Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1.
2019; 75: 1?8
Neurodevelopmental outcome following prenatal diagnosis of a short corpus callosum.
Statins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.At E14.5, untreated pregnant wild-type (WT, n=13-18), untreated HO-1+/- (Het, n=6-9), and Het mice treated with pravastatin (Het+Pravastatin, n=12-14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.Compared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0-73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2-5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.
View details for PubMedID 30712660
Personalized charts for the fetal corpus callosum length.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio.Historical prospective cohort study including pregnant women who were referred for fetal neurosonogram due to abnormal CC. Short CC was defined below the 5th percentile according to reference charts. Twenty cases were included in the study group and compared with a control group of 59 normal cases. The patients in the study group were divided into two groups according to CC length/EFW ratio. Children's neurodevelopment was assessed using the Vineland Adaptive Behavior Scale (VABS).VABS scores were within normal range in 90% of the cases. There was no significant statistical difference between the study group and the control group. In addition, there was no statistically significant difference between fetuses reclassified as normal callosal length according to CC length/EFW ratio in comparison to the control group.The neurodevelopmental outcome of fetuses with diagnosed short CC did not differ from the neurodevelopment of normal fetuses in the control group.
View details for DOI 10.1002/pd.5460
View details for PubMedID 30980563
'The obesity paradox': a reconsideration of obesity and the risk of preterm birth.
Journal of perinatology : official journal of the California Perinatal Association
To personally customize the antenatal ultrasound charts for the fetal corpus callosum (CC) length.A retrospective analysis of fetal neuro-sonography scans. Cases were grouped as normal neuro-sonographic evaluation (normal) or as high risk and suspected brain anomaly (abnormal). The normal group was subcategorized according to Cignini's CC length charts. Data of fetuses with a CC length between the 5th-95th percentile served for creating new charts, describing the ratio of the CC length to the major biometric parameters as a function of gestational age (GA).A total of 410 measurements were included. Of them 255 were normal and 155 abnormal. The CC length/estimated fetal weight (EFW) ratio had the strongest linear association with GA (R2 = 0.929). Applying charts using this ratio to the normal group, significantly increased the percent of CC length measurements defined as normal from 84.7 to 94.5% (p < 0.001). Conversely, applying these charts to the abnormal group nonsignificantly decreased the number of measurement defined as normal from 89 to 83.2% (p = 0.137) Conclusions: The CC length/EFW ratio is strongly and linearly associated with GA. Using this personalized ratio may improve the diagnostic accuracy of CC evaluation by adjusting the CC length to the fetus natural proportions.
View details for PubMedID 29779410
Reduced fetal movement: factors affecting maternal perception.
journal of maternal-fetal & neonatal medicine
2016; 29 (8): 1318-1321
The association between obesity and spontaneous preterm births (sPTBs) has been shown to be influenced by obesity-attendant comorbidities. Our objective was to better understand the complex relationship of obesity and its attendant comorbidities with sPTBs.A retrospective analysis utilizing maternally linked hospital and birth certificate records of 2 049 196 singleton California deliveries from 2007 to 2011. Adjusted relative risks (aRRs) for sPTBs were estimated using multivariate Poisson regression modeling.Obese women had higher aRRs for sPTBs than their normal body mass index (BMI) controls. aRRs (95% confidence interval) increased with increasing BMI category: Obese I=1.10 (1.08 to 1.12); Obese II=1.15 (1.12 to 1.18); and Obese III=1.26 (1.22 to 1.30). When comparing only obese women without comorbidities to their normal BMI controls, aRRs reversed, that is, obese women had lower aRRs of sPTBs: Obese I=0.96 (0.94 to 0.98), Obese II=0.95 (0.91 to 0.98); and Obese III=0.98 (0.94 to 1.03). This same reversal of aRR direction was also observed among women with comorbidities: 0.92 (0.89 to 0.96); 0.89 (0.85 to 0.93); and 0.89 (0.85 to 0.93), respectively. Increasing BMI increased the aRRs for sPTBs among patients with gestational diabetes (P<0.05), while decreasing the risk among patients with chronic hypertension and pregnancy-related hypertensive disease (P<0.05).The obesity and preterm birth paradox is an example of what has been described as 'Simpson's Paradox'. Unmeasured confounding factors mediated by comorbidities may explain the observed protective effect of obesity upon conditioning on the presence or absence of comorbidities and thus resolve the paradox.Journal of Perinatology advance online publication, 27 July 2017; doi:10.1038/jp.2017.104.
View details for PubMedID 28749482
Twin Anemia-Polycythemia Sequence: Perinatal Management and Outcome.
Fetal diagnosis and therapy
2016; 40 (1): 28?34
Evaluate physiologic factors associated with reduced maternal perception of fetal movements (RFM).A historical cohort study of all women (years 2011-2013, n = 399) that visited the maternal emergency room (ER) (gestational age 24 + 0-42 + 0) due to RFM (group A), that was compared to a control group consisted from women with normal perception of fetal movements (group B). Groups were compared for maternal characteristics (age, gravity, parity, BMI), gestational age, placental location, gestational age at birth and fetal outcomes (birth-weight and Apgar scores).In a multivariate regression analysis, including maternal age, height, weight, BMI, gestational age on admission to ER, gravity, parity and placental location, only two variables remained significantly associated with RFM - nulliparity (OR = 2.28, p = 0.001) and anterior placenta (OR = 1.44, p = 0.034). Group A was not associated with lower Apgar scores (1 and 5-min, p = 0.40 and 0.57, respectively) or low birth-weight (p = 0.76), nor was it associated with prematurity (p = 0.41), low (<7) 5-min Apgar score, fetal death or neonatal death.Reduced fetal movements are associated with anterior placenta and nulliparity.
View details for DOI 10.3109/14767058.2015.1047335
View details for PubMedID 26177055
Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro.
Reproductive biomedicine online
To determine the perinatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS).All monochorionic twins diagnosed with TAPS between 2011 and 2014 were included. Each twin pair with TAPS (study group) was compared with 2 uncomplicated monochorionic twin pairs who were matched for gestational age at delivery (control group). Neonatal morbidity and mortality were evaluated.During the study period, 179 monochorionic twins were followed at our center, of whom 46 underwent laser ablation due to twin-to-twin transfusion syndrome. TAPS was diagnosed in 10 cases; 8 of them were spontaneous, and 2 occurred following laser surgery. Out of 7 patients diagnosed prenatally with TAPS, 5 cases were managed expectantly, and 2 cases were treated with intrauterine blood transfusion. The rates of severe and mild central nervous system lesions on postnatal ultrasound were similar in the TAPS group and control group (5.0 vs. 2.5%, p = 0.61, and 5.0 vs. 12.5%, p = 0.25, respectively). Additionally, severe neonatal morbidity was comparable between the groups. All neonates were alive at 1 month of age.The neonatal outcome of monocohorionic twins affected by TAPS is favorable and comparable to gestational age-matched uncomplicated monochorionic twins.
View details for DOI 10.1159/000441451
View details for PubMedID 26580546
Interdisciplinary exchange of ideas: progestagens for autoimmunity, biologics for pregnancy complications
2015; 61 (1-2): 31-34
How chemotherapy affects dormant ovarian primordial follicles is unclear. The 'burnout' theory, studied only in mice, suggests cyclophosphamide enhances primordial follicle activation. Using 4-hydroperoxycyclophosphamide (4hc) and phosphoramide mustard (PM), this study assessed how the active cyclophosphamide metabolites 4-hydroxycyclophosphamide (4-OHC) and PM, affect human primordial follicles. Frozen-thawed human ovarian samples were sliced and cultured with basic culture medium (cultured controls) or with 4hc/PM (3?µmol/l/10?µmol/l) (treated samples) for 24-48?h. Follicular counts and classification, Ki67 and anti-Müllerian hormone (AMH) immunohistochemistry and an apoptosis assay were used for evaluation, and 17?-oestradiol and AMH were measured in spent media samples. Generally, there was primordial follicle decrease and elevated developing follicle rates in treated samples compared with cultured (P = 0.04 to P < 0.0005) and uncultured controls (P < 0.05 to P < 0.0001). No traces of apoptosis were found. There were almost twice the levels of AMH and 17?-oestradiol in treated compared with untreated samples (AMH with 4hc 3?µmol/l; P = 0.04). All follicles stained positively for AMH included treated samples. Ki67 positive staining was noted in all samples. Cyclophosphamide metabolites seem to enhance human primordial follicle activation to developing follicles, in vitro. Study findings support the 'burnout' theory as the mechanism of chemotherapy-induced ovarian toxicity.
View details for DOI 10.1016/j.rbmo.2016.10.005
View details for PubMedID 27815062
Does bariatric surgery improve ovarian stimulation characteristics, oocyte yield, or embryo quality?
JOURNAL OF OVARIAN RESEARCH
In recent years, there has been a growing interest in the role of immune, alloimmune and autoimmune processes in the pathogenesis of spontaneous preterm birth and recurrent pregnancy loss. The association between an inflammatory response and preterm labor has been established. Indeed, many women suffering from preterm labor have elevated inflammatory markers such as tumor necrosis factor alpha, interleukin 6 and matrix metaloproeinase 8. The role of immune processes in the pathogenesis of recurrent pregnancy loss has also been widely researched. Progesterone induces many physiologic effects necessary for healthy pregnancy, and progestagens supplementation has been used as an approach to prevent preterm labor and recurrent pregnancy loss. Progestagens also have potent anti-inflammatory and immunomodulatory actions. Because preterm labor and recurrent pregnancy loss are associated with abnormal inflammation, progestagens may maintain healthy pregnancy through both endocrine and immunologic actions. These immunologic actions, such as suppression of Th1- and Th17-related responses, enhancement of regulatory T cell (Tregs) activity and suppression of inflammation, may also be involved in pregnancy-induced remission of certain autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Accordingly, there is growing interest in the potential therapeutic role of progestagens in the treatment of MS and RA. In this review, we suggest that biologic autoimmune modulators, especially those which affect immune pathways similar to progestagens, may provide more potent and specific effects, and hence better results than progestagens, in preventing preterm labor and recurrent pregnancy loss.
View details for DOI 10.1007/s12026-014-8621-1
View details for Web of Science ID 000349004900005
View details for PubMedID 25550090
[Obesity, bariatric surgery and future fertility].
2014; 153 (8): 478-?
Obesity is a major global health concern associated with multiple co-morbidities. Bariatric surgery has been considered a good treatment option in cases of morbid obesity. This preliminary study aims to investigate the effect of bariatric surgery on ovarian stimulation characteristics and IVF treatment cycle outcome.A retrospective study that was performed in a tertiary, university-affiliated medical center and included all patients who underwent IVF treatment both before and after bariatric surgery. Data on ovarian stimulation variables of IVF treatment cycle prior and following the bariatric surgery were reviewed and compared.From January 2005 to June 2014, seven women fulfilled the inclusion criteria. After the operation, BMI was significantly reduced (mean?±?SD) (43.1?±?3.3 vs. 29.6?±?7.33, p?=?0.018), as was the number of gonadotropin ampoules required during stimulation (69.3?±?10.5 vs. 44.5?±?17, p?=?0.043). No between-cycle differences were observed in peak estradiol level, the number of oocytes retrieved, and percentage of mature oocytes.To the best of our knowledge, this preliminary case series is the first comparison of IVF cycle characteristics prior to and following bariatric surgery. The operation seems to reduce treatment costs without affecting oocyte or embryo quality. Further large studies are required to establish the surgery's effect on IVF outcome among infertile women.
View details for DOI 10.1186/s13048-014-0116-0
View details for Web of Science ID 000347193000002
View details for PubMedID 25491501
View details for PubMedCentralID PMC4265478
Is the modified natural in vitro fertilization cycle justified in patients with "genuine'' poor response to controlled ovarian hyperstimulation?
FERTILITY AND STERILITY
2014; 101 (6): 1624-1628
Obesity is an increasingly widespread health problem. In addition to comorbidities such as diabetes, hypertension, dyslipidemia and cardiovascular disease, obesity has a significant impact on reproductive life, including infertility, miscarriages and high prevalence of pregnancy complications. The present review describes the possible benefits of bariatric surgery regarding fertility and pregnancy outcome. It is well established that bariatric surgery leads to regular ovulatory cycles and improves spontaneous conception rates in obese women. While pregnancy after bariatric surgery is safe and associated with reduced pregnancy complications, pregnant women following bariatric surgery are still at high risk for preterm births and small dimensions of gestational age offsprings. The optimal interval that should be kept between surgery and subsequent pregnancy is controversial, with recent studies emphasizing the importance of nutritional balance rather than the time from surgery to conception as being the most important determinant. Strict peri-conceptional surveillance is mandatory in order to prevent nutritional deficiencies and for the early diagnosis of abnormal fetal growth.
View details for PubMedID 25286641
To examine whether patients with poor ovarian response (POR) during conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may benefit from a modified natural cycle (MNC)-IVF.Cohort historic study.Tertiary, university-affiliated medical center.One hundred eleven patients with POR, defined according to the Bologna criteria, who underwent a subsequent MNC-IVF within 3 months of the previous failed conventional IVF/ICSI cycle. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of "genuine" poor responder patients, those who yielded up to three oocytes after controlled ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU.Modified natural cycle IVF protocol with GnRH antagonist (GnRH-a) supplementation. Gonadotropin-releasing hormone antagonist treatment was started when a follicle of 13 mm was present. Two to three ampules of hMG were coadministered daily during the GnRH-a treatment.Live birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of embryos transferred.Live birth rate in "genuine" poor ovarian responders was <1%. Furthermore, in the subgroup of patients with POR who underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte, no pregnancies were achieved during the MNC-IVF cycle.Modified natural cycle-IVF is of no benefit for genuine poor ovarian responders and the option of egg donation should be seriously considered for this population.
View details for DOI 10.1016/j.fertnstert.2014.02.036
View details for Web of Science ID 000337364300031
View details for PubMedID 24680364