The potential causal effect of the pre-pregnancy dietary phytochemical index on gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders. RESULTS: During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593). CONCLUSIONS: Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.

Co-culture of human cryopreserved fragmented ovarian tissue with theca progenitor cells derived from theca stem cells.

PURPOSE: Despite the significant advances in the in vitro development of human primordial follicles, it is still a challenging approach with great potential for improvements. Therefore, the present study aimed to investigate the effect of a feeder layer of human theca progenitor cells (hTPCs) on the development of primordial follicles embedded in human ovarian tissue. METHODS: Fragments of frozen-thawed ovarian tissue were activated using the vanadate-derivative dipotassium bisperoxo (5-hydroxy-pyridine-2-carboxylic) oxovanadate (V) and kit ligand for 24 h. Then, the specimens were divided into the co-culture and mono-culture groups and were cultured with and without a hTPC feeder layer for 6 days, respectively. Afterward, the follicles were counted and classified, and the hormone levels and expression levels of apoptosis- and folliculogenesis-related genes were assessed. RESULTS: Both culture groups showed significant follicle growth (P < 0.05). However, the co-culture group had a significantly higher number of growing follicles compared to the other group (P < 0.05). Moreover, the expression levels of ZP1, ZP2, ZP3, BMP-7, AMH, and GDF9 were significantly higher in the co-culture group compared to the other group (P < 0.05), while the expression levels of P53 and CASP3 were significantly lower (P < 0.05). Also, the concentrations of estradiol, progesterone, testosterone, and androstenedione were significantly higher in the co-culture group compared to the other group (P < 0.05). CONCLUSION: The present study results provided novel evidence on the direct role of hTPCs in the growth and development of human primordial follicles. However, there is a need for future studies to illustrate the underlying mechanisms. Schematic summary of the results. According to our results, the expression of ZP1, ZP2, ZP3, and GDF9 in the oocytes, AMH in the granulosa cells, and BMP4 in the theca cells of the co-culture group were significantly higher than those of the mono-culture and non-culture groups, while the expression of apoptotic genes (BAX, CASP3, and P53) was significantly lower. Moreover, the co-culture group showed significantly increased levels of estradiol, progesterone, testosterone, and androstenedione in its culture media compared to the mono-culture groups.

The effect of hydroxychloroquine on pregnancy outcomes in patients with unexplained recurrent pregnancy loss: a placebo-controlled study "pilot study".

This double-blind placebo-controlled study investigated the effect of hydroxychloroquine on pregnancy outcomes in people with unexplained recurrent pregnancy loss (URPL). The inclusion criteria included gestational age ≤6 weeks and a history of at least two miscarriages. The exclusion criteria included any known cause for previous abortions or a history of any chronic diseases. Participants were given 200 mg hydroxychloroquine or placebo twice a day until gestational week 20. Twenty-nine women were enrolled. There was no statistically significant difference between the two groups in terms of age, BMI, gravidity, previous abortion, relative married couple, and infertility. Miscarriage occurred in five women including one in the hydroxychloroquine group (7.69%) and four women in the placebo group (28.57%) (OR: 2.36, 95% PL CI:1.07, 8.93). However, after adjusting for potential confounders, there was no significant difference between the two groups (aOR: 2.96, 95%CI: 0.91, 10.02).IMPACT STATEMENTWhat is already known on this subject? Miscarriage, a prevalent concern in the field reproductive medicine, causes psychological and family problems for couples. Unfortunately, no effective treatment has been yet found for URPL. There are some hypotheses about the role of immunological factors in URPL. Hydroxychloroquine (HCQ) has various immunological effects and may theoretically have a role in the treatment of URPL. Although few studies have been registered to investigate the effect of HCQ on URPL, none of them has been published.What do the results of this study add? In our double-blind placebo-controlled trial, the prevalence of abortion in the HCQ group was four times lower than that in the placebo group, however, this difference was not statistically significant, which can be attributed to the small sample size.What are the implications of these findings for clinical practice and/or further research? We hope that HCQ will be of interest to researchers and future research help clarify the role of HCQ in preventing URPL.

CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene.

Preeclampsia (PE) is a major complication of pregnancy and remains a leading cause of neonatal and maternal mortality worldwide. Several studies have revealed that the incidence of preeclampsia is high in mothers who carried a fetus with Rubinstein-Taybi Syndrome due to the mutation in CREBBP. We aimed to compare the expression level of the CERBBP gene between preeclamptic and healthy placenta in our study. The expression level of CREBBP gene was evaluated in a total of one hundred placental biopsies from PE patients and healthy pregnant women after delivery using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the differential expression of CREBBP was assessed between the maternal and fetal sides of the placenta. Expression of the CREBBP gene was higher in preeclampsia patients compared with the controls (Fold change = 2.158; P = 0.018). Moreover, the gene expression was slightly higher in the fetal side of the placenta, although it was not significantly different (Fold change = 1.713, P = 0.254). Our findings show a role for CREBBP in the pathogenesis of PE. Due to the important role of CREBBP in angiogenesis and hypoxia, the gene may serve as a promising target in future studies.

Mothers and their children's health (MATCH): a study protocol for a population-based longitudinal cohort.

BACKGROUND: The quality of prenatal care is critical for the prevention of adverse pregnancy outcomes. However, according to the World Health Organization (WHO), only 64 % of women worldwide have access to over four sessions of prenatal care throughout their pregnancy. Thus, studies that address factors affecting maternal and child health status before and after pregnancy are of immense importance. The primary aim of the mothers and their children's health (MATCH) cohort study is to evaluate the effect of nutrition, sleep quality, and lifestyle on maternal and neonatal outcomes. METHODS: A prospective cohort of > 2500 pregnant women in the first trimester (before 12 weeks' gestation) will be recruited at Arash Women's Hospital in Tehran, Iran between February 2020 and August 2021. All eligible pregnant women will be followed from their first trimester of pregnancy until delivery at four time points and assessed through a series of in-person visits with interviewer-administered questionnaires and telephone interviews. Detailed data will be collected on maternal demographics, lifestyle, medical history, reproductive history, obstetric history, dietary intake, sleep pattern, blood specimens, and anthropometric measurements, alongside paternal demographics, lifestyle, and family history. The outcomes will include antenatal, peripartum, and postnatal maternal complications and infant growth and neurodevelopment. DISCUSSION: The results of the MATCH cohort study will support the development of contextual interventions that can enhance antenatal, peripartum, and postnatal status, neonatal outcomes, and longevity mother and child.

Assisted conception as a potential prognostic factor predicting insulin therapy in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM. METHODS: In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy. RESULTS: A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years [OR: 2.91, 95% CI: (1.28-6.62)], high serum FBS [1.10: (1.04-1.16)], HbA1c [1.91 (1.09-3.34)], and ART treatment [2.94: (1.24-6.96)] were independent risk factors for insulin therapy in GDM women. CONCLUSIONS: Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.

An intron variant in the FLT1 gene increases the risk of preeclampsia in Iranian women.

Background: Preeclampsia is a hypertensive disorder that affects pregnancy, mother, and fetus. Pathogenesis of preeclampsia could be associated with the angiogenesis pathways. The vascular endothelial growth factor (VEGF) family is one of the important factors for normal pregnancy and angiogenesis. Genetic variations in the gene family members may play a role in the etiology of preeclampsia. We investigated the possible association between VEGFA gene rs3025039, and VEGFR1 (FLT1) gene rs722503 polymorphisms and preeclampsia in a sample of Iranian patients. Methods: Genotyping was performed in 395 women, including, 204 pre-eclamptic pregnant women and 191 healthy normotensive pregnant women by using the PCR-RFLP method. Results: The rs722503 polymorphism was associated with preeclampsia under the dominant model (P = 0.04, OR = 1.53, 95% CI: 1.03-2.27). No significant difference was observed for the rs3025039 alleles and genotypes in the studied groups. Conclusions: Based on our study, rs722503 polymorphism in the FLT1 gene may play an important role in susceptibility to preeclampsia.

'Elective caesarean section at 38-39 weeks gestation compared to > 39 weeks on neonatal outcomes: a prospective cohort study.

BACKGROUND: This study was conducted to compare neonatal complications in scheduled cesarean sections (CS) between 38 and 39 gestational weeks with CS performed after 39 gestational weeks in Iranian low -risk pregnant women. METHODS: In this cohort study, 2086 patients were enrolled based on the inclusion and exclusion criteria. The neonates were evaluated in terms of the following items: transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), sepsis, need for NICU hospitalization, birth weight, birth height, head circumference, and the first minute and fifth minute Apgar score. Several multiple logistic regression models were performed for each response variable (adverse outcome) separately. RESULTS: The incidence of NICU admission was significantly higher in neonates born at 38-39 gestational weeks than those who were born after 39 gestational weeks. No significant differences were found in the incidence of neonatal sepsis, TTN, and RDS between the two groups. CONCLUSION: According to our study results, elective CS at 38-9 weeks' gestation is associated with a higher rate of TTN and NICU admission in comparison with elective CS performed after 39 completed gestational weeks.

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC). METHODS: Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs). RESULTS: Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24-22.15)], preeclampsia [aOR:7.78 (1.62-37.47)], APH [aOR:3.46 (1.28-9.33)], emergency CS [aOR:2.64 (1.43-4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51-10.10)], LBW [aOR:3.11 (1.04-9.30)] and NICU admission [aOR:4.36 (1.82-10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50-16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31-12.89)], emergency CS [aOR: 2.01 (1.09-3.73] and LGA [aOR: 5.20 (1.07-25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02-11.68), preeclampsia 5.29 (1.03-27.09), and NICU admission [aOR: 2.53 (1.05-6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group. CONCLUSION: The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

Association study of FOXP3 gene and the risk of 0020 pre-eclampsia.

Pre-eclampsia (PE) is a multifactorial pregnancy disorder, with serious consequences for both the mother and the fetus. Despite intense studies, the pathophysiology of PE remains enigmatic. Previous studies suggested that Treg dysfunction is involved in the pathogenesis of PE. We hypothesized that functional variants of the FOXP3 gene might be associated with PE via dysregulation of Treg cells. Of the 276 subjects, we genotyped three variants of FOXP3 by PCR-RFLP and Tetra ARMS-PCR methods. The genotypic frequencies of rs2232365 were found to be protective from the development of PE under codominant [odds ratio (OR) 0.49, 95 percent confidence interval (CI) 0.28-0.87, p-value = 0.043], dominant [odds ratio (OR) 0.54, 95 percent confidence interval (CI) 0.32-0.94, p-value = 0.027] and over dominant [odds ratio (OR) 0.57, 95 percent confidence interval (CI) 0.35-0.92, p-value = 0.02] models. Moreover, the rs3761548 conferred a risk of PE in recessive model [odds ratio (OR) 2.05, 95 percent confidence interval (CI) 1.08-3.88, p-value = 0.025]. However, no mutation was detected in FOXP3 exon2 in any of the studied samples. Based on our results, thought that FOXP3 variants may be an important contributor for the progression of PE in Iranian women.

Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case-control study.

PURPOSE: To evaluate predictive factors for gestational diabetes mellitus (GDM) in singleton pregnancy following assisted reproductive technology (ART). METHODS: This nested case-control study was performed during October 2016-June 2017. Pregnant women who conceived following ART procedures referred to infertility clinic were selected and categorized into GDM and non-GDM based on ADA/IAPDSG criteria. The study variables including age, educational status, first-degree family history of chronic diseases, systolic and diastolic blood pressure, previous obstetric and perinatal outcomes, infertility history, and ART cycle characteristics were collected from medical records. Prediction model to develop GDM was employed by binary logistic regression analysis after adjustment for age and body mass index, family history of diabetes, and gravidity. RESULTS: In total, 270 women with singleton pregnancies (consisted of 135 GDM and 135 non-GDM women) conceived were studied. According to the final model, significant predictors of GDM were history of polycystic ovarian syndrome (PCOS), previous ovarian hyper-stimulation syndrome (OHSS) risk and progesterone injections. Administration of injectable progesterone during the first 10-12 weeks of pregnancy was associated with an approximately twofold increased risk of developing GDM [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.27-4.09)] compared to vaginal progesterone. In addition, the regression analysis revealed that previous OHSS risk (OR 2.40, 95% CI 1.34-4.31) and history of PCOS (OR 2.76, 95% CI 1.26-6.06) were other most important predictors of GDM. CONCLUSIONS: The route of progesterone administration, previous OHSS risk and history of PCOS seem to be putative risk factors for GDM in women conceived by ART.

Slow freezing versus vitrification technique for human ovarian tissue cryopreservation: An evaluation of histological changes, WNT signaling pathway and apoptotic genes expression.

This study compared slow freezing and vitrification of ovarian tissue by evaluation of histological changes, WNT signaling pathway and apoptotic genes expression. Ovarian tissue was obtained from women aging 27-38 years old. Ovarian cortex from each patient was divided into three pieces and randomly grouped as slow freezing, vitrification and control groups for investigation of WNT signaling gene expression and ß-CATENIN presence as well as histological studies. The stromal structure of all ovaries were preserved. The number of secondary follicles decreased in vitrified group (P < 0.05). WNT-3, ß-CATENIN, FZD-2 and GSK-3ß expressions were significantly higher in slow frozen and vitrified groups, compared to control group (P < 0.05). On the contrary, AXIN1 expression in slow frozen samples were significantly lower than that of the vitrified and control group. The expression of apoptotic genes, excluding CASP3, was significantly decreased in slow-frozen samples (P < 0.05). Conversely, BAX:BCL-2 percentage significantly increased in vitrification versus slow freezing and control(P < 0.05). Follicles in slow frozen samples displayed nuclear and cytoplasmic ß-CATENIN staining, while control and vitrification groups only showed ß-CATENIN protein in the cytoplasm. The presented data show that slow freezing results in a better preservation regardless of the type of follicle. Therefore, it is concluded that slow freezing is still an ideal method for ovary cryopreservation.

17-alpha-hydroxyprogesterone caproate versus vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix: A randomized controlled trial.

AIM: The aim of this study was to compare 17-alpha-hydroxyprogesterone caproate (17OHP-C) with vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix and to evaluate the changes of the cervical length (CL) over time. METHODS: In this prospective randomized controlled trial, eligible patients were asymptomatic pregnant women with a sonographically short cervix. The participants in group 1 (n = 147) received vaginal progesterone suppositories at a dose of 400 mg daily and the women in group 2 (n = 150) received an i.m. dose of 250 mg 17OHP-C once a week. Transvaginal sonography was repeated every 3 weeks until 36 gestational weeks or the occurrence of preterm labor. RESULTS: A total of 304 singleton pregnant women between 16 and 24 gestational weeks with CL < 25 mm were enrolled in our study. The rates of preterm birth were 10.4% in the progesterone group and 14% in the 17OHP-C group: a difference that was not statistically significant (P = 0.416). Moreover, 264 participants underwent ultrasound examination five times and CL changes were studied for 15 weeks. The results showed that the CL changes over 15 weeks were statistically significant (P < 0.001), but the method of intervention (progesterone/17OHP-C) had no significant effect on CL change (P = 0.64). CONCLUSION: Our findings showed that vaginal progesterone and 17OHP-C had the same effect on the risk of preterm labor in asymptomatic women with a sonographically short cervix. We detected no significant difference between the effect of 17OHP-C and vaginal progesterone on CL changes over time.

Placental implantation and migration following a previous caesarean section scar.

This prospective cohort study was conducted in Arash Women's Hospital between August 2014 and August 2015 to define the relationship between caesarean section scar and placental implantation and migration. Seven hundred and thirty women with one previous birth (caesarean section or vaginal delivery) and a singleton pregnancy underwent three ultrasound examinations for placental evaluation at 11-14, 20 and 34 weeks gestation. Previous caesarean section was related to the increased odds of anterior placental implantation but no relation was seen between low-lying placenta or placenta praevia and previous caesarean. The placental migration from low-lying to non-low-lying position was similar between women with and without previous caesarean.

Gestational diabetes mellitus its association with obesity: a prospective cohort study.

PURPOSE: The aim of this study was to investigate the association between pre-pregnancy body mass index (BMI) and gestational diabetes mellitus (GDM). METHODS: This prospective study was conducted on 256 pregnant women without diabetes referred for prenatal care in the first trimester of pregnancy to two referral University Hospitals (Shariati and Arash Hospitals) during the years 2012 and 2013. Eligible participants were selected consecutively and were followed until delivery and 6 weeks after that. Body weight and fasting plasma glucose were measured in each trimester, and BMI was calculated. Incidence of GDM was recorded, and BMI in this group was compared with those without GDM. RESULTS: Mean age of women was 28.70 ± 5.57 years and among them, 78 women (30.5 %) developed GDM of which 21 were obese (52.5 %), 25 overweight (27.8 %), and 32 (25.4 %) were normal weight (p = 0.004). Pre-pregnancy obesity (OR 2.74, 95 % CI 1.28-5.88, p = 0.009), family history of diabetes (OR 2.01, 95 % CI 1.13-3.56, p = 0.016), and maternal age more than 30 years (OR 2.20, 95 % CI 1.25-3.88, p = 0.006) were three independent predictors for GDM, and pre-pregnancy obesity was the most potent predictor of GDM. CONCLUSION: Women with high BMI and obesity have a significantly higher risk for developing GDM. Pre-pregnancy obesity, family history of diabetes, and age more than 30 years are three independent risk factors for GDM.

Combined treatment with cervical pessary and vaginal progesterone for the prevention of preterm birth: A randomized clinical trial.

AIM: We compared the effectiveness of a combined treatment involving cervical pessary plus vaginal progesterone to vaginal progesterone alone in decreasing the rate of preterm birth in women with short cervix in the second gestational trimester. METHODS: This prospective, open-label, randomized clinical trial was conducted on 144 pregnant women with singleton pregnancy who had a cervical length ≤ 25 mm, at 18-22 gestational weeks (GW). Seventy-three patients were assigned to receive 400 mg of daily vaginal progesterone (group A), and 73 to receive cervical pessary plus 400 mg of daily vaginal progesterone (group B), until the 37th GW. The patients were then followed until delivery. RESULTS: The rates of preterm birth were 16.4% in group A and 19.7% in group B, which were not statistically different (P = 0.6). There were no statistically significant differences in the rates of preterm birth at <37, <34, <32, and ≤26 GW between participants randomized to each group (P = 0.55). The rates of low-birthweight delivery were 17.8% in group A, and 23.9% in group B, which were not statistically different (P = 0.36). The rates of premature rupture of membranes, chorioamnionitis, the requirement for neonatal intensive care unit admission, and fetal and neonatal deaths were similar between the two groups. CONCLUSION: In pregnancies with short cervix at mid-pregnancy, combination therapy of cervical pessary plus daily vaginal progesterone does not have any additional benefit over daily vaginal progesterone alone in reducing the rate of preterm birth and adverse pregnancy outcomes.

Congenital microtia in a neonate due to maternal isotretinoin exposure 1 month before pregnancy: Case Report.

Isotretinoin is a drug used for treating severe cystic/nodular acne. Severe malformations have been documented in neonates whose mothers had taken isotretinoin during pregnancy. Women who became pregnant one cycle after completing therapy are believed to be at teratogenic risk not higher than baseline. We describe the case of a newborn whose mother had taken the drug for 4 weeks. The woman then had contraception for 4 weeks (after the drug treatment had finished), and became pregnant after that period. The newborn had isolated bilateral microtia due to suspected isotretinoin exposure. His mother also had a history of urine tract infection in the second week of pregnancy that was treated with cephalexin. The parents were not from a consanguineous marriage and had no family history of congenital malformations. To reduce the risk, effective contraception should be continued in fertile women more than 1 month after completing therapy.

Role of 'angle of progression' in prediction of delivery mode.

AIM: The aim of this study was to investigate the role of the 'angle of progression' (AOP) in the prediction of vaginal delivery. MATERIAL AND METHODS: In this prospective study, we followed 70 singleton pregnant women. AOP was measured at admission time and also at the beginning of the second stage immediately after digital examination. Digital and ultrasound examiners were unaware of each other's results. The digital examiner decided on the delivery mode based on clinical assessment. RESULTS: Sixty-five (92.9%) women had vaginal delivery. In the first stage of labor, the area under the curve was 87.5% (95% confidence interval [CI], 77.9-97.1; P = 0.005) for the AOP and 85.5% (95%CI, 75.2-95.6; P = 0.009) for digital examination and in the second stage of labor, the area under the curve was 90.2% (95%CI, 81-99.3; P = 0.003) for the AOP and 94.9% (95%CI, 89.1-100; P = 0.001) for digital examination. An AOP of ≥113° at the second stage was associated with a 90.8% probability of vaginal delivery. CONCLUSION: We found a significant relation between AOP and cervical dilatation during the first stage of labor. A larger angle at the beginning of the second stage was significantly associated with shorter time to delivery.

Promotion of cardiac microtissue assembly within G-CSF-enriched collagen I-cardiogel hybrid hydrogel.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31+ tube-like structures as well as vimentin+ cardiac fibroblasts and cTNT+ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.

COVID­19 vaccine hesitancy among pregnant women and their reported reasons for vaccine refusal - A prospective study in Tehran, Iran.

OBJECTIVE: Evaluation of covid­19 vaccine hesitancy among pregnant women and their reported reasons for vaccine refusal. METHODS: This prospective study was performed in Arash women's Hospital, Tehran, Iran, between December 1, 2021 and January 1, 2022. All pregnant women who were attended to prenatal care unit were considered eligible for inclusion. A validated questionnaire was used for data gathering. Written informed consent was obtained from all participants. RESULTS: Finally, 477 pregnant women were recruited and were divided into two groups according the status of vaccine acceptance (237 accepted and 240 women refused vaccination). The mean age of accepted participants was higher (31.65 ± 5.69 vs 30.39 ± 5.5; P = 0.01). There was a significant statistical difference between the groups regarding education level. Access to internet and social media were also significantly different between the two groups (94.8% in accepted vs 86.6% in refused group; P = 0.002). There was more rate of severe COVID-19 infection in friends or relatives of accepted group (50% vs 38%). we did not find any statistically significant differences in obstetric characteristics and the rate of obstetric complications between the two groups. The most common reasons reported by participants for vaccine refusal, was fear of vaccination side effects on the fetus (86.5%), and the less common reported reasons were husband's disagreement (9.7%), use of traditional medicine (5.6%), religious beliefs (3.7%), and information obtained from social media (2.8%). After advices from medical staff, most of these mothers (86.5%) still refused vaccination. CONCLUSION: Based on the results of the present study,rate of COVID-19 vaccine hesitancy was about 50% and its most common reported reason was fear of probable side effects of vaccine on the fetus.