Pre-implantation genetic testing in ART: who will benefit and what is the evidence?

Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to identify euploid embryos during IVF. The suggested populations of patients that can benefit from it are infertile women of advanced maternal age, with a history of recurrent miscarriages and/or IVF failures. However, a general consensus has not yet been reached.After the clinical failure of its first version based on cleavage stage biopsy and 9 chromosome-FISH analysis, PGD-A is currently performed by 24 chromosome screening techniques on trophectoderm (TE) biopsies. This approach has been clearly demonstrated to involve a higher clinical efficiency with respect to the standard care, in terms of sustained pregnancy rate per transfer and lower miscarriage rate. However, data about PGD-A efficacy calculated on a per intention-to-treat basis, as well as an analysis of its cost-effectiveness, are still missing.TE biopsy is a safe and extensively validated approach with low biological and technical margin of error. Firstly, the prevalence of mosaic diploid/aneuploid blastocysts is estimated to be between 0 and 16 %, thus largely tolerable. Secondly, all the comprehensive chromosome screening (CCS) technologies adapted to, or designed to conduct PGD-A are highly concordant, and qPCR in particular has been proven to show the lowest false positive error rate (0.5 %) and a clinically recognizable error rate per blastocyst of just 0.21 %.In conclusion, there is a sufficient body of evidence to support the clinical application of CCS-based PGD-A on TE biopsies. The main limiting factor is the need for a high-standard laboratory to conduct blastocyst culture, biopsy and vitrification without impacting embryo viability.     

Single umbilical artery: what does it mean for the fetus?

Single umbilical artery (SUA) is the most common anomaly of the umbilical cord which affects between 0.5 and 2.5% of all pregnancies. AIM: Our purpose was to determine whether there was a significant relationship between SUA and other anatomical anomalies. MATERIAL AND METHODS: All cases of fetal single umbilical artery identified in our hospital between 2002-2005 were reviewed for other ultrasound detected abnormalities. RESULTS: 18 cases of single umbilical artery were diagnosed on the basis of initial sonograms. 17 cases formed the study population (in 10 cases the left artery and in 7 the right artery was absent). In one case we diagnosed an umbilical cord tumor. 33.3% had other anatomical anomalies. The mean of women in the study was 30.5 years, the mean gestational age at examination was 28 weeks. CONCLUSIONS: In most cases the SUA occurs to be an isolated anomaly. In cases of SUA, the detailed ultrasound examination should be performed. Left artery absence is more common and also in these cases other anatomical anomalies are more likely to be observed as well. In our study we did not find a correlation between SUA and IUGR.     

Hypotension in small preterms: what does it mean?

Abstract

Introduction: Small preterms often have low blood pressure readings in the first few days of life. However, what is hypotension in preterms? Should there be an aggressive approach to its management? What are the immediate and long-term side effects of powerful medications? Alternatively, could a low blood pressure be accepted instead?

Materials and methods: Data were collected from files of all live babies with gestational age (GA) between 23^0/7 and 31^6/7 weeks over two different periods: years 2000–2004 and 2008–2012.

Results: Our data show that, despite extremely low gestational age (ELGA)/extremely low birth weight (ELBW) neonates, almost half of these tiny babies have neither low mean arterial pressure (MAP) readings nor clinical signs of impaired perfusion. Yet, many of them are, variously treated or not, depending on individual decisions, rather than on sound evidence.

Discussion: We suggest, should it be required to treat persistent hypotension, rather than treating just a low MAP recording, to address the whole issue of hypotension in the overall picture of clinical settings; we to assess organ dysfunction caused by low output and use the least aggressive measures, preferably within written protocols, tailored to the given unit, but equally, sufficiently flexible to individual babies. Furthermore, allow for “permissive hypotension” especially if transient, in the absence of clinical signs of hypoperfusion, with normal superior vena cava (SVC) flow, normal cardiac output, and normal brain scanning with normal cerebral Doppler flows. Whether treating hypotension, by whichever definition, “per se”, will make any difference to both, immediate and late outcomes; in the end, treating remains open to questioning and calls for careful follow-up of these very susceptible preterms.     

When and why does the dream die? Or does it?

A large percentage of patients discontinues infertility treatment despite a reasonable prognosis and benefits that cover the costs. Recognition of this problem and appropriate intervention may play a role in helping couples remain in treatment.     

Myocardial motion and deformation: what does it tell us and how does it relate to function?

The assessment of cardiac pump function and the potential of local myocardium to contribute to the overall performance are of great importance in many cardiovascular abnormalities. Assessing intrinsic cardiac function requires obtaining information on the true contractility of the heart muscle, assessed locally but interpreted in the context of its contribution to the global ejection performance and potential to adapt to changing circumstances. Contemporary imaging techniques offer the possibility of noninvasive quantification of myocardial deformation. These new clinical tools are attractive to use for the assessment of ventricular function. However, it is of great importance to understand cardiac mechanics - a complex interplay between the tissue structure/shape, force development, and interaction with the environment/neighbors - to interpret alterations in deformation and to extract clinically relevant conclusions. The combination of insight into the measurement techniques and their limitations, together with knowledge of myocardial mechanics and physiology, opens new perspectives to improve the assessment and management of fetal, pediatric, and adult patients.     

Euphoria or despair? Coping with multiple births from ART: what patients don't tell the clinics

Patients' perception of family life after a multiple birth: euphoria or Pandora's box? The aim of this article is to explore the realities of parenting children from a multiple pregnancy as an aid to decision-making about the number of embryos transferred. Outcome research regarding parenting of children from twin, triplet and higher order births is described and, in particular, children of multiple births from assisted reproductive technology. Current understanding of interpersonal relationships in multiple birth families is also discussed. The evidence from these various sources is put in the framework of social risk factors as an aid to predicting outcomes and as an essential part of decision-making with the full participation of patients. The implications of such an approach is presented in relation to support for such families. Case studies are included of three triplet families. Reference is made to fetal reduction as an option.     

Post-discharge nutrition: what does the evidence support?

Although there are no official recommendations for specific nutrient intakes in premature infants after hospital discharge, it is agreed that the goal should be to achieve the body composition and rate of growth of that of a normal fetus of the same postmenstrual age during the entire first year of life. A general recommendation to use the special formulas designed for preterm infants after hospital discharge in place of the formulas for term infants cannot be made from the available evidence at this time. Infants fed human milk after discharge are of the greatest concern as human milk does not in theory meet the requirements for growth in these infants. Such infants should remain on supplemental vitamins and Fe while breastfeeding, and growth as well as serum levels of phosphorus and alkaline phosphatase should be carefully monitored. The increased risk of preterm infants for obesity and the metabolic syndrome secondary to the metabolic/nutritional events early in life (programming) is likely to be small compared with the contribution of other risk factors, such as parental size, weight as an adolescent, and various lifestyle factors such as physical activity.     

Hypoglycemia: what is it for the neonate?

The definition of hypoglycemia in the newborn infant has remained controversial because of lack of significant correlation between plasma glucose concentration, clinical symptoms, and long-term sequelae. A threshold value for plasma glucose at which clinical intervention should be considered is important because of the potential for serious neurological injury. In this review, we have described threshold values for plasma glucose in the newborn infant, based upon available data, at which the clinician should consider close monitoring and therapeutic interventions aimed at increasing the glucose level. In clinically symptomatic infants, plasma glucose concentrations of 45 mg/dL (2.5 mmol/L) or less should be considered as threshold for intervention. In an asymptomatic baby and in those at risk for hypoglycemia, irrespective of gestational and postnatal age, plasma glucose values less than 36 mg/dL (2.0 mmol/L) should be considered as threshold levels. Variances from these criteria, as in breast-fed infants, are discussed. The threshold values described for surveillance and intervention should be separated from the targeted therapeutic values which should be in the range of 72-90 mg/dL (4-5 mmol/L).     

Bladder perforation during tension-free vaginal tape surgery: does it matter?

OBJECTIVE: To analyze the incidence, possible risk factors, preoperative morbidity and outcome results in tension-free vaginal tape (TVT) cases complicated by lower urinary tract injury in a large, heterogeneous, consecutive group of women. STUDY DESIGN: Four hundred sixty consecutive women who underwent TVT surgery for correction of urodynamically proven stress urinary incontinence were enrolled prospectively. All the procedures were performed at 1 center by 3 experienced surgeons. RESULTS: In this series, 3.9% cases of lower urinary tract injury occurred. Most of the injuries occurred during the learning curve. TVT-related urinary tract injury was not associated with increased perioperative morbidity. The cure rates were similar with and without injury. De novo urge and persistent urge incontinence were slightly more common in patients with bladder perforation. CONCLUSION: Lower urinary tract injury during the TVT procedure is directly related to the inexperience of the surgeon. However, TVT-related lower urinary tract injury does not appear to affect medium-term outcome results.     

Sleep disruption during pregnancy: how does it influence serum cytokines?

Women report their sleep to be disrupted during pregnancy. Sleep deprivation has been linked to elevations in pro-inflammatory cytokine levels. No information currently addresses the sleep-immune relationship during pregnancy. This study explores the relationship between subjectively reported sleep variables and circulating serum cytokine levels. Pregnant women (n=35; mean age=31.0+/-3.7 years) seen once a trimester completed sleep questionnaires, gave blood and recorded their sleep on a sleep diary at home for 2 weeks. Nonpregnant women (n=43; mean age=28.2+/-5.2 years) underwent the same protocol once. Subjective sleep variables were compared to serum cytokine levels for IL-4, -6, -10 and TNF-alpha as well as C-reactive protein (CRP) determined by ELISA. Nonparametric analyses and linear regression were performed to explore relationships between the sleep and immune variables. Pregnant women subjectively reported their sleep to be worse than in the nonpregnant group. Serum cytokine levels differed between the two groups and varied by trimester. As anticipated, IL-10 was significantly higher in all trimesters; however CRP, an indicator of systemic inflammation, was higher in all trimesters compared to the nonpregnant sample. Subjectively reported sleep disruption was associated with increases in TNF-alpha in the pregnant sample and CRP in the nonpregnant sample. These data confirm that disrupted sleep experienced during pregnancy, as well as during the nonpregnant state, is related to increases in inflammatory markers. Future exploration of these relationships should include functional assessments of immunity as well as polysomnographically recorded sleep.     

The secular growth acceleration: does it appear during fetal life?

Abstract

Objective: To test if secular growth acceleration occurs during fetal life.

Methods: ANOVA Kruskal–Wallis and Mann–Whitney U-test have been used for the biometric characteristics comparison of nowadays fetal population with those three decades ago and to test the hypothesis about the existence of secular growth acceleration during fetal life. For this purpose, we first calculated mean values of particular biometric parameters for the whole pregnancy. During the period 2002–2009 biparietal diameter, fetal length and abdominal circumference measurements in singleton uncomplicated pregnancies between 22 and 41 gestational weeks were obtained. Gestational age was estimated according to Naegele's rule and confirmed with an early ultrasound examination. Pregnancies with fetal cromosomopathies and malformations were excluded as well as those resulting in perinatal death.

Results: There were no statistically significant differences of the examined fetal biometric parameters measured by ultrasound between contemporary fetal population and those from 35 years ago.

Conclusion: Our investigation did not undoubtedly prove that significant changes of fetal biometric parameters occurred in the last three decades. It is possible that secular growth acceleration does not exist in prenatal period but also the observed time period could have been short for this phenomenon to manifest.     

Theatre sending: how long does it take and what is the cost of late starts?

This study seeks to identify areas of poor utilisation of theatre time and estimate the cost of late starts. Retrospective study of elective gynaecological operations from September to November 2008 in a district general hospital was conducted. Primary outcome measures were time to send, time for anaesthesia and procedure time. Secondary outcome measures were time to send for the first patient and cost of late starts (N = 164). The mean time to send was 19 ± 8.10 min (95% CI: 18–20). The mean time for anaesthesia was 9 ± 6.40 min (95% CI: 7.91–9.86). The mean procedure time was 60 ± 35 (95% CI: 55–65). On average time to send for the first patient on the morning list took 20 ± 9.83 min (95% CI: 17–23) and resulted in 93% of lists starting late. The surgical team waited a mean of 22 ± 19 min (95% CI: 17–27) for the first patient to arrive after the list was due to start. Total time wasted on late starts was 910 min (15 h), costing an estimated ￡3,640 over the 3-month period. This figure is based on local theatre staff wages of ￡236.30 per hour. Sending for patients 30 min before the list is due to start is an auditable standard that could increase theatre efficiency and enable 15 h of currently wasted resources to be used to shorten waiting lists and enhance staff training opportunities.