International Journal Of Fertility and Sterility
Volume:14 Issue: 3, Oct-Dec 2020

Although application of superparamagnetic iron oxide nanoparticles (SPIONs) in industry and medicinehas increased, their potential toxicity in reproductive cells remains a controversial issue. This study was undertakento address the response of sperm, oocyte, and resultant blastocyst to dextran-coated SPIONs (D-SPIONs) treatmentduring murine in vitro fertilization (IVF).

In this experimental study, murine mature oocytes were randomly divided into three groups:control, and low- and high-dose groups in which fertilization medium was mixed with 0, 50 and 250 μg/ml of DSPIONs,respectively. Sperm and/or cumulus oocyte complexes (COCs) were cultured for 4 h in this medium for electronmicroscopic analysis of sperm and COCs, and assessment of developmental competence and genes expression ofGpx1, Sod1, catalase, Bcl2l1 and Bax in the resultant blastocysts.

Ultrastructural study of sperm, oocyte, and granulosa showed destructed mitochondria and membranes inspermatozoa, vacuolated mitochondria and distorted cristae in oocytes, and disrupted nuclei and disorganized cellmembranes in granulosa in a dose-dependent manner. Data showed that cleavage and blastocyst rates in the 250 μg/mlof D-SPIONs were significantly lower than in the control group (p <0.05). Gene expression of GPx1, Sod1, catalase,Bcl2l1 and Bax in resultant blastocysts of the high-dose group and catalase and Bax in resultant blastocysts of thelow-dose group, was higher than the controls.

There is considerable concern regarding D-SPIONs toxic effects on IVF, and mitochondrial and cellmembrane damage in mouse spermatozoa and oocytes, which may be related to oxidative stress and apoptotic events.

One of the important factor associated with male infertility is high production of reactive oxygen species(ROS). The main function of Nuclear factor erythroid 2-related factor 2 (NRF 2) is to activate the cellular antioxidantresponse by inducing the transcription of a wide array of genes that can combat the harmful effects of factorssuch as oxidative stress. The purpose of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC), as anantioxidant drug, on NRF 2 Gene Expression in Asthenoteratozoospermia Men.

In this randomized, blinded clinical trial study, included 50 infertile men with asthenoteratozoospermia,who received NAC (600 mg, three times daily). Sperm parameters analyzed according to the world health organization(WHO; 2010). Sperm DNA fragmentation, relative NRF 2 expression, and seminal plasma level of antioxidant enzymeswere measured by TUNEL assay, reverse transcription polymerase chain reaction (RT-PCR) and ELISA test, respectively.

After NAC treatment, findings showed a significant increase in sperm concentration and motility comparedto pre-treatment status, whereas the percentage of abnormal morphology and DNA fragmentation was significantlydecreased (p <0.05). A significant improvement in expression of NRF 2 gene and antioxidant enzyme levels were observedcompared to pre-treatment by NAC (p <0.05). Significant correlations were observed between NRF 2 mRNAexpression level, specific sperm parameters and level of antioxidant enzymes (p <0.05).

The results demonstrated that NAC oral supplementation protected against oxidative stress by enhancingNRF 2 expression. This could improve semen parameters quality parameters in asthenoteratozoospermia men (Registrationnumber: IRCT20170830035998N4).

Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell developmentin vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growthdifferentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitoryfactor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM(hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes.

In this experimental study, 360 germinal vesicle (GV) oocytes were obtained from NMRImice, aged 4-6 weeks that had received 5 IU pregnant mare's serum gonadotropin (PMSG) 48 hours before. GVoocytes were subjected to IVM. 120 GV oocytes were cultured in each medium; hTCCM as the test group, DMEM+ 20%FBS as the control group and Ham’s F10 + HFF medium as the sham group. The rates of the IVM and perivitellinespace (PVS) changes were recorded at 8, 16 and 24 hours after culture. The metaphase II (MII) oocytes weresubjected for in vitro fertilization (IVF) and the fertilization rate was evaluated after 1, 2, and 3 days.

There was a significant difference between the maturation rates in hTCCM (31.67% MII) and the control [0% MII,p <0.05, (7.5% MI, 52.5% deg. and 40%GV)] groups but there was not a significant difference between the maturation ratesin hTCCM and the sham group (53.33% MII, P>0.05). IVF success rate for MII oocytes obtained from IVM in the hTCCMgroup was 28.94% (n=11). Our data showed that hTCCM is an effective medium for GV oocyte growth and maturationcompared to the control medium.

Our findings show that TCCM supports oocyte IVM in mice and affect oocyte morphology.

This cross-sectional study pointed to assess the relationship between major dietary patterns and dietarydiversity score with semen parameters, in infertile Iranian males.

In this cross-sectional study, 260 infertile men (18-55 years old) who met the inclusioncriteria, entered the study. Four Semen parameters, namely sperm concentration (SC), total sperm movement (TSM),normal sperm morphology (NSM) and sperm volume were considered according to spermogram. A 168-item foodfrequency questionnaire (FFQ) was used to collect dietary intakes and calculate dietary diversity score. Factor analysiswas used to extract dietary patterns.

The following four factors were extracted: “traditional pattern”, “prudent pattern”, “vegetable-based pattern” and“mixed pattern”. After adjusting potential confounders, those in the highest quartile of the traditional pattern had 83% lessodds for abnormal concentration, compared with the first quartile (OR=0.17, 95% CI: 0.04-00.73); however, subjects inthe highest quartile of this pattern had 2.69 fold higher odds for abnormal sperm volume as compared with those of thefirst quartile (95%Cl: 1.06-6.82). Men in the second quartile of prudent pattern had 4.36 higher odds of an abnormal spermvolume in comparison to the reference category (95%CI: 1.75-10.86), after considering potential confounders. With regardto mixed pattern, men in the second, third and fourth quartile of this pattern had respectively 85 (5%Cl: 0.03-0.76,), 86(95%Cl: 0.02-0.75) and 83 % (95%Cl: 0.034-0.9) less odds of abnormal concentration, compared with the first quartile.Additionally, no significant association was found between dietary diversity score and sperm quality parameters.

Higher intake of the traditional diet was linked to lower abnormal semen concentration and poorer spermvolume. Also, the mixed diet was associated with reduced prevalence of abnormal semen concentration.

Endometriosis is one of the most common pelvic diseases associated with dyspareunia, pelvic pain,and infertility. The primary aim of this study is to evaluate the role of diet on the risk of endometriosis among Iranianwomen.

This case-control study was conducted in two health research centres between 2015 and2016. There were 207 women with endometriosis (case) and 206 women without endometriosis (control) who wereevaluated by laparoscopy. The women were asked about their frequency of consumption per week of portions of selecteddietary items in the Iranian diet in the year before the interview.

The results indicated that intake of green vegetables (odds ratio [OR]=0.39, 95% confidence interval[CI]=0.21–0.74, Ptrend=0.004), red meat (OR=0.61, 95% CI=0.41–0.91, Ptrend=0.015) and dairy products (milk[OR=0.65, 95% CI=0.47–0.92, Ptrend=0.014], cheese [OR=0.53, 95% CI=0.37–0.76, Ptrend<0.001]), fresh fruit(OR=0.68, 95% CI=0.50–0.93, Ptrend=0.015) and grain legumes (OR=0.59, 95% CI=0.47–0.77; Ptrend<0.001) had asignificant association with lower risk of endometriosis. Consumption of carrots, green tea, fish, eggs and oil was notsignificantly related to the risk of endometriosis.

This study suggests that certain types of dietary components may be related to the risk of endometriosis.

Endometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of thisstudy was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells(Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endometriosiswith a control group.

In this case control study, PB and PF samples were collected from women aged 24-40 yearswho underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and comparedbetween three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control(no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups.

No statistically significant difference was found between the study groups regarding the numbers of Th1, Th2and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells comparedto the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase(P=0.035).The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046).However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (p values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PBin the advanced stages of endometriosis (P= 0.013).

There were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis,which could be related to the severity of this disease.

The purpose of this study to determine the relationship between endometrial length and positive pregnancytest in patients who underwent assisted reproductive technology (ART). 
This cross-sectional study included patients who were referred for in vitro fertilisation/intracytoplasmicsperm injection (IVF/ICSI) therapy from 2013 to 2016. All nulliparous women who met the inclusioncriteria were between 20-38 years of age and presented for ultrasound measurements prior to fresh embryo transfer(ET). Endometrial length was measured by transvaginal ultrasound (TVS) with a Medison Accuvix device on the dayof human chorionic gonadotropin (hCG) administration. The relationship between endometrial length and treatmentsuccess was assessed. The independent sample t test, receiver operating characteristic (ROC) curve and the area underthe curve (AUC) index and chi-square test were used for data analysis. P values <0.05 were statistically significant.
There was a significant relationship between endometrial length (41.5%) and treatment success (p <0.05).The endometrial length of 41.5(mm) with a sensitivity of 66.7%, specificity of 50.6%, positive predictive value of46.8%, negative predictive value of 69.4%, and efficiency of 56.62% can be used as a proper cut-off point with anAUC of 0.63. The value of 41.5(mm) for endometrial length can be used as a proper cut-off point for prediction of ahigher ART success rate. We recommend TVS as the first step for assessment of uterine and endometrium receptivityin the ART cycle.

We investigated the impact of the choice of catheter type and tenaculum use on pregnancy related outcomesin intrauterine insemination (IUI) treatments.

A total of 338 consecutive IUI cycles were assessed in this retrospective study. Participantswere divided according to the insemination technique - soft catheter (group 1; n=175), firm catheter (group 2; n=100),or tenaculum (group 3; n=63). Clinical, laboratory, semen parameters and pregnancy related outcomes were compared.

Demographic characteristics and laboratory parameters were similar between the groups (P>0.05). The clinicalpregnancy rate (CPR) was significantly higher in the firm catheter (19%, 19/100) and tenaculum (31.7%, 20/63)groups compared to the soft catheter group (5.1%, 9/175, P<0.001). There were no significant differences betweenthe groups in live birth and miscarriage rates per clinical pregnancy (P>0.05).

Our findings indicate that the use of a firm catheter or tenaculum for IUI might result in a higher CPR, butmight not have a considerable effect on the live birth rate (LBR). Further prospective randomized studies are requiredto determine the long-term effects of the catheter type or tenaculum use on IUI success.

Mucin-1(Muc1) is one of the first molecules in the endometrium that confronts implanting embryos.There is insufficient knowledge about the impacts of diabetes and drugs developed for diabetes treatment on expressionof this molecule at the time of implantation. Therefore, this study aimed to investigate the impacts of diabetes andinsulin, metformin and pioglitazone on Muc1 expression at the time of implantation. This experimental study was conducted on a total of 63 female Wistar rats divided into 9groups. To induce type 1diabetes, streptozotocin (STZ) and for induction of type 2 diabetes, nicotinamide (NA) andSTZ were injected intraperitoneally. For superovulation, human menopausal gonadotropin (HMG) and human chorionicgonadotropin (HCG) were used. Insulin, metformin and pioglitazone were administered for two weeks. Finally,the endometrial expression of Muc1 was evaluated by quantitative real-time reverse transcription–polymerase chainreaction (RT-PCR). Muc1 expression was non-significantly increased in type 1 and type 2 diabetic groups compared to the controlgroup (P=0.61 and 0.13, respectively); also, it increased in insulin-treated type 1 diabetic group compared to thecontrol group (P=0.0001). Its expression was increased in insulin-treated type 1 diabetic group compared to untreateddiabetic group (P=0.001). The expression level of Muc1 was significantly reduced in superovulated and insulin-treatedtype 1 diabetic group compared to the insulin-treated type 1 diabetic group (P=0.001). One of the causes of fertility problems in diabetes, is changes in Muc1 expression during implantation.On the other hand, the use of insulin in these patients can even lead to overexpression of this gene and worsen thecondition. However, these changes can be partially mitigated by assisted reproductive technology (ART) such as superovulation.Also, treatment with metformin and pioglitazone can restore Muc1 expression to near normal levels andhas beneficial effects on implantation

3,4-Methylenedioxymethamphetamine (MDMA) disrupts function of the endocrine system and differentorgans such as heart, blood vessels, kidney, liver and nervous systems. This study was conducted to evaluateimpact of MDMA on apoptosis and Zinc in the MDMA-induced apoptosis of cultured Sertoli cells by measuringCaspase-3 gene expression.

In this experimental study, Sertoli cells were incubated with MDMA (0, 0.5, 1, 3, 5 mM),Zinc (0, 8, 16, 32, 64 μM) and Zinc (8 μM) prior to adding MDMA (5 mM) for 24 and 48 hours. MTT assay wasused for evaluating impacts of these conditions on the viability of Sertoli cells. Caspase-3 gene expression level wasdetected using quantitative reverse transcription PCR (qRT-PCR) in all of the tested groups.

Finding showed that cellular viability was decreased and level of Caspase-3 mRNA was increased in MDMAtreated cells. Additionally, pre-treatment with Zinc (8 μM) attenuated MDMA-induced apoptosis and down-regulatedcaspase-3. The mean of caspase-3 mRNA level (fold change ± SE) was 3.98 ± 1.18, 0.31 ± 0.28, and 1.72 ± 0.28 in respectivelyMDMA (5 mM), Zinc (8 μM), and Zinc+MDMA groups vs. control group. The mean of Caspase-3 mRNA(fold change) was not statistically different in the tested groups (P>0.05), unless MDMA (5 mM) group (P = 0.008).

We suggest that MDMA toxicity could be involved in apoptosis of Sertoli cells. In addition, Zinc couldreduce MDMA-induced apoptosis by down-regulation of Caspase-3 mRNA levels.

The glial cell-derived neurotrophic factor (GDNF) family plays essential roles in the maintenance,growth, regulatory and signalling pathways of spermatogonial stem cells (SSCs). In this study, we analysed the expressionof anti-GDNF family receptor alpha 1 antibody (GFRa1) by immunohistochemistry (IHC), immunocytochemistry(ICC), Fluidigm real-time polymerase chain reaction (RT-PCR) and flow cytometry analyses. In this experiment study, ICC, IHC, Fluidigm RT-PCR and flow cytometry were used toanalyse the expression of the germ cell marker GFRa1 in testis tissue and SSC culture. IHC analysis showed that there were two groups of GFRa1 positive cells in the seminiferous tubules basedon their location and expression shape - a small round punctuated shape on the basal compartment donut shape anda C-shaped expression located between the basal and the luminal compartments of the seminiferous tubules. OCT4and PLZF positive cells may have similar patterns of expression as the first group. Assessment of the seminiferoustubule sections demonstrated that about 27% of the SSCs were positive for GFRa1. Fluidigm RT-PCR confirmed thesignificant expression (p <0.001) of GFRa1 in the SSCs compared to testicular stromal cells (TSCs). Flow cytometryanalysis demonstrated that about 75% of the isolated SSCs colonies were positive for GFRa1. The results indicated that GFRa1 had a specific expression pattern both In Vivo and In Vitro . This finding could be helpful for understanding the proliferation, maintenance and signalling pathways of SSCs, and differentiation
of meiotic and haploid germ cells.

The most common mental disorders in infertile patients are depression and anxiety. The four-itemPatient Health Questionnaire-4 (PHQ-4) is a widely used tool that consists of the PHQ-2 depression and GeneralizedAnxiety Disorder-2 (GAD-2) scales. Given that PHQ-4 has not been validated in infertile patients, this study aimed toexamine its reliability and validity in this population. Participants in this cross-sectional study consisted of 539 infertile patients from a referralfertility centre in Tehran, Iran. The PHQ-4, Hospital Anxiety and Depression Scale (HADS), World Health Organisation-Five Well-Being Index (WHO-5), Penn State Worry Questionnaire (PSWQ) and demographic/infertility questionnaireswere administered to all participants. Factor structure and internal consistency of PHQ-4 were evaluatedvia confirmatory factor analysis (CFA) and Cronbach’s alpha, respectively. The convergent validity of this scale wasexamined by its relationship with HADS, WHO-5 and PSWQ. CFA results provided support for a two-factor model of PHQ-4. Internal consistency of the PHQ-4 and its subscalesboth were elevated with Cronbach’s alpha coefficients of 0.767 (PHQ-4), 0.780 (PHQ-2) and 0.814 (GAD-2). Inter-itemcorrelations were between 0.386 and 0.639, and corrected item-total correlations were between 0.576 and 0.687. PHQ-4,PHQ-2 and GAD-2 showed positive correlations with measures of HADS-anxiety, HADS-depression, and PSWQ and negativecorrelations with WHO-5, which confirmed convergent validity. Among demographic/fertility variables, we observedthat gender, infertility duration, and failure in previous treatment were correlated with PHQ-4 and its subscales scores. The PHQ-4 is a reliable and valid ultra-brief screening instrument for measuring both anxiety and depressivesymptoms in infertile patients.

Despite significant advances in reproductive technology, using donor assisted reproductive technologyis a double-edged sword that has numerous challenges. One of the most challenging issues for couples is whether ornot to disclose this information to donor offspring. This study, therefore, explored infertile couples’ decision to disclosedonor conception to their future child. This qualitative study was conducted using content analysis approach in 2012 in the MiladInfertility Centre, Mashhad, Iran. Data were collected through semi-structured interviews with 32 infertile personsincluding nine couples and 14 women who were selected by purposive sampling. Data were analysed by conventionalqualitative content analysis adopted by Graneheim and Lundman using MAXQDA 2010 software. Two categories were emerged: ‘not to disclose information to the child’ and ‘to disclose information tothe child’. The first category consisted of three subcategories: 1. child support from probable harms; 2.to maintainhealthy family relationships; and 3. lack of a compelling reason to disclose this information. The second categoryembraced four subcategories: 1. awareness of the others; 2. emergence of new living conditions; 3. appreciation forthe donor; and 4. honesty among family members. The main reason for not disclosing information was to protect thechild from probable harm. Although protecting children from possible harms was a major reason for infertile couples' secrecy,keeping this secret would not be always easy. Therefore, increasing public awareness about the donation process inorder to change the beliefs of community and eliminate the infertile couples’ concerns would help them to overcomethis problem. Additionally, long-term psychological counselling during and after the donation process is highly recommended.

Birth spacing, especially the first birth interval (FBI), is a suitable index to investigate the delayed fertilitythat results in a low fertility pattern. Non-parametric familiar alternatives to the Cox proportional hazard regression(CPH) model include survival trees that can automatically discover certain types of covariate interactions according tothe survival length. The aim of this research is to study FBI influential factors by applying survival trees. In this cross-sectional study, 610 married women (aged 15-49 years), were selected fromdifferent regions of Tehran, Iran in the Winter and Spring of 2017. Classification and regression trees (CART) for theFBI survival tree were fitted by taking into consideration the predictors of each woman’s age, age at first marriage,educational level, partner’s educational level, activity, region, house ownership, kinship, partner’s race, marriage timeattitude, and expenditure using R packages. Since the PH assumption of the CPH model was not confirmed for the covariates of age at first marriage (P=0.001),kinship (P=0.000), partner’s race (P=0.001), and marriage time attitude (P=0.042), the results of this model were not valid.Thus, a CART survival tree was fitted. The validity of the fitted model in assessing FBI was confirmed by the significantresult of the log rank test (P<0.01) for the terminal nodes and the value of the separation measure, which was greater than1. The fitted tree had 13 terminal nodes and the most vital FBI predictor was women’s age. The longest FBI belonged toeducated and employed women, ages 30-37 years. Analysing patterns of birth spacing by selecting the appropriate statistical method provides important informationfor health policymakers. In order to formulate appropriate demographic policies, it is essential to take into considerationage, educational level and job status of the women, all of which have essential roles on their decision to have children.

The most common mesenchymal tumours of the uterine corpus originate from smooth muscle cells. Leiomyomas arecommonly found in women of child bearing age; however, leiomyosarcomas occur later in life (50-55 years of age).Most uterine leiomyosarcomas occur de novo, but rare cases of leiomyosarcomas that arise from leiomyomas havebeen reported. We present two cases of fertile women with submucosal leiomyomas that became malignant and discusstheir pathologic features and immunohistochemistry studies for P16, P53 and Ki67.

Coronavirus disease 2019 (COVID-19) prevalence has caused many problems in society and disrupted many regular aspects of life. COVID-19 contains major structural proteins that among them, S protein can promote fusion of the viral and cellular membranes and facilitate the entry of coronavirus into the host cells. Basigin (BSG) is one of the most important receptors for COVID-19 that mediates its entry to host cells. Also, Basigin has an important role in male and female reproduction. Basigin is expressed in the uterus and plays an important role during embryo implantation and needed for successful implantation. Therefore, disruption or inhibition of Basigin causes to a weakness in embryo implantation. Therefore, if a woman or a man is infected with COVID-19, it is recommended that they do not attempt to conception until their treatment is complete. It is also recommended tests for COVID-19 be performed on infertile couples before using assisted reproductive technology (ART).

In this article, we reviewed and compareed some of COVID-19 and pregnancy guidelines, which is useful for pregnant women including who have a history of infertility specially who have undergone assisted reproductive techniques. The general advice given for prenatal care is to reduce face-to-face visits. All women who refer for prenatal visits should be evaluated for signs of the infection at the time of entry. The triage of suspected women should be separate from other patients. Outpatient monitoring with a 14-day self-quarantine can be considered for asymptomatic infected women and also for women with mild symptoms. Inpatient management criteria include moderate to severe symptoms and the target level of oxygen saturation is considered between 92% and 95% in different guidelines. In the presence of fever, it is important to conduct a thorough examination of the other causes of the fever. It is important to monitor fluid intake and output, maintain fluid and electrolyte balance and prevent fluid overload. Thromboembolic prophylaxis is recommended. Corticosteroid administration in based on obstetrics indications, unless in severe critical ill cases which should be based on MDT decision. A positive COVID-19 result which lacks other obstetrics causes can not be considered as indicationfor delivery in mild and asymptomatic cases. In critically ill pregnant women, an individualized decision should be made about delivery time by the MDT. General anesthetic should be avoided unless inevitable for standard procedures such as intubation is an aerosol-generating procedure. There is agreement that babies born to infected mothers, even if isolated from the mother at birth, should be considered a close contact of the mother and tested for COVID-19 and also separated from other neonates. Breastfeeding is encouraged and hand hygiene and face mask during feeding is highly recommended by all guidelines.