Adding L-carnitine to antagonist ovarian stimulation doesn't improve the outcomes of IVF/ ICSI cycle in patients with polycystic ovarian syndrome: a double-blind randomized clinical trial.

OBJECTIVE: To investigate the effect of L-carnitine supplementation during the controlled ovarian stimulation (COS) cycle with antagonist protocol in patients with polycystic ovary syndrome (PCOS) diagnosis undergoing IVF/ICSI treatment. METHODS AND MATERIALS: This was a double-blind clinical trial study including 110 patients with PCOS attended to Royan Institute between March 2020 and February 2023. At the beginning of the COS cycle, the eligible patients were allocated into two groups randomly according to the coding list of the drugs prepared by the statistical consultant. In the experimental group, patients received 3 tablets daily (L-carnitine 1000 mg) from the second day of menstruation of the previous cycle until the puncture day in the cases of freeze-all embryos (6 weeks) or until the day of the pregnancy test (8 weeks) in fresh embryo transfer cycle. In the control group, patients received 3 placebo tablets for the same period of time. Weight assessment and fasting blood sugar and insulin tests, as well as serum lipid profile were also measured at the baseline and ovum pick-up day. The results of the COS cycle as well as the implantation and pregnancy rates were compared between groups. RESULTS: Finally, 45 cases in L-carnitine group versus 47 cases in the placebo group were completed study per protocol. Data analysis showed that the two groups were homogeneous in terms of demographic characteristics and baseline laboratory tests and severity of PCOS. There is no statistically significant difference in terms of the oocyte recovery ratio and oocyte maturity rate, and the number and quality of embryos, as well as the rates of the fertilization, chemical and clinical pregnancy between groups. However, the means of weight (P < 0.001) and serum levels of fasting blood sugar (P = 0.021), fasting insulin (P = 0.004), triglyceride (P < 0.001) and cholesterol (P < 0.001), LDL (P < 0.001) have significantly decreased in women after consuming L-carnitine supplementation. CONCLUSION: The oral intake of L-carnitine during COS in PCOS women for 6 weeks had no effect on COS and pregnancy outcomes. However, taking this supplement for 6 weeks has been associated with weight loss and improved lipid profile and serum glucose. TRIAL REGISTRATION: The study was registered in the Clinicaltrials.gov site on December 17, 2020 (NCT04672720).

Fatty acid profiles and Delta9 desaturase (stearoyl-CoA desaturase; SCD 1) expression in adipose tissue surrounding benign and malignant breast tumors.

The progression of tumors occurs through interactions between the tumor and the stroma. Understanding the role of adipose tissue (AT), as the main component of the breast tumor microenvironment (TME) in the development of cancer, is crucial for the early detection of breast cancer (BC). This study compared the FA profiles, desaturase index (DI), and stearoyl CoA desaturase 1 (SCD1) mRNA levels in the AT that surrounds tumors in women with BC and benign breast disease (BBD). Specimens were collected from 40 Iranian women who had undergone breast surgery. These women were age- and BMI-matched and were divided into two groups: BC (n = 20) and BBD (n = 20). Gas chromatography and quantitative real-time PCR were used to analyze the FA profiles and SCD1 mRNA levels, respectively. The DI was calculated by dividing the amounts of monounsaturated FAs by the amount of saturated FA. There were no significant differences in age and BMI between women with BC and BBD. The FA profiles and DI were also similar in both groups. However, mRNA levels of SCD1 were found to be 5 times higher in the breast AT of BC than in the breast AT of BBD (p < 0.0001). We showed that SCD1 was significantly upregulated in the AT surrounding BC tumors, even though the DI and FA profiles were unchanged compared to those in the AT of BBD patients. It is important to note that the breast AT of women with BBD has previously been overlooked and warrants further studies.

Serum and follicular fluid levels of soluble receptor for advanced glycation end-products in women with and without polycystic ovary syndrome.

BACKGROUND: Advanced glycation end products (AGEs) are known to associate with the pathogenesis of several chronic diseases via interaction with their corresponding receptor (RAGE). The soluble forms of RAGE (sRAGE) are considered as anti-inflammatory agents by inhibiting the consequent adverse effects of AGE. We aimed at comparing sRAGE levels in the follicular fluid (FF) and serum of women with or without Polycystic Ovary Syndrome (PCOS) who underwent controlled ovarian stimulation for in vitro fertilisation (IVF). METHODS: A total of forty-five eligible women (26 non-PCOS (control) and 19 patients with PCOS (case)) were included the study. sRAGEs in FF and blood serum were measured using ELISA kit. RESULTS: No statistically significant differences were found in FF and serum sRAGE between case and control groups. Correlation analysis showed a significant and positive relationship between serum levels of sRAGE and FF sRAGE in PCOS (r = 0.639; p = 0.004), in control participants (r = 0.481; p = 0.017), and in total participants (r = 0.552; p = 0.000). Data revealed a statistically significant difference in FF sRAGE concentration among all participants by body mass index (BMI) categories (p = 0.01) and in controls (p = 0.022). Significant differences were found for all the nutrients and AGEs consumption according to Food Frequency Questionnaire in both groups (p = 0.0001). A significant reverse relationship was found between FF levels of sRAGE and AGE in PCOS (r = -0.513; p = 0.025). The concentration of sRAGE in serum and FF is the same in PCOS and control. CONCLUSION: The present study revealed for the first time that there are no statistically significant differences between the concentration of serum sRAGE and FF sRAGE among Iranian women with and without PCOS. However, BMI and dietary intake of AGEs have more significant effects on sRAGE concentration in Iranian women. Future studies in developed and developing countries with larger sample sizes are required to determine the long-term consequences of chronic AGE over consumption and the optimal strategies for minimizing AGE-related pathology, specifically in low income and developing countries.

Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial.

BACKGROUND: Currently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist. METHODS: In this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically. RESULTS: The statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004). CONCLUSIONS: On the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk. TRIAL REGISTRATION: NCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www. CLINICALTRIAL: gov/ NCT03876145.

Preterm Birth and Breast Cancer Risk: A Systematic Review and Meta-Analysis.

BACKGROUNDS: Changes in estrogen levels during pregnancy as well as histologic changes in breast tissue can justify the relationship of preterm birth (PTB) and the risk of BC. Therefore, there is a hypothesis that the duration of pregnancy can be associated with BC, so the aim of this study was to find out whether PTB is a risk factor for BC. METHODS: Published studies were located back to the earliest available publication date (1983), using the Medline/PubMed, Embase, Scopus, and Web of Science bibliographic databases. This review included the cohort or case control studies that assessed the association between PTB and BC. Pooled effect sizes with corresponding 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Thirteen studies including a total of 2,845,553 women were included in this meta-analysis. Pooled results suggested that PTB could increase the risk of BC (RR: 1.03, 95% CI: 1.00, 1.07; I2= 62.5%). The risk was significantly increased in women who delivered at 37-39 (RR: 1.03, 95% CI: 1.01, 1.06) and 26-31 weeks of gestation (RR: 1.25, 95% CI: 1.04, 1.47) compared to women who delivered at 40-41 weeks of gestation. A significant increment in the risk of BC was observed in primiparous (RR: 1.05, 95% CI: 1.01, 1.08) and women older than 45 years (RR = 1.12, 95% CI: 1.01, 1.24). There was no difference between other gestational age categories. CONCLUSIONS: Our findings add to evidence that short gestation pregnancies may increase the risk of BC, especially in primiparous and women older than 45 years. Considering the methodological weaknesses existed in included studies, minor clinical differences, and the complexity of the exact pathophysiology of PTB on BC, the precise position of PTB as a risk factor for BC in clinical practice is undetermined. Further studies are still needed.
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Duration of estradiol supplementation in luteal phase support for frozen embryo transfer in hormone replacement treatment cycles: a randomized, controlled phase III trial.

PURPOSE: In this study, we intend to evaluate pregnancy outcomes in women who undergo artificial frozen embryo transfer (FET) and stop estradiol (E2) after vaginal ultrasound observation of a gestational sac and heartbeat. METHODS: In this randomized phase III clinical trial, we recruited 291 patients who underwent FET. We randomly assigned 64 pregnant women to a study or a control group after observation of a gestational sac and heartbeat at 6-week gestational age. E2 administration continued until week 12 of gestational age for the control group, but was discontinued for the study group. Progesterone-in-oil administration continued until week 12 of gestational age for both groups. Serum levels for E2 and progesterone were measured on the initial progesterone and embryo transfer (ET) days, and at weeks 6 and 12 of pregnancy in both groups. RESULTS: The miscarriage rate was 1/32 (3.13%) in the study group and 6/32 (18.75%) in the control group after the intervention and confirmation of a fetal heartbeat. This difference was statistically significant. All patients who remained under intervention, which included 29 in the study group and 24 in the control group, had live births. Although the mean serum E2 and progesterone levels steadily increased from the initial day of progesterone administration to week 12 of gestational age, they were not significantly different between the two groups. Maternal complications were significantly more common in the control group. CONCLUSION: Earlier discontinuation of E2 for luteal phase support of FET cycles may be taken into consideration. Additional clinical studies should be conducted to determine an accurate estimation of the time when E2 should be discontinued during FET luteal phase support. TRIAL REGISTRATION: NCT04013438, registered 9 July 2019-Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT04013438?cond=NCT04013438&draw=2&rank=1.

Endometrial preparation for vitrified-warmed embryo transfer with or without GnRH-agonist pre-treatment in patients with polycystic ovary syndrome: a randomized controlled trial.

RESEARCH QUESTION: What are the effects on pregnancy outcome in patients with polycystic ovary syndrome (PCOS) in endometrial preparation cycles for vitrified-warmed embryo transfer with or without gonadotrophin releasing hormone (GnRH) agonist pre-treatment? DESIGN: A total of 212 patients with PCOS referred to Royan Institute, Tehran, Iran, between 20 August 2017 to 20 June 2018 were included. The patients were randomly assigned to receive oestradiol after downregulation with GnRH agonist (group A) or without GnRH agonist down-regulation (group B). RESULTS: A total of 188 patients with PCOS completed the trial, 93 patients in group A and 95 patients in group B. Basal oestradiol and LH levels were significantly higher in group B (26.66 versus 41.61, P = 0.01 and 0.93 versus 5.33, P < 0.0001, respectively). Clinical pregnancy rates were not significantly different in both groups (31.2% versus 33.7%). Similarly, no significant differences were found between groups A and B in miscarriage (9.7% versus 11.6%), implantation (0.58 versus 0.51) and live birth (21.7% versus 22.1%) rates and for medical complications during pregnancy and neonatal anomalies. CONCLUSIONS: Our findings indicate that endometrial preparation for frozen-thawed embryo transfer with and without ovarian suppression by GnRH agonist provides similar results.

The effect of synbiotics supplementation on anthropometric indicators and lipid profiles in women with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Different therapies have been suggested for polycystic ovary syndrome (PCOS), but changes in lifestyle and diet have been considered. Diet and dietary factors can be very effective in modifying the disease. The positive effects of probiotic and synbiotics supplementation on improving lipid profiles and anthropometric indices have been examined in various diseases. This study was conducted to evaluate the effects of synbiotics supplementation on lipid and anthropometric profiles in infertile women with PCOS. METHODS: PCOS patients aged 19-37 years old were randomized to receive either synbiotics supplement (n = 50) or placebo (n = 49) for 12 weeks. RESULTS: Consumption of synbiotics compared to the placebo, resulted in a significant decrease in Low-density lipoprotein cholesterol (LDL) value (Change Mean Difference (CMD): 4.66, 95%CI: 0.20, 9.13) and a significant increase in high-density lipoprotein cholesterol (HDL) (CMD: 1.80, 95%CI: 0.34, 3.26). Although we failed to find a significant effect of synbiotics consumption on total cholesterol (TC) and triglyceride (TG) levels. We did not find differences in anthropometric indices between groups. CONCLUSIONS: Overall, 12 weeks of synbiotics supplementation among PCOS women resulted in beneficial effects on LDL and HDL, although it is not yet clear how much our findings are clinically significant and more clinical studies with larger sample sizes are still needed. TRIAL REGISTRATION: Iranian Registry of clinical Trial, IRCT.ir, ID: IRCT2014110515536N2. Registered on 19 December 2015.

Response to Letter to the Editor Entitled: Concerning the Article by Arezoo Maleki-Hajiagha et al. Entitled Serum Prostate-Specific Antigen Level in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Dear Editor,We thank Kunicki et al. 1 for their interest in our paper 2 and for taking the time to give relevant and important comments regarding the inclusion of hirsutism or hyperandrogenism cases in our study. We agree with Kunicki et al. that the title is not appropriate, and it was better if the title of the article was: Serum Prostate-Specific Antigen Level in Women with Polycystic Ovary Syndrome and Hyperandrogenism: A Systematic Review and Meta-Analysis. Also, we should make some minor editing in the manuscript text.

Preservation of Childbearing Potential in Cancer Survivors: a Survey of Gynecologists' and Embryologists' Current Knowledge, Attitude, and Practice.

Cancer is one of the life-threatening diseases, and cancer therapy may produce severe side effects such as impaired fertility. Saving childbearing potential after cancer treatment is of high importance to cancer survivors. This study assessed gynecologists' and embryologists' current practice, knowledge, and attitude concerning fertility preservation (FP) in cancer survivors. This current survey was performed on a convenience sample of 277 gynecologists and embryologists who attended large international congresses held across Iran. A 23-item self-administered questionnaire that included questions on knowledge, attitudes, and practice was used. Questions had either yes/no responses, or were answered based on a 4-point (1 to 4) Likert scored scale. Total mean score for knowledge of all FP options was 2.97 ± 0.62. Total mean scores for knowledge of all FP options in gynecologists and embryologists were 3.03 ± 0.65 and 2.95 ± 0.61, respectively (p = 0.33). These scores were above the median value of 2.5 obtained using the 4-point Likert scale. Participants regarded the patient age as the most important reason for discussing FP with patients (mean scores 3.74 ± 0.71 and 3.73 ± 0.52 for gynecologists and embryologists, respectively; p = 0.93). The majority of the participants (i.e., 95.2% (79 gynecologists) and 92.2% (166 embryologists)) referred cancer patients to centers providing FP services (p = 0.15). This sample of Iranian gynecologists and embryologists had considerable information on FP methods to develop appropriate attitudes and practices in relation to FP for cancer patients in order to prevent loss of fertility.

Serum Prostate-Specific Antigen Level in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

We undertook a comprehensive search of all published original articles evaluating the diagnostic value of prostate-specific antigen (PSA) for the detection of polycystic ovary syndrome (PCOS). Finally, 25 studies with a total of 1865 participants (1104 cases and 761 controls) met the inclusion criteria. Mean serum PSA levels were significantly higher in PCOS women compared to healthy women [Standardized mean difference (SMD)=1.73 ng/ml, 95% CI=1.22 to 2.25, p<0.001]. Only 5 studies reported accuracy indicators and were included in the bivariate random-effects model; with a total of 509 samples that included 332 (65.22%) confirmed PCOS women. The sensitivity of serum PSA for the diagnosis of PCOS varied between 66.3 and 90.6%, and, the specificity ranged from 62.5-86.7%. Meta-analysis revealed a pooled sensitivity of 72.3% (95% CI 67.1-77.00%) and specificity of 74.6% (95% CI 67.5-80.8%) with an area under the summary ROC curve equal to 0.82 (95% CI 0.75-0.83). The summary estimates were 2.92 (95% CI 1.98-4.31) for positive LR and 0.37 (95% CI 0.26-0.51) for negative LR. The pooled estimate of diagnostic odds ratio (DOR) of serum PSA was 9.01 (95% CI 4.35-18.64). Considering the methodological weaknesses existed in studies, lack of sufficient data regarding the accuracy indicators, and the complexity of the exact pathophysiology of PSA secretion in women, the precise position of PSA, as a diagnostic test for the detection of PCOS, in clinical practice is undetermined, and further studies are still needed.

Little information about fertility preservation is provided for cancer patients: A survey of oncologists' knowledge, attitude and current practice.

The objective of this survey was to explore the knowledge, attitude and current practice of Iranian oncologists about fertility preservation (FP) services provided to cancer patients. Oncologists who completed this survey were a convenience sample of 103 specialists in radiation oncology and haematology who attended large national and international congresses and symposia across Iran. A 23-item self-administered questionnaire included questions on knowledge, attitudes and practice. The most well known of the FP methods among Iranian oncologists were gonadotropin-releasing hormone therapy and sperm cryopreservation, with scores of 2.77 (1.10) and 2.64 (1.00) respectively. These scores were above the median value of 2.5 on a 4-point Likert scale, in contrast to a mean knowledge score across all the FP options of 2.25 (0.71). With regard to attitudes, age was the most important reason for discussing FP with patients, mean score 3.75 (0.54), while heredity was the least important, mean score 2.98 (0.87). In terms of practice, most oncologists did not provide their patients with written information about FP. However, 74 (72.5%) said they referred cancer patients on to reproductive specialists. This sample of Iranian oncologists would benefit from more information on FP methods and prevent loss of fertility among cancer patients.

The Effects of Supplementation with Chromium on Insulin Resistance Indices in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Recently, the effects of nutritional supplementation on improvement or prevention of polycystic ovary syndrome (PCOS) have been considered. Several studies have been carried out on the effect of chromium supplementation in improving PCOS patients. This study aimed to summarize the available findings regarding the effect of chromium on improving the polycystic ovary syndrome. The review includes randomized controlled trials (RCTs) comparing chromium treatment with placebo or other treatments in women with PCOS. Women with PCOS diagnosed according to the ESHRE/ASRM or NIH criteria in reproductive age were eligible. Electronic searches using the MeSH terms were conducted in the following databases: Medline, Embase, Scopus, Web of Science, and The Cochrane Library. Effects were measured as weighted mean difference (WMD) and 95% confidence intervals (CI) for studies of PCOS and control subjects were calculated by using random-effects model. The initial search yielded potentially 100 relevant articles of randomized clinical trials on dietary chromium supplements: 16 from Pubmed, 36 from Embase, 29 from Scopus, and 19 from Web of Science. After studying these publications, 5 were potentially eligible and retrieved in full text. The five studies included in the meta-analysis reported data on 137 women with PCOS and 131 controls. A meta-analysis of 5 studies showed a non-significant difference in fasting insulin between chromium, and placebo or other treatment (mean difference (MD): -1.14; (95% CI: -4.11 to 1.83, p=0.45). We retrieved two randomized controlled trials, in which Quantitative Insulin Sensitivity Check Index (QUICKI) was compared between chromium, and placebo or other treatment in 156 women with PCOS. Meta-analysis of two RCTs showed no significant difference in QUICKI score between chromium and placebo (MD: 0.01; 95% CI: -0.01 to 0.04, p=0.34). Two randomized controlled trials compared Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) between chromium, and placebo or other treatment in 81 women with PCOS. After combining the data, there was a significantly lower HOMA-IR in the chromium group (MD: -1.68; 95% CI: -2.42 to -0.94, p<0.001). One RCT reported a significant difference in Homeostatic Model Assessment-beta-cell function (HOMA-B) between chromium and placebo groups (-15.5±32.3 vs. +13.6±23.1, p<0.001). No significant effect of chromium on fasting insulin and QUICKI score was found in women with PCOS. Chromium supplementation significantly improved HOMA-IR and HOMA-B among patients with diabetes. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials in well characterized studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.