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Abstract: Endometrial cancer is gynecologic cancer that occurs in the uterus. Endometrial cancer stem cells (ECSC) are a small population of cancer cells that represent a crucial role in the metastasis of endometrial cancer cells to other organs in the body. ECSC can proliferate and give rise to mature cancer cells, which are found to participate in the aggressiveness of metastatic lesions. Therefore, targeting ECSC can be a valuable strategy for drug development against the metastasis of endometrial cancer. Previous studies have demonstrated that several signaling pathways, including Wnt, mTOR, EGFR, NOTCH, STAT3, VEGF, and SHH show modest effects and regulate the growth, epithelial-to-mesenchymal transition (EMT), and tumorigenesis of ECSC. Non-coding RNAs (ncRNAs) also play an important role in ECSC self-renewal, progression, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for endometrial cancer diagnosis and therapy. This mini-review aims to characterize the main signaling pathways involved in the stimulation of ECSCs proliferation and tumorigenesis.

Introduction: Most infertility treatment centers are currently using semen analysis to differentiate between fertile and infertile individuals. Recent studies have evaluated the expression and secretion of independent insulin and related beta receptor (IR-β) in mammals’ ejaculated spermatozoa such as humans and pigs, and its effect on motility parameters capacitation and acrosomal reaction. Objectives: This study aimed to investigate the expression of insulin, IR-β and the parameters of sperm and DNA fragmentation index (DFI) in men with intracytoplasmic sperm injections (ICSI) failed. Patients and Methods: This study was conducted on 15 men with unknown infertility with a history of unsuccessful ICSI and 10 fertile men. After collecting samples, sperm parameters (concentration and motility), sperm DNA fragmentation and expression of insulin and IR-β genes were investigated. To assess DFI from SDFA kit and to review the expression, the genes were analyzed via RT-PCR method. Data were analyzed statistically by t-test and covariance tests. Results: Based on the findings of this research, the concentration and percentage of motility in infertile men with a history of unsuccessful ICSI was significantly lower than fertile individuals, moreover, the amount of DNA fragmentation significantly increased in infertile men with a history of unsuccessful ICSI compared to fertile men (P < 0.05). Insulin expression in the sperm of infertile men with a failed ICSI history was significantly lower than fertile men (P < 0.05); however, the IR-β expression rate was not significantly different between the two groups. Conclusion: Evaluation of insulin gene expression can be helpful as a good marker for identifying infertility with an unknown cause.

Background Recent evidence suggests that routine semen analysis has limited power to predict male fertility. Several efforts have been made to best discriminate between fertile and subfertile men using several sperm features. So, there is a need to more reliable assays for providing molecular data to evaluate sperm quality and predict male fertility. Objectives Present study aimed to investigate relationship between sperm miR-26a-5p and its target PTEN transcript content and sperm parameters in unexplained infertile and healthy fertile men. Materials and methods Sperm parameters and transcript content of miR-26a-5p and PTEN in ejaculated spermatozoa were assessed in fertile (n = 15) and normozoospermic infertile (n = 15) men. Results Sperm transcript levels of miR-26a-5p were lower in unexplained infertile men than in fertile controls (P = .021). High sperm PTEN expression is correlated with low miR-26a-5p transcript levels in ejaculated spermatozoa. High levels of sperm miR-26a-5p transcript were associated with high sperm motility and normal morphology. Receiver operating characteristic curve (ROC) analysis indicated miR-26a-5p has a fairly good diagnostic value to distinguish fertile and unexplained infertile men with an area under curve (AUC) of 0.747 (95% confidence interval: 0.560-0.933; P = .021). Discussion This study suggests that sperm miR-26a-5p and its target PTEN transcript content may contribute to infertility etiology in unexplained infertile patients. Conclusion miR-26a-5p has a potential to use as a diagnostic biomarker and provide new therapeutic approaches for male infertility.

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p

Background: Preimplantation genetic diagnosis (PGD) has been used as an option for couples with the possibility of having a baby with a genetic disorder. The common method for performing this test involves isolating 1 cell from day 3 or a few cells from day 5 embryos and performing genetic studies on the cell-extracted DNA. This method is invasive and can cause abortion after implantation in the uterus. Because of this, 2 noninvasive methods for performing a PGD have been studied: PGD using blastocyst fluid and PGD using embryo culture medium. Objective: The aim of this study is to determine the sensitivity of the polymerase chain reaction (PCR) technique to detect the Y chromosome using cell-free DNA within a culture medium for gender prediction of blastocysts. Materials and Methods: In this study, the gender of 30 embryos on day 5 was determined using embryonic DNA extraction from the culture medium and the PCR technique to evaluate the sex-determining region Y and fragile X mental retardation genes. Then, the accuracy was assessed using ultrasound. Results: The results of the PCR technique showed that 7 embryos were male, but an ultrasound revealed that 13 were male. Conclusion: The given results indicated that, because of the low amount of DNA extracted from the culture medium, the diagnosis of the existence of the Y chromosome by this method is still not accurate enough for detecting the gender of the embryo. Key words: Preimplantation diagnosis, Embryo implantation, Culture media, Blastocyst, Polymerase chain reaction.

Toxoplasma gondiiis an obligate intracellular protozoan parasite causing toxoplasmosis in animals and humans. Primary maternal infection with toxoplasmosis during pregnancy is frequently associated with transplacental transmission to the fetus. However it is not certain whetherToxoplasmainfection can cause recurrent abortion. The aim of this study was to determine the relationship betweenToxoplasmainfection and abortion via detection of anti-Toxoplasma gondiiantibodies in sera of women with obstetrical problems and compare the results with control group consisting of women with history of normal delivery. Sera from 130 women with abortion and sera of 130 women with normal delivery were tested for IgG and IgM anti-Toxoplasma gondiiantibodies by ELISA method. The present study revealed 24.6% of the samples with abortion and 21.5% of the samples with normal delivery were positive for IgG antibodies. However, statistical analysis indicated no significant differences(P>0.05). In addition, IgM antibody was detected in one woman who had aborted but not in women with normal childbirth. This study showed no significant difference between the case and control groups in IgG anti-Toxoplasmaantibody but detected one sample with IgM antibodies in woman with abortion during the first trimester of pregnancy. In order to determine the relationship betweenToxoplasmainfection and abortion, anti-ToxoplasmaIgG avidity and PCR to discriminate between recent and prior infections are recommended.

Background Caesarean section (CS) is one of the most commonly undertaken operations worldwide with numerous potential complications such as subsequent infertility. Thus, the aim of this study was to evaluate subsequent infertility after CS. Methods This retrospective epidemiological study was conducted in Obstetrics and Gynecology of Ahvaz Imam Hospital from 2011 to 2015. During the five years, 2047 patient records were collected representing that only 218 patients had secondary infertility after CS or vaginal delivery (including 114 (52.29%) after CS and 104 (47.7%) after vaginal delivery). Then, information of all patients was extracted from infertility clinic records. Results The results showed that there was no significant difference between the groups in terms of demographic features and sign and symptoms such as dysmenorrhea (P = 0.386), dyspareunia (P = 0.357), hirsutism (P = 0.622), and galactorrhea (P = 0.352). Moreover, associated disorders including Men disorders (P = 0.577), Uterine disorders (P = 0.286), Fallopian tube disorders (P = 0.394), and Ovulation disorders (P = 0.21) did not have any significant differences between the groups. Conclusions The results of this study suggest that CS did not increase the risk of subsequent infertility when compared to vaginal delivery. Therefore, in patients who have infertility problems after the first CS, we should evaluate other reasons in order to treat it.

SummaryThis study aimed to assess the morphological changes in neonate vitrified testicu-lar grafts after host treatment with melatonin. Neonate vitrified testes, candidatesfor transplantation to treated and nontreated groups receiving melatonin, werethawed in media containing or not containing 100 l M melatonin. Followingtransplantation, melatonin (20 mg kg 1 per day) and saline were given to thetreated and nontreated groups for up to 9 weeks. The testicular status wasassayed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP)-biotin nick-end labelling TUNEL, semi-thin section andultra-structure studies. Chi-squared test was used to compare categorical vari-ables between the groups. Overall, the degenerative and apoptosis changes in thevitrified testis parenchyma were not significant. However, atrophic seminiferouscords and jumbled appearance of the interstitial space were more often observedin the nontreated group than in the treated ones. Semi-thin sections showed thatthe germinal epithelium was taken in a normal arrangement on the testiculargrafts of both groups. Nevertheless, ultrastructural analysis revealed that thecharacteristics of interstitial space cells, basement membrane BM and epithelialcells of seminiferous tubules in the treated group were better than those in thenontreated group. The study revealed a beneficial effect of melatonin on vitrifiedneonatal testes and after that, on restoring testicular grafts.IntroductionThe natural spermatogenesis process in the testes of can-cer patients treated with radiotherapy and chemotherapyis may be disrupted and lead to a loss of fertility (Agarwal& Allamaneni, 2005).In general, freezing of semen with subsequent assistedreproductive technology (ART) is a method that can helpcancer patients overcome this problem (Lass et al., 2001).However, these techniques can only be used in adult casesand those who have partners. It should be noted that about2% of all malignant cancers occur during childhood andinfancy (Brougham & Wallace, 2005). Furthermore, somestudies reported that freezing of semen with subsequentART among the treated cancer patients did not give a goodresult in restoration of fertility (Blackhall et al., 2002).Spermatogonia stem cells lack acrosome and also theirmetabolic activity is relatively inactive. In addition, dueto the large size of spermatogonia stem cells, the influ-ence of cryoprotectives (CPA) through freezing isneglected, and cytogenetic abnormalities are less observed(Schlatt et al., 2002). Therefore, it seems that these cellsare more resistant to the damage caused by the freezingprocess in comparison with mature spermatozoa (Cozzo-lino & Lamb, 2000). Therefore, over the past few years,researchers’ attention has been shifted to use of these cellsor testis parenchyma for freezing and transplantation ininfertile men. These techniques have been introduced assuitable methods that can restore the impaired reproduc-tive and testicular activity of cancer patients who haveovercome the disease (Neri et al., 2009).However, despite the introduction of new methods formanaging freezing and selection of suitable sites for trans-plantation, the quality and quantity of spermatogoniastem cells and parenchyma of the grafted testes are notsatisfactory (Wyns et al., 2008; Neri et al., 2009). Because

Background: Mullerian anomalies are relatively common and contributing to the problems of infertility and poor pregnancy outcomes. But their molecular pathophysiology has been insufficiently studied. On the other hand, polycystic ovary syndrome (PCOS) is found in nearly 80% of women with hyperandrogenism and also in 8%-25% of normal ones. It seems that anti-mullerian hormone (AMH) which inhibits the formation of the mullerian ducts in male increases in women with PCOS. Therefore, the aim of the study is whether PCOS is associated with mullerian anomalies. Methods: In this case-control study, 83 women with PCOS and 83 cases without PCOS were evaluated with transvaginal ultrasound (TVS) for the diagnosis of mullerian anomalies. The results of each group were compared with other groups. Results: In the PCOS patients, TVS revealed mullerian anomalies in the uterine cavity in 29 out of 83 women. Among 29 patients who had lesions in their uterine cavity, 27 cases had septate uterus and two had arcuate uterus. In the healthy women, TVS revealed 6 septate uterus and 4 arcuate uterus abnormality cases of the uterine cavity. There were significant correlation between polycystic ovary syndrome of the patients and the mullerian anomalies lesions (i.e. septate and arcuate uterus) which were seen in them. Conclusion: Mullerian anomalies were more common in women with PCOS and the most common anomaly was uterine septum. In fact, the present results revealed that it seemed a cause-effect relationship between the mullerian anomalies and PCO syndrome may in fact exist.

Background Small for gestational age (SGA) fetuses have birth weights below 10th percentile or abdominal circumference less than 10th percentile for gestational age Objectives This study aimed to determine the prevalence of SGA and its associated risk factors in Iran. Patients and Methods This is a retrospective study. A total of 341 pregnant women were evaluated in fetal health care clinic of perinatology from January 2013 to January 2014. Results Of 312 pregnant women, 33 had SGA fetuses. The average of body mass index (BMI) was lower in SGA group than non-SGA. Pulsatility index has no stastical meaningful between SGA and nonSGA groups. In Gestational age had no difference between 2 groups. Severe SGA (< 3rd centile estimated fetal weight) was observed in 2.6% of all cases. Conclusions In conclusion, the prevalence of SGA was approximately one tenth of all pregnancies. SGA incidence was associated with nulliparity and more frequently seen in lower age group.

Citation Hemadi M, Shokri S, Pourmatroud E, Moramezi F, Khodadai A. Follicular dynamic and immunoreactions of the vitrified ovarian graft after host treatment with variable regimens of melatonin. Am J Reprod Immunol 2012; 67: 401–412 Problem This study investigates dose-dependent effects of melatonin on ovarian graft. Method of Study Vitrified-thawed whole ovaries of newborn mice were grafted into ovariectomized mature ones. Melatonin (20, 50, 100, and 200 mg/kg/day) was administrated to separate groups of host mice for 32 days. IgM and IgG antibodies, Th1 and Th2 cytokines, and melatonin in recipient’s blood were measured. Subsequent survival of the grafted ovaries was scored. An assessment of follicular morphology was performed using TUNEL assay and hematoxylin-eosin staining. Results The administration of melatonin did not disturb the circadian rhythm of melatonin concentration. The ovarian graft lifespan was prolonged at 200 mg/kg/day melatonin (P

1Fertility, Infertility and Perinatology Research Center, Imam Khomeini Hospital, Medicine Faculty, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran *Corresponding author: Mojgan Barati, Fertility, Infertility and Perinatology Research Center, Imam Khomeini Hospital, Medicine Faculty, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran. Tel: +98-9161187090, Fax: +98-6133335399, E-mail: barati_m70@yahoo.com

Uterine disorders like usual infertility factors (male factor, ovarian and tubal problems of women) may affect the outcome of infertility treatment in infertile patients. In our clinical trial, 110 couples diagnosed with infertility were candidate for intra uterine insemination (IUI). The patients were divided randomly into two equal groups (n = 55): In group one (control group), patients without hysteroscopy underwent ovulation induction by clomiphene citrate and hCG followed by intrauterine insemination. The second group (experiment group), patients were undergoing hysteroscopy before intra uterine insemination on the day 21 of the cycle and due to abnormal findings, going under surgical treatment if they needed. The rates of pregnancy complications in patients were evaluated. The age, BMI, kind of infertility, duration of infertility, number of previous trial, duration of stimulation, the type of procedures used and semen analysis (TMC, Motility and morphology of sperm) were similar for both groups and no statistically significant differences emerged at all between them. In experimental group, hysteroscopy revealed pathology in the uterine cavity in 26 out of 55 cases. The overall rates of clinical pregnancy were higher in experimental group compared to the control group. The findings from this study showed that the use of hysteroscopy as a diagnostic or therapeutic procedure before IUI, can increase the rate of pregnancy and finally decrease the failure rate of infertility treatment and perinatal complications in infertile couples.

This study investigates dose-dependent effects of melatonin on ovarian graft.Vitrified-thawed whole ovaries of newborn mice were grafted into ovariectomized mature ones. Melatonin (20, 50, 100, and 200 mg/kg/day) was administrated to separate groups of host mice for 32 days. IgM and IgG antibodies, Th1 and Th2 cytokines, and melatonin in recipient's blood were measured. Subsequent survival of the grafted ovaries was scored. An assessment of follicular morphology was performed using TUNEL assay and hematoxylin-eosin staining.The administration of melatonin did not disturb the circadian rhythm of melatonin concentration. The ovarian graft lifespan was prolonged at 200 mg/kg/day melatonin (P0.001). However, in doses of higher than 20 mg/kg/day melatonin, the proportion of healthy follicles and ovary size decreased. Th1 cytokines levels were reduced dose dependently. However, the effect of melatonin on Th2 cytokines was not pronounced. IgM and IgG2a decreased in recipients receiving 200 mg/kg/day melatonin in comparison with non-treated group (P0.001), while this variables were significantly increased at the dose of 50 mg/kg/day (P0.001).Melatonin at 200 mg/kg/day has an immunosuppresent effect and produce prolongation of graft survival. However, the associated reduction in healthy follicles suggests that melatonin in doses of higher than 20 mg/kg/day has no preventative ischemic action.

Background: Abnormal uterine bleeding (AUB) is one of the most common clinical problems in gynecology. Transvaginal sonography (TVS) and hysteroscopy are two diagnostic methods for patients with AUB. For most of the patients with AUB, diagnostic hysteroscopy can be done in clinic with minimal discomfort and much lower expense than operative room. Materials and Methods: In our clinical trial study, from March 21, 2005 to March 20, 2007, patients with AUB in Ahwaz Imam Khomayni hospital, after history and physical examinations underwent TVS. Of those, 147 patients with normal TVS entered the study and were considered for outpatient hysteroscopy. Patients with endometrial cavity lesion were scheduled for operation room, and those with empty endometrial cavity aspiration biopsy were done outpatiently. Specimens were sent to pathologist for examination. Results: All the patients were divided into three groups: group 1 or minority was under 30 years old (7 women), group 2 was 30-40 years, and group 3 or majority was over 40 years old (96 women). 115 patients (78.2%) had normal and 32 patients (21.8%) had abnormal hysteroscopic results. 116 patients (78.8%) had normal and 31 patients (21.2%) had abnormal pathologic results; moreover, cervical canal polyp was the most common lesion hysteroscopically and pathologically in all groups. Conclusion: Of 147 patients (100%) with AUB and normal TVS, 32 patients (21.8%) were abnormal hysteroscopically. Cervical canal polyps may be missed by transvaginal sonography, but can be diagnosed by hysteroscopy. In patients with AUB and normal TVS, hysteroscopy can be used as the second step.