The use of vaginal progesterone as a maintenance therapy in women with arrested preterm labor: a double-blind placebo-randomized controlled trial.

BACKGROUND: The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone (n = 45) or placebo (n = 40) until 34 weeks of gestation. The primary outcomes were the time until delivery (latency period) and cervical length after 1 week of treatment. Secondary outcome were GA on delivery, type of delivery, incidence of low birth weight, perinatal morbidity and mortality. RESULTS: Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) days p = .0001; longer mean of gestational age on delivery (37.5 ± 2.2 versus 34.2 ± 2.1) weeks p = .0001; cervical length after 1 week of treatment (27.5 ± 5.5 versus 20.7 ± 3.1) mm p = .0001; low birth weight 12 (29.3%) versus 19 (57.6%) p = .01; and NICU admission 9 (22%) versus 15 (45.5%), were significantly different between the two groups. No significant differences were found between neonatal death 1 (2.4%) versus 2 (6.1%), p = .43; RDS 5 (12.2%) versus 8 (24.2%), p = .17; and need to mechanical ventilator 2 (5.4%) versus 6 (18.2%) p = .136, for the progesterone and placebo groups, respectively. CONCLUSION: Daily administration of 400 mg vaginal progesterone after successful parenteral tocolysis may increase latency preceding delivery and improves cervical shortening and neonatal outcome in women with preterm labor. Further confirmatory studies are warranted.

Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum.

This study aimed to assess the maternal features, Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PLGF) in the Placenta Accreta Spectrum (PAS); then, to determine a predictive value of VEGF and PLGF in the PAS. This prospective case-control study was conducted on 90 pregnant women including 45 PAS, and 45 Normal Placenta (NP). Maternal age, gravidity, C/S, and serum levels of VEGF and PLGF were assessed between NP and PAS, and among NP and PAS sub-groups, including Placenta Accreta (PA), Placenta Increta (PI), and Placenta Percreta (PP). The Multi-gravidity, previous C/S, maternal age, and serum level of PLGF were significantly higher in the PAS group compared to the NP group OR = 42, 8.1, 1.17, and 1.002 (p-value <.05 for all); however, there was no difference regarding serum level of VEGF (p-value >.05). The same differences were seen among NP with PA, PI, and PP sub-groups (p-value <.05 for all, but p-value >.05 for VEGF). Placenta Previa was uniformly distributed across the PAS sub-groups (p-value >.05), also the VEGF and PLGF serum levels did not differ between PAS with Previa and PAS without Previa groups (p-value >.05). A valid cut-off point for PLGF was reported at 63.55. A predictive value of PLGF for the PAS patients is presented enjoying high accuracy and generalisability for the study population.Impact statementWhat is already known on this subject? The Placenta Accreta Spectrum (PAS), in which the placenta grows too deep in the uterine wall, is responsible for maternal-foetal morbidity and mortality worldwide; so, the antenatal diagnosis of PAS is an important key to improve maternal-foetal health. Normal placental implantation requires a fine balance among the levels of angiogenic and anti-angiogenic factors, such as the Placenta Growth Factor (PLGF), the Vascular Endothelial Growth Factor (VEGF), and soluble Fms-like tyrosine kinase-1. However, there is still controversy regarding The PLGF and VEGF level changes in PAS patients.What do the results of this study add? Despite traditional measuring the levels of PLGF and VEGF from the placenta at the time of delivery; in this study including 90 participants (28-34 weeks of gestation) the maternal serum levels of PLGF and VEGF were measured in advance (temporality causation), resulted in presenting a more valid cut-off point for PLGF in PAS group. In addition, the serum level of PLGF was significantly higher in the PAS and PAS sub-groups compared to the Normal Placenta group. Also, the Previa status of PAS patients did not affect the VEGF and PLGF serum levels.What are the implications of these findings for clinical practice and/or further research? PLGF cut-off point derived from the maternal serum level could predict PAS validly and, if used as a screening test in an earlier pregnancy, the maternal-foetal morbidity and mortality would decrease.

A 5-year experience on perinatal outcome of placenta accreta spectrum disorder managed by cesarean hysterectomy in southern Iranian women.

BACKGROUND: We aimed to investigate the risk factors of placenta accreta spectrum (PAS) disorder, management options and maternal and neonatal outcomes of these pregnancies in a resource-limited clinical setting. METHODS: All women diagnosed with placenta accreta, increta, and percreta who underwent peripartum hysterectomy using a multidisciplinary approach in a tertiary center in Shiraz, southern Iran between January 2015 until October 2019 were included in this retrospective cohort study. Maternal variables, such as estimated blood loss, transfusion requirements and ICU admission, as well as neonatal variables such as, Apgar score, NICU admission and birthweight, were among the primary outcomes of this study. RESULTS: A total number of 198 pregnancies underwent peripartum hysterectomy due to PAS during the study period, of whom163 pregnancies had antenatal diagnosis of PAS. The mean gestational age at the time of diagnosis was 26 weeks, the mean intra-operative blood loss was 2446 ml, and an average of 2 packs of red blood cells were transfused intra-operatively. Fifteen percent of women had surgical complications with bladder injuries being the most common complication. Furthermore, 113 neonates of PAS group were admitted to NICU due to prematurity of which 15 (7.6%) died in neonatal period. CONCLUSION: Our findings showed that PAS pregnancies managed in a resource-limited setting in Southern Iran have both maternal and neonatal outcomes comparable to those in developed countries, which is hypothesized to be due to high rate of antenatal diagnosis (86.3%) and multidisciplinary approach used for the management of pregnancies with PAS.

Antioxidant ameliorative effect of caffeic acid on the ectopic endometrial cells separated from patients with endometriosis.

OBJECTIVE: Considering the role of oxidative stress in the development and progression of endometriosis, the ameliorative effect of caffeic acid treatment on ectopic, eutopic endometrial cells enzyme activities was investigated. We also determined the underlying cellular mechanisms. MATERIALS AND METHODS: Ectopic endometrial specimens were collected from women with confirmed cases of endometriosis (n = 10) and eutopic specimens from (n = 10) controls. Following endometrial cell isolation and culture, eutopic and ectopic endometrial cells were treated with caffeic acid. Then, reactive oxygen species (ROS) level, NAD(P)H quinone oxidoreductase 1 (NQO1), and Heme oxygenase 1 (HO-1) enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf-2) gene expression were measured. RESULTS: In ectopic endometrial cells, caffeic acid caused a significant elevation in Nrf-2 gene expression level, NQO1, and HO-1 enzyme activities. In addition, reduced ROS level was observed in caffeic acid-treated ectopic endometrial cells in comparison with the control. On the contrary, we did not observe any significant changes in caffeic acid-treated eutopic endometrial ones. CONCLUSION: Caffeic acid can protect the endometrial cells against oxidative stress and might be able to prevent the progression of endometriosis and its related complications, such as pain and infertility.

In utero xenotransplantation of mice bone marrow-derived stromal/stem cells into fetal rat liver: An experimental study.

BACKGROUND: Animals can play an important role in preparing tissues for human through the development of xenotransplantation protocols. The most common problem with liver transplantation like any other organ transplantation is organ supply shortage. OBJECTIVE: To evaluate the in utero xenotransplantation of mouse bone marrow-derived stromal/stem cells (BMSCs) to the liver of rat fetus to produce mouse liver tissue. MATERIALS AND METHODS: BMSCs were isolated and confirmed from enhanced green fluorescent protein (eGFP)-genetic labeled mice. Using a microinjection protocol, mice BMSCs were injected into the liver of rat fetuses in utero on day 14 of pregnancy. After birth, livers were collected and the presence of mice eGFP-positive cells in rat livers was evaluated through polymerase chain reaction. RESULTS: The eGFP mRNA was detected in the liver of injected infant rats. BMSCs of adult mice were capable to remain functional probably as hepatocyte-like cells in liver of infant rats after in utero xenotransplantation. CONCLUSION: BMSCs have the potential for intrauterine xenotransplantation for the treatment of liver dysfunction before birth. This method can also be used for xenoproduction of liver tissue for transplantation.

Patients' self-reported factors influencing cervical cancer screening uptake among HIV-positive women in low- and middle-income countries: An integrative review.

Cervical cancer is among the most common causes of cancer-related deaths in low- and middle-income countries (LMICs). Despite the strong evidence regarding cervical cancer screening cost-effectiveness, its utilization remains low especially in high risk populations such as HIV-positive women. The aim of this review was to provide an overview on the patient-reported factors influencing cervical cancer screening uptake among HIV-positive women living in LMICs. We systematically searched EMBASE, PUBMED/MEDLINE and Web of Science databases to identify all quantitative and qualitative studies investigating the patient-reported barriers or facilitators to cervical cancer screening uptake among HIV-positive population from LMICs. A total of 32 studies met the inclusion criteria. A large number of barriers/facilitators were identified and then grouped into three categories of personal, social and structural variables. However, the most common influential factors include knowledge and attitude toward cervical cancer or its screening, embarrassment, fear of cervical cancer screening and test results, patient-healthcare provider relationship, social support, screening costs and time constraints. This review's findings highlighted the need for multi-level participation of policy makers, health professionals, patients and their families in order to overcome the barriers to uptake of cervical cancer screening among HIV-positive women, who are of special concern in LMICs.

Effects of prophylactic iron supplementation on outcome of nonanemic pregnant women: A non-randomized clinical trial.

BACKGROUND: The aim of the current study was to investigate the effects of prophylactic iron supplementation on the pregnancy outcome of nonanemic pregnant women in a sample of Iranian population. METHODS: This non-randomized clinical trial was conducted during a 2-year period in obstetrics clinics of Shiraz, southern Iran. We included a sample of singleton pregnancies registered in our clinics. Those with comorbidities were excluded. Serum ferritin was measured at baseline and participants were classified accordingly: those with normal serum ferritin levels (≥30 µg/dL) who received standard prophylactic iron supplementation during the pregnancy (Group 1); those who had minor thalassemia and elevated serum ferritin levels (≥30 µg/dL) who did not receive prophylactic iron supplementation or those with normal ferritin levels (≥30 µg/dL) who refused to receive iron supplementation due to gastrointestinal upset (Group 2); and those with iron deficiency anemia with low serum ferritin levels (<30 µg/dL) who received standard iron supplementation during pregnancy (Group 3). All the participants were followed to the delivery and maternal and neonatal outcomes were recorded and compared between three study groups. RESULTS: Overall we included 30 pregnant women in each group with mean age of the participants was 28.66 ± 6.02 years. There was no significant difference between three study groups regarding gestational age at delivery (p = 0.250), birthweight (p = 0.893), Apgar at 1 (p = 0.532) and 5 (p = 0.590) minutes, and route of delivery (p = 0.590). The overall rate of maternal complication of the pregnancy was comparable between the three study groups (p = 0.188). However, those in group 1, had significantly higher rate of gestational diabetes mellitus (GDM) when compared to other two groups (p = 0.038). CONCLUSION: Prophylactic iron supplementation in pregnant women with normal ferritin levels is associated with increased risk of GDM. Other pregnancy and neonatal outcomes are not affected by the prophylactic iron supplementation.

Combination Effect of Caffeine and Caffeic Acid Treatment on the Oxidant Status of Ectopic Endometrial Cells Separated from Patients with Endometriosis.

BACKGROUND: Endometriosis is a common gynecological disease in which oxidative stress is a potential factor. Caffeine and caffeic acid are present in various foods and beverages with anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. In this study, we aimed to investigate the ameliorative effects of caffeine, caffeic acid, and caffeine+caffeic acid treatments on oxidative stress in ectopic endometrial cells taken from patients and eutopic ones from women without endometriosis. METHODS: In this experimental study, eutopic and ectopic endometrial cells were obtained from biopsies of women free of disease (n=10) and patients with endometriosis (n=10) who referred to Shiraz reference hospitals (2017-2018). Both eutopic and ectopic endometrial cells were divided into four groups: Treated with caffeine, with caffeic acid, with caffeine+caffeic acid, and the control. Also, antioxidant enzyme activities and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined in each group. The data were analyzed using independent sample t test and one-way ANOVA followed by Tukey post-hoc test. RESULTS: Caffeic acid, but not caffeine treatment demonstrated a decrease in MDA level (P<0.001) as well as an increase in GSH level (P<0.001) and antioxidant enzyme activities in ectopic endometrial cells. Also, the treatment of the cells with caffeine+caffeic acid caused similar effects as those ectopic cells treated with caffeic acid. CONCLUSION: According to the findings of the present study, caffeic acid reduced oxidative stress which may alleviate the complications associated with endometriosis. However, more investigations are needed for evaluating the efficiency and safety of caffeic acid.

Fetal Central Nervous System Anomalies Detected by Magnetic Resonance Imaging: A Two-Year Experience.

BACKGROUND: Magnetic resonance imaging (MRI) is gradually becoming more common for thorough visualization of the fetus than ultrasound (US), especially for neurological anomalies, which are the most common indications for fetal MRI and are a matter of concern for both families and society. OBJECTIVES: We investigated fetal MRIs carried out in our center for frequency of central nervous system anomalies. This is the first such report in southern Iran. MATERIALS AND METHODS: One hundred and seven (107) pregnant women with suspicious fetal anomalies in prenatal ultrasound entered a cross-sectional retrospective study from 2011 to 2013. A 1.5 T Siemens Avanto scanner was employed for sequences, including T2 HASTE and Trufisp images in axial, coronal, and sagittal planes to mother's body, T2 HASTE and Trufisp relative to the specific fetal body part being evaluated, and T1 flash images in at least one plane based on clinical indication. We investigated any abnormality in the central nervous system and performed descriptive analysis to achieve index of frequency. RESULTS: Mean gestational age ± standard deviation (SD) for fetuses was 25.54 ± 5.22 weeks, and mean maternal age ± SD was 28.38 ± 5.80 years Eighty out of 107 (74.7%) patients who were referred with initial impression of borderline ventriculomegaly. A total of 18 out of 107 (16.82%) patients were found to have fetuses with CNS anomalies and the remainder were neurologically normal. Detected anomalies were as follow: 3 (16.6%) fetuses each had the Dandy-Walker variant and Arnold-Chiari II (with myelomeningocele). Complete agenesis of corpus callosum, partial agenesis of corpus callosum, and aqueductal stenosis were each seen in 2 (11.1%) fetuses. Arnold-Chiari II without myelomeningocele, anterior spina bifida associated with neurenteric cyst, arachnoid cyst, lissencephaly, and isolated enlarged cisterna magna each presented in one (5.5%) fetus. One fetus had concomitant schizencephaly and complete agenesis of the corpus callosum. CONCLUSIONS: MRI is superior to ultrasound and physical exam of live births in detection of CNS anomalies. In this investigation within a single referral center in southern Iran, anomalies included Dandy-Walker variant and Arnold-Chiari II as the most common findings. Other findings with lower incidence were complete and partial agenesis of corpus callosum, aqueductal stenosis, anterior spina bifida, schizencephaly, arachnoid cyst, lissencephaly, and isolated enlarged cisterna magna.

Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine.

Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells. Expression levels of PR, ER, and VEGF in human endometrial stromal primary cells treated with nicotine (0, 10-11, 10-8, and 10-6 µM) for 24 h were measured by quantitative real-time PCR. MTT assay demonstrated that nicotine decreased cell viability in a dose-dependent manner. Real-time PCR data showed that despite decrease in ER expression in the nicotine-treated groups compared with the control, nicotine exerted an increased inhibitory effect on PR expression compared to that on ER expression. VEGF mRNA expression in nicotine-treated endometrial stromal cells was increased. The results from this study provide novel evidence for inhibitory effects of nicotine on steroid hormones receptor expression in human primary endometrial cells. Also, our data suggest that nicotine might have angiogenesis effects on these cells.

Induction of Asherman's Syndrome in Rabbit.

BACKGROUND: Uterine synechiae or Asherman's syndrome is a condition that can cause infertility. The present experimental study was designed to establish the rabbit as an animal model for human Asherman's syndrome using the endometrial curettage. METHODS: In an experimental study, female adult rabbits (n=18) were randomly divided into intact and ovariectomized groups. One third of caudal part of both uteri was submitted to traumatic endometrial curettage. One group was simultaneously ovariectomized. The intact rabbits were artificially induced ovulation during 10 days after surgery. One third of cranial part of both uteri was selected as the control. Synechiae occurring, luminal area/total area (LA/TA), endometrial area/total area (EA/TA), myometrial and perimetrial area/total area (MPA/TA), endometrial area/uterine wall area (EA/UWA), and myometrial and perimetrial area/uterine wall area (MPA/UWA) ratios of both uteri in six subdivided groups (n=6) were analysed in curetted and intact control parts. On days 15, 30 and 45 following surgery by two-way ANOVA and LSD test (p<0.05). RESULTS: Histopathologic findings showed significant epithelial damage together with significant inflammatory reaction in the intact curettage group. The LA/TA ratios of the intact curettage group on days 15 and 45 were more than the intact control group on day 15. The EA/TA ratio of the intact curettage group on day 30 was less than the intact control group on day 30. CONCLUSION: Uterine fibrosis was observed in intact curettage group, and this modified animal model showed a pathogenesis condition similar to intrauterine adhesions observed in human.

Growth Kinetics, Characterization, and Plasticity of Human Menstrual Blood Stem Cells.

One of the readily available sources of mesenchymal stem cells (MSCs) is menstrual blood-derived stem cells (Men-SCs), which exhibit characteristics similar to other types of MSCs. This study was performed to determine the growth kinetics, plasticity, and characterization of Men-SCs in women. During spring 2014 in the southern Iranian city of Shiraz, menstrual blood (5 mL) was obtained from 10 women on their third day of menstruation in 2 age groups of 30 to 40 and 40 to 50 years old. Ficoll was used to separate the mononuclear cell fraction. After the Men-SCs were cultured, they were subcultured up to passage 4. Growth behavior and population doubling time were evaluated by seeding 5×10(4) cells into 12- and 24-well culture plates, and the colonies were enumerated. The expression of CD44, CD90, and CD34 was evaluated. The osteogenic potential was assessed by alizarin red staining. The Men-SCs were shown to be plastic adherent and spindle-shaped. Regarding the growth curves in the 12- and 24-well culture plates, it was demonstrated that in the women aged between 30 and 40 years, population doubling time was 55.5 and 62 hours, respectively, while these values in the women aged between 40 and 50 years were 70.4 and 72.4 hours, correspondingly. Positive expression of CD44 and CD90 and negative expression of CD34 were noted. In the osteogenic differentiation medium, the cells differentiated toward osteoblasts. As human Men-SCs are easily collectable without any invasive procedure and are a safe and rapid source of MSCs, they can be a good candidate for stem cell banking and cell transplantation in women.

Comparison of Abnormal Cervical Cytology from HIV Positive Women, Female Sex Workers and General Population.

BACKGROUND: Sex workers and HIV seropositive women are at high risk of abnormal cervical cytology. The objective of this study was to compare the cervical cytology among three groups of women: active sex workers, HIV-infected women, and general population in Iran. METHODS: This was a cross-sectional study performed in Hazrat Zeinab, Lavan clinics and drop in center (DIC) in Shiraz, Iran. This study was performed from October 2009 to October 2011. A total of 266 patients were assigned into three groups: sex-workers (85), HIV positive patients (100), and general population (81). Pap smear was performed for all participants from the exocervix and endocervix, using a plastic Ayres's spatula and cytobrush. The samples were sent to a pathology center, using a liquid-based media. RESULTS: The risk of cervical infection in sex workers and HIV positive women was greater than the general population (OR=5.47, 95% confidence interval [CI]:2.24, 13.40), (OR=3.71, 95% CI:1.52, 9.09), respectively. The frequency of abnormal cervical cytology in the HIV positive and sex worker groups was higher than the general population (OR=6. 76, 95% CI:2.25, 20.32), (OR=3. 80, 95% CI:1.19, 12.07), respectively. Low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) were associated with CD4 cell count<200Í106/L, P=0.021 and P<0.001, respectively. CONCLUSION: Vaginal infections were seen more often in the sex worker group, and abnormal cervical cytology was greater in the HIV positive group.