Francesco Padula

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.

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.

The role of ultrasonography in the diagnosis of fetal isolated complete agenesis of the corpus callosum: a long-term prospective study.

Objective. To evaluate the role of a dedicated neurosonographer in prenatal diagnosis of isolated complete agenesis of the corpus callosum (iCACC) and to asses the postnatal outcome of these infants. Methods. Prospective study between January 2004 to December 2004 at Fetal Maternal Medical Centre ‘Artemisia’, Rome, Italy. A detailed ultrasound scan was performed in fetuses affected by iCACC by a dedicated fetal neurosonographer (CG). In all cases, magnetic resonance imaging (MRI) within 5 weeks and 13–15 months after birth was performed. A comparison was made between prenatal findings following the ultrasound scan and postnatal MRI. In these cases, a follow-up of 4-years was performed with a neurological evaluation. Results. Among 23 cases of ACC diagnosed at our centre in the study period, CACC was diagnosed in 17 fetuses. Two were then excluded due to associated malformations, one was lost at follow-up and one patient opted to terminate her pregnancy. Newborn MRI confirmed the ultrasonographic diagnosis of iCACC in all 13 cases. A regular development was present in 92.3% of prenatally diagnosed iCACC. Conclusion. A dedicated neurosonographer could diagnose the iCACC with the same accuracy as MRI and in up to 90% of cases the newborn will have a regular development.

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

Abstract 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.

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

The purpose of this study was to establish reference charts for fetal corpus callosum length in a convenience sample.

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

Abstract 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.

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

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.

Laser-assisted hatching of human embryos: may two alternative approaches (thinning versus drilling) impact on implant rate?

Oocytes and early embryos are surrounded by a 13–15-μm thick of zona pellucida layer that is involved in the formation of binding with the spermatozoa, hardening process, induction of acrosome reaction, egg fusion, and prevention of polyspermy [1]. Its function becomes less important once the structural junctions between blastomeres in the compaction process are established [2]. Hatching is the physiological process in which the embryo, at the blastocyst stage, comes out of the zona pellucida. This process is a fundamental prerequisite for implantation [3]. Several studies indicate that a zona pellucida thinning is an active process of embryo development already in the early stages [4], and it was demonstrated that not-cleaved embryos do not show changes in thickness of the zona pellucida in culture [5]. The inability of the blastocyst to hatch from the zona pellucida may be one of the factors involved in the high implant failure rate in human in vitro fertilization (IVF) [6], maybe due to a loss of elasticity of the zona pellucida in IVF embryos, similarly to an aging process [7] and to a reduced sensitivity to low pH. Assisted hatching (AH) is the methodology used in IVF to mimic the normal hatching stage of embryonic development and it should increase the implant rate among poor prognosis patients or on embryos noted to have a thick zona pellucida [8, 9]. It has been suggested that AH facilitates the implantation because it allows an early contact between embryo and endometrial tissues and exposing it to growth factors fundamental for the subsequent stages of the blastocyst’s development [10]. AH can be obtained by different methods: mechanical, chemical, or by laser energy. The mechanical techniques are performed by micromanipulator stabilizing the embryo by a holding pipette while a microneedle is pushed tangentially through the zona pellucida. This technique is quick to perform but the size of the hole cannot be standardized. The chemical approach is performed by preloading the microneedle with acid Tyrode and injecting it in a blastomere-free area. This technique requires a very high skill in handling the micromanipulator to perform it as quick as possible to prevent an unnecessary exposure of the embryo to the toxic acid solution. Laser-assisted hatching (LAH) can be applied through different techniques: drilling that is an artificial hole of the zona pellucida, just to the opposite side where the embryo is formed, and thinning that is just a thinning of the outer protective glycoprotein layer. LAH has the benefit of a non-contact mode on the embryos and is the easiest approach to perform. However, although many works compare the various methods [11], there are insufficient data that compare the different techniques within the same method [12]. The primary aim of this work is to retrospectively compare the implant rate after the application of two different techniques (drilling and thinning) obtained by LAH. * Stella Capriglione s.capriglione@unicampus.it

A new approach for Next Generation Sequencing in prenatal diagnosis applied to a case of Charcot–Marie–Tooth syndrome

In recent years, Next Generation Sequencing (NGS) has become an important tool, not only for gene discovery and research, but also for clinical diagnosis. Genetic diagnosis of rare disorders has developed considerably through the application of massively parallel sequencing methods. To date, a great effort has been made to introduce NGS in noninvasive prenatal testing both for the detection of aneuploidy associated to chromosomes 21, 18 and 13 and, in the latest studies, for single gene disorder analysis. Regarding invasive prenatal diagnosis, NGS has been applied to whole exome or whole genome studies; however, in these cases NGS did not prove useful in routine clinical application, because of many factors, including the necessity of bioinformatics skills during data analysis, the large amount of variants with uncertain clinical significance which were obtained, and the time required for analysis. We have introduced a new target resequencing NGS approach in prenatal diagnosis, called Next Generation Prenatal Diagnosis (NGPD), for the screening of a wide range of genetic disorders in high-risk pregnancies when an ultrasound screening fails to show a definite clinical phenotype, in cases where ultrasound indications must be supported by a molecular genetic diagnosis, or in cases where one or both parents are carriers of a genetic disorder. To the best of our knowledge, this is the first report that describes the use of a multi-gene NGS panel optimized for clinical prenatal diagnosis with a relatively fast turn-around time that can be multiplexed to allow simultaneous analysis of multiple samples. In this report the NGPDmethod was applied for the prenatal genetic diagnosis of Charcot–Marie–Tooth (CMT) disease in a fetus whose mother was affected by early onset CMT. Of all the types of hereditary sensory-motor polyneuropathy, CMT syndrome is the most frequent. From a clinical point of view, the disorder is characterized by distal muscular atrophy associated with malformation of the feet, osteotendinous hyporeflexia and alterations in sensibility. Based on motor conduction velocity, it is possible to identify type 1 (demyelinating form with a particularly reduced conduction speed) and type 2 (axonal form with a normal conduction speed). From a genetic point of view, many genes responsible for CMT have been identified, and transmission can be autosomal dominant, recessive or X linked. At the time of analysis, the 12th week of gestation, the patient was still without a genetic diagnosis. The patient showed postural tremor, sensory impairment and distal muscle atrophy. Weakness and deafness were also present. From the clinical and family history, we could assume a probability of an autosomal dominant-transmitted form of CMT syndrome. At the time of the ultrasound scan no clinical signs emerged. After genetic counseling, the patient underwent a chorionic villous sampling and parents’ blood samples were taken. After exclusion of any chromosomal microdeletions and microduplications associated with CMT disease, through aCGH analysis on CVS and mother’s blood, we used the NGPD method on the same DNA samples. We proceeded directly to trio analysis, followed by confirmation of any mutations identified on the fetus, to reduce time of prenatal diagnosis, which would otherwise have been delayed. Trio analysis was useful not only for identifying variants, but also for studying inheritance patterns. Variants were sorted for autosomal recessive, autosomal dominant, X-linked and de novo mode of inheritance. For the library preparation, we used the Trusight One Sequencing Panel (TSO, Illumina), which enriches for 62 000 exons of 4813 genes. The genes contained in this library were selected by Illumina according to the Human

Comment on "Customized Fetal Growth Charts for Parents' Characteristics, Race, and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian Study".

To the Editor: We read with great interest the article by Ghi et al1: “Customized Fetal Growth Charts for Parents’ Characteristics, Race, and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian Study”. We agree with the limits and the strengths that the authors discussed. Nevertheless, apart from typing errors (such as “gesational” in Figure 1), we are amazed by several biased data interpretations in the article that do not let us to create the customized reference charts. First, when the authors provide the example of how to compute the 95th percentile for head circumference of a fetus at 30 weeks’ gestation, they express maternal and paternal heights in meters (1.80 and 1.60), even if in the statistical analysis they are declared to be expressed in centimeters. According to the article, the 95th percentile for head circumference at 30 weeks is 247.8; that is too low according to other different reference charts2–4; whereas it is 292.5, expressing the heights in centimeters. Furthermore, in Figure 2, a new example has these covariates expressed in centimeters. Second, the aforementioned formula contains a further mistake: the authors did not multiply the appropriate value for Central African race (5.9088 as reported in Table 3), but used the SE value (5.8718). Third, in the “Results” section, the authors state that different covariates were not statistically significant for each parameter and/or for all of the percentiles. However, there is a slight discrepancy between the P values (Tables 2–5) and the description of the influence of covariates according to the percentiles. We report only one example: the authors declared that the influence of parity was present for values in the 50th percentile and higher for head circumference. However, in Table 3, it should be true until the 90th percentile, as P values for the 95th and 97th percentiles were .1646 and .3882, respectively. Last but not least, the log(wk) 25th percentile for abdominal circumference (Table 4) is incorrect, as it leads to an inconsistent value according to the trend. We hope that these suggestions could be helpful to better appreciate the article, and we thank the editor for giving us an opportunity to clarify these issues.