miRNA expression for early diagnosis of preeclampsia onset: hope or hype?

PURPOSE: Preeclampsia (PE) is a multi-systemic disease characterized by hypertension, proteinuria and other typical signs that can negatively affect the development of pregnancy. The outcome of the disease is strongly linked to the possibility of early diagnosis, in order to prevent the clinical manifestations. Pathogenesis is still unknown, although abnormalities of placenta development linked to angiogenesis alterations and abnormal trophoblastic invasion seem to be involved, corroborating the epigenetic theory. Basing on these elements, this review aims to summarize the possible role of miRNAs in PE onset, both as increased or decreased expression in placenta or as maternal serum markers. MATERIALS AND METHODS: We considered eligible all original articles (randomized, observational and retrospective studies), published between 2000 and 2016 in English language, about miRNA expression in placenta and maternal serum levels both in uncomplicated and PE pregnancies. RESULTS: Available data support a direct correlation between selective miRNAs high/low expression in placenta and maternal serum, although it is still unclear how these epigenetic changes may affect the development and outcomes of the disease. CONCLUSION: Future studies should aim to identify a robust panel of miRNA markers in order to predict the onset and development of PE.

The introduction of the absolute risk for the detection of fetal aneuploidies in the first-trimester screening.

PURPOSE: Maternal age is a crucial factor in fetal aneuploidy screening, resulting in an increased rate of false-positive cases in older women and false-negative cases in younger women. The absolute risk (AR) is the simplest way to eliminate the background maternal age risk, as it represents the amount of improvement of the combined risk from the maternal background risk. The aim of this work is to assess the performance of the AR in the combined first-trimester screening for aneuploidies. MATERIALS AND METHODS: A retrospective validation of the AR in the combined first-trimester screening for fetal aneuploidies, in an unselected population at Altamedica Fetal-Maternal Medical Center in Rome, between March 2007 and December 2008. RESULTS: Of 3845 women included in the study, we had a complete follow-up on 2984. We evaluated that an AR < 3 would individuate 22 of 23 cases of aneuploidy with a detection rate of 95.7% (95%CI 87.3-100), a false-positive rate of 8.7% (95%CI 7.7-9.7) and a false-negative rate of 4.3% (95%CI 0-12.7). CONCLUSIONS: In our study, the AR ameliorates the detection rate for aneuploidy. Further research and a prospective study on a larger population would help us to improve the AR in detecting most cases of aneuploidy.

Additive Manufacturing Techniques for the Reconstruction of 3D Fetal Faces.

This paper deals with additive manufacturing techniques for the creation of 3D fetal face models starting from routine 3D ultrasound data. In particular, two distinct themes are addressed. First, a method for processing and building 3D models based on the use of medical image processing techniques is proposed. Second, the preliminary results of a questionnaire distributed to future parents consider the use of these reconstructions both from an emotional and an affective point of view. In particular, the study focuses on the enhancement of the perception of maternity or paternity and the improvement in the relationship between parents and physicians in case of fetal malformations, in particular facial or cleft lip diseases.

Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?

Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several "acute" pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s) which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials) on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent) of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient's reproductive desire and possible risk for his fertility.

Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes.

Fertility outcome after laparoscopic salpingostomy or salpingectomy for tubal ectopic pregnancy A 12-years retrospective cohort study.

AIM: To compare the subsequent reproductive outcome after laparoscopic salpingostomy or salpingectomy for tubal ectopic pregnancy (EP). MATERIAL OF STUDY: A retrospective cohort study was conducted between January 2002 and May 2014 on 132 women admitted to Unit of Gynecology and Obstetrics of the Department of Human Pathology in Adulthood and Childhood "G. Barresi", "Gaetano Martino" Hospital, University of Messina (Italy), with EP and who received surgical treatment, including laparoscopic salpingectomy (n=57) or salpingostomy (n=75). Main outcomes included intrauterine pregnancy (IUP), recurrent EP and persistent trophoblastic disease rates. RESULTS: The IUP rates up to 24 months after surgery were 56.1% for salpingectomy and 60% for salpingostomy. The 2-year recurrent EP rates were 5.3% for salpingectomy and 18.7% for salpingostomy. The persistent trophoblastic disease rate were 1.8% for salpingectomy and 12% for salpingostomy. DISCUSSION: Our results show that the reproductive outcomes after laparoscopic salpingectomy are similar to those observed after conservative treatment. CONCLUSIONS: In the surgical treatment of EP, the clinician should choose the best treatment in accordance with the patient, considering the severity of the disease, the clinical characteristics of the patient and her desire to preserve fertility. KEY WORDS: Ectopic pregnancy, Salpingectomy,Salpingostomy.

Congenital high airway obstruction syndrome (CHAOS): discussing the role and limits of prenatal diagnosis starting from a single-center case series.

OBJECTIVES: we aimed to report our experience about congenital high airway obstruction syndrome (CHAOS) that is a rare and fatal congenital anomaly; laryngeal atresia is the most frequent cause. Sonographic findings are enlarged echogenic lungs, dilated trachea, and ascites. METHODS: we performed a single-center case series analysis collecting antenatally through ultrasound examination, and some of them confirmed by autopsy. RESULTS: we report six cases of CHAOS diagnosed by antenatal ultrasonography between 2007 and 2013. CONCLUSION: to date literature provides very few individual case reports. This work describes typical sonographic findings of this syndrome and it underlines the importance of early prenatal diagnosis to improve prognosis thought an ex utero intrapartum treatment, that seems to be the only chance of survival for the affected fetus.

Management, prognosis and reproductive outcomes of borderline ovarian tumor relapse during pregnancy: from diagnosis to potential treatment options.

BACKGROUND: fertility sparing surgery is the first option for treatment of childbearing age women affected by borderline ovarian tumor (BOT). This review put in evidence the benefits and the risks of conservative surgery procedure. Moreover, the literature review is aimed to analyze the possibility of fertility sparing surgery in BOTs and to define a standard treatment in the management of this pathology during pregnancy. METHODS: systematic analysis of the relevant literature for fertility sparing during pregnancy for BOT, accessed through MEDLINE (1982-2015), bibliographies, and interactions with investigators. The data were assimilated into a rigorous and objective contemporary description, enriched by prospective, controlled, and evidence-based studies. RESULTS: there are not many studies about BOT during pregnancy. It can reasonably assumed that after the diagnosis of a suspected BOT during the third trimester of pregnancy, an attitude of close surveillance could be adopted. To the best of our knowledge, we report the only case in literature focused about the treatment and management of borderline ovarian tumor relapse detected during pregnancy. CONCLUSION: basing on our experience and on literature reported, the conservative management of BOT during gestation up to delivery could be considered feasible. The conservative debulking surgery should be performed at the time of cesarean section in a third referral center for gynecologic oncology.

What Is the Rate of Incomplete Fetal Anatomic Surveys During a Second-Trimester Scan? Retrospective Observational Study of 4000 Nonobese Pregnant Women.

OBJECTIVES: The purpose of this study was to estimate the rate of incomplete fetal anatomic surveys during a second-trimester scan due to an unfavorable fetal position in a nonobese population. METHODS: All pregnant women who came to the Altamedica Fetal-Maternal Medical Center, a specialized center for prenatal diagnosis, for a routine second-trimester scan between January 2012 and April 2013 were retrospectively included in the analysis. Patients with a body mass index higher than 30.0 kg/m(2) or anterior fibroids larger than 5 cm were not included in the study. RESULTS: Of 4000 pregnant women admitted for a second-trimester scan, 169 (4.2%) came back within 2 weeks to complete the examination because of an unfavorable fetal position. In particular, 104 (2.6%) needed visualization of only 1 view, and 65 (1.6%) needed more than 1 view. The most difficult organ to visualize was the corpus callosum, in 73 cases (1.8%); the face was not visualized in 69 cases (1.7%); the cerebellar vermis was not seen in 47 fetuses (1.1%); and the heart could not be completely examined in 40 fetuses (1.0%). Of the 4000 women, 169 (4.2%) had a nonexhaustive scan; 149 (3.7%) needed a second scan to complete the second-trimester survey; 14 (0.35%) needed a third scan; and 2 (0.05%) remained with a not completely exhaustive scan. CONCLUSIONS: There is always a small percentage of incomplete fetal anatomic surveys during a second-trimester scan, which cannot be modified by the sonographer's skill or by technical sonographic innovations.

Management of uterine fibroids in pregnancy: recent trends.

PURPOSE OF REVIEW: The review analyzes how fibroids may influence pregnancy and how myomas may be modified by pregnancy. The most important clinical aspect concerns the impact of myoma on pregnancy and the possibility of a well tolerated surgical treatment for the mother and her fetus, preserving maternal reproductive capacity. RECENT FINDINGS: Fibroids significantly increase in size during early pregnancy and then decrease in the third trimester. Although most women with uterine fibroids have a regular pregnancy, data from the literature suggest that they may have a higher risk of fertility problems and pregnancy complications. SUMMARY: Myomectomy can increase the rate of pregnancy in women with infertility, attempting to restore a normal anatomy and reduce uterine contractility and local inflammation associated with the presence of fibroids, improving the blood supply. Current evidence does not suggest routine myomectomy during pregnancy or at the cesarean birth, as fibroids-related complications are rare and may be overcome by the risks of surgery. However, in selected cases, myomectomy is a feasible and safe technique and associated to a good outcome.The diagnosis of myomas in pregnancy may require attention for the adequate management to preserve maternal and fetal well-being.

Effects of exogenous progesterone on fetal nuchal translucency: an observational prospective study.

OBJECTIVE: Nuchal translucency (NT) seen ultrasonographically at 11-14 weeks' gestation is a sensitive marker for Down syndrome. Despite its important role for Down syndrome screening, its use is still considered controversial due to high false-positive rates. We speculated that progesterone could lead to abnormal blood flow patterns and, subsequently, to increased NT. Our primary endpoint was to evaluate the effects of exogenous progesterone on NT thickness compared to controls. The secondary endpoint was to evaluate these effects in a subgroup at low risk for fetal aneuploidies, identifying the strongest factors influencing NT variation. The tertiary endpoint was to evaluate, within the treatment group, if there is any difference in NT according to the type of progesterone administered, route of administration, and dose regimen. STUDY DESIGN: All women who came to measure NT at 11-14 weeks' gestation (crown-rump length between 45-84 mm) were considered eligible. We divided patients into 2 groups: women receiving exogenous progesterone and controls. Afterwards, 3 NT scans were performed for each case, and the largest value, accurate to 2 decimal points, was recorded. RESULTS: In all, 3716 women were enrolled and analyzed. In a crude analysis, NT (P < .05) increased in the exogenous progesterone group. The same results were obtained in the low-risk group (P < .05). The factorial analysis of variance model confirmed a correlation between altered NT and gestational age (P < .0001) and progesterone exposure (P < .05). The characteristics of treatment (route, formulation, dose) were examined separately and no statistically significant differences among the subgroups were observed. CONCLUSION: Exogenous progesterone increases NT.

Supplementation with a dietary multicomponent (Lafergin(®)) based on Ferric Sodium EDTA (Ferrazone(®)): results of an observational study.

During pregnancy, iron deficiency anemia is recognized as a specific risk factor for both adverse maternal and perinatal outcome. We decided to test the hypothesis that the daily administration of Lafergin(®), a dietary multicomponent based on Ferrazone(®) (Ferric Sodium EDTA), Lactoferrin, Vitamin C and Vitamin B12, from first trimester of pregnancy until the end of gestation, may significantly reduce, in anemic women, the severity of anemia compared to controls who received ferrous sulfate or liposomal iron.

Six consecutive false positive cases from cell-free fetal DNA testing in a single referring centre.

INTRODUCTION: recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta. CASE: WE REPORT SIX CASES OF WOMEN WHO UNDERWENT CHORIONIC VILLUS SAMPLING (CVS) OR AMNIOCENTESIS TO CONFIRM THE RESULTS FROM NIPT: two Turner syndromes, two Triple X, one Patau syndrome, one Edward syndrome. RESULTS: using classic cytogenetic analysis and, also, Array - Comparative Genomic Hybridization (Array CGH) the karyotype of all 5 fetuses was found to be normal. CONCLUSION: results from NIPT must always be confirmed by invasive prenatal diagnosis. It is mandatory to inform the patient that the CVS and amniocentesis still represent the only form of prenatal diagnostic test available.

Reference charts for fetal corpus callosum length: a prospective cross-sectional study of 2950 fetuses.

OBJECTIVES: The purpose of this study was to establish reference charts for fetal corpus callosum length in a convenience sample. METHODS: A prospective cross-sectional study was conducted at the Artemisia Fetal-Maternal Medical Center between December 2008 and January 2012. Among 16,975 fetal biometric measurements between 19 weeks and 37 weeks 6 days' gestation, 3438 measurements of the corpus callosum (20.3%) were available. After excluding 488 measurements (14.2%), a total of 2950 fetuses (85.8%) were considered and analyzed only once. Parametric and nonparametric quantile regression models were used for the statistical analysis. To evaluate the robustness of the proposed reference charts with respect to various distributional assumptions on the sonographic measurements at hand, we compared the gestational age (GA)-specific reference curves produced by the statistical methods used. RESULTS: The mean corpus callosum length was 26.18 mm (SD, 4.5 mm; 95% confidence interval, 26.01-26.34 mm). The linear regression equation expressing the length of the corpus callosum as a function of GA was length (mm) = -11.17 + 1.62 × GA. The correlation between the dimension and gestation was expressed by the coefficient r = 0.83. Normal mean lengths according the parametric and nonparametric methods were defined for each week of gestation. CONCLUSIONS: This work provides new quantile-based reference charts for corpus callosum length measurements that may be useful for diagnosis of congenital corpus callosum anomalies in fetal life.