age (P value= 0.005, r= 0.139). We even realized that there was a significant relationship between polymorphism number and recurrent number of miscarriages (P value= 0.018, r= 0.6).
    Conclusion
    We showed that polymorphisms analysis for thrombophilia factors is a more precious test than cytogenetics analysis (study of the banded pattern of chromosomes during metaphase of the cell cycle). We even indicated that no association was found between thrombophilia polymorphisms in the control and RPL groups. This means that screening for Factor V Leiden, prothrombin G20210A, MTHFR C677T, ACE I/D, and PAI-1 and cytogenetic analysis in patients with a history of RPL is not recommended.
    Keywords: Thrombophilia factors, Cytogenetic, Recurrent Pregnancy Loss, Polymorphism, Chromosomal Abnormalities}
  • Sujithaa Nagarajan MD*, Suma Hottigoundar, Latha Chaturvedula
    Background

    The present study aims to assess chromosomal instabilities between fertile couples and couples with recurrent pregnancy loss (RPL) and the causative relation of chromosomal instabilities with RPL.

    Methods

    A case-control study was performed with a study sample of 27 couples with a history of RPL who attended the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) and twenty-seven healthy fertile couples as controls. The procedure done was Cytokine Blocked Micronucleus Assay (CBMN). After obtaining consent and details of the couple, 3 ml of heparinized blood was collected from cases and controls. Cases comprising couples with RPL (gestational age ≤ 24 weeks) were included, and couples with a history of diabetes mellitus, thyroid disorders, and hypertension were excluded. Among cases, women with a history of two or more two spontaneous abortions ≤ 24 weeks of gestation were selected. Blood was collected and assessed from both male and female partners. The lymphocytes were cultured per the standard protocol and were screened as the number of micronuclei per 1000 binucleate cells under X 200 magnification in CBMN.

    Results

    Chromosomal instabilities in the form of micronuclei in cases were found to be 7.52±3.99 and 0.07±0.26 in controls (p˂0.05). A statistically significant difference was revealed among those with and without chromosomal instability.

    Conclusion

    Chromosomal instability serves as a significant causative factor for those couples leading to pregnancy losses

    Keywords: Chromosomal instabilities, Micronucleus assay, Recurrent pregnancy loss}
  • نرجس نوری، فرنوش سادات قاسمی هاشمی، جاوید دهقان، مرضیه قاسمی*
    مقدمه

    سقط مکرر به وقوع 2 یا تعداد بیشتر سقط پشت سر هم قبل از هفته 20 بارداری اطلاق می شود که دارای شیوع بالایی می باشد و شناسایی علل و فاکتورهای موثر بر آن امری ضروری است، لذا مطالعه حاضر با هدف بررسی فراوانی فاکتورهای مختلف موثر بر سقط در بیماران با سابقه سقط مکرر انجام شد.

    روش کار

    این مطالعه مقطعی بر روی 280 نفر از زنانی که دارای حداقل 2 مورد سقط جنین زیر 20 هفته بودند و در سال 97-1396 به تنها مرکز درمان ناباروری در استان سیستان و بلوچستان مراجعه کرده بودند، انجام شد. جمع آوری داده های مربوط به سقط بر اساس پرونده بیماران بود. تجزیه و تحلیل داده ها با استفاده از نرم افزار آماری SPSS (نسخه 20) و آزمون های کلوموگروف - اسمیرنوف با اصلاح لی لی فرس، تی دانشجویی، من ویتنی و دقیق فیشر انجام شد. میزان p کمتر از 05/0 معنی دار در نظر گرفته شد.

    یافته ها

    بیشترین فاکتورهای مشاهده شده مربوط به اختلالات آناتومیکی رحم (64/44%) و سپس سقط خود به خودی با علل ناشناخته (93/38%) بود. اختلالات آندوکرین (35%)، علل مردانه (43/6%)، آندومتریت مزمن (21/8%)، اختلالات ژنتیکی (57/3%)، ترومبوفیلی ارثی (86/2%) و عوامل ایمونولوژیکی (43/1%) در رتبه بعدی بودند.

    نتیجه گیری

    شایع ترین اختلالات منجر به سقط مکرر در مرکز ناباروری مولود زاهدان، اختلالات آناتومیکی رحم (46/44%) و سپس سقط خودبه خود با علل ناشناخته (93/38%) بود، اما اختلالات اندوکرینی (35%) پس از آن شایع ترین علل بود. در صورت تشخیص و درمان به موقع ممکن است بتوان میزان سقط مکرر را کاهش داد.

    کلید واژگان: اختلالات آناتومیکی, آندوکرین, آندومتریت, ترومبوفیلی ارثی, سقط مکرر}
    Narjes Nouri, Farnoosh Sadat Ghasemi Hasemi, Javid Dehghan, Marzieh Ghasemi *
    Introduction

    Recurrent pregnancy loss refers to the occurrence of two or more consecutive abortions before the 20th week of pregnancy, which has a high prevalence and it is necessary to identify the factors affecting it. Therefore, this study was performed with aim to investigate the frequency of various factors affecting pregnancy loss in patients with history of recurrent pregnancy loss.

    Methods

    This cross-sectional study was performed on 280 women with at least two abortions less than 20 weeks who had referred to the only infertility treatment center in Sistan and Balouchestan province in 2017-2018. Data related to abortion was collected based on the patients' file. Data were analyzed using SPSS software (version 20) and Kolmogorov-Smirnov test with lilliefors correction, Student t, Mann-Whitney and Fisher's exact tests. P<0.05 was considered statistically significant.

    Results

    The most common causes of recurrent pregnancy loss included: uterus anatomical abnormalities (44.64%) and then spontaneous abortion with unexplained causes (38.93%). Endocrine causes (35%), male causes (6.43%), chronic endometritis (8.21%), genetic causes (3.57%), inherited thrombophilia (2.86%), and immunological causes (1.43%) were in the next ranks..

    Conclusion

    The most common disorders leading to recurrent abortions in Moloud Infertility Center of Zahedan were uterus anatomical disorders (44.46%) and then spontaneous abortions with unknown causes (38.93%) but endocrine disorders (35%) was the next most common cause. In case of timely diagnosis and treatment, it may be possible to reduce the rate of recurrent abortion.

    Keywords: Anatomical disorders, endocrine, Endometritis, Inherited thrombophilia, Recurrent pregnancy loss}
  • رضوان حاتمی، سولماز منیری جوادحصاری*، جعفر محسنی، ناصر پولادی
    مقدمه

    زنان با بیش از 2 بار تجربه سقط جنین، مبتلا به سقط خودبه خودی مکرر هستند که حدود 4/1-8/0% زوجین را دربرمی گیرند. ژن HULC به عنوان یک RNA غیررمزگذار بسیار مهم در سرطان کبد شناسایی شده و بعدها ارتباط آن با برخی از بیماری ها شامل سقط جنین مورد توجه قرار گرفت. مطالعه حاضر با هدف بررسی ارتباط چندشکلی تک نوکلیوتیدی G>A rs17144343 در ژن HULC با استعداد سقط های خودبه خودی مکرر در جمعیت زنان آذربایجان شرقی انجام شد.

    روش کار

    در این مطالعه مورد- شاهدی که در سال های 99-1398 انجام گرفت، DNA ژنومی از خون محیطی 150 فرد بیمار و 150 فرد سالم به روش رسوب نمکی استخراج شد و ژنوتیپ افراد با استفاده از Tetra-ARMS-PCR تعیین شد. داده های ژنوتیپی با استفاده از بسته نرم افزاری آنلاین جاواستات و SPSS  (نسخه 23) مورد تجزیه و تحلیل آماری قرار گرفت.

    یافته ها

    توزیع ژنوتیپی rs17144343 برای ژنوتیپ های GA  وGG  به ترتیب در گروه بیماران 7/24% و 3/75% و در گروه کنترل 2% و 98% به دست آمد. همچنین فراوانی آللA  در افراد مبتلا 4/12% و در گروه شاهد 1% بود. میان استعداد بروز سقط مکرر و چندشکلی G>A rs17144343 ژن HULC ارتباط معنی داری وجود داشت (001/0>p). همچنین در بررسی ارتباط این چندشکلی با برخی ویژگی های بالینی و پاتولوژیک، ارتباط معنی داری میان ژنوتیپ های این لکوس و رابطه خویشاوندی والدین زوجین وجود داشت (003/0=p).

    نتیجه گیری

    میان چندشکلیrs17144343  ژن HULC و استعداد ابتلاء به سقط خودبه خودی مکرر ارتباط معنی داری مشاهده شد. با این وجود، مطالعات بر روی نمونه جمعیتی بزرگ تر می تواند در تایید بیشتر این یافته موثر باشد.

    کلید واژگان: چندشکلی تک نوکلئوتیدی rs17144343, ژن lncRNA HULC, سقط خودبه خودی مکرر}
    Rezvan Hatami, Solmaz Moniri Javadhesari *, Jafar Mohseni, Nasser Pouladi
    Introduction

    Women who experience more than two miscarriages suffer from recurrent pregnancy loss(RPL) which involves about 0.8% to 1.4% of couples. The lncRNA HULC gene was first discovered for its significant regulatory function in Hepatocellular carcinoma and then was considered in other diseases including RPL. The present study was performed with aim to investigate the association of G>A single nucleotide polymorphism of rs17144343 in HULC gene with susceptibility to recurrent miscarriages in women population of Eastern Azerbaijan of Iran.

    Methods

    In this case-control study which was performed in 2019-2020, genomic DNAs of 150 patients and 150 healthy individuals were extracted from the peripheral blood samples by salting-out method. Then, genotyping of rs17144343 locus was determined by TETRA-ARMS-PCR assay. Finally, the genotyping data were statistically analyzed using the software package javastat online statistics and SPSS (version 23).

    Results

    The genotypic distribution of rs17144343 for GA and GG genotypes were respectively 24.7% and 75.3% for cases and 2% and 98% for the control group. The frequency of allele A in controls was 1% and in case individuals was 12.4%. There was a significant relationship between the risk of recurrent pregnancy loss and rs17144343 polymorphism of HULC gene (P<0.001). Also, by considering some clinical and pathological characteristics, it was revealed that there is a significant relationship between genotypes and the familial relationship between the couple's parents (P=0.003).

    Conclusion

    The results obtained in his study demonstrated that G>A polymorphism of rs17144343 in HULC gene has a significant role in susceptibility to recurrent pregnancy loss, but larger sample studies are required to further verify this finding.

    Keywords: LncRNAHULC gene, Recurrent pregnancy loss, rs17144343 Single-nucleotide polymorphism}
  • Hourieh Khani, MohammadAli Hosseinpour Feizi*, Jafar Mohseni, Mehdi Haghi, Reza Safaralizadeh
    Objective

    The objective of this research was focused on the development of new organoclay based composite that serves as both antibacterial and dye removing agent for the treatment of microbial and dyes contaminated water from the source.

    Material and Methods

    The cation exchange capacity (CEC) of the kaolinite was improved through acid treatment. Chlorhexidine- loaded zinc- kaolinite was prepared via adsorption of chlorhexidine acetate (0.5 mmol/L) on zinc-kaolinite. The composites were characterized using Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX). The antibacterial assays of the composites were conducted against Staphylococcus aureus (S. aureus) and Salmonella typhi (S. typhi) using disc diffusion technique (DDT), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC).

    Results

    The CEC value of the acid treated kaolinite (Kaot2) was improved from 9.26 + 0.82 to 13.43+1.61 meq/100g, the morphology of the composite remains intact and indicate the presence of Zinc (Zn) after formulation. The target composite (Chx-Zn-Kaot2) shows its effectiveness against S. aureus and S. typhi showing the inhibition zones of 26 mm and 1.5 mm respectively. Similarly, MIC, with 120 mg/mL inhibit both organisms while MBC revealed that the target composite, 60 mg/mL kills S. aureus and 120 mg/mL kills S. typhi respectively.

    Conclusion

    The formulated target composite is a good candidate for the treatment of drinking water contaminated with such microorganisms and can be able to remove substantial content of dyes.

    Keywords: MTHFR C677T, MTHFR A1298C, FV G1691A, FII G20210A, PAI-1 -675 4G, 5G, Recurrent pregnancy loss}
  • Masoud Habibi, Zohreh Fakhari Zavareh, Behzad Abbasi, Vahid Esmaeili, Abdolhossein Shahverdi, MohammadAli Sadighi Gilani, Marziyeh Tavalaee *, MohammadHossein Nasr-Esfahani
    Background

    Increased sperm DNA damage is known as one of the causes of recurrent pregnancy loss(RPL) which can be due to increased levels of oxidative stress. In this study, the effect of alpha-lipoic acid (ALA) as an antioxidant soluble in water and fat was investigated on sperm parameters and sperm function tests in couples with a history of RPL.

    Materials and Methods

    In this preliminary study, a total of 37 patients (n=12 and n=25 for placebo and ALA groups, respectively) were considered. Men with high sperm DNA damage were treated with ALA (600 mg/day) or placebo for 80 days. Semen samples were acquired from the participants before initiation and after completion of the medication course and assessed regarding conventional sperm parameters, DNA damage/integrity, intracellular oxidative stress, lipid peroxidation, and seminal antioxidant characteristics. Individuals were further followed up for twelve months for pregnancy occurrence and outcomes. Finally, after excluding patients with no history of RPL, the data was analyzed.

    Results

    No statistically significant difference was observed between the baseline measures except for seminal volume. However, after the intervention, the mean sperm DNA damage (TUNEL), nuclear protamine deficiency, and persisted histones were significantly lower in the ALA group than placebo receivers (p<0.05). We noticed a decrease in the mean levels of seminal total antioxidant capacity (p=0.03), malondialdehyde (p=0.02), and SCSA-assayed sperm DNA damage (p=0.004) as well as an increase in mean sperm total motility (p=0.04) after treatment with ALA. In addition, the mean of nuclear protamine deficiency and remnant histone content were declined post-ALA therapy (p=0.003 and 0.002, respectively). Regarding post-medication pregnancy loss, no statistically significant difference was observed between the two groups (p=0.15).

    Conclusions

    ALA-therapy attenuates sperm DNA damage and lipid peroxidation while enhancing sperm total motility and chromatin compaction in the male partner of couples with RPL.

    Keywords: Alpha-lipoic acid, DNA damage, Oxidative stress, Recurrent Pregnancy Loss}
  • مقدمه

    درصد بالایی از موارد سقط مکرر با عوامل ایمونولوژیک مرتبط است.

    هدف

    این مطالعه ارتباط بین پلی مورفیسم های تک نوکلیوتیدی ژن پروتیین مرتبط با لنفوسیت T کشنده (CTLA-4) را در خانم ها با سابقه سقط مکرر در مقایسه با خانم های سالم بررسی کرد.

    مواد و روش ها

    این مطالعه بصورت مورد-شاهدی بر روی دو گروه شامل 120 خانم سالم بدون سابقه سقط و حداقل یک زایمان (شاهد) و 120 خانم با سابقه دو یا بیشتر سقط مکرر اولیه (مورد) انجام شد. پنج میلی لیتر نمونه خون محیطی از همه افراد تهیه گردید. پلی‌مورفیسم‌های ژن هایی rs3087243 و rs231775 با PCR-RFLP و rs5742909 با استفاده از روش HRM-RT-PCR مورد سنجش قرار گرفت.

    نتایج

    میانگین سنی خانم ها در گروه کنترل و افراد با سابقه سقط مکرر به ترتیب 23/4 ± 03/30 (محدوده 37-21) و 61/3 ± 64/28 سال (محدوده 35-20) بود. تعداد موارد سقط در خانم ها با سابقه سقط مکرربین 2 تا 6 متغیر بود. و خانم های کنترل بین 1 تا 4 مورد سابقه بارداری موفق داشتند. تجزیه و تحلیل آماری تفاوت معنی داری را بین ژنوتیپ های GG و AG در دو گروه در پلی مورفیسم rs3087243 نشان داد (00/1 OR در مورد ژنوتیپ GG و 87/2 OR برای ژنوتیپ AG و 0043/0 = p) فراوانی ژنوتیپ پلی‌مورفیسم‌های rs231775 و rs5742909 در دو گروه تفاوت معنی‌داری نداشت (به ترتیب 37/0 = p و 095/0 = p).

    نتیجه گیری

    یافته‌های ما نشان داد که پلی‌مورفیسم CTLA-4، rs3087243، ممکن است با خطر ابتلا به سقط مکرر درخانم های ایرانی مرتبط باشد.

    کلید واژگان: سقط مکرر, پلیمرفیسم تک نوکلئوتیدی, ژن CTLA-4}
    Fereshteh Vaziri Nezamdoust, Hossein Hadinedoushan, Nasrin Ghasemi
    Background

    A large proportion of cases of recurrent pregnancy loss (RPL) are associated with immunological factors.

    Objective

    This study investigated the association between single nucleotide polymorphisms of cytotoxic T-lymphocyte-associated protein (CTLA)-4 gene in women with a history of RPL compared to healthy women.

    Materials and Methods

    A case-control study was performed on 2 groups consisting of 120 healthy women with no history of abortion and at least one delivery (control) and 120 women with a history of 2 or more primary RPLs (case). In addition, 5 mL of peripheral blood sample was taken from all subjects. The frequencies of CTLA-4 rs3087243 and rs231775 polymorphisms were assayed by restriction fragment length polymorphism polymerase chain reaction and rs5742909 using the high-resolution melting real-time polymerase chain reactionmethod.

    Results

    The mean age of the women in the control and RPL groups were 30.03 ± 4.23 (range 21-37), and 28.64 ± 3.61 yr (range 20-35), respectively. Pregnancy loss numbers ranged between 2-6 in women with a history of RPL, and between 1 and 4 in the successful pregnancy group. Statistical analysis showed a significant difference between the genotypes of GG and AG in the 2 groups in rs3087243 polymorphism (OR 1.00 for GG genotype and OR 2.87 for AG genotype, p = 0.0043). No significant difference was observed in the genotype frequencies of rs231775 and rs5742909 polymorphisms, of the 2 groups (p = 0.37, and p = 0.095), respectively.

    Conclusion

    Our findings indicated that CTLA-4 polymorphism, rs3087243, might be associated with a risk of RPL in Iranian women.

    Keywords: Recurrent pregnancy loss, Single nucleotide polymorphisms, CTLA-4 gene}
  • Saeed Harirzadeh, Farshid Kafilzadeh*, Hengameh Zandi, Mohamad Kargar
    Background and Aims

    Recurrent pregnancy loss (RPL) is one of the important complications of pregnancy. Only 50% of cases have a known cause of RPL. One of the causes of RPL is Waddlia Chondrophila (W. Chondrophila), but no information is available regarding its in Iran. This study aimed to develop a Taqman Real-Time polymerase chain reaction assay to detect recA Gene of W. Chondrophilain biological samples from women with RPL in Yazd city.

    Materials and Methods

    Clinical samples of women with a history of RPL, normal childbirth, and standard strain WSU 86–1044 were provided. Primers and probes of W. Chondrophila were designed. Positive control was provided based on the PUC57 vector. Technical performance was examined using a control plasmid.

    Results

    Analytical sensitivity was 5 ng/µl of control plasmid DNA. No cross-amplification was observed when testing other pathogens that can detect in human vaginitis. The Taqman Real-Time PCR assay exhibited good reproducibility. This Real-Time PCR was then applied to 100 vaginal swabs. No samples were revealed to be Waddlia positive.

    Conclusions

    This new TaqMan Real-Time PCR assay represents a diagnostic tool that may be used to further study the prevalence of W. Chondrophila infection in clinical specimens.

    Keywords: Recurrent pregnancy loss, Taqman real-time PCR, Waddlia chondrophila}
  • Reza Najafipour, Zahar Rashvand, Khadijeh Taherkhani, Solmaz Chamanara, Shokoh Abotorabi, Sahar Moghbelinejad*
    Background

    It has been reported that less than 5% of women experience recurrent pregnancy loss (RPL). different matrix metalloproteinases (MMPs) have proteolysis function with a main role in the stable development of the fetus.

    Objective

    This study aims to assess the associations between two single nucleotide polymorphisms (rs2509013 C>T and rs11225395 G>A) of MMP-8 gene and RPL among 130 Iranian women with a history of RPL and 130 controls.

    Methods

    Genotyping of the MMP-8 gene was done for the two polymorphisms by using Sanger sequencing method.

    Results

    High frequency of AA genotype (OR: 2.5, 95%CI:1.02-4.1, P<0.01) and A allele (OR:1.95, 95% CI:0.95-3.1, P<0.001) of rs11225395 G>A polymorphism in patients compared to controls. This high frequency was also reported in the haplotypes and combined genotypes of polymorphism.

    Conclusion

    The MMP-8 gene may be involved in RPL risk and is a potential biomarker for RPL susceptibility.

    Keywords: Recurrent pregnancy loss, Matrix metalloproteinase, MMP-8, Polymorphism}
  • مقدمه

    تخمین زده می شود که 5-1% زوجین از سقط مکرر رنج می برند. تحقیقات اخیر تاثیر پلی مورفیسم های ژنی را در سقط مکرر را نشان داده است.

    هدف

    هدف از این مطالعه، ارزیابی تاثیر سه پلی مورفیسم ژنی (rs1048943 از ژن CYP1A1، rs28371725 از ژن CYP2D6 و rs7830 از ژن NOS3) در سقط مکرر است. به منظور بررسی ارتباط این پلی مورفیسم ها با بیماری و در صورت امکان، استفاده از آنها به عنوان فاکتورهای غربال گری می باشد.

    مواد و روش ها

    نمونه های خون مورد از 136 زن دارای حداقل دو سقط مکرر و نمونه های خون کنترل از 136 زن بدون سابقه سقط و حداقل یک بارداری موفق از جمعیت ایرانی-آذری جمع آوری گشت. این مطالعه بین سال های 2020-2018 انجام گرفت. به منظور ژنوتایپینگ هر یک از این پلی مورفیسم ها در هریک از نمونه های DNA ژنومی استخراج شده، از روش ARMS-PCR استفاده شد. متعاقب این مرحله، بررسی های آماری جهت حصول نتیجه ی ارتباط یا عدم ارتباط پلی مورفیسم های مذکور با سقط مکرر انجام گرفت.

    نتایج

    از بین این سه پلی مورفیسم، فقط rs1048943 از ژن CYP1A1 ارتباط معنی داری با سقط مکرر در زنان ایرانی-آذری نشان داد.

    نتیجه گیری

    مطالعه ما پیشنهاد می کند که پلی مورفیسم rs1048943 از ژن CYP1A1 می تواند با ریسک پایین ابتلا به بیماری در ارتباط باشد. مطالعات دیگر در جمعیت های دیگر و یا در همین جمعیت با اندازه نمونه بزرگتر (مورد و شاهد) و همچنین آنالیزهای ژنومیکس عملکردی یا مطالعات اپی ژنتیکی به منظور تایید نتایج ما مورد نیاز است.

    کلید واژگان: سقط مکرر, پلی مورفیسم, CYP1A1, CYP2D6, NOS3}
    Mahsa Yousefian, Abdolhamid Angaji*, Elham Siasi, Seyed Ali Rahmani, Shamsi Abbasalizadeh Khiaban
    Background

    It is estimated that 1-5% of couples suffer from recurrent pregnancy loss (RPL). Recent studies have shown the effects of gene polymorphisms in RPL.

    Objective

    The aim of this study was to evaluate 3 gene polymorphisms including rs1048943 of CYP1A1, rs28371725 of CYP2D6, and rs7830 of NOS3 in idiopathic RPL to identify their association with RPL.

    Materials and Methods

    Blood samples were collected from 136 women with at least 2 consecutive idiopathic miscarriages (case group) and 136 women with no history of miscarriage and at least one successful pregnancy (control group) from the Iranian Azeri population. This study was carried out between April 2018-April 2020. Amplification-refractory mutation system polymerase chain reaction was used for the rs7830, rs1048943 and rs28371725 polymorphisms in order to genotype each extracted genomic DNA sample. After that, Chi-square, Fisher’s exact test and logistic regression were used to investigate whether each of these polymorphisms is associated with RPL.

    Results

    Among these polymorphisms, only rs1048943 of CYP1A1 showed a statistically significant association with RPL in the Iranian Azeri women studied.

    Conclusion

    Our results suggest that CYP1A1 gene polymorphisms might be associated with a reduced risk of RPL. Further studies in other populations and in the same population with a larger sample size, as well as functional genomics analyses such as gene expression analyses or epigenetic studies are required to validate our results.

    Keywords: Recurrent pregnancy loss, Polymorphism, CYP1A1, CYP2D6, NOS3}
  • بهاره مزروعی، محمدمهدی حیدری*، مهری خاتمی
    مقدمه

    سقط عارضه شایعی است که به پایان زودرس بارداری، با مرگ جنین پیش از هفته 20 بارداری اطلاق می شود. بررسی ها نشان می دهند که ژن های فراوانی در بروز این اختلال دخالت دارند. ژن CX3CR1 یکی از این ژن های پاسخ التهابی در دستگاه ایمنی است. در این مطالعه، با به کارگیری روش های مختلف آنالیز بیوانفورماتیکی، به اثبات بیماری زایی واریانت های rs3732378 و rs3732379 پرداخته شد.

    مواد و روش ها

    در این مطالعه، از ابزارهای بیوانفورماتیکی برای پیش بینی اثر جهش های rs3732378 و rs3732379 شامل SIFT، PolyPhen 2، PROVEAN، Predict SNP و Exome Variant Server استفاده گردید. تغییرات پایداری پروتیین جهش یافته با ابزارهای I-Mutant و DynaMut بررسی شد؛ همچنین مدل سازی، بررسی ساختار پروتیین، داکینگ و برهم کنش پروتیین-لیگاند به ترتیب با استفاده از ابزارهای SWISS-MODEL، SwissDock و FRODOCK، نرم افزار PyMOL، Hawkdock و نرم افزار MolSoft انجام گرفت.

    یافته ها:

     پلی مورفیسم های بسیار فراوانی در ارتباط با ژن CX3CR1 شناخته شده اند. از میان پلی مورفیسم های گزارش شده، تعداد 244 پلی مورفیسم مربوط به جهش بدمعنی در بانک اطلاعاتی dbSNP گزارش شده بود که از این تعداد، 2 جهش بدمعنی rs3732378 (g.39307162 G>A و p.Thr280Met) و rs3732379 (g.39307256 C>T و p.Val249Ile) مربوط به بیماری سقط مکرر بود و بررسی گردید. نتایج به دست آمده از نرم افزارهای بیوانفورماتیکی نشان داد که احتمالا هر دو واریانت به عنوان جهش بیماری زا پیش بینی شده و باعث تغییر پایداری ساختار پروتیین گردیده اند و در میان کنش با لیگاند تاثیرگذارند.

    بحث و نتیجه گیری:

     یافته های این مطالعه نشان می دهد که این دو جهش بدمعنی ژن CX3CR1، به عنوان کاندید مهمی برای بیماری زایی سقط مکرر عمل می کنند و شناسایی آن ها در بیماران مبتلا به سقط مکرر می تواند به عنوان یک عامل خطر در نظر گرفته شود.

    کلید واژگان: بیوانفورماتیک, ژن CX3CR1, جهش بیماری زا, سقط مکرر}
    Bahareh Mazrouei, MohammadMehdi Heidari*, Mehri Khatami
    Introduction

    Abortion is a common complication that refers to the early termination of pregnancy with the death of the fetus before the 20th week of pregnancy. Previous studies show that many genes are involved in this disease, including the CX3CR1 gene, which is one of the inflammatory response genes in the immune system. The pathogenicity of these variants was determined in this study using bioinformatics analysis.

    Material & Methods

    In this study, the effects of rs3732378 and rs3732379 mutation were predicted using bioinformatics tools including SIFT, PolyPhen2, PROVEAN, Predict SNP, and Exome Variant Server. Changes in the stability of mutant proteins were investigated using I-Mutant and DynaMut tools. Moreover, modeling of the protein structure, docking, and protein-ligand interaction were performed using SWISS-MODEL, SwissDock, and FRODOCK tools as well as PyMOL, Hawkdock, and MolSoft software, respectively.

    Findings

    Many polymorphisms related to the CX3CR1 gene have been known to date. Out of 244 missense mutations in the dbSNP database, two variants (rs3732378 and rs3732379) have been reported in association with recurrent pregnancy loss related to the CX3CR1 gene. The results of bioinformatics analyses showed that both variants were predicted as pathogenic mutations and changed the stability of the protein structure and played a key role in interaction with the ligand.

    Discussion & Conclusion

    The findings of this study indicate that two missense mutations in the CX3CR1 gene are an important candidate for recurrent miscarriage and their identification in patients with recurrent miscarriage can be regarded as a risk factor.

    Keywords: Bioinformatics, CX3CR1 gene, Pathogenic mutation, Recurrent pregnancy loss}
  • سقط مکرر یک اختلال مشخص است که به عنوان از دست دادن حداقل دو حاملگی قبل از هفته 20 بارداری تعریف شده است. از آنجایی که نیمی از ژنوم جنین متعلق به پدر می باشد، لذا یکپارچگی ژنوم اسپرم برای بارداری موفقیت آمیز ضروری است؛ بطور معمول در زوجین دچار سقط مکرر تنها بررسی کریوتیپ برای مردان توصیه می شود و نقش عوامل پدر در سقط مکرر همچنان بصورت ناشناخته باقی مانده است. در این مقاله، ما در مورد بعضی از آزمایشات برای ارزیابی ژنوم اسپرم در مردانی که همسر آنها دچار سقط مکرر است بحث خواهیم کرد.

    کلید واژگان: فراگمنتاسیون DNA, اسپرم, کروموزوم Y, سقط مکرر}
    Soheila Pourmasumi, Parvin Sabeti, Nasrin Ghasemi*

    Recurrent pregnancy loss is a distinct disorder defined as the loss of at least 2 pregnancies before the 20th wk of gestation. With one half of the genome of the embryo belonging to the father, the integrity of the sperm genome is crucial for a successful pregnancy. Semen analysis is recommended for men in such cases to evaluate sperm concentration, morphology, vitality and motility. However, other important sperm parameters such as sperm epigenetics, aneuploidy, Y chromosome microdeletion and chromatin integrity also correlate with successful pregnancy and delivery rate. This article examines the use of different sperm tests and their importance in male partners of women suffering from recurrent pregnancy loss.

    Keywords: DNA fragmentation, Sperm, Y chromosome, Recurrent pregnancy loss}
  • صنم دولتی، محمدصادق سلطانی زنگبار، جلال اعتمادی خیاوی، مریم مجاهدی، شهلا دانایی، جواد احمدیان هریس*، مهدی یوسفی
    زمینه و هدف

    سقط مکرر به 2 یا تعداد بیشتر شکست مکرر بارداری قبل از هفته بیستم گفته می شود که در 5-2 درصد زنان در سنین بارداری رخ می دهد. با در نظر گرفتن نقش قابل توجه سیستم ایمنی در روند یک بارداری موفق، انتظار می رود در کنار درمان های رایج و شناخته شده ای که برای بیماران مبتلا به سقط مکرر تا به امروز استفاده شده اند، لنفوسیت تراپی داخل جلدی نیز موثر واقع گردد.

    مواد و روش ها

    30 نفر از بیماران مبتلا به سقط مکرر با زمینه اختلالات ایمونولوژیک، و 30 نفر در گروه کنترل متشکل از زنان سالم با سابقه بارداری های موفق وارد مطالعه شدند. بعد از دریافت نمونه خون و بررسی های اولیه، افراد مبتلا به سقط مکرر درمان لنفوسیتی را دریافت کردند. قبل و پس از انجام مداخله میزان بیان میکرو RNA های  miR -146a ، miR -10a،  miR -106b, miR -25، در هر دو گروه مورد مطالعه سنجیده شده و تفاوت های ایجاد شده ناشی از تاثیرات این مداخله مورد بررسی قرار گرفت.

    یافته ها

    میزان بیان میکرو RNA های ضد التهابی miR-146a و miR-10a، در زنان مبتلا به سقط مکرر بعد از دریافت درمان لنفوسیتی در مقایسه با قبل از درمان افزایش معنی داری نشان داد. در حالی که میزان بیان میکرو RNA های التهابی  miR-106bو  miR-25 بعد از دریافت لنفوسیت کاهش معنی داری در مقایسه با قبل از درمان نشان داد.

    نتیجه گیری

    هدف از لنفوسیت تراپی داخل جلدی افزایش تحمل سیستم ایمنی مادر نسبت به آنتی ژنهای پدری موجود در جنین و تعدیل پاسخ های التهابی در زنان بارداری که مبتلا به سقط مکرر هستند می باشد. با توجه به نتایج حاصل از این مطالعه می توان از این روش برای کاهش میزان التهاب در بین زنان مبتلا به سقط مکرر استفاده کرد.

    کلید واژگان: سقط مکرر, لنفوسیت درمانی, میکرو RNA, التهاب}
    Sanam Dolati, MohammadSadegh Soltani-Zangbar, Jalal Etemadi Khiavi, Maryam Mojahedi, Shahla Danaii, Javad Ahmadian Heris*, Mehdi Yousefi
    Background

    Recurrent Pregnancy Loss (RPL) is 2 or more recurrent miscarriages before the twentieth week, which occurs in 2-5% of women of gestational age. Considering the significant role of the immune system in the process of a successful pregnancy, it is expected that in addition to the common and well-known treatments used for patients with recurrent miscarriage to date, intracutaneous lymphocyte therapy will also be effective.

    Methods

    30 patients with RPL with immunological disorders, and 30 patients in a control group consisting of healthy women with a history of successful pregnancies were included in the study. After receiving blood samples and initial examinations, people with RPL received lymphocytic treatment. Before and after the intervention, the expression levels of miR-146a, miR-10a, miR-106b, and miR-25 were measured in both groups and the differences caused by the effects of this intervention were examined.

    Results

    The expression of anti-inflammatory miR-146a and miR-10a, in women with RPL showed a significant increase after receiving lymphocyte treatment compared to before treatment. While the expression of pro-inflammatory miR-106b and miR-25 showed a significant decrease after receiving lymphocytes compared to before treatment.

    Conclusion

    The aim of intradermal lymphocyte therapy is to increase the maternal immune system's tolerance to paternal antigens in the fetus and to modulate inflammatory responses in pregnant women with RPL. According to the results of this study, this method can be used to reduce inflammation in women with recurrent miscarriage.

    Keywords: Recurrent Pregnancy Loss, Lymphocyte therapy, MicroRNA, Inflammation}
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