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Objective: To assess the impact of a hysteroscopic myoma resection (HMR) two-day training course on non-technical (cognitive) surgical skills among gynecologists. Materials and methods: A 2-day educational course was held in which 95 consultant gynecologic surgeons and beginner infertility fellowship residents took part. Among all 80 participants (84.2%) had ever performed diagnostic hysteroscopy and 30 (31.3%) had performed non-resectoscopic operative hysteroscopy. The training program included instructive speeches, simulated surgical presentations, and a live hands-on myomectomy workshop. Non-technical skills were assessed two times, once before and the other after the course through two written tests with 10 multiple-choice questions for each. Results: Concerning the 95 participants, 43 (47.3%) took the pre-course test and all of them (100%) took the post-course one. The mean score improved significantly from 3 (interquartile range [IQR], 0-4.0) to 7 (IQR, 5.0-8.0) [bootstrap p<0.0001] for each of the randomly chosen pairings. The majority of candidates showed significantly improved cognitive skills after the HMR course despite their poor cognitive skills before the course. According to further analysis, there were significant enhancements in grades for all topics, especially regarding the basic principles of the procedure and management of complications (bootstrap p<0.0001). The odds ratio for the pre- versus post-course mean test results was 5.23. Due to the confidentiality stipulation, the pre- and post-course scores were not matched. Conclusion: A two-day continuing medical educational course could be efficient in improving the nontechnical (cognitive) skills for HMR. [ABSTRACT FROM AUTHOR]

Background: Considering the considerable influence of the vaginal microbiome on endometrial receptivity and embryo implantation, we hypothesized that cases of recurrent implantation failure (RIF) might benefit from the intravaginal probiotic administration. Objective: Evaluation of the effects of intravaginal probiotic administration before frozen embryo transfer (FET) on the rates of pregnancy and the status of vaginal lactobacillary flora in cases of RIF. Materials and Methods: This was a randomized, parallel-group, clinical trial conducted at an infertility clinic in Tehran, Iran between January 2021 and September 2022. A total of 166 reproductive-aged women with a history of unexplained RIF were randomly assigned to either the probiotic group or the control group (n = 83/each group). The probiotic group received intravaginal probiotics (LactoVag®) daily for 2 wk from the second day of the menstrual cycle along with the routine treatment of FET. The control group received only the routine treatment of FET. The primary outcome was the chemical pregnancy rate, and the secondary outcomes were the clinical pregnancy rate and the status of vaginal lactobacillary flora. Results: A total of 163 participants were included in the final analysis. The probiotic group had a slightly higher chemical pregnancy rate than the control group (39.02% vs. 33.33%), but the difference was not statistically significant (risk ratio: 1.71, 95% CI: 0.77-1.76; p = 0.449). The clinical pregnancy rate was also non-significantly higher in the probiotic group than the control group (37.80% vs. 33.33%; RR: 1.14, 95% CI: 0.76-1.74; p = 0.623). Conclusion: Intravaginal probiotic administration did not significantly improve the pregnancy rates in RIF cases undergoing FET. Further studies are needed to explore the optimal dose, duration, and timing of probiotic administration, as well as the mechanisms of action and the potential adverse effects of probiotics on the vaginal microbiome and the implantation process. [ABSTRACT FROM AUTHOR]

Objective: Dual oxidases (DUOX1, DUOX2) belong to the NADPH oxidase (NOX) family, which produce H2O2 necessary for thyroid hormone biosynthesis. This study aims to evaluate gene expression for DUOX1, DUOX2 in PCOS patients and its relation with thyroid hormone and magnesium levels. Materials and methods: Totally 88 cases were studied including 24 people with PCOS and hypothyroidism, 44 people with PCOS and normal thyroid function, and 20 hypothyroid patients without PCOS. In comparison 40 healthy controls in the age group of 16-35 years matched for age group and BMI were evaluated. Using Vegaro syringe 5 cc of blood was sampled from all 128 people and after RNA extraction and cDNA synthesis using Real-Time PCR technique, the expression level of DUOX1 and DUOX2 genes was investigated. Results: The results of hormonal tests showed that there is a significant difference between the level of T4, T3, and TSH hormones in hypothyroid patients with or without PCOS in comparison to the control group. Regarding the level of Mg, the results showed that there is a significant difference between the levels of Mg in PCOS group with or without hypothyroidism in comparison to the control group. Gene expression results showed that the relative changes of DUOX1 gene expression in different groups compared to the control group were significantly reduced P<0.05. In the polycystic group with hypothyroidism, the gene expression level showed a decrease compared to the normo-thyroid polycystic group and the hypothyroid non-PCO group, which was statistically significant P<0.05. Conclusion: According to the results of the present study and the previous studies that have been published in the field of Duox1, it can be assumed that the reduction of Duox1 expression can interfere with the oxidative stress system. Further studies with other molecular techniques may help to understand the exact action mechanism of these genes. [ABSTRACT FROM AUTHOR]

Objectivess: This study aimed to determine the relationships between endometrial compaction and pregnancy outcome in patients receiving artificial endometrial preparation for frozen embryo transfer (FET) cycles. Materials and Methods: This prospective cohort study was performed in a university-affiliated fertility clinic from March 2020 to March 2021. The eligible women undergoing their first or second FET cycle and having the top grading cleavage stage embryos were enrolled. All patients received the same endometrial preparation regime. The alteration in endometrial thickness (EMT) between the day of progesterone initiation and the day of embryo transfer (ET) was measured using consecutive transvaginal sonography. The patients were divided into three groups based on the percentage of endometrial compaction (i.e., the difference of EMT at end of the estrogen-only phase and after three days of progesterone administration (ET day) divided by the EMT on the terminal day of the estrogen-only exposure). Results: Overall, 300 eligible women were evaluated and only 27.3% (82/300) of the studied cycles showed =5% compaction, whereas 72.6% (218/300) either expanded or showed minimal compaction. The clinical and ongoing pregnancy rates in group 2 (any expansion) were significantly higher than those in groups 1 and 3 (P = 0.002 and P = 0.01, respectively). Multivariable logistic regression test indicated that the cycles with any expansion in ET were independently associated with 3.1 times improvement in clinical pregnancy rate in comparison to those with any compaction (P = 0.002). Conclusion: Gross endometrial compaction occurred in one-third of FET cycles with no significant positive effect on pregnancy outcomes after cleavage-stage ET. [ABSTRACT FROM AUTHOR]

Background: Ovarian tissue extract (OTE) and sodium selenite (SS) enhance the growth and maturation of preantral follicles in a dose-dependent manner. Objective: The present study was designed to bring more information regarding the mechanism of OTE and SS on the mRNA expression of follicle-stimulating hormone receptors (FSHR) and the proliferation cell nuclear antigens (PCNA) of in vitro matured isolated follicles. Materials and Methods: The tissue extract was prepared from adult ovaries. The preantral follicles (n = 266) were isolated from 12-16-day-old mice and cultured in the control, experimental I (10 ng/ml SS), and experimental II (OTE) groups for 12 days. The follicular diameter, survival, and maturation rates, also, the production of 17-ß-estradiol and progesterone, and the follicular expression of PCNA and FSH receptor genes were analyzed. Results: The survival rate of follicles in the SS-treated group (84.58%) was significantly higher than that OTE (75.63%; p = 0.023) and control (69.38%; p = 0.032) groups. The mean diameter of culture follicles in experimental group I (403.8 µm) and experimental group II (383.97 µm) increased significantly in comparison with the control group (342.05 µm; p = 0.032). The developmental rate of follicles, percentages of antrum formation, released metaphase II oocytes (p = 0.027; p = 0.019 respectively), production of hormones and the expression of 2 studied genes were significantly increased in both experimental groups in compare with control group (p = 0.021; p = 0.023 respectively). Conclusion: The OTE and SS have a positive effect on development of mouse preantral follicles via over-expression of FSHR and PCNA genes. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system (SNS) is hyperactive in women with polycystic ovary syndrome (PCOS). This study was designed in two sections: in vivo/in vitro with clonidine as the alpha-2 adrenoceptor (ADR-α2) agonist for modulating this hyperactivity. Eighty women with PCO participated in this randomised clinical trial (in vivo). A clonidine (0.1 mg) tablet was given twice a day for two months. Polycystic ovary morphology (PCOM) and pregnancy rate were the main outcome measurements. In the candidates for in vitro fertilisation (IVF), clonidine was added to the culture medium during IVF for two study groups (PCO-clonidine/PCO-without) and two control groups (egg donors-clonidine/egg donors-without). Our results showed that the pregnancy rate significantly was higher in the study group (p =.002). The mRNA expression of ADR-α1 and ADR-β2 in PCO was higher than control group (p value <.001). But ADR-α1 expression in PCO-clonidine group decreased (p value =.042), the same as ADR-α2 expression. The intensity of this effect showed a pattern for ADR-α122. Increase of antral follicle count (AFC) growth and pregnancy rate indicate the significant role of ADR-α2 in PCOS. Clonidine reduced gene expression and protein levels, confirming the above results. These results would aid in pharmacological treatments, as well as assisted reproductive technologies (ARTs). What is already known on this subject? In women with PCOS, sympathetic nerve activity is higher than in healthy women. Clonidine is widely used as an alpha-2 presynaptic adrenoceptor (autoreceptor) agonist to modulate the output of the sympathetic nervous system (SNS). Our in vivo/in vitro results showed that the optimal dose of clonidine can increase the oocyte maturity and pregnancy rate in PCO women. This finding was also confirmed by the results in cumulus cell culture. What do the results of this study add? The results of administration of 0.2 mg of clonidine (in vivo) for oocyte maturation and pregnancy rate confirms the in vitro response in the cumulus cell culture of PCO women's follicle. What are the implications of these findings for clinical practice and/or further research? These findings can be used in pharmacological treatment of anovulation and assisted reproductive technology (ART). [ABSTRACT FROM AUTHOR]

Objective: COVID-19 pandemic has affected all aspects of human life including social, economic, healthy behaviors and even individual relationships. This study aimed to investigate the effect of corona virus outbreak on assisted reproductive technology (ART) outcome. Materials and methods: In this retrospective and prospective cohort, 260 ART cycles of ovum pick up (OPU), fresh embryo transfer (ET) and frozen embryo transfer (FET) were evaluated in 223 women (from December 2019 to February 2020) and during COVID-19 outbreak (February and July 2020) in an infertility center. Primary and secondary outcomes of ART cycles including chemical and clinical pregnancy rate were evaluated. Results: The mean±SD (standard deviation) age of women was 34.17±6.56 years. Chemical and clinical pregnancy rates were 23.91% (33/138) per embryo transfer and 75.8% (25/33) per positive pregnancy test, respectively while ongoing pregnancy was seen only in 69.7% (23/33) of those with positive pregnancy test. Spontaneous abortion rate was 15.15% (5/33) per laboratory pregnancy. COVID-19 symptoms were reported in 2.83% and 15.38% of women during and after ART cycles, respectively. Conclusion: It seems that COVID-19 pandemic has not negative effect on outcome of ART cycles except for cancelation rate due to COVID-19 that increased at the beginning of COVID-19 outbreak as it was unknown at that time and awareness was limited. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system (SNS) is hyperactive in women with polycystic ovary syndrome (PCOS). This study was designed in two sections: in vivo/in vitro with clonidine as the alpha-2 adrenoceptor (ADR-α2) agonist for modulating this hyperactivity. Eighty women with PCO participated in this randomised clinical trial (in vivo). A clonidine (0.1 mg) tablet was given twice a day for two months. Polycystic ovary morphology (PCOM) and pregnancy rate were the main outcome measurements. In the candidates for in vitro fertilisation (IVF), clonidine was added to the culture medium during IVF for two study groups (PCO-clonidine/PCO-without) and two control groups (egg donors-clonidine/egg donors-without). Our results showed that the pregnancy rate significantly was higher in the study group (p = .002). The mRNA expression of ADR-α1 and ADR-β2 in PCO was higher than control group (p value <.001). But ADR-α1 expression in PCO-clonidine group decreased (p value = .042), the same as ADR-α2 expression. The intensity of this effect showed a pattern for ADR-α1

Objective: This study evaluated a novel in vitro implantation model using human endometrial mesenchymal stem cells (EMSCs), SUSD2+, and myometrial smooth muscle cells (SMCs) that were co-cultured with mouse blastocysts as the surrogate embryo. Materials and Methods: In this experimental study, SUSD2+ MSCs were isolated from human endometrial cell suspensions (ECS) at the fourth passage by magnetic-activated cell sorting. The ECS and SUSD2+ cells were separately co-cultured with human myometrial muscle cells for five days. After collection of mouse blastocysts, the embryos were placed on top of the co-cultured cells for 48 hours. The interaction between the embryo and the cultured cells was assessed morphologically at the histological and ultrastructural levels, and by expression profiles of genes related to implantation. Results: Photomicrographs showed that trophoblastic cells grew around the embryonic cells and attached to the ECS and SUSD2+ cells. Ultrastructural observations revealed pinopode and microvilli-like structures on the surfaces of both the ECS and SUSD2+ cells. Morphologically, the embryos developed to the egg-cylinder stage in both groups. Gene expression analysis showed no significant differences between the two groups in the presence of an embryo, but an increased expression of αV was detected in SUSD2+ cells compared to ECS cells in the absence of an embryo. Conclusion: This study showed that SUSD2+ cells co-cultured with SMCs could interact with mouse embryos. The co-cultured cells could potentially be used as an implantation model. [ABSTRACT FROM AUTHOR]

Aim: Considering the wide impact of endometriosis on various aspects of health, this study aimed to explore the impact of endometriosis on Iranian women's lives. Design: The present study used a qualitative approach and conventional content analysis. Methods: Twenty patients suffering from endometriosis referring to Imam Khomeini Hospital in Tehran took part in this study. The sampling was done purposefully until data saturation. After deep semi‐structured interviews, the content analysis of the interviews was done according to the steps proposed by Zhang and Wildemuth. Results: The mean age of the participants was 34.53 (SD: 5.81) years (range: 23–43) with duration of illness of 6.30 ± 5.86 years. Their educational level varied from high school to university, and most of them were employed. Analysis of the data from participants' experiences led to the formation of 5 categories under the titles "Physical suffering, instability of marital life, mental disorder, disruption in social life and self‐care" and 11 subcategories. Conclusion: The findings of the present study showed that endometriosis can adversely affect women's lives including physical, sexual, psychological and social problems. Although in some cases patients adopt different strategies for self‐care, the need for more support is felt. [ABSTRACT FROM AUTHOR]

Abstract Background A cross sectional study was designed to survey the relationship between anxiety/depression and duration/cause of infertility, in Vali-e-Asr Reproductive Health Research Center, Tehran, Iran. Methods After obtaining their consents, 370 female patients with different infertility causes participated in, and data gathered by Beck Depression Inventory(BDI) and Cattle questionnaires for surveying anxiety and depression due to the duration of infertility. This was studied in relation to patients' age, educational level, socio-economic status and job (patients and their husbands). Results Age range was 17–45 years and duration and cause of infertility was 1–20 years. This survey showed that 151 women (40.8%) had depression and 321 women (86.8%) had anxiety. Depression had a significant relation with cause of infertility, duration of infertility, educational level, and job of women. Anxiety had a significant relationship with duration of infertility and educational level, but not with cause of infertility, or job. Findings showed that anxiety and depression were most common after 4–6 years of infertility and especially severe depression could be found in those who had infertility for 7–9 years. Conclusions Adequate attention to these patients psychologically and treating them properly, is of great importance for their mental health and will improve quality of their lives.

Objective: To compare the effect of dydrogesterone and GnRH antagonists on prevention of premature luteinizing hormone (LH) surge and pregnancy outcomes in infertile women undergoing IVF/ICSI. Materials and methods: In a Randomized controlled trial (RCT), two-hundred eligible women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were randomly assigned into two groups. Human menopausal gonadotropin (HMG) was administered for controlled ovarian stimulation (COS) in both groups. Intervention group (group 1) received 20 mg dydrogesterone from day 2 of menstrual cycle till trigger day and control group (group2) received GnRH antagonist from the day that leading follicle reached 13 mm in diameter till trigger day. Serum levels of LH, estradiol and progesterone were measured on the trigger day. The primary outcome measure was the incidence of a premature LH surge, and the secondary outcomes investigated were the chemical and clinical pregnancy rates in the first FET cycles. Results: There were no significant differences in patients' age, BMI, AMH levels, previous IVF cycle, and cause of infertility between the two groups. None of the patients in two groups experienced a premature luteinizing hormone surge. The numbers of retrieved oocytes, the MII oocytes and good quality embryos, were significantly higher in the intervention group than antagonist group (p < 0.05). The overall chemical pregnancy rate in intervention group (43/91: 46.2%) and control group (45/91: 49.5%) (p = 0.820) was similar. Meanwhile, the clinical pregnancy rate was similar between groups too. Conclusion: Regarding the cost, efficacy and easy usage of dydrogestrone, it may be reasonable to use it as an alternative to GnRH antagonist for the prevention of premature LH surge. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The study assesses the effect of the vitrification procedure on the integrity, morphology, follicular development and gene expression of stimulated human ovarian tissue after warming and two weeks of in vitro culture. Methods: Ovarian specimens were divided into non‐vitrified and vitrified groups and were cultured for two weeks. Morphological analysis and immunohistochemistry were performed. The 17‐β estradiol and anti‐Müllerian hormone levels in collected media were assessed. Gene expression was analyzed using real‐time reverse transcription polymerase chain reaction. Results: The morphology and immunohistochemistry of bcl‐2‐like protein 4 and B‐cell lymphoma 2 of human stimulated ovarian tissue were similar in both groups. There was no significant difference in the percentage of normal follicles between the groups before and after in vitro culture. In spite of an increase in the percentage of growing follicles in cultured tissues compared to the non‐cultured groups, the rate of normal follicles was significantly decreased in both cultured groups (P < 0.05). Gene expression was no different in vitrified tissues compared to the control; however, the expression of growth differentiation factor 9 and follicle stimulating hormone receptor genes were increased and factor in germ line alpha and kit ligand genes were decreased during in vitro culture (P < 0.05). In the two cultured groups, the level of 17‐β estradiol was increased (P < 0.05), but the anti‐Müllerian hormone concentration was not statistically altered. Conclusions: These results showed that the integrity of stimulated human ovarian tissue after vitrification/warming was well preserved; however, the in vitro culture condition needs improvement. [ABSTRACT FROM AUTHOR]

Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2x106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments. [ABSTRACT FROM AUTHOR]

To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four-week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients. [ABSTRACT FROM AUTHOR]

Objective: Endometriosis is a common disease in which the endometrial stroma and glands grow abnormally outside the uterine cavity. The establishment of animal models can be effective for determining the etiology of endometriosis. In this study we compare two endometriosis models using endometrial fragments and isolated cultured endometrial cells. Methods: We obtained endometrial tissues that were in the proliferative or secretory phases from women who underwent hysteroscopies for benign reasons at Imam Khomeini Hospital (Tehran). Following confirmation of the tissue's normality, we cut the tissues into 2 mm cube pieces. The remainder of endometrial tissues were used for isolation and cultured to the fourth passage. In the first model of endometriosis, the endometrial tissue fragments and in the second model, 2×106 isolated endometrial cells were subcutaneously transplanted into gamma irradiated mice. The mice were kept under controlled, sterile conditions for 20 days. The mice sera were collected before and after transplantation for assessment of 17β estradiol. The ectopic tissues in both models were assessed for morphological staining using hematoxylin and eosin, as well as periodic acid Schiff (PAS) for gland secretion. The gland sections per mm2 were analyzed. Results: At 20 days after tissue transplantation, we observed endometrial-like glands in the subcutaneous tissue of both endometriosis models. The number of gland sections was 57.55 ± 17.18/mm2 for the first model and 271.57 ± 77.98/mm2 for the second model. This result was significantly higher in the second model when compared to the first model. Gland secretion was positive for PAS. The level of 17β estradiol was higher in both models compared to the control group. This level was significantly higher in the second model compared to the first (P≤0.05). Conclusion: The endometriosis model that used cultured endometrial cells showed more efficiency in morphology, gland formation and level of 17β estradiol. [ABSTRACT FROM AUTHOR]