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.

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).

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.

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.

Maternal death due to COVID-19.

BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. STUDY DESIGN: We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. RESULTS: Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.

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.

Modified methylated DNA immunoprecipitation protocol for noninvasive prenatal diagnosis of Down syndrome.

AIM: Methylated DNA immunoprecipitation real-time quantitative polymerase chain reaction (MeDIP-real-time qPCR) has been introduced as noninvasive prenatal test that has shown absolute detection rate in the screening of Down syndrome. Herein, we aimed to propose a novel modification of MeDIP-qPCR and assess its potential to alleviate the overall cost of the test, being used in very early weeks of pregnancy, and develop it to a noninvasive prenatal diagnosis biosensor in future researches. METHODS: Cell-free fetal DNA (cffDNA) isolated from 60 pregnant women, including 29 normal and 31 trisomy 21 pregnancies, were analyzed using proposed MeDIP protocol. Enriched methylated DNA sequences were amplified through real-time qPCR using eight fetal-specific primer pairs. The status of samples was determined through the calculation of D-value with the cutoff point of zero. RESULTS: The sensitivity and specificity of the MeDIP protocols using nanoparticles were 100% and 100%, respectively. CONCLUSION: Remarkable decrease in the price of MeDIP test per each patient would be a reasonable factor to confirm it on larger sample size. Moreover, the high detection rate of screening and the availability of the required instruments around the world make satisfactory reasons to be tested in earlier weeks of pregnancy, thanks to the high sensitivity of gold shell nanoparticles.

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.

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum ß-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure.

Effect of nerve growth factor on sperm quality in asthenozoosprmic men during cryopreservation.

BACKGROUND: Although routinely used in assisted reproductive technology, human sperm cryopreservation is not an entirely successful procedure. This study determined the effect of nerve growth factor (NGF) supplementation of cryopreservation medium on post-thaw viability, motility, intracellular nitric oxide (NO) concentration, and DNA fragmentation of human spermatozoa in asthenozoospermic men. METHODS: Semen samples were collected from 25 asthenozoosprmic men and divided into the following groups (n = 5/group): fresh semen (control); frozen-thawed semen without treatment; frozen-thawed semen with NGF treatment (0.5, 1, and 5 ng/ml). Prior to dividing the asthenozoospermic samples, 200 µl of each sample was collected for NGF content assessment by ELISA and then compared with normozoospermic semen samples (25 normozoospermic men). Sperm motility and viability were assessed according to WHO criteria. Furthermore, intracellular nitric oxide and DNA fragmentation were evaluated by Flow Cytometry. RESULTS: NGF content was significantly higher in normozoospermic compared with asthenozoospermic men. Cryopreservation of asthenozoospermic semen samples significantly decreased sperm viability and motility, and increased intracellular nitric oxide concentration and DNA damage (p < 0.01). In asthenozoospermic frozen-thawed samples treated with 0.5 ng/ml exogenous NGF, we observed a significantly increased viability, motility, and decreased DNA fragmentation (p < 0.05), but intracellular nitric oxide concentration was not reduced. The other high doses (1 and 5 ng/ml) had no significant effect on the variables. CONCLUSION: Supplementation with exogenous NGF could have partial and limited protective effect during cryopreservation of human spermatozoa but further research is needed to evaluate the possible clinical applications.

Outcomes of assisted reproduction treatment after dopamine agonist -cabergoline- for prevention of ovarian hyper stimulation syndrome.

BACKGROUND: Release of vascular endothelial growth factor (VEGF) by ovaries in response to HCG administration is one of the main mechanisms of ovarian hyper stimulation syndrome. Since Dopamine/dopamine receptor2 (Dp-r2) pathway activity -mediated by VEGF/ Vascular endothelial growth factor receptor 2 (VEGFR- 2) signaling-, is associated with angiogenic events, dopamine agonists were used for the management of severe forms of OHSS. In order to assess the effects of Cabergoline on angiogenesis in the human endometrium, and subsequently its impacts on the implantation rate this study was conducted. METHODS: This historical cohort study was conducted based on existing data of 115 patients (20-40 years) whom underwent assisted reproductive treatment (ART) and with a high probability for developing OHSS between March 2007 and September 2008. Forty five cases received Cabergoline were compared to 70 control subjects. The statistical methods used were: Unpaired t-test for continuous variables and the chi-square test (or Fisher's exact test if required) for categorical variables. RESULTS: None of the patients (treatment or control group) developed OHSS. The etiologies of infertility and administration of GnRH agonist or antagonist protocols were similar in two groups (p>0.2). Number of transferred embryos and zygote intra-fallopian transfer (ZIFT) did not differ between the two groups (p≥0.06). Implantation rate in treatment (3.1%) and control (6.6%) subjects was similar (p=0.4). No significant difference was observed in fertilization rate, chemical, clinical and ongoing pregnancies between the two groups (p>0.5). CONCLUSION: Cabergoline can be safely administered in ART protocols to prevent OHSS, without compromising ART outcomes.

Embryo transfer in days 2 to 4 following intracytoplasmic sperm injection: a prospective cohort study.

BACKGROUND: Improvement of assisted reproductive technique (ART) results in higher pregnancy rates from positive Beta HCG to take home baby statistics. Despite developments in culture media allowing blastocyst stage transfer, some centers apply second, third and sometimes fourth day post injection for embryo transfer. This study aimed to compare their reproductive outcomes. METHODS: This prospective cohort study conducted on 218 infertile couples with at least 4 oocytes retrieved and 2 good quality embryos. They were divided consecutively into 2nd (ET2) or 3rd (ET3) day embryo transfer. Some patients experienced 4rd (ET4) day embryo transfer due to weekend reasons, so we included them in our comparison as well. There were 98, 97 and 23 patients in the aforementioned groups, respectively. Reproductive and pregnancy outcomes were evaluated by Chi square and t-test with the significance level set at α=0.05. RESULTS: Totally, 73 patients (33%) had positive beta HCG and 39.7 percent of them (n=29) experienced pregnancy loss. Positive Beta HCG was detected in 31(31.6%) of ET2 patients, 38 (39.2%) of ET3 patients and 4 (17.4%) of ET4 group. Abortion or pregnancy loss was reported in 9 (29%) of ET2 patients, 18 (47.4%) of ET3 patients and 2 (50%) of ET4 group. CONCLUSION: Our study demonstrated that there may be a higher pregnancy as well as higher abortion in day 3 embryo transfer.

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.

Effects of Thyroid Stimulating Hormone (TSH) level on clinical pregnancy rate via In Vitro Fertilization (IVF) procedure.

BACKGROUND: Subclinical hypothyroidism may adversely affect In Vitro Fertilization (IVF) outcomes. However the cutoff of thyroid-stimulating hormone (TSH) for diagnosis and treatment is controversal. The aim of this study was to find the association of clinical pregnancy rate with regard to TSH levels in women undergoing IVF. METHODS: A historical cohort study of 816 infertile patients who underwent IVF in 2011 and 2012 was conducted. The study subjects were categorized in two groups according to their baseline TSH level; one with 0.5 ≤TSH< 2.5 mIU/L and other with 2.5 ≤TSH< 4.5 mIU/L. All patients were followed up for 6 weeks after embroyonic transfer. The outcomes of the study were consisted of rates for Human Chorionic Gonadotropin (HCG) and evaluation of their clinical pregnancies. RESULTS: About 60% of the study subjects had serum TSH level < 2.5 mIU/L and 40% ≥ 2.5 mIU/L. There were no statistically significant differences in age, years of infertility, BMI, baseline FSH and estradiol level of patients and the type of induction protocols between the study groups. The HCG rise was occurred in 30.4% of the subjects with TSH level < 2.5 mIU/L versus 26.3% of the subjects with TSH ≥ 2.5 mIU/L (p value= 0.2). The clinical pregnancy rates in the group of patients with TSH < 2.5 mIU/L and those with ≥ 2.5 mIU/L were 27.1% and 23.9% respectively (p value= 0.3). CONCLUSION: Our results were similar to various studies in which reported lack of association between TSH level in the range of 0.5- 4.5 mIU/L and IVF outcomes. It seems that lowering the upper limit of normal TSH should be still considered as a scientific debate.

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.

The modulating effects of astaxanthin on apoptosis in women with polycystic ovarian syndrome: A randomized clinical trial.

Objective: Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced apoptosis/anti-apoptosis signaling has been considered the major pathogenesis of PCOS. In a randomized clinical trial, we tested the impact of ASX on the apoptotic pathway in PCOS granulosa cells (GCs). The present study hypothesizes that ASX may improve apoptosis in PCOS patients. Materials and Methods: This trial recruited patients with confirmed PCOS. A total of 58 patients were randomly assigned to take ASX (12 mg) or placebo for 8 weeks. Aspirated follicular fluid (FF) and blood samples were taken from both groups to measure BAX and BCL2 protein expression. Following FF aspiration, GCs from both groups were obtained; Real-Time PCR and Western blotting were used to evaluate the apoptotic pathway's gene and protein expression levels in GCs.BAXBCL2. Results: In GCs analysis, ASX reduced DR5 gene and protein expression after 8 weeks compared to placebo(p<0.05). Also, Caspase8 (p>0.05) and BAX (p<0.05) gene expression declined, although the difference was not statistically significant for Caspase8. Besides,ASX treatment contributed to an elevated BCL2 gene expression in GCs(p<0.05). In FF and serum analysis, a statistically significant increase was found in BCL2 concentration in the ASX group (p<0.05). Moreover, a reduction in BAX level was confirmed in both FF and serum of the ASX group; however, this change was not significant in the serum (p>0.05). Conclusion: It seems that ASX consumption among women with PCOS improved serum and FF levels of apoptotic factors and modulated genes and protein expression of the apoptosis pathway in GCs. Nevertheless, further investigations are needed to reveal the potential role of this compound in PCOS treatment.

Luteinizing hormone supplementation in controlled ovarian stimulation: the Iran Delphi consensus.

Introduction: Numerous consensus documents worldwide address luteinizing hormone (LH) supplementation in controlled ovarian stimulation, yet to the best of our knowledge, only one consensus paper has been published in the Arab region. This study presents a Delphi consensus by seven Iranian infertility experts, offering real-world clinical perspectives. The aim was to develop evidence-based opinions on LH's role alongside FSH in various aspects of assisted reproductive technology (ART), including LH levels, monitoring, r-hLH use, and suggested activity. Methods: Employing the Delphi consensus approach, the Iran consensus unfolded in three steps. In Step 1, eight out of 10 statements gained approval, while two unclear statements were removed. In Step 2, the 20-member extended panel voted on the remaining eight statements. Results: Only one (statement 3) lacked consensus (55% agreement), prompting a modification. The revised statement (noted as statement 3') obtained an 83% agreement. Discussion: The clinical perspectives included in this consensus complement clinical guidelines and policies that help further improve treatment outcomes, especially for patients with FSH and LH deficiencies.

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.

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.