Does The Culture of Post-Thawed Cleavage-Stage Embryos to Blastocysts Improve Infertility Treatment Outcomes of Frozen-Thawed Embryo Transfer Cycles? A Randomised Clinical Trial.

BACKGROUND: There is a definite shift in assisted reproductive centres from cleavage-stage embryo transfer (ET) to blastocyst transfer that is attributed to improvements in laboratory environments and advances in the development of embryo culture media. The aim of the study was to investigate the reproductive outcomes of thawed cleavage-stage ET versus blastocysts derived from an extended culture of these embryos. MATERIALS AND METHODS: This open-label, randomised, parallel group clinical trial study enrolled 182 women aged ≤37 years who underwent frozen-thawed ET from November 2015 to June 2020 at Royan Institute Research Centre, Tehran, Iran. The women were randomly assigned to either the thawed cleavage ET group (n=110) or the post-thaw extended culture blastocysts group (n=72). The primary outcome measure was the clinical pregnancy rate. Secondary outcome measures were implantation rate, live birth rate (LBR), and miscarriage rate. A P<0.05 indicated statistical significance. RESULTS: There were no significant differences between the two groups in terms of demographic characteristics. Both the mean numbers of embryos transferred and good quality embryos transferred were significantly lower in the postthaw extended culture blastocysts group compared to thawed cleavage-stage ET cycles. However, the post-thaw extended culture blastocysts group had higher clinical pregnancy (56.94 vs. 40.91%, P=0.034), implantation (34.43 vs. 19.84%, P=0.001) and live birth (49.3 vs. 33.63%, P=0.036) rates compared to the thawed cleavage-stage ET group. Miscarriage and multiple gestations rates were comparable between the groups. CONCLUSION: These results allow us to take a position in favour of post-thaw extended culture blastocysts; thus, it is important to improve the post-thawing extended culture technique (registration number: NCT02681029).

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.

Epidemiology of sperm DNA fragmentation in a retrospective cohort of 1191 men.

BACKGROUND: The scientific and clinical communities now recognize that sperm DNA integrity is crucial for successful fertilization, good embryo development, and offspring quality of life. Despite the apparent unanimity, this criterion is rarely evaluated in clinical practice. We evaluated the sperm DNA fragmentation index of nearly 1200 sperm samples and its connections based on the patient's age, body mass index, the season of sperm collection, geographical location, medical history, and addictive behaviors. METHODS: A cohort of 1503 patients who were referred to the Royan Institute between July 2018 and March 2020 was examined. Only 1191 patient records with demographic data, complete semen analysis, and DNA fragmentation index measurements were included in the final cohort. Documents were classified, incorporated into statistical models, and analyzed. RESULTS: The results confirmed previous findings that the sperm DNA fragmentation index was significantly higher in aging men. The sperm DNA fragmentation index and high DNA stainability levels were significantly higher in spring and summer samples than in those of other seasons. No correlation was found between semen DNA fragmentation index and patient body mass index, although the study cohort was significantly overweight. Contrary to what might be expected, we observed that the sperm DNA fragmentation index was higher in rural than in urban patients. Intriguingly, epileptic patients exhibited significantly higher sperm DNA fragmentation index levels. DISCUSSION AND CONCLUSION: Age is the factor that is most strongly associated with sperm DNA fragmentation index levels. Our analysis of 1191 samples indicates that between the ages of 19 and 59, the sperm DNA fragmentation index increases by an average of 2% each year. Intriguingly, from an epidemiological perspective, the warm season (spring/summer) is associated with a higher sperm DNA fragmentation index in the study population, possibly due to the deleterious effect of temperature on sperm quality. Some neurological diseases, such as epilepsy, are associated with decreased sperm DNA integrity. This observation could be related to the iatrogenic effects of associated therapies. In the study cohort, body mass index did not appear to be correlated with the DNA fragmentation index.

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.

The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study.

BACKGROUND: To detect the predictive value of beta human chorionic gonadotropin (ß-hCG) levels 16 days post embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology (ART) cycles. MATERIALS AND METHODS: In this cross-sectional study, we reviewed the database of Royan Institute from January 2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive ß-hCG levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented serum ß-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients' files. A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement of ß-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for each of the estimates. RESULTS: The mean levels of ß-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The ß-hCG thresholds predictive of ongoing pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8- 81.7%. However, this relationship was not found in IUI cycles. CONCLUSION: Based on these findings, if ß-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended, until either the diagnosis of EP or miscarriage is established.

How much obesity and diabetes do impair male fertility?

BACKGROUND: Subfertility in obese and diabetic men during the reproductive age is evident, but the mechanisms by which obesity and diabetes mellitus cause male infertility are not entirely understood. The current study aimed to evaluate the effects and potential mechanisms of obesity and diabetes on male fertility. METHODS: We enrolled control = 40, obese = 40, Lean-DM = 35, and Obese-DM = 35 individuals. The obesity-associated markers, diabetic markers, hormonal and lipid profile, inflammatory indices, and semen analysis were assessed in four experimental groups. RESULTS: Our finding showed that diabetic markers were significantly increased in two diabetic groups, while obesity indices were markedly increased in two obese groups. Conventional sperm parameters were significantly lower in three groups compared with the control. Serum levels of total testosterone and sex hormone-binding globulin were significantly lower in men with obesity and DM compared with the control. There was a significant difference in the concentration of high-sensitivity C-reactive protein among four experimental groups. Moreover, serum leptin was significantly increased in obese DM, lean DM, and obese groups. Serum insulin levels had a positive correlation with metabolic-associated indices and high-sensitivity C-reactive protein levels, whereas it had a negative correlation with count, motility, and morphology. CONCLUSIONS: Our findings showed the metabolic changes, hormonal dysfunction and inflammatory disturbance might be suspected mechanisms of subfertility in obese and diabetic subfertile men.

Birth prevalence of genital anomalies among males conceived by intracytoplasmic sperm injection cycles: A cross-sectional study.

Background: Several studies have been conducted worldwide to evaluate the prevalence and relative risks of congenital anomalies associated with assisted reproductive technology cycles; however, there is limited data in Iran. Objective: To investigate male genital anomalies among live births from assisted reproductive technology. Materials and Methods: This cross-sectional study was conducted on children born after intracytoplasmic sperm injection (ICSI) at Royan Institute, Tehran, Iran from April 2013-December 2015. The prevalence of male genitalia disorders that included hypospadias, epispadias, cryptorchidism, micropenis, and vanishing testis were reported. The relationship between the cause of infertility and type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and birth weight with these male genitalia anomalies were evaluated. Results: In total, 4409 pregnant women were followed after their ICSI cycles to evaluate genitalia anomalies in their children. Out of 5608 live births, 2614 (46.61%) newborns were male, of which 14 cases (0.54%) had genital anomalies. The prevalence of various anomalies were cryptorchidism (0.34%), hypospadias (0.038%), micropenis (0.038%), vanishing testis (0.038%), and epispadias (0.077%). No relationship was found between the cause of infertility, type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and male genital malformation (p = 0.33, p = 0.66, and p = 0.62, respectively). Conclusion: The prevalence of each male genital anomaly after the ICSI cycle was rare and less than 0.5%; however, no significant infertility-related factor was observed with these anomalies.

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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Awareness and attitude toward oocyte cryopreservation for non-medical reasons: a study on women candidates for social egg freezing.

PURPOSE: The present study was to investigate awareness and attitudes toward female fertility and aging, desire for a child and motherhood, and oocyte freezing for non-medical reasons among women candidates for Social Egg Freezing (SEF). MATERIALS AND METHODS: This was a cross-sectional study on all 216 women who sought oocyte cryopreservation for nonmedical reasons at Royan Institute. A 24-item self-administered questionnaire measured knowledge and attitudes to SEF. Responses were as yes/no or a 4-point Likert scale. RESULTS: Only 40% of participants accurately indicated that having a sexual partner does not help to preserve their fertility. A quarter of women correctly recalled chance of pregnancy with unprotected intercourse during a period of a year, for women 20 to 40 years old. Only one-third of respondents accurately identified the age-related fertility decline at 35-39 years. Only 6.9% correctly mentioned the low chance of pregnancy after egg freezing at 35 years old. Almost a third of women knew that the age range of 31-35 years is the right age to freeze an egg with the highest chance of pregnancy. Aging and health of offspring were most influential in women's decisions on SEF. CONCLUSION: In conclusion, there was significant gaps in knowledge about age-related fertility decline, and egg cryopreservation conditions and its complications. It is crucial to impart to these women a better knowledge about fertility and a realistic picture about SEF, especially on the number of high-quality retrieved mature oocytes and live birth rates depend on women's age.

Unexplained Total Fertilization Failure after Intracytoplasmic Sperm Injection Cycles: A Case-Control Study on Predictive Factors and Retreatment Prognosis.

BACKGROUND: The aim of our study was to detect the rate of unexplained total fertilization failure (TFF) after intracytoplasmic sperm injection (ICSI) and identify its risk factors and retreatment prognosis. MATERIALS AND METHODS: In this retrospective case-control study, we searched the computerized database of the Royan Institute (Tehran, Iran) from March 2015 to March 2019 and retrieved all cases diagnosed with TFF after ICSI. TFF cases that did not have any recognized risk factors were classified as unexplained (subgroup A). Cases with recognized risk factors were classified as subgroup B. The control group was randomly selected from infertile couples who underwent ICSI cycles with fertilization of at least one oocyte during the same time interval. Characteristics and treatment outcomes of the cases with unexplained TFF (subgroup A) were compared to the control group, and to the other TFF cases (subgroup B). RESULTS: Out of 18,750 couples who underwent ICSI cycles, 296 (1.58%) experienced TFF for the first time. Of these, 49 (16.5%) couples were diagnosed as unexplained TFF (subgroup A) and 247 (83.5%) were placed in subgroup B, TFF with expected risk factors. Multivariable logistic regression analysis showed that the total number of mature oocytes (P<0.001), duration of infertility (P=0.043), and women's body mass index (BMI, P<0.001) were significant predictive factors for unexplained TFF. In the ICSI cycle after TFF, clinical pregnancy and live birth rates in subgroup A were higher than subgroup B. Although differences between these groups were not statistically significant (P=0.14 and P=0.07, respectively), this finding could be clinically important. CONCLUSION: Unexplained TFF following ICSI is a rare event significantly related to a lower number of mature oocytes, longer duration of infertility and higher female BMI. It has a good prognosis in retreatment cycles in comparison with expected TFF cases. Clinicians should take this into consideration for patient counseling and management.

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.

Potential Impact of Diabetes and Obesity on Alveolar Type 2 (AT2)-Lipofibroblast (LIF) Interactions After COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new emerging respiratory virus, caused evolving pneumonia outbreak around the world. In SARS-Cov-2 infected patients, diabetes mellitus (DM) and obesity are two metabolic diseases associated with higher severity of SARS-CoV-2 related complications, characterized by acute lung injury requiring assisted ventilation as well as fibrosis development in surviving patients. Different factors are potentially responsible for this exacerbated response to SARS-CoV-2 infection. In patients with DM, base-line increase in inflammation and oxidative stress represent preexisting risk factors for virus-induced damages. Such factors are also likely to be found in obese patients. In addition, it has been proposed that massive injury to the alveolar epithelial type 2 (AT2) cells, which express the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), leads to the activation of their stromal niches represented by the Lipofibroblasts (LIF). LIF are instrumental in maintaining the self-renewal of AT2 stem cells. LIF have been proposed to transdifferentiate into Myofibroblast (MYF) following injury to AT2 cells, thereby contributing to fibrosis. We hypothesized that LIF's activity could be impacted by DM or obesity in an age- and gender-dependent manner, rendering them more prone to transition toward the profibrotic MYF status in the context of severe COVID-19 pneumonia. Understanding the cumulative effects of DM and/or obesity in the context of SARS-CoV-2 infection at the cellular level will be crucial for efficient therapeutic solutions.

Placental alpha microglobulin-1 (PartoSure) test for the prediction of preterm birth: a systematic review and meta-analysis.

OBJECTIVES: To assess the accuracy of the placental alpha microglobulin-1 (PAMG-1) to predict preterm birth (PB) in women with symptoms of PB through use of formal methods for systematic reviews and meta-analytic techniques. METHODS: We performed a comprehensive search of medical bibliographic databases to identify observational studies that reported on the predictive accuracy of PAMG-1 for PB. Two investigators independently assessed studies, assessed quality of studies, and extracted data. Summary receiver operating characteristic (SROC) curves, pooled sensitivities, specificities, likelihood ratios (LR), and diagnostic odds ratio (DOR) were generated. RESULTS: Seventeen studies involving 2590 women met the inclusion criteria. Meta-analysis of 15 studies (including 1906 women) revealed a pooled sensitivity of 66.2% (95% CI: 59.1, 72.7) and specificity of 96.1% (95% CI: 95.1, 97.0) with the SROC equal to 0.97 (95% CI: 0.95, 0.98) for prediction of delivery within 7 d of testing. The summary estimates were 15.26 (95% CI: 11.80, 19.75) for LR + and 0.31 (95% CI: 0.17, 0.55) for LR - for prediction of delivery within 7 d of testing. Pooled estimate of DOR for predicting delivery within 7 d of testing was 55.13 (95% CI: 35.32, 86.06). The sensitivity, specificity and the SROC of PAMG-1 pooled from 10 studies (including 1508 women) for prediction of delivery within 14 d of testing were 64.4% (95% CI: 56.8, 71.5), 96.9% (95% CI: 95.8, 97.7) and 0.97 (95% CI: 0.95, 0.98). The overall pooled LR + and LR - of PAMG-1 for predicting delivery within 14 d of testing among the included studies were 16.72 (95% CI: 12.03, 23.23) and 0.42.1 (95% CI: 0.31, 0.56), respectively. The pooled DOR of the PAMG-1 for prediction delivery within 14 d of testing was equal to 44.65 (95% CI: 26.30, 75.78). CONCLUSION: Cervical PAMG-1 had a high accuracy to predict PB within 7 and 14 d of testing in symptomatic pregnant women.

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.