International Journal Of Fertility and Sterility
Volume:17 Issue: 4, Oct-Dec 2023

Recurrent pregnancy loss (RPL) or recurrent miscarriage is the failure of pregnancy before 20-24 weeks that influencesaround 2-5% of couples. Several genetic, immunological, environmental and physical factors may influenceRPL. Although various traditional methods have been used to treat post-implantation failures, identifying the mechanismsunderlying RPL may improve an effective treatment. Recent evidence suggested that gene expression alterationspresented essential roles in the occurrence of RPL. It has been found that long non-coding RNAs (lncRNAs) playfunctional roles in pregnancy pathologies, such as recurrent miscarriage. lncRNAs can function as dynamic scaffolds,modulate chromatin function, guide and bind to microRNAs (miRNAs) or transcription factors. lncRNAs, by targetingvarious miRNAs and mRNAs, play essential roles in the progression or suppression of RPL. Therefore, targetinglncRNAs and their downstream targets might be a suitable strategy for diagnosis and treatment of RPL. In this review,we summarized emerging roles of several lncRNAs in stimulation or suppression of RPL.

Endometriosis is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside theuterine cavity. Several authors have reported on the association between changes in inflammatory marker levelsand the maintenance or progression of endometriosis and associated infertility. Interleukin-6 (IL-6) is the moststudied cytokine in endometriosis and has important functions in reproductive physiology. The aim of this study isto review systematically available evidence about altered IL-6 concentrations in endometriosis-related infertility.This is a systematic review including all studies until December 2022 in which IL-6 in serum, peritoneal fluid,follicular fluid, or endometrial biopsy specimens was measured and that correlated their findings with endometriosis-associated infertility. Fifteen studies were included in the systematic review. There seems to be a correlationbetween elevated serum and peritoneal fluid IL-6 concentrations and the occurrence of endometriosis-associatedinfertility. IL-6 may be a potential diagnostic or biomarker tool for the prediction of endometriosis-related infertility.However, the numerous biases affecting the available studies, and challenges in endometriosis research reproducibilitymust be considered. Future investigations should pay attention to factors that may affect the results, suchas the choice of suitable control groups, and carefully consider other pathological conditions affecting the patients,endometriosis stage, and type of lesion.

Human leukocyte antigen G (HLA-G) levels are among the biomarkers suggested for pre-eclampsia (PE). This studyis aimed at determining the possible relationship between low soluble HLA-G (sHLA-G) levels in maternal blood atthe beginning of pregnancy and subsequent PE. We searched the international scientific databases of Web of Science,Embase, PubMed, Cochrane, and Scopus. We extracted the studies investigating the relationship between the serumlevels of HLA-G in the first trimester of pregnancy and the onset of PE using the appropriate keywords. The collecteddata were analyzed using the random-effects meta-analysis model and STATA (version 14). A total of 5 studies metthe eligibility criteria, and the total sample size was 668 subjects. The mean and SD age of case subjects was 31.41 ±4.16 years, while it was 30.56 ± 3.5 for control subjects. According to the findings, there was an inverse relationshipbetween HLA-G serum level in the first trimester of pregnancy and the subsequent onset of PE, standard mean difference(SMD)=-1.51 [95% confidence interval (CI): -2.26, -0.75, I2=90.8%, P=0.000]. Based on these results, lowsHLA-G level in early pregnancy has a positive correlation with subsequent PE, and the significant role of sHLA-Gin the early stages of placentation can be proven.

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. 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). 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. 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.

Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterinetissue. Women undergoing assisted reproductive technologies (ART), particularly frozen embryo transfer (FET), arein high-risk populations for EP. Mucin1 (MUC1), fibroblast growth factor-2 (FGF2), and Heparin-binding epidermalgrowth factor (HBEGF) genes are involved in the endometrial receptivity pathway, leading to normal eutopic implantation;Although, their relevance in the tubal pregnancy after FET is unknown. We aimed evaluation of Mucin1, FGF2,and HBEGF expression fold as endometrial receptive markers in the EP patients following the FET cycle. A case-control study was conducted on ten patients (five EP patients and five women in thepseudo-pregnancy group, as the control samples). Pseudo-pregnancy group was established in women who were candidatesfor hysterectomy for benign diseases. Fallopian tube biopsies and corresponding endometrial tissues from thesepatients were taken during the hysterectomy. However, the fallopian tube and endometrial tissues of EP patients wereobtained during salpingectomy. The mRNA expressions of MUC1, FGF2, and HBEGF genes in the fallopian tube andendometrial tissues were measured by real-time polymerase chain reaction (PCR) assay. MUC1 mRNA expression level in the endometrium of the case group was higher than in the control group(P=0.04); however, its mRNA expression in the fallopian samples of the case group in comparison with the control groupwas significantly decreased (P=0.001). The HBEGF mRNA expression level was not significantly different between thecase and control endometrium, whereas its expression was significantly increased in the case fallopian samples comparedwith the control ones (P=0.001). The same pattern was observed for FGF2 mRNA expression level in the fallopian samplesof the case group but was significantly reduced in the endometrial samples in comparison with the control samples (P=0.03). MUC1, FGF2, and HBEGF gene mRNA expression changes may explain the embryo rejection from theuterus and the establishment of a receptive phenotype in fallopian cells.

Polycystic ovary syndrome (PCOS) and oral health are found to share a reciprocal link. Previous substantiatingevidences suggest that PCOS may have a confounding effect on periodontal health and may quantitatively modifythe composition of the oral microbiome. To analyze the role of PCOS as a risk factor in causing periodontal disease, wecompared and evaluated the levels of Porphyromonas gingivalis and Fusobacterium nucleatum in patients with polycysticovary syndrome, polycystic ovary syndrome, chronic periodontitis, polycystic ovary syndrome, and gingivitis, andhealthy controls. In this case-control study, 40 female participants are enrolled and grouped into four groupswhich included healthy female individuals, patients with PCOS, patients with PCOS and gingivitis, and patients withPCOS and periodontitis. Periodontal examination is assessed primarily on all the participants using a UNC-15 probe.Dental plaque is then collected using a sterile curette in one stroke and transferred into an Eppendorf tube containingTE Buffer (Tris-EDTA buffer) solution. The level of Porphyromonas gingivalis and Fusobacterium nucleatum wasestimated by real-time polymerase chain reaction (PCR). The levels of Fusobacterium nucleatum were observed to be significantly higher in group with patients withPCOS and periodontitis. PCOS may have an impact on the composition of oral microflora causing repercussions in periodontalhealth.

Corona virus disease-19 (COVID-19) pandemic also led to a reduction or even the suspension of electivehealth services. These decisions affected in vitro fertilization (IVF) programs worldwide. Therefore, it is essential to mapthe readiness of IVF clinics in providing safety in this situation and in the future. This is a retrospective qualitative and quantitative research done in 2021 that involved three IVFclinics of Jakarta, Indonesia. Those three clinics were government-owned, private-owned, and educational and trainingcenter. The qualitative data of each clinic’s readiness towards COVID-19 was obtained from interviews with the clinicsstaff. The quantitative data were collected from the clinics patients’ number and demographic data from 2019-2021 as wellas from COVID-19 databases. Both data sets were analysed descriptively and only for the quantitative analysis Stata version16 was used. There were changes in the domiciles and number of patients attending the three clinics. The ratio of patientsfrom Jakarta increased while patients from outside Java Island decreased. There was a drop in annual patient numbersin 2020. However, from June 2020 to December 2021, the number of monthly IVF cycles increased significantly by 3.5cycles per month (P=0.001). There was no association between IVF patients’ attendance numbers and COVID-19 cases(P=0.785). One of the clinics had a negative pressure operating theatre, which made them more confident in treatingpatients with COVID-19 positive and made them even had higher IVF cycles started than the pre-pandemic period. Those three clinics are prepared in facing COVID-19, as they complied with government regulations. Asthe COVID-19 pandemic progressed, the number of patients gradually returned to normal.

During the Coronavirus disease 2019 (COVID-19) pandemic, there was always concern about damageto different organs of the body. In this study, we aimed to determine if coronavirus 2 (SARS-CoV-2) could influencethe sperm parameters in inpatient adult men with COVID-19. In this prospective study during 2021, 22 patients with COVID-19 diagnosed with polymerasechain reaction (PCR) test and clinical symptoms and history of admission and 19 volunteer healthy menas the control group participated. They were asked to provide semen samples at 2 and 6 months after hospital dischargeand the same time for the control group. The following parameters were measured in all semen samples andbeside the demographic data, they compared between the two groups: volume (mL), sperm concentration (106/mL),total motile sperm percentage, progressive percentage, normal morphology percentage, and DNA fragmentationindex (DFI). The mean ± SD age of the participants in the COVID and control groups was 46.36 ± 9.94 and 45.84 ±10.21 years, respectively (P=0.869). The mean ± SD body mass index (BMIs) of the participants in the COVID andcontrol groups were 28.6 ± 5.460 and 29.6 ± 6.092, respectively (P=0.579). The mean ± SD number of children was1.41 ± 1.054 in the COVID group and 1.47 ± 1.073 in the control group (P=0.847). All the sperm parameters weresignificantly impaired after 2 months in the COVID group in comparison with the control group (P<0.05). After 4months from first sampling, all the parameters were improved significantly (except normal morphology) but had notyet reached the level of the control group. SARS-CoV-2 affected semen parameters in patients admitted because of COVID-19, in the short term. Itis expected that this will improve with time.

In vitro fertilization (IVF) remains a main treatment for infertility cases. Post-injection human chorionic gonadotropin(hCG) level is an essential factor in determining oocyte maturation rate in IVF. This study aimed to determine therelationship between 12 hours post-injection serum hCG level and oocyte maturation rate among IVF participants. A cross-sectional study on IVF participants was done at a tertiary hospital in Indonesia fromJanuary 2020 to December 2021. Subjects were injected with 250 μg of recombinant-hCG (r-hCG) subcutaneously.Twelve hours post-injection serum hCG levels and oocyte maturation rate data were retrieved and analyzed accordingly. Twenty-eight subjects were recruited into the study. Higher 12 hours post-injection serum hCG was relatedto oocyte maturation rate (P=0.046). The cut-off point of 12 hours post-injection serum hCG to predict better oocytematuration rate was 90.15 mIU/mL (sensitivity 68.2%, specificity 83.3%). Oocyte maturation rate may be predictedusing body mass index (BMI) and 12 hours post-injection serum hCG. Higher 12 hours post-injection serum hCG was associated with a higher oocyte maturation rate in IVFsubjects.

In many diabetic patients, spermatogenesis complications are frequent causing infertility problems.This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes.

In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for onemonth and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats withmore than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided intofour groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2(G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphatebuffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month.

In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly:The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Baxgene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone(P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008),sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 geneexpression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values thatwas significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantlyimproved these abnormal changes in Forskolin-treated group.

Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improvessperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

This study aimed to evaluate the predicting factors affecting sperm retrieval. We prospectively assessedthe relationship between sonographic and microdissection testicular sperm extraction (mTESE) findings in Klinefeltersyndrome (KS).

In this prospective study, 44 azoospermic men with 47, XXY karyotypes participated in thisstudy. In order to evaluate the amount of blood supply in different parts of testicular tissue, a doppler ultra-sonographicwas performed. Also, for the detection of sperm in this group mTESE technique was performed.

The age average of positive mTESE and negative mTESE groups was 29.4 and 33.6 years, respectively. Bycomparing the testicle volume (based on the data obtained from the clinical examinations conducted by the urologist)it was determined that there is no significant difference between mTESE positive and negative groups. Folliclestimulatinghormone (FSH) levels in men with negative mTESE (P=0.03) and testosterone levels in men with positivemTESE significantly increased (P=0.017). The overall rate of testis vascularity was significantly higher in the positivemTESE group than in the negative mTESE group. The clinical pregnancy rate in positive mTESE men was 9% percycle, 16.6% per embryos were transferred (ET), and 12.5% per cycle.

Totally, our observation indicated that there is not a significant relationship between sonographic and mTESEresults in KS patients. However, more investigations with bigger sample Size can be useful to validate our results.

Monosodium glutamate (MSG) is a popular food flavor enhancer, and a glutamate subset that inducesdifferent toxicities such as hepatotoxicity, neurotoxicity, reproductive toxicity, and nephrotoxicity. This study wasconducted to assess the effects of MSG on the α7 and α4 nicotinic acetylcholine receptor (nACHR) protein subunitsexpression of adult rat testis and the safety role of vitamin C. For this experimental research, 24 rats were haphazardly grouped into four equal groups(n=6) and orally gavaged for 30 days as follows: control group (distilled water gavage), MSG group (3 g/kg/b.w/day), vitamin C group (150 mg/kg/b.w/day), and MSG+vitamin C group (3 g/kg/b.w/day+150 mg/kg/b.w/day,respectively) that rats of all groups on the 30th day were anesthetized, and the left testes were used for of α4 andα7 nACHR protein subunit evaluation by immunohistochemistry (IHC). Statistical computations were performedusing Graph Pad Prism software. The present study revealed a significant reduction in the expression and optical density (OD) of α7 nACHRand α4 nACHR in the seminiferous tubules and intertubular connective tissue in the MSG group compared to thecontrol group. In the MSG+vitamin C group, the expression and OD of α7 nACHR and α4 nACHR increased in theseminiferous tubules and intertubular connective tissue but this improvement was not significant compared to theMSG group. MSG decreased the expression level of nACHR protein subunits, α7 and α4, in the seminiferous tubulesand interstitial testicular tissue. Vitamin C in the MSG+vitamin C group could not significantly improve the expressionof α7 and α4 nACHR subunits in testicular tissue. Probably, MSG toxicity can be compensated with higher doses ofvitamin C.

Sperm chromatin abnormalities are defects in nuclear maturation and DNA integrity. These defectsoriginated from defective spermatogenesis due to a lack of DNA repair during chromatin remodeling. Changes insemen elements can cause damage to chromatin. There is little information about the relationship between changesin trace metal elements and total antioxidant capacity (TAC) with sperm chromatin damage. The present study wasconducted to determine the relationship between Selenium (Se), Iron (Fe), Zinc (Zn), Copper (Cu) and the TAC ofsemen with the status of human sperm chromatin.

In this experimental study, semen samples (n=30) were collected from healthy men referredto Kermanshah Motazadi Hospital and stored in liquid nitrogen; after thawing and centrifugation, sperm were separated.The atomic absorption method was used to measure the concentration of metal elements. The TAC was evaluatedusing the ferric-reducing antioxidant capacity of the plasma method. Furthermore, the integrity of sperm chromatinwas measured using the sperm DNA fragmentation (SDF) method.

The status of sperm chromatin had a non-significant correlation with body mass index (BMI, P=0.25, r=0.21)and a non-significant negative correlation with sperm count (P=0.71, r=-0.71) and motility (P=0.75, r=0.61). In addition,there was no significant relationship between sperm chromatin and the TAC of semen (P=0.92, r=0.01). Additionally,there was no significant correlation between Se, Zn, or Cu concentration (P>0.05) and Fe concentration,which had a partially positive relationship with the chromatin state of sperm (P=0.24, r=0.20).

The trace metal elements in the seminal fluid did not play a significant role in the status of sperm chromatin.

Bisphenol A (BPA) is known as an endocrine disruptor that has harmful effects on general health. It iscommonly used in various industrial products. In this study we tried to evaluate the amount of BPA in urine samplesof the men referred to an infertility center.

The cross-sectional study population consisted of male partners of infertile couples, who werereferred to infertility clinic in Mazandaran, a northern state of Iran. Questionnaires included demographic characteristics,medical history, lifestyle factors, physical examinations. A semen sample and a spot urine sample were taken from eachparticipant. In the initial study group of 240 men, 3 groups were excluded, and 122 men remained for the analysis. Highperformanceliquid chromatography (HPLC) was applied to measure the amount of BPA in the urine samples.

BPA was not detected in about half of the samples (53.3%). Multiple linear regression analysis showed thatno significant relationship existed between the urine concentrations of BPA, semen parameters and male reproductivehormones. However, in a comparison with semen parameters in people with detectable urine BPA versus nondetectableones, an inverse association was noticed with sperm concentration. In other parameters, differences were notsignificant. Smoking had no effects on sperm parameters, but body mass index (BMI) ≥25 reduced the percentage ofnormal sperm parameters.

In most participants, urinary BPA was not detected. Probably in this study low environmental exposure toBPA is the cause of lower urine BPA concentrations compared to other industrially developed countries. Therefore, nooverall relationship was observed between BPA level and male infertility.

One of the most common endocrine disorders of reproductive age women is polycystic ovary syndrome(PCOS). Women with PCOS are at risk for infertility, endometrial cancer, metabolic disorders, and cardiovascular disease.Awareness of the signs and symptoms of PCOS can be effective in diagnosing early stage PCOS and promotingquality of life (QoL). This study assesses the awareness of PCOS in schoolgirls and their mothers. This cross-sectional study was carried out on 1580 high school girls and 480 of their mothersin Tehran (capital of Iran) in 2017 and 2018. We used the stratified sampling method and divided Tehran into fivegeographic regions: north, south, east, west, and central. Schools were randomly selected from each of these regions.Students and their mothers separately answered a self-administered questionnaire that pertained to their knowledgeof PCOS. Statistical analyses were carried out with SPSS, version 22 (Inc. Chicago, IL, USA) and R version 3.2.1. Students had an average age of 16.97 ± 0.84 years and their mothers’ average age was 45.19 ± 5.03 years.The average body mass index (BMI) of the students was 22.01 ± 5.54 kg/m2. The results of this study showed that only48 students (3.2%) and 148 mothers (27%) had acceptable knowledge about PCOS. The knowledge of students aboutPCOS was positively related to their mothers’ knowledge about PCOS (P<0.001). The level of PCOS awareness in Iranian women is insufficient and this may affect their QoL. Therefore,the health authorities should implement educational programs to challenge women’s incorrect beliefs about PCOS andincrease their awareness of this disease.

Women who undergo in vitro fertilization (IVF) cycles should successfully go via multiple stages (i.e.,clinical pregnancy, no abortion under 12 weeks, no abortion under 20 weeks, and delivery) to achieve a live birth. Inthis study, data from multiple IVF cycles and its multiple stages were reanalyzed to illustrate the success factors associatedwith various stages of IVF cycles in a population of Iranian infertile women. This historical cohort study includes 3676 assisted reproductive technology (ART) cycles.Covariates take into account in this study were women’s age, type of infertility (primary, secondary), body mass index(BMI), cause of infertility, history of abortion, duration of infertility, number of oocytes, number of embryos, fertilizationrate, semen factors (Spermogram) and having polycystic ovarian syndrome (PCOS) during IVF cycles. Joint modelingwas fitted to apply informative cluster size. Increasing age un women was associated with an increase in the BMI and a positive history of abortion andPCOS, and also, an increase in the number of treatment cycles, while in men was associated with the negative spermogram.With the increase in the number of treatment cycles, the result of the IVF success decreased, but with theincrease in the number of embryos, fertilization rate and also, quality and / or quantity parameters of spermogram, weencountered with an increase in the IVF success rate. It seems that a joint model of the number of treatment cycles and the result of IVF is a valuable statistical modelthat does not ignore the significant effect of cycle numbers, while this issue is ignored usually in the univariate models.