International Journal Of Fertility and Sterility
Volume:16 Issue: 1, Jan - Mar 2022

Recent studies have indicated that epigenetic alterations are critical for normal function and development of spermatozoa during the fertilization process. This review will focus on the latest advances in epigenome profiling of the chromatin modifications during sperm development, as well as the potential roles of epigenetic mechanisms in the context of male infertility. In this review, all data were collected from published studies that considered the effect of epigenetic abnormalities on human spermatogenesis, sperm parameters quality, fertilization process, embryo development and live births. The database PubMed was searched for all experimental and clinical studies using the Keywords “epigenetic modifications”, “male infertility”, “spermatogenesis”, “embryo development” and “reproductive function”. Post-translational modifications of histone, DNA methylations and chromatin remodeling are among the most common forms of epigenetic modifications that regulate all stages of spermatogenesis and fertilization process. Incorrect epigenetic modifications of certain genes involved in the spermatogenesis and sperm maturation may be a main reason of male reproductive disorder and infertility. Most importantly, abnormal patterns of epigenetic modifications or transgenerational phenotypes and miRNAs expression may be transmitted from one generation to the next through assisted reproductive techniques (ART) and cause an increased risk of birth defects, infertility and congenital anomalies in children. Epigenetic modifications must be considered as a one of the main factors of unexplained male infertility etiology. Due to high risk of transmitting incorrect primary imprints to offspring, there is a need for more research into epigenetic alterations in couples who benefit of ART support.

Observational studies that inspected the association of USP26, TEX15, and TNP2 novel single nucleotidepolymorphism (SNP) with odds of male infertility are sparse. Male infertility prevalence in Iran is reported morethan global prevalence, while about 30-50% of infertile male have no distinct reason yet and they are considered asidiopathic male infertility. This study was conducted to investigate association of different SNPs of USP26, TEX15,and TNP2 genes with male infertility among the Iranian population.

In this population-based case-control study, 120 diagnosed idiopathic azoospermia or severeoligospermia infertile cases range of 25-45 years old, and 120 age-matched fertile controls were recruited. Overall,six different variants from three genes were genotyped including USP26 rs61741870, USP26 rs144039408, TEX15rs323344, TEX15 rs61732458, TNP2 rs11640138 and TNP2 rs199536093 by using amplification-refractory mutationsystem polymerase chain reaction (ARMS-PCR) methods.

Although there was no significant association of USP26 gene variants (rs61741870 and rs144039408) withmen infertility, we found a significant association of TEX15 rs323344 T allele and odds of idiopathic azoospermiacompared to recessive allele (odds ratio [OR]: 0.259, confidence intervals [CI]: 0.083-0.811). We determined significantassociations of TEX15 rs61732458 AC and CA+AA with male infertility compared to normal homozygote (OR:3.776, CI: 2.049-6.957, OR: 3.818, CI: 2.077-7.016, respectively). Significant association was seen among TNP2rs199536093 GG genotype and idiopathic azoospermia compared to normal homozygote (OR: 0.348, CI: 0.129-0.939). We also observed heterozygote overdominance in TEX15 rs61732458 and TNP2 rs199536093.

We found novel polymorphisms related to male infertility among Iranian population. However, largerstudies are needed to confirm the obtained results.

Implementation of sperm preparation techniques based on cellular and molecular characteristics can improve the clinical outcomes of couples with male factor infertility. These methods attempt to select better sperm compared to classical methods of preparation such as swim-up and density gradient centrifugation (DGC). In this view, the aim of this study was the comparison of clinical outcomes of magnetic-activated cell separation (MACS) followed by DGC or DGC alone in infertile men undergoing intracytoplasmic sperm injection (ICSI). For this prospective single parallel blind clinical trial study, 206 infertile couples with male factor infertility and having abnormal sperm morphology higher than 96% were included. 106 and 100 couples were considered for the study (MACS-DGC) and control group (DGC), respectively. Clinical outcomes of ICSI; fertilization, embryo quality, and implantation, pregnancy rates were compared between two groups. Mean of fertilization (80.19 ± 1.88 vs. 75.63 ± 2.06, P=0.1), top embryo quality on the day 3 (30.22 ± 3.59 vs. 17.96 ± 2.9, P=0.009), clinical pregnancy (30.76% vs. 22.22%, P=0.19), and implantation rate (18.12% vs. 10.42%, P=0.04) were higher in the study group compared to the control group. Sperm preparation by MACS followed by DGC in teratozoospermic men could improve the clinical outcomes after ICSI (Registration number: IRCT201610317223N8).

Somatic cell nuclear transfer (SCNT) is an approach for the propagation of elite animals. In vitro condition, especially the composition of culture media has a profound effect on the developmental competency of in vitro derived e mbryos. There are limited studies evaluating the effect of culture media on SCNT outcomes. To address this gap, we compare the effect of two culture media synthetic oviduct fluid (SOF) vs. commercial bracket-oliphant (BO) on developmental comptenecy. In this experimental study, embryos derived from in vitro fertilized (IVF) and SCNT were cultured in both BO and SOF media for 7 days. In addition to the assessment of cleavage and blastocyst on day 3, and 7, the quantitative expression of 16 genes in theresultant blastocysts were assessed. The resultant SCNT blastocysts from SOF and BO groups were also transferred to the synchronized recipient for developmental competency to term. The blastocyst rate in the BO medium was significantly higher than that of the SOF medium in the SCNT group (P<0.05). All of the examined genes showed increased expression levels in SCNT blastocyst in both media compared to IVF Blastocyst. In the IVF group, Oct4, Bmpr1, and Gcn5 showed significantly higher expression in the SOF medium compared to the BO medium while Akt, Fgfr4, Sox2 showed significantly lower expression in the SOF medium compared to the BO medium. In the SCNT group, Fgfr4, Gcn5, Fzd, Ctnnb, Bmpr1, and Fgfr4 showed significantly higher expression in SOF compared to BO derived blastocyst. It appears that in SCNT blastocysts, gene regulation is less controlled compared to IVF ones, irrespective of the type of medium. In addition, there are differences regarding certain genes expressions between IVF and SCNT derived blastocysts between SOF and BO, reiterating that culture composition affects developmental competency and gene expression.

Minocycline is a widely used bacteriostatic antibiotic with various functions. The aim of this study wasto investigate impact of apoptotic genes in ovary of the torsion/detorsion treated rat model by minocycline. This experimental study was performed in 32 female Wistar rats classified in four groups,including: i. sham, ii. TD: torsion/detorsion group received normal saline, iii. TDM: torsion/detorsion group treatedwith 40 mg/kg Minocycline, and iv. MC: healthy group received 40 mg/kg Minocycline. After treatment period (7days), histoplogical parameters, oxidative stress markers and hormone profile of serum as well as the expression ofBax and Bcl-2 genes were measured in the ovary of rats. Levels of superoxide dismutase (SOD), glutathione peroxidase (GPX) and estrogen were decreased in theTD group and significantly increased in the treated groups (P=0.001). Levels of malondialdehyde (MDA) and testosteronewere increased in the TD group and decreased in the treated groups (P=0.001). Expression level of Bax waselevated in the TD group, while it was attenuated in the treated groups (P=0.001). Expression level of Bcl-2 wassignificantly increased in treated groups (P=0.001). Minocycline can repair oxidative damage in ovarian tissue and regulate apoptotic-related gene expressions.

It is thought that genetic factors are influential in the etiology of polycystic ovarian syndrome (PCOS),the most frequent endocrinological disorder of females in their reproductive age. This study was carried out to elucidatethe association of rs13429458 and rs12478601 single nucleotide polymorphisms (SNPs) of the THADA gene andthe risk of the PCOS among a population of Iranian female patients. This case-control study contains 66 infertile women with PCOS (patient group) and 44healthy women without PCOS (control group) that referred to the IVF Unit of the Infertility Research Center of theAcademic Center for Education, Culture and Research (ACECR). The polymerase chain reaction (PCR) was utilizedto amplify genome DNA as well as direct sequencing to determine SNPs. The THADA rs12478601 and rs13429458genotypes were consequently examined with amplification refractory mutation system-PCR (ARMS-PCR). In this study, we observed that rs13429458 polymorphism was not associated with PCOS risk in two groups (P=0.42). On the other hand, data analysis indicated that the rs12478601 genotype significantly increased the risk of PCOS in the case group (P=0.032) in compared with control group. We found that the “T” allele of rs12478601 in the THADA gene had a significant relation to PCOS in the case group (odds ratio [OR]: 2.574, 95% confidence interval [CI]: 1.439-4.604, P=0.001). This study has presented further evidence that TT and CT genotype of THADA rs12478601 is associatedwith a high risk of PCOS.

The aim of our study was to detect the rate of unexplained total fertilization failure (TFF) after intracytoplasmic sperm injection (ICSI) and identify its risk factors and retreatment prognosis. In this retrospective case-control study, we searched the computerized database ofthe Royan Institute (Tehran, Iran) from March 2015 to March 2019 and retrieved all cases diagnosed withTFF after ICSI. TFF cases that did not have any recognized risk factors were classified as unexplained (subgroupA). Cases with recognized risk factors were classified as subgroup B. The control group was randomlyselected from infertile couples who underwent ICSI cycles with fertilization of at least one oocyte during thesame time interval. Characteristics and treatment outcomes of the cases with unexplained TFF (subgroup A)were compared to the control group, and to the other TFF cases (subgroup B). Out of 18,750 couples who underwent ICSI cycles, 296 (1.58%) experienced TFF for the first time.Of these, 49 (16.5%) couples were diagnosed as unexplained TFF (subgroup A) and 247 (83.5%) were placedin subgroup B, TFF with expected risk factors. Multivariable logistic regression analysis showed that the totalnumber of mature oocytes (P<0.001), duration of infertility (P=0.043), and women’s body mass index (BMI,P<0.001) were significant predictive factors for unexplained TFF. In the ICSI cycle after TFF, clinical pregnancyand live birth rates in subgroup A were higher than subgroup B. Although differences between thesegroups were not statistically significant (P=0.14 and P=0.07, respectively), this finding could be clinicallyimportant. Unexplained TFF following ICSI is a rare event significantly related to a lower number of matureoocytes, longer duration of infertility and higher female BMI. It has a good prognosis in retreatment cycles incomparison with expected TFF cases. Clinicians should take this into consideration for patient counseling andmanagement.

The differential diagnosis between uterine fibroid and adenomyosis is sometimes difficult; a precise diagnosis is required in women with infertility because of the different choice of treatments. Ultrasound elastography (UE) is a novel technique to evaluate the elasticity or the stiffness of the tissue of interest. The present study aims to compare UE shear wave velocity (SWV) among normal uterine myometrium, uterine fibroid, and adenomyosis, and assess the accuracy of shear wave elastography in the diagnosis of adenomyosis. This cross-sectional study recruited 25 subjects for each group (control, adenomyosis, and fibroid) from April 2019 to April 2020. Transvaginal UE using an Aplio 500 (Toshiba Medical Systems, Japan) with ultrasound mapping for point of tissue biopsy was performed for all subjects. The diagnosis was confirmed by histology. Masson’s trichrome staining for collagen was performed and quantified. The mean ± standard deviation (SD) for SWV was 3.44 ± 0.95 m/seconds (control group), 4.63 ± 1.45 m/seconds (adenomyosis group), and 4.53 ± 1.07 m/seconds (fibroid group). The mean SWV differed when comparing normal myometrium and adenomyosis after adjustments for age and endometrial pathology (P=0.019). The cut-off point of SWV at 3.465 m/seconds could differentiate adenomyosis from the normal uterus with an 80% sensitivity, 80% specificity, and an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.68-0.93) (P<0.001). No significant difference in SWV between the adenomyosis and fibroid groups was detected. Shear wave elastography could be an alternative tool to distinguish between normal myometrium and adenomyosis; however, it could not differentiate adenomyosis from uterine fibroid or uterine fibroid from normal myometrium.

Polycystic ovary syndrome (PCOS) is a common condition with a multifactorial aetiology. Chronic periodontitis (CP) is an immunoinflammatory disease that is linked to PCOS via the excessive production of reactive oxygen species (ROS), which leads to an imbalance in the antioxidant system. However, limited studies have evaluated the relationship between these diseases. The current study aims to evaluate the levels of advanced oxidation protein products (AOPP) in patients with periodontitis and PCOS. Four groups, each consisting of 12 patients, with both PCOS and CP (PCOSCP), systemically healthy women with CP, periodontally healthy women with PCOS (PCOSPH), and periodontally and systemically healthy women (PH) were included in the study. Clinical parameters such as clinical attachment loss, bleeding on probing (BOP), and periodontal inflamed surface area (PISA) index were noted. AOPP were evaluated in the saliva and serum samples by spectrophotometric detection. Salivary and serum AOPP levels were highest in the PCOSCP group (75.16 ± 7.50 μmol/l, 97.92 ± 6.50 μmol/l, respectively). Statistical significance (P<0.05) was noted between the salivary AOPP levels of the PCOSCP group and PCOS group. PISA was greatest in the PCOSCP group (1338.40 ± 285.96 mm2) followed by the PCOS group (680.33 ± 79.49 mm2), which showed the impact of PCOS on gingival inflammation. According to the results of this study, increased levels of advanced oxidative protein products appeared to show the effect of CP on worsening PCOS.

Hydatid cysts are caused by Echinococcus granulosus. The usual organs in which the parasite lodges are theliver and lungs. One of the most peculiar locations for cyst formation is the ovary and most of these cases aresecondary. It has been reported that some cases are formed iatrogenically. In our practice, we encounteredthree cases of ovarian hydatid cysts with a common symptom of abdominal pain. Imaging studies showed thepresence of cystic lesions.Our first case was particularly interesting as the ultrasonographic characteristicswere consistent with malignancy; however, surgical intervention showed that she had a hydatid cyst. Of note,this appeared to be a primary cyst because no other lesion was detected at the time. Our second case was diagnosedwith infertility and under treatment prior to referral to our centre. Ultrasound (US) imaging showed thepresence of a large cyst. The patient underwent laparoscopic cystectomy and the parasitic lesion was removed;however, she was subsequently diagnosed with urticaria and admitted to the intensive care unit (ICU). Shemade an uncomplicated recovery. Our third case was a pregnant woman with a previous diagnosis of a hydatidcyst. She underwent surgery for a suspected ruptured cyst, which was determined to be parasitic. Due tosimilarities in appearance, these cysts can be confused with other lesions. Careful management of these cystsin highly prevalent areas must be considered. Despite advanced technology, hydatid cysts present challengesfor both surgeons and radiologists.