The Relationship Between Infertility, Stress, and Quality of Life with Posttraumatic Stress Disorder in Infertile Women

Background: The infertility experience and its treatment are accompanied by the symptoms of posttraumatic stress disorder (PTSD). The aim of this study was determining the relationship between posttraumatic stress disorder and quality of life and the infertile women’s stress. Methods: In this descriptive-analytic study, 172 infertile women were divided in four groups. Convenience sampling was done and eligible infertile women referred to Qafqaz Infertility Center in Iran were included in the study. The data was collected between January and March 2019 through posttraumatic stress disorder checklist, The Fertility Quality of Life (FertiQoL) questionnaire, and Newton's infertility stress questionnaire. Pearson correlation, linear regression analysis, and two-way analysis of variance (ANOVA) were applied for data analysis with a significance level of 0.05. Results: The results of two-way analysis of variance (ANOVA) revealed that there was no significant relationship between the type of treatment (p=0.548) and the reception of psychological intervention (p=0.450). In addition, the results of Pearson correlation showed that there was an inverse significant relationship between the total score of posttraumatic stress disorder and quality of life (r=-0.91, p<0.001) and a direct relationship between the total score of posttraumatic stress disorder and level of stress (r=0.56, p<0.001). Conclusion: The results of this study showed that 41.3% of the infertile women had the symptoms of posttraumatic stress disorder. Due to the relationships of posttraumatic stress disorder with the quality of life and infertility stress, providing regular designed psychological interventions is recommended for infertile individuals.

Comparison of Tamoxifen and Clomiphene Citrate for Ovulation Induction in Women with Polycystic Ovarian Syndrome: A Prospective Study

Background: The purpose of this study was to compare the efficacy of tamoxifen and clomiphene citrate in induction of ovulation in women with PCOS and anovulation. Methods: In this prospective cohort study, 104 women with PCOS and primary infertility were enrolled after fulfilling the inclusion and exclusion criteria. The patients were allocated in two groups; group A (n=54) received tamoxifen 40 mg once daily (Days 3-7) and group B (n=50) received clomiphene citrate 100 mg once daily (Days 3-7). Serial ultrasounds were done till the administration of human chorionic gonadotropin (hCG). The ovulation and pregnancy rates in both groups were compared. The number of dominant follicles, estradiol levels, and endometrial thickness were also studied. Comparison was done using chi-square and student’s t-test and a p-value of less than 0.05 was considered statistically significant. Results: The number of dominant follicles and serum estradiol levels were significantly higher in group B (p<0.05), whereas the endometrial thickness was significantly more in group A (p<0.05). The ovulation rates were similar in both groups (66.6% vs. 70%, p=0.715). Pregnancy rate per treatment cycle and per ovulatory cycle was marginally higher in group A (14.81% and 22.22%, respectively), as compared to group B (14% and 20%, respectively), but the difference was not statistically significant (p>0.05). Conclusion: Tamoxifen and clomiphene citrate are both equally effective in induction of ovulation and achieving a pregnancy in women with PCOS.

Ovarian Stem Cells Differentiation into Primary Oocytes Using Follicle Stimulating Hormone, Basic Fibroblast Growth Factor, and Neurotrophin 3

Background: In vitro obtaining oocytes can be an appropriate alternative for patients with gonadal insufficiency or cancer survivors. The purpose of the current research was isolating stem cells from ovarian cortical tissue as well as evaluating the effectiveness of follicle stimulating hormone (FSH), basic fibroblast growth factor (bFGF), and neurotrophin 3 (NT3) in differentiating to oocyte-like cells. Methods: A human ovary was dissected and cortical tissue pieces were cultured for cell isolation. Isolated cells were divided into 8 groups (3 cases in each group) of control, FSH, NT3, bFGF, FSH+NT3, FSH+bFGF, NT3+bFGF, and FSH+NT3+ bFGF. Pluripotency specific gene (OCT4-A and Nanog), initial germ cells (c-KIT and VASA) and PF growth initiators (GDF-9 and Lhx-8) were evaluated by qRT-PCR. Experiments were performed in triplicate and there were 3 samples in each group. The results were analyzed using one-way ANOVA and p-value less than 0.05 was considered statistically significant. Results: Flow cytometry results showed that cells isolated from the ovarian cortex expressed markers of pluripotency. The results showed that the expression of Nanog, OCT4, GDF-9 and VASA was significantly increased in FSH+NT3 group, while treatment with bFGF caused significant expression of c-KIT and Lhx-8 (p<0.05). Also, according to the results, isolated cells treated with NT3 significantly increased c-KIT expression. Conclusion: According to our results, the ovarian cortex cells could be differentiated into primordial follicles if treated with the proper combination of FSH, bFGF, and NT3. These findings provided a new perspective for the future of in vitro gamete proudest.

Unusual Cases of Pure Malignant Germ Cell Tumors of the Ovary: A Case Series on 10 Years Experience at a Tertiary Care Center

Background: Malignant ovarian germ cell tumors (MOGCTs) are rare female cancers, constituting up to 10% of ovarian cancers. Dysgerminoma is the most common histological variant. Surgical removal of the tumor with optimal debulking is the treatment of choice. Multidrug chemotherapy following surgery offers high remission rates. Considering the prevalence of these tumors in adolescent and young females, fertility-sparing treatment is of paramount importance. Methods: The data of all patients with ovarian malignancy admitted at a tertiary-care-teaching hospital from September 2009-March 2019 were analyzed. Ten patients of MOGCTs were treated in this period. The clinical features, radiological and biochemical findings, and management and treatment outcome were evaluated. Results: The median age of patients was 23 years. Histological subtypes included immature teratoma (n=3), endodermal sinus tumor (n=4), and dysgerminoma (n=3). Tumor markers namely AFP, βHCG, and LDH increased in all except the patients with immature teratoma. Two patients with dysgerminoma were in the second trimester of pregnancy. All patients except one underwent surgery followed by BEP chemotherapy. Two patients had developed metastasis within six months of treatment and died. In seven patients, no evidence of disease was reported till date. Conclusion: Management of antenatal patients with dysgerminoma by surgery followed by BEP chemotherapy has favorable prognosis. Fertility-sparing surgery with adjuvant chemotherapy offers great advantage in young girls. However, risk stratification based on prognostic factors should be implemented in order to individualize the treatment for achieving higher survival rates. The option for oocyte-cryopreser-vation prior to surgery must be discussed with patients desiring future fertlity.

Controlling Semi-Invasive Activity of Human Endometrial Stromal Cells by Inhibiting NF-kB Signaling Pathway Using Aloe-emodin and Aspirin

Background: Inflammation and its master regulator, Nuclear Factor-kB (NF-kB), have been implicated in the development of endometriosis. Inhibition of NF-kB pathway using small molecules ameliorated disease progression and reduced the lesion size; nevertheless, the underlying mechanism is not fully understood. Therefore, this study, is an attempt to assess whether inhibiting NF-kB signaling by aloe-emodin (AE) or aspirin (Asp), as anti-inflammatory compounds, can suppresses the invasive activity of human endometrial stromal cells at stage IV endometriosis. Methods: The eutopic and healthy endometrial biopsies from a total of 8 infertile women with confirmed endometriosis and 8 women without endometriosis were digested and the single cells were cultured. Gene and protein markers of proliferation, migration, adhesion, and invasion of eutopic endometrial stromal cells (EuESCs) with and without treatment with AE or Asp, as well as control endometrial stromal cells (CESCs) was analyzed using q-PCR and immunofluorescence staining, respectively. Comparison between groups was performed using one-way ANOVA and the Bonferroni post hoc and p≤0.5 was considered statistically significant. Results: There was an association between NF-kB overexpression and higher proliferation/adhesion capacity in EuESCs. EuESCs (at stage IV endometriosis) displayed no invasive and migratory behaviors. Pre-treatment of EuESCs with AE or Asp significantly attenuated NF-kB expression and reduced proliferative, adhesive, invasive, and migratory activity of endometrial cells (p≤0.5). Conclusion: Eutopic endometrial stromal cells seem to have a semi-invasive activity which is largely suppressed by AE or Asp. It can be suggested that both Asp and AE (as potent NF-kB inhibitors) can be used as a supplement in conventional endometriosis treatments.

Clinical Outcomes of Rescue Intracytoplasmic Sperm Injection at Different Timings Following In Vitro Fertilization

Background: Although rescue intracytoplasmic sperm injection (r-ICSI) is extensively used worldwide, the indication of r-ICSI and its optimal timing remains obscure. This study aimed to assess the outcomes of r-ICSI following in vitro fertilization in different timings when fertilization is confirmed. Methods: This study included 5,156 cycles (47,785 eggs). Fertilization was confirmed by polar body analysis after 4 and 6 hr of coincubation of the sperm and oocyte. Oocytes that underwent IVF were divided into two groups based on the time when a second polar body was detected in more than 30% of all oocytes (Four-hr group and six-hr group). If the second polar body was not detected or was present in less than 30% of all oocytes after six hr of coincubation, rescue-ICSI (r-ICSI) was performed for oocytes without a second polar body (r-ICSI group). Results: The fertilization rates of two pronuclear (2PN) oocytes in the three groups (Four-hr group, six-hr group, and r-ICSI group) were 70.7%, 51.3%, and 58.0%, respectively. The blastocyst formation rates were 62.8%, 53.4%, and 42.9%, respectively. Conclusion: Performing r-ICSI after six hr of coincubation can salvage cases with fertilization failure in IVF. The higher fertilization rate of r-ICSI indicates that all oocytes without signs of fertilization after six hr of coincubation should undergo r-ICSI.

Kallmann Syndrome and X-linked Ichthyosis Caused by Translocation Between Chromosomes X and Y: A Case Report

Background: Xp22.3 region is characterized by low frequency of interspersed repeats and low GC content. Several clinically important genes including ANOS1 (KAL1) reside in this region. This gene was first identified due to translocation between chromosomes X and Y in a patient with Kallmann syndrome. Case Presentation: A 20 year old male presented with complaints of delayed secondary sexual characteristics, impaired sense of smell, and poor scholastic performance. On examination, he had short stature (151 cm; <3rd centile). His sexual maturity corresponded to Tanner stage 3. Stretched penile length was 3.6 cm (<3rd centile). Right testis was undescended with low left testicular volume (12 ml). There was mild ichthyosis over abdomen and back. He had hyposmia, hoarse voice, and synkinesia. Investigations were suggestive of hypogonadotrophic hypogonadism. Karyotype revealed an extra chromosomal material on p arm of chromosome X (46,Xp+,Y). On cytogenetic microarray, deletion of 8.3 Mb on Xp22.33 region and duplication of 12.8 Mb on Yq11.22 region were identified. The breakpoint on X chromosome resulted in deletion of exons 7-14 of ANOS1 gene and complete STS, NLGN4X, ARSL (ARSE), SHOX, and VCX genes. Conclusion: Patients diagnosed with Kallmann syndrome should receive careful clinical evaluation to detect presence of a contiguous gene syndrome.

Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report

Background: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene. Case Presentation: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation. Conclusion: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations.

Association of Novel Single Nucleotide Polymorphisms of Genes Involved in Cell Functions with Male Infertility: A Study of Male Cases in Northwest Iran

Background: Infertility is a global health problem caused by various environmental and genetic factors. Male infertility accounts for 40–50% of all cases of infertility and approximately half of them are grouped as idiopathic with no definitive causes. Previous studies have suggested an association between some SNPs and infertility in men. In this study, an attempt was made to investigate the association of 7 different SNPs of 4 genes involved in common cell functions with male infertility. Methods: MTHFR rs1801131 (T>G), MTHFR rs2274976 (G>A), FASLG rs80358238 (A>G), FASLG rs12079514 (A>C), GSTM1 rs1192077068 (G>A), BRCA2 rs4987117 (C>T), and BRCA2 rs11571833 (A>T) were genotyped in 120 infertile men with idiopathic azoospermia or severe oligospermia and 120 proven fertile controls using ARMS-PCR methods. Next, 30% of SNPs were regenotyped to confirm the results. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using SPSS statistical software to evaluate the strength of association. The p˂0.05 were considered statistically significant. Results: Statistical analysis revealed significant association between MTHFR rs-2274976 AA variant (OR: 10.00, CI: 3.203-31.225), FASLG rs12079514 AC variant (OR: 0.412, CI: 0.212-0.800), and BRCA2 rs11571833 TT variant OR: 6.233, CI: 3.211-12.101) with male infertility, but there was no significant difference between case and control groups in MTHFR rs1801131 (p= 0.111), GSTM1 rs1192077068 (p=0.272), BRCA2 rs4987117 (p=0.221), and FASLG rs80358238 (p=0.161). Conclusion: Our findings suggested that some novel polymorphisms including MTHFR rs2274976, FASLG rs12079514, and BRCA2 rs11571833 might be the possible predisposing risk factors for male infertility in cases with idiopathic azoospermia.

The Necessity to Retrieve Testicular Sperm in Infertile Non-Azoospermic Men with High Levels of SDF

The article's abstract is not available.