Efficacy of Ethanol Sclerotherapy Versus Laparoscopic Excision in the Treatment of Ovarian Endometrioma.

Objective: The purpose of this study was to examine the recurrence rates of ovarian endometrioma, dysmenorrhea, dyspareunia, and related complications between sclerotherapy and laparoscopic ovarian cystectomy in individuals aged 25 to 38. Methods: Eighty-eight women participated in this retrospective, single-center study between January 2020 and February 2022. Patients received either laparoscopy or sclerotherapy, depending on the opinion of the pertinent physician. In this study, the following parameters were retrospectively analyzed in follow-up visits 2, 6 and 12 months after sclerotherapy and laparoscopy: dysmenorrhea and dyspareunia by visual analog scale, complications following the intervention, and serial pelvic sonograms for endometrioma cyst recurrence. Moreover, serum Anti-Müllerian hormone (AMH) level before and 6 months after sclerotherapy/surgery were analyzed. The collected data were then analyzed using R software. Results: The results demonstrate the efficiency of both sclerotherapy and laparoscopic techniques in reducing endometrioma-related dysmenorrhea and dyspareunia over a 12-month period. There was no statistically significant difference in the occurrence of complications and recurrence rate between these two therapies, and both are equally beneficial. Also, the rate of AMH decline after laparoscopy was higher than sclerotherapy; however there was not a statistically significant change in serum level of AMH in laparoscopy compared to the sclerotherapy after 6 months. Conclusion: Considering all the data, it appears that sclerotherapy, with its lower cost, shorter hospital stay, and quicker return to activities, can be a laparoscopic alternative to endometrioma cyst removal. More studies are required.

Comparison of progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in terms of preventing premature LH surge and assisted reproductive technology outcome in infertile women: a randomized controlled trial.

INTRODUCTION: Progesterone can be used instead of GnRH agonists and antagonists in order to avert a premature LH surge during controlled ovarian stimulation (COS) protocol. Nonetheless, there is limited knowledge regarding its utilization. Thus, this study compared the effects of progesterone and GnRH antagonists (GnRH-ant) on premature LH surges and assisted reproductive technology (ART) results in infertile women undergoing ART. MATERIALS AND METHODS: In this clinical trial, the progesterone protocol (study group) and GnRH-ant protocol (control group) were tested in 300 infertile individuals undergoing IVF/ICSI. The main outcome was the number of oocytes retrieved. The secondary outcomes included premature LH rise/surge, the quantity of follicles measuring ≥ 10 and 14 mm, oocyte maturity and fertilization rate, the number of viable embryos, high-quality embryo rate and pregnancy outcomes. RESULTS: The study group exhibited a statistically significant increase in the number of retrieved oocytes, follicles measuring 14 mm or greater, and viable embryos compared to the control group (P < 0.05). The study group also increased oocyte maturity, chemical pregnancy rate, and clinical pregnancy rate (P < 0.05). Both groups had similar mean serum LH, progesterone, and E2 levels on trigger day. The control group had more premature LH rise than the study group, although this difference was not statistically significant. CONCLUSION: In conclusion, it can be stated that the progesterone protocol and the GnRH-ant protocol exhibit similar rates of sudden premature LH surge in infertile patients. However, it is important to note that the two regiments differ in their outcomes in ART. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT-ID: IRCT20201029049183N, 2020-11-27).

Astaxanthin supplementation impact on insulin resistance, lipid profile, blood pressure, and oxidative stress in polycystic ovary syndrome patients: A triple-blind randomized clinical trial.

Astaxanthin (ASX) is a natural carotenoid compound found in several of microorganisms and seafood. It may have numerous therapeutic benefits for polycystic ovarian syndrome (PCOS) patients. The aim of this study was to investigate the effect of ASX on lipid profile, insulin resistance (IR), blood pressure (BP), and oxidative stress (OS) levels in infertile PCOS patients. Overall, 58 infertile women with diagnosed PCOS participated in this triple-blind randomized clinical trial. They were randomly assigned to two groups, taking either a placebo or ASX (2 × 6 mg/day) for 8 weeks. Blood serum samples were collected from patients before and after the intervention. Fasting Insulin (FI), fasting blood glucose (FBS), OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], and total antioxidant capacity [TAC]), and lipid profiles were evaluated in serum. Moreover, based on the relevant formula, several indices associated with IR were calculated. BP was also assessed at the start and end of the study. After 8 weeks of ASX consumption, a significant reduction was observed in fasting blood sugar, HOMA-IR, FI, MDA, low-density lipoprotein-cholesterol, and TC/HDL-C. Conversely, ASX significantly increased TAC, HDL-C, and QUICKI. After adjusting the analysis for the baseline values of age, body mass index, and biochemical parameters, non-significant values were obtained for QUICKI and FI, along with no changes in other findings. Overall, ASX appears to be an effective and safe supplement that alleviates insulin metabolism, lipid profile parameters, and OS in infertile PCOS patients.

High Anti-Müllerian Hormone Strongly Correlates with Reproductive Outcomes in Women Undergoing Assisted Reproduction.

BACKGROUND: In a retrospective cohort of 881 women with gynecologic and unexplained infertility, we aimed to study the relationship between serum AMH levels and ART outcomes. This retrospective cohort includes 881 infertile women aged 20 - 45 who underwent their first fresh autologous non-preimplantation genetic diagnosis ART cycles between 2012 and 2020. METHODS: We assessed the correlation between AMH levels and reproductive outcomes among infertile women with different causes of infertility (including endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility). RESULTS: We found a strong correlation between high AMH levels and reproductive outcomes independent of age and the cause of infertility in women undergoing ART. In all patients with gynecologic and unexplained infertility, higher AMH correlated with the improved number of oocytes (p < 0.001), MII oocytes (p < 0.001), good-quality embryos (p < 0.001), chemical pregnancy rate (p < 0.001 in women < 37; and p = 0.002 in women over 37), clinical pregnancy rate (p < 0.05), and live birth rate (p = 0.05). CONCLUSIONS: Serum AMH concentrations can be invaluable for predicting ovarian reserve and reproductive outcomes in young and advanced-age infertile patients undergoing ART. However, it should not be used as the sole predictive marker for disqualifying infertile women from ART treatment. Further large cohort studies are warranted to determine an exact cutoff point for AMH to provide an accurate ART success prediction.

Astaxanthin treatment ameliorates ER stress in polycystic ovary syndrome patients: a randomized clinical trial.

Astaxanthin (ASX), as a natural carotenoid compound, exists in various types of seafood and microorganisms. It has several possible beneficial therapeutic effects for patients with polycystic ovary syndrome (PCOS). Patients with PCOS also suffer from endoplasmic reticulum (ER) stress. In the present work, it was hypothesized that ER stress could be improved by ASX in PCOS patients. Granulosa cells (GCs) were obtained from 58 PCOS patients. The patients were classified into ASX treatment (receiving 12 mg/day for 60 days) and placebo groups. The expression levels of ER stress pathway genes and proteins were explored using Western blotting and quantitative polymerase chain reaction. To assess oxidative stress markers, follicular fluid (FF) was gained from all patients. The Student's t test was used to perform statistical analysis. After the intervention, ASX led to a considerable reduction in the expression levels of 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and X-box-binding protein 1 compared to the placebo group, though the reduction in the messenger RNA (mRNA) expression level of activating transcription factor 6 was not statistically significant. However, ASX significantly increased the ATF4 expression level. GRP78 and CHOP protein levels represented a considerable decrease in the treatment group after the intervention. In addition, a statistically significant increase was found in the FF level of total antioxidant capacity in the treatment group. Based on clinical outcomes, no significant differences were found between the groups in terms of the oocyte number, fertilization rate, and fertility rate, but the ASX group had higher rates of high-quality oocytes, high-quality embryo, and oocyte maturity compared to the placebo group. Our findings demonstrated that ER stress in the GCs of PCOS patients could be modulated by ASX by changing the expression of genes and proteins included in the unfolding protein response.Trial registration This study was retrospectively registered on the Iranian Registry of Clinical Trials website ( www.irct.ir ; IRCT-ID: IRCT20201029049183N, 2020-11-27).

The effect of metabolic syndrome on controlled ovarian stimulation outcome in infertile women with polycystic ovary syndrome undergoing assisted reproductive technology cycles

ABSTRACT Objective: To evaluate the effect of metabolic syndrome (MetS) diagnosis on oocyte quality and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS) who undergoing antagonist-controlled ovarian stimulation (COS) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Subject and methods: This prospective cohort study was conducted from November 2019 to November 2020 across two university-affiliated infertility centers in Iran. The PCOS diagnosis was defined according to the Rotterdam criteria. The patients prior to IVF/ICSI cycles were evaluated for MetS diagnosis. MetS was detected according to the National Cholesterol Education Program/Adult Treatment Panel III with the presence of at least three or more of the specific clinical criteria. The cycle outcomes were compared between MetS and non-MetS groups. Results: Overall, 68 eligible infertile PCOS patients with MetS diagnosis and 126 without MetS participated. The MetS diagnosis was associated with the increased requirement of gonadotropins and the COS duration significantly (P = 0.001). Although the total numbers of retrieved and MII oocytes, obtained and top-quality embryos as well as clinical pregnancy and live birth rates in the MetS group were lower than those of in the non-MetS group, the differences were not statistically significant (P > 0.05). In follow-up of the obstetrics complications, the rate of preeclampsia was significantly higher in patients with MetS (P = 0.02). Conclusion: MetS diagnosis in PCOS patients was associated with non-significant poor COS and pregnancy outcome. Further studies with larger sample sizes are recommended to clarify the risk of MetS in patients undergoing ART cycles.

The effect of metabolic syndrome on controlled ovarian stimulation outcome in infertile women with polycystic ovary syndrome undergoing assisted reproductive technology cycles.

Objective: To evaluate the effect of metabolic syndrome (MetS) diagnosis on oocyte quality and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS) who undergoing antagonist-controlled ovarian stimulation (COS) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This prospective cohort study was conducted from November 2019 to November 2020 across two university-affiliated infertility centers in Iran. The PCOS diagnosis was defined according to the Rotterdam criteria. The patients prior to IVF/ICSI cycles were evaluated for MetS diagnosis. MetS was detected according to the National Cholesterol Education Program/Adult Treatment Panel III with the presence of at least three or more of the specific clinical criteria. The cycle outcomes were compared between MetS and non-MetS groups. Results: Overall, 68 eligible infertile PCOS patients with MetS diagnosis and 126 without MetS participated. The MetS diagnosis was associated with the increased requirement of gonadotropins and the COS duration significantly (P = 0.001). Although the total numbers of retrieved and MII oocytes, obtained and topquality embryos as well as clinical pregnancy and live birth rates in the MetS group were lower than those of in the non-MetS group, the differences were not statistically significant (P > 0.05). In followup of the obstetrics complications, the rate of preeclampsia was significantly higher in patients with MetS (P = 0.02). Conclusion: MetS diagnosis in PCOS patients was associated with non-significant poor COS and pregnancy outcome. Further studies with larger sample sizes are recommended to clarify the risk of MetS in patients undergoing ART cycles.

Can Laparoscopic Cystectomy Improve Pregnancy Outcomes in Endometrioma? A Prospective Clinical Trial Study.

BACKGROUND: The purpose of this prospective study was to compare the ovarian response and pregnancy outcomes
in the infertile women with endometrioma undergoing assisted reproductive technologies (ART) in two
groups, who were underwent laparoscopic cystectomy and received gonadotropin releasing hormone-agonist
(GnRH-agonist) and who only received GnRH-agonist without any surgery.
Materials and Methods: In this prospective clinical trial study, 79 infertile women with asymptomatic endometriomas
cyst (2-6 cm) were enrolled and randomly assigned to two groups. First group underwent laparoscopic
cystectomy and received GnRH-agonist. Second group only received GnRH-agonist without any surgery. Following
ovulation induction, all patients underwent intracytoplasmic sperm injection (ICSI). Different parameters
such as the number of retrieved oocytes and embryos; were made our outcomes that analyzed using SPSS.
Results: The pregnancy rate, chemical and clinical, and live birth rate were higher in the combined group,
although these differences were not statistically significant (48.48% vs. 30.8%, P=0.12, 36.36% vs. 25.6%,
P=0.32, 36.36% vs. 23.1%, P=0.29). The number of injections, antral follicles, retrieved oocytes, mature oocytes,
total embryos, transferred embryos and duration of stimulation were similar in two groups.
Conclusion: Laparoscopic cystectomy followed by receiving GnRH-agonist improves pregnancy outcomes in endometrioma
prior to treatment with ART (registration number: IRCT201106116689N2).

The effect of intrauterine hCG injection before embryo transfer on pregnancy rate in frozen embryo transfer cycles.

Objective: HCG (human chorionic gonadotropin), which is secreted by cytotrophoblast cells, plays an important role in improving pregnancy outcomes among patients with infertility or related problems. In this study, we evaluate the effect of intrauterine hCG injection prior to frozen embryo transfer on pregnancy outcomes. Methods: In this clinical trial study, among women with infertility problems referred to (XXX) and those with frozen embryos were included in the study. 155 patients in the intervention group received 500 units of hCG while 157 in control group received saline prior to embryo transfer. Along with demographic data, successful in vitro fertilization and clinical pregnancy, loss of pregnancy, successful transplantation, and biochemical parameters were compared among the two groups. Results: The mean age of the patients included in the study was 32.97 ± 3.31 years. The level of anti-Mullerian hormone, follicle stimulating hormone and the grade of frozen embryos were not significantly different between the two groups (P > 0.05). The rate of laboratory pregnancy in the intervention group was significantly higher than in the control group (51% vs 35%), p = 0.006. The rate of successful implantation and clinical pregnancy in the intervention group was also significantly higher, p = 0.01 and p = 0.006, respectively. Overall loss of pregnancy in intervention group was 78.1% and 86.0% in control group which was not significantly different, p = 0.068. Conclusion: The outcomes of our study showed that 500 IU of hCG prior to embryo transfer improves the rate of clinical and laboratory pregnancy. However, it does not reduce the rate of loss of pregnancy. Further studies are therefore required in this area.

Uterine Cavity Irrigation With Office Hysteroscopy During Ovarian Stimulation for IVF: A Randomized Controlled Trial.

Objective: This was a non-blinded randomized controlled study to evaluate whether endometrial irrigation via office hysteroscopy during the early follicular phase would lead to a higher level of live birth rates compared to no irrigation in the fresh embryo transfer cycle. Method: The study was conducted in Tehran university of medical sciences from June 2015 to June 2016. women under the age of 40 with primary infertility without history of previous IVF/ICSI or hysteroscopic examination, were included. Controlled ovarian hyperstimulation was done. Hysteroscopy was performed in the early mid-follicular phase of a stimulation cycle (day 5-7) with a vaginoscopy approach and saline irrigation in hysteroscopy group. Embryo-transfer was done in the same cycle. Results: 228 patients completed their participation in the study. In the fresh cycle, clinical pregnancy rate was 46% in the hysteroscopy group and 40.43% in the control group. (p-value= 0.326, RR= 1.16 [95%CI: 0.862 to 1.56]). Live birth rate was 41.28% in the hysteroscopic group and 31.93% in the control group (p-value=0.143, RR= 1.293 [95%CI: 0.916 to 1.825]). For those patients having surplus cryopreserved embryos, after 2 months, a second embryo transfer was performed. The cumulative LBR was 44.05% in the hysteroscopic group and 32.25% in the control group (p-value=0.029, RR= 1.368 [95%CI: 1.031 to 1.815], RD= 11.9% [95%CI: 1.2% to 22.3%] and NNT= 8 [95%CI: 4 to 85]). Conclusion: The current study clearly demonstrated a significantly higher cumulative live birth rate in the intervention group. Clinical Trial Registration: [https://www.irct.ir/trial/19586], identifier IRCT2016011022795N2.

Residency training amid the COVID-19 pandemic: exploring the impact on mental health and training, a lesson from Iran.

BACKGROUND: COVID-19 has affected the training programs and the clinical schedules of surgical wards in many countries, including Iran. Also, the continuous involvement with COVID-19 patients has caused stress in health care workers; among them, residents are on the frontlines of care delivery. Therefore, we designed a study to assess the mental effects of these circumstances, and the effects on General Surgery and Obstetrics & Gynecology residency training in the busiest surgical departments of our university. METHODS: Participants of this cross-sectional study were residents of General Surgery and Obstetrics & Gynecology of Tehran University of Medical Sciences, and the conventional sampling method was used. We used a questionnaire consisting of 47 questions (mostly using multiple choice questions and answers on the Likert scale) about personal, familial, and demographic characteristics; training activities, and mental effects of COVID-19. RESULTS: The response rate was 63.5%. (127 filled questionnaires). Around 96% of the residents had emotional problems, 85.9% were highly stressed about contracting COVID-19, 81.3% were worried about transferring it to their families; and 78% believed that their residency training had been impaired. CONCLUSION: Overall, our study shows the negative impact of COVID-19 on mental health and the training of residents. We propose that appropriate emotional support and suitable planning for compensation of training deficits is provided for residents.

Cell-free mtDNA level and its biomarker potency for ART outcome are different in follicular fluid of PCOS and non-PCOS women.

INTRODUCTION: Lack of reliable biomarkers for estimating the outcome is one of the current gaps in ART. In this study, we assessed whether cell-free mitochondrial DNA within the follicular fluid (FF cf-mtDNA) of PCOS patients has biomarker applicability or not. Furthermore, probable involved mechanisms in the FF cf-mtDNA pathway were evaluated. METHODS: The level of FF cf-mtDNA was compared between 50 PCOS patients and 50 women without any certain reproductive disorder, and analyzed for correlations with ART outcome. The associations between levels of FF cf-mtDNA and TFAM, POLG, and RNase H1 genes expression in mural granulosa cells (MGCs), as well as IL-6, and TNFα in follicular fluid (FF) were assessed. RESULTS: We identified that FF cf-mtDNA level was significantly lower in PCOS women and was accompanied by a reduction in the expression of mtDNA biogenesis genes in MGCs of the patients. Although a significant association between FF cf-mtDNA level and ART outcome was observed in the control group, no correlation could be proved in the PCOS group. Moreover, the expression level of TFAM was negatively associated, while amounts of IL-6 and TNFα were positively correlated with FF cf-mtDNA level in both groups. CONCLUSION: PCOS patients present a lower FF cf-mtDNA level in comparison with non-PCOS women. FF cf-mtDNA has biomarker applicability for ART outcome in women without any certain reproductive disorder, but not for those with PCOS. It seems that mtDNA packaging dysfunction results in elevated FF cf-mtDNA, and subsequent effects are triggered by increasing the inflammatory cytokines.

Quercetin protects human granulosa cells against oxidative stress via thioredoxin system.

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H2O2) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H2O2. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2'-7'-dichlorodihydrofluorescein diacetate fluorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H2O2. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.

Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.

OBJECTIVES: Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters. METHODS: In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR. RESULTS: As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05). CONCLUSIONS: Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.

Comparison of Efficacy and Safety of Two Different Enoxaparin Products in Prevention of Venous Thromboembolism Following Major Obstetric-gynecological Surgeries: An Open-label Randomized Clinical Trial.

Venous thromboembolism (VTE) occurs in about 5 percent of patients undergoing major abdominal surgeries. Prophylaxis of VTE is recommended using unfractionated heparin (UF) or low molecular weight heparin (LMWH) in high-risk patients. In spite of advantages and confirmed cost-effectiveness of LMWH, high costs of enoxaparin branded preparations limit its use. We aimed to compare the efficacy and safety of two enoxaparin preparations. In this open-label randomized clinical trial, 200 patients were recruited to recieve PDxane® or Clexane®, 40 mg subcutaneously daily, from the day of surgery for 10 days. The patients were evaluated for VTE occurrence and side effects considering clinical and laboratory examinations at the beginning and day 10. No cases of proximal or distal VTE or life threatening bleeding were observed among 102 and 98 patients who received PDxane® and Clexane®, respectively. The adverse effects observed in PDxane® and Clexane® groups included injection site reactions (rash: P = 0.97; pain: P = 0.55 and erythema: P = 0.33), anemia (P = 0.32), hematuria (P = 0.16), confusion (P = 0.3), and increased liver transaminases (AST ≥ 3 × ULN: P = 0.16 and ALT ≥ 3 × ULN: P = 0.66). In according to the study results PDxane® was of similar efficacy and safety compared to Clexane® in preventing VTE following major obstetric-gynecological surgeries. Considering lower cost of PDxane®, it could be a safe and effective alternate for VTE prophylaxis in the patients undergoing such types of surgeries.

Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS).

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies that affects women in reproductive age. MicroRNAs (miRNAs) play crucial roles in normal function of female reproductive system and folliculogenesis. Deregulated expression of miRNAs in PCOS condition may be significantly implicated in the pathogenesis of PCOS. We determined relative expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells (GLCs), follicular fluid (FF), and serum of PCOS patients. METHODS: Human subjects were divided into PCOS (n = 20) and control (n = 21) groups. GLCs, FF, and serum were isolated and stored. RNA isolation was performed and cDNA was reversely transcribed using specific stem-loop RT primers. Relative expression of miRNAs was calculated after normalization against U6 expression. Correlation of miRNAs' expression level with basic clinical features and predictive value of miRNAs in FF and serum were appraised. RESULTS: Relative expression of miR-145 and miR-182 in GLCs was significantly decreased in PCOS, but miR-182 in FF of PCOS patients revealed up-regulated levels. Significant correlations between level of miRNAs in FF and serum and hormonal profile of subjects were observed. MiR-182 in FF showed a significant predictive value with AUC of 0.73, 76.4% sensitivity, and 70.5% specificity which was improved after combination of miR-182 and miR-145. CONCLUSIONS: A significant dysregulation of miR-145 and miR-182 in GLCs of PCOS may indicate their involvement in pathogenesis of PCOS. Differential up-regulation of miR-182 in FF of PCOS patients with its promising predictive values for discrimination of PCOS reinforced the importance of studying miRNAs' profile in FF.

Differential Expression of miR-93 and miR-21 in Granulosa Cells and Follicular Fluid of Polycystic Ovary Syndrome Associating with Different Phenotypes.

The heterogeneous and multifactorial essence of polycystic ovary syndrome (PCOS) renders a remarkable significance to microRNAs (miRNAs). Normo-androgenic (NA) and hyperandrogenic (HA) PCOS patients were compared with matched healthy women. Expression of miRNAs and TGFß signaling genes was studied by qRT-PCR and western blotting. Effect of androgen on expression of miR-93 and miR-21 and involvement of androgen receptor were appraised. In granulosa cells (GCs), miR-93 and miR-21 showed significantly increased levels in HA patients compared to NA patients. On the contrary, follicular fluid (FF) levels of both miRNAs were significantly decreased in HA group compared to control women. No significant change in the expression of miRNAs in serum samples was detected. Furthermore, mRNA levels of SMAD7 and TGFBR2 were significantly downregulated in GCs of HA group compared to NA and control subjects. TGFBR2 protein level was significantly decreased in HA patients compared to controls. Free testosterone and free androgen index were positively correlated with expression of miR-93 and miR-21 in GCs of PCOS group. Our findings show distinct molecular signature of different subtypes of PCOS. Intermediary position of miRNAs as androgen responsive factors may play critical role in the pathogenesis of PCOS in hyperandrogenic condition.

Low-dose human chorionic gonadotropin adjunct to an antagonist protocol in assisted reproductive technology: a randomized trial study.

The aim of this study was to evaluate the outcomes of adding low-dose hCG (human chorionic gonadotropin), as an LH active supplement, to a GnRH antagonist protocol in patients undergoing assisted reproduction techniques. In this parallel-group randomized clinical trial, 137 infertile female outpatients aged 20 - 39 years were randomized into two groups: hCG group and non-hCG group. All patients received r-FSH (150-300 IU) and then a GnRH-antagonist, Cetrorelix (0.25 mg/day). Concomitantly with Cetrorelix, patients in the hCG group received low-dose hCG (200 IU daily), but the patients in the non-hCG group did not. 10,000 IU Urinary hCG (10,000 IU) was injected to all patients, and ICSI was performed after oocyte retrieval. The primary outcome of this study was comparing the pregnancy rates between two study groups. Other differences between two groups such as serum estradiol concentration, fertilization rate, etc. were considered as secondary outcomes. A total of 130 patients completed this trial. No significant difference was detected between pregnancy rates of the two groups (P=0.52) as well as the fertilization, implantation and ongoing pregnancy rates (P=0.11, P=0.75 and P=0.06 respectively). The only significant difference between two groups was a higher concentration of estradiol in the hCG-treated patients (P<0.05). HCG-treated patients experienced a shorter treatment duration and a lower r-FSH required dose than the non-hCG group, but none of these differences were statistically significant (P=0.19 and P=0.10, respectively). The findings of the current study did not support advantages of adding low-dose hCG to GnRH antagonist plus r-FSH protocol in an unselected population of patients. Well-designed trials with a larger sample size for specific patients' subgroups are warranted.

Hysteroscopy in patients with repeated implantation failure improves the outcome of assisted reproductive technology in fresh and frozen cycles.

AIM: Repeated implantation failure (RIF) is still a problem for many patients and their physicians. Some interventions have been practiced to overcome the problem; one is uterine cavity assessment before assisted reproductive technology (ART) cycles. This study aimed to evaluate the effect of hysteroscopy in women experiencing recurrent implantation failure with apparently normal uterine cavity before assisted reproductive techniques. MATERIAL AND METHODS: This was a cohort study with historical controls conducted in a university hospital. A total of 353 women with RIF undergoing ART with normal hysterosalpingography and transvaginal ultrasound were evaluated. The intervention group underwent hysteroscopy with a rigid, 30°, 4-mm hysteroscope in the menstrual cycle just before ART; in the control group hysteroscopy was not performed. Basal characteristics, stimulation parameters and pregnancy rates were compared between the two groups. RESULTS: Chemical pregnancy occurred in 58.5% of women in the hysteroscopy group versus 34.1% of control women (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.7-4.2; P < 0.001). Clinical pregnancy occurred in 50.7% and 30.3% of women in the hysteroscopy and control groups, respectively (OR: 2.4; 95%CI: 1.5-3.7; P < 0.001). Delivery rate was 35.5% in hysteroscopy women and 21.1% in control women (OR: 1.9; 95%CI: 1.2-3.1; P = 0.008). The results of hysteroscopy were normal in 103 women (72.5%), and they revealed inflammation in 22 (15.5%), polyp in 16 (11.3%) and Asherman syndrome in one patient (0.7%). CONCLUSIONS: Hysteroscopy in the menstrual cycle before ovarian stimulation in fresh cycles and before endometrial preparation in frozen thawed cycles in women experiencing recurrent implantation failure with apparently normal uterine cavity significantly increases the pregnancy rates in fresh and frozen cycles, respectively.

No Superiority of Granisetron Over Metoclopramide in Prevention of Post-operative Nausea and Vomiting: A Randomized Clinical Trial.

PURPOSE: Post-operative nausea and vomiting (PONV) is considered as one of the most disturbing sequels of surgeries under general anesthesia, which if not controlled appropriately increases post-operative morbidity, nursing burden, and general healthcare costs. In this study, we compared granisetron with its brand Kytril(®) and also with metoclopramide regarding PONV management. METHODS: A total of 180 obstetrics and gynecology patients who underwent surgeries under general anesthesia participated in this prospective study at the Dr. Shariati Teaching Hospital, Tehran, Iran. The patients were randomly assigned to single-dose generic granisetron (40 mcg/kg), Kytril(®) (40 mcg/kg), or metoclopramide (0.2 mg/kg) at the end of the surgery. Two episodes of emetic symptoms (nausea and vomiting) were recorded by a gynecologist who had no knowledge of which treatment each patient had received. This gynecologist observed the patients at three different intervals: 0-6, 6-12, and 12-18 h post-surgery. RESULTS: One hundred and thirty-seven patients (76.1 %) underwent hysterectomy and 40 patients (22.2 %) underwent myomectomy. Each group consisted of 60 patients (33 %). The incidence of vomiting in the first 6, 12, and 18 h post-surgery was 22, 15.2, and 13.3 % for granisetron; 18.6, 10, and 8.3 % for Kytril; and 22, 11.9, and 5 % for generic metoclopramide, respectively. There was no significant difference in the incidence of PONV with any of these agents. CONCLUSIONS: All three anti-nausea and vomiting agents, granisetron, its brand (Kytril), and generic metoclopramide, have a similar effect to manage PONV in obstetrics and gynecological surgeries. Trial registration This trial is registered with www.irct.ir, number IRCT201010134927N1.