Unexplained infertility and age-related infertility: indistinguishable diagnostic entities but different IVF prognosis.

STUDY QUESTION: Is IVF indicated for couples with age-related infertility? SUMMARY ANSWER: IVF may be of doubtful utility for age-related infertility. WHAT IS KNOWN ALREADY: A diagnosis of unexplained infertility is drawn when the diagnostic work-up fails to identify any patent cause. Although typically managed uniformly, unexplained infertility is likely to comprise a wide range of conditions, including age-related infertility (at least in older women). Unfortunately, no validated tests for the identification of age-related infertility exist and these women are typically treated as unexplained cases. However, homologous ART may be less effective for these women because these techniques may be unable to treat the detrimental effects of ageing on oocyte competence. STUDY DESIGN, SIZE, DURATION: Women aged 18-42 years who underwent IVF procedures between January 2014 and December 2021 were selected retrospectively. In the first part of the study, we aimed to assess whether the proportion of women with unexplained infertility (i.e. without patent causes of infertility) increased with age. In the second part of the study, women with unexplained infertility were matched 1:1 by age, study period, and duration of infertility, to those with a patent cause of infertility. If our hypothesis is valid, the first part of the study should highlight an increase in the proportion of unexplained infertility with age. Moreover, in the second part of the study, one should observe a sharper decrease in the rate of IVF success of the procedure with age in women with an unremarkable work-up compared to those with a definite cause of infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were included if: they had been trying to conceive for more than 2 years, they had retrieved more than three oocytes, and had not undergone previous IVF attempts. We exclude couples with severe male factor (criptozoospermia), chronic anovulation, untreated hydrosalpinx, or intracavitary diseases. The first part of the study aimed at investigating the relative proportion of unexplained infertility with age. The outcome of the second part was the distribution of the live births between unexplained versus explained infertility, in women younger or older than 35 years. Only the results of the first IVF cycle were considered (including both fresh and frozen cycles). The live birth rate corresponded to the cumulative chance of a live birth per oocyte retrieval. MAIN RESULTS AND THE ROLE OF CHANCE: One thousand five hundred and thirty-five women were selected for the first part of the study; 742 of them had unexplained infertility (48%). The frequency of this diagnosis was lower among women aged <35 years (40%) compared to those ≥35 years (52%) (P < 0.001). A clear gradient emerged when considering smaller intervals of age (P < 0.001). A total of 1134 women (567 unexplained cases and 567 explained cases) were selected for the second part of the study. Baseline variables were comparable between women with unexplained and explained infertility. Among women younger than 35 years (n = 229 unexplained cases and 229 explained cases), 108 live births were observed in women with unexplained infertility (47%) and 88 in those with explained infertility (38%). In comparison, among women older than 35 years, the live births occurred in 90 (27%) and 114 (34%) couples, respectively (P = 0.03). The adjusted odds ratio (OR) for a live birth in older women with unexplained infertility was 0.63 (95% CI: 0.43-0.94). In other words, the effectiveness of IVF in older women with unexplained infertility is reduced by an additional 37% when compared to women of similar age with a patent cause of infertility. Moreover, when considering smaller intervals of age, a gradient of the adverse effect of age on the distribution of live births between unexplained and explained infertility emerged (P = 0.003). Overall, these results support the hypothesis that IVF may be of modest benefit in women with age-related infertility. The decline in IVF success is sharper in women with unexplained infertility compared to those with explained infertility, indirectly suggesting that IVF cannot effectively treat age-related infertility. LIMITATIONS, REASONS FOR CAUTION: We postulated that the greater decline in IVF success with age in the unexplained group could be related to the concomitant increase in the proportion of women with age-related infertility. However, even if this is theoretically logical, the unavailability of validated tools to diagnose age-related infertility makes our inference speculative. We cannot exclude that the prevalence of other unknown causes of infertility that cannot also be effectively overcome with IVF could increase with age. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that IVF may be of modest utility for treating age-related infertility. Offering this procedure to older women with an unremarkable infertility work-up may be questioned. However, the diagnosis of age-related infertility remains challenging and identifying a biomarker that could reliably diagnose age-related infertility is a priority. STUDY FUNDING/COMPETING INTEREST(S): The study was partially funded by the Italian Ministry of Health-current research IRCCS and by a specific grant supported by Ferring. ES declares receiving honoraria for lectures at meetings from IBSA and Gedeon-Richter and he also handles private grants of research from Ferring, IBSA, Theramex, and Gedeon-Richter. All the other authors do not have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Return rate following a live birth obtained with ART: frequency and determinants.

PURPOSE: To understand how often couples return to ART centres for a second child. METHODS: Retrospective monocentric cohort study including women who had a first live birth with IVF. The primary objective was to assess the rate of those returning for a second child within five years of the previous pregnancy. The secondary aim was to disentangle the determinants of this rate. RESULTS: A total of 374 patients were included, of whom 188 returned (50%, 95% CI 45-55%). Among those who did not return (n = 186), four (2%) referred to another ART Center and 24 were unreachable. Of the 158 contacted subjects that did not refer for ART, 53 (34%, 95% CI 27-41%) conceived naturally, 57 (36%, 95% CI 29-44%) abandoned their intent of parenthood, and 48 (30%, 95% CI 24-38%) unsuccessfully attempted natural conception. These 48 women (13%) who expressed interest in a second child but did not undergo ART were compared to those seeking a second pregnancy through ART. Baseline characteristics were similar except for an older age (Median 36, IQR: 34-38 vs 34, IQR: 32-36, p = 0.001). Additionally, in terms of IVF cycle characteristics, women who did not return were more likely to achieve their first pregnancy with a fresh transfer rather than a frozen transfer (75% vs 59%, p = 0.05). They also had a higher number of retrieved oocytes (Median 10, IQR: 7-13 vs 9, IQR: 5-12) and less frequently cryopreserved embryos (27% vs 52%, p = 0.003). CONCLUSION: The proportion of couples who have conceived with ART and who are interested in having a second child is high. Our results underline the importance of paying more attention to the number of intended children, as this information could influence clinical management.

ART and the forgotten siblings: a call for research.

A broader definition of infertility is the incapacity to have the intended number of children. However, most literature on ART exclusively focuses on live birth as an outcome, rather than on the capacity to fully realize the reproductive wishes of the couples. This issue has probably received scant attention because the total fertility rate is below replacement levels in affluent countries, and one may simplistically assume that only a minority of couples may be interested in more than one child. This assumption, however, is unproven and presumably erroneous. Unfortunately, evidence on the rate of return in couples who conceived their first child with ART is scant and information on the intended number of children in infertile couples is lacking. In general, we plea for more research on this subject. The documentation of an intended number of children above two and a high return rate in infertile couples may lead to changes in clinical practice, such as the storage of oocytes or embryos prior to initiating embryo transfers. This could improve the chance of conceiving the second child when the couple comes back some years later. In addition, the identification of the determinants for non-return as well as those explaining the gap between the intended and the realized number of children may reveal specific barriers and possibly how to tackle them. However, at present, available evidence is insufficient to advocate any intervention. Thorough research is warranted.

Endometriosis and IVF treatment outcomes: unpacking the process.

Advanced endometriosis is associated with a reduction of IVF success. Surgical damage to the ovarian reserve following the excision of endometriomas has been claimed as a critical factor in the explanation of this detrimental effect. However, it is generally inferred that other mechanisms might also hamper IVF success in affected women. They include diminished responsiveness to ovarian stimulation, altered steroidogenesis, a decline in oocyte quality, reduced fertilization and embryo development, and impaired implantation. To navigate these limitations, we scrutinized available literature for studies specifically designed to address distinct phases of the IVF process. Utmost consideration was given to intra-patient ovarian response comparisons in women with unilateral endometriomas and to studies applying a meticulous matching to control confounders. The following observations have been drawn: 1) endometriosis has a negligible impact on ovarian response. A slight reduction in stimulation response can only be observed for endometriomas larger than 4 cm. Follicular steroidogenesis is unaffected; 2) oocyte quality is not hampered. Fertilization rates are similar, and intracytoplasmic sperm injection (ICSI) is not justified. Embryonic development is uncompromised, with no increase in aneuploidy rate; 3) endometrial receptivity is either unaffected or only slightly impacted. In conclusion, our study suggests that, aside from the well-known negative effect on ovarian reserve from excisional endometrioma surgeries, endometriosis does not significantly affect IVF outcomes.

Endometrial preparation does not affect the risk of hypertensive disorders of pregnancy in low-risk women undergoing frozen embryo transfer.

OBJECTIVE: Frozen embryo transfer (FET) is associated with a higher risk of hypertensive disorders in pregnancy. The objective of the present study is to evaluate the effect of different protocols of endometrial preparation on the risk of these disorders. METHODS: We conducted a retrospective cohort study on 594 singleton pregnancies achieved by embryo transfer of single frozen-thawed blastocysts. Women with preexisting risk factors for hypertensive disorders were excluded. Women were divided into two groups according to the endometrial preparation protocol: either natural cycle (n = 495) or programming cycle with hormonal replacement therapy (n = 97). The primary outcome was the frequency of hypertensive disorders in pregnancy: specifically, gestational hypertension and preeclampsia. RESULTS: No differences emerged between women following the natural cycle and those following the programming cycle in the frequency of gestational hypertension (5 vs. 4%) and preeclampsia (1.1 vs. 1.2%). No impact emerged also after multivariate analyses. CONCLUSIONS: Women receiving hormonal replacement therapy have the same risk of gestational hypertension and preeclampsia as women following natural cycles when considering low-risk singleton pregnancies.

Fibroids and natural fertility: a systematic review and meta-analysis.

Available evidence from IVF studies supports a detrimental effect of submucosal and intramural fibroids on embryo implantation. It is misleading, however, to infer evidence obtained in IVF settings to natural fertility. Therefore, a systematic review and meta-analysis was conducted on the effect of fibroids on natural fertility. Studies comparing fertile and infertile women, and those investigating whether the presence of fibroids was a risk factor, were reviewed, as well as studies comparing women with and without fibroids. The aim was also to establish whether the frequency of infertility differed between the two groups. Seven out of 11 selected studies did not aim to establish whether fibroids caused infertility but, rather, whether a history of infertility could be a risk factor for fibroids. A meta-analysis of the four remaining studies that concomitantly evaluated the presence of fibroids and infertility studies highlighted a common odds ratio of fibroids in subfertile women of 3.54 (95% CI 1.55 to 8.11). When focusing on the two most informative studies, i.e. the studies comparing time to pregnancy in women with and without fibroids, the common OR was 1.93 (95% CI 0.89 to 4.18). In conclusion, the association between fibroids and infertility has been insufficiently investigated. Epidemiological studies suggest, but do not demonstrate, that fibroids may interfere with natural fertility. Given the high prevalence of these lesions in women seeking pregnancy, further evidence is urgently needed.

Clinical relevance of SARS-CoV-2 infection in late pregnancy.

BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.

Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies.

According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/ß-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis.

Epigenetic clocks and female fertility timeline: A new approach to an old issue?

Worldwide increase in life expectancy has boosted research on aging. Overcoming the concept of chronological age, higher attention has been addressed to biological age, which reflects a person's real health state, and which may be the resulting combination of both intrinsic and environmental factors. As epigenetics may exert a pivotal role in the biological aging, epigenetic clocks were developed. They are based on mathematical models aimed at identifying DNA methylation patterns that can define the biological age and that can be adopted for different clinical scopes (i.e., estimation of the risks of developing age-related disorders or predicting lifespan). Recently, epigenetic clocks have gained a peculiar attention in the fertility research field, in particular in the female counterpart. The insight into the possible relations between epigenetic aging and women's infertility might glean additional information about certain conditions that are still not completely understood. Moreover, they could disclose significant implications for health promotion programs in infertile women. Of relevance here is that the impact of biological age and epigenetics may not be limited to fertility status but could translate into pregnancy issues. Indeed, epigenetic alterations of the mother may transfer into the offspring, and pregnancy itself as well as related complications could contribute to epigenetic modifications in both the mother and newborn. However, even if the growing interest has culminated in the conspicuous production of studies on these topics, a global overview and the availability of validated instruments for diagnosis is still missing. The present narrative review aims to explore the possible bonds between epigenetic aging and fertility timeline. In the "infertility" section, we will discuss the advances on epigenetic clocks focusing on the different tissues examined (endometrium, peripheral blood, ovaries). In the "pregnancy" section, we will discuss the results obtained from placenta, umbilical cord and peripheral blood. The possible role of epigenetic aging on infertility mechanisms and pregnancy outcomes represents a question that may configure epigenetic clock as a bond between two apparently opposite worlds: infertility and pregnancy.

Endometriosis increases the risk of gestational diabetes: a meta-analysis stratified by mode of conception, disease localization and severity.

To review the current evidence on the risk of gestational diabetes mellitus (GDM) in women with endometriosis, taking into account relevant confounders such as the higher frequency of Assisted Reproductive Technologies (ART) conceptions. Database searches on PubMed, Medline, Embase and Scopus through June 2022, using combinations of relevant keywords. A total of 18 studies, involving N = 4,600,885 women, were included. The overall risk of GDM in endometriosis patients was significantly higher than in controls (OR, 1.23; 95% CI 1.07-1.51). This significant association persisted in natural pregnancies (OR, 1.08; 95% CI 1.04-1.12) but not in pregnancies conceived through ART (OR, 0.93;95% CI 0.70-1.24). Based on the limited number of studies that examined this association in relation to endometriosis phenotype, an increased risk was found in more severe stages (OR, 3.20; 95% CI 1.20-8.54) but independently from localization of the lesions. Endometriosis increases the risk of GDM, with a possible progressive effect in more advanced stages of the disease. Although the effect magnitude may be limited in some subgroups, this finding has a clinically relevant impact due to both the strong biological plausibility and to the relatively high incidence of both endometriosis and GDM.

Impact of Endometrial Preparation on the Maternal and Fetal Cardiovascular Variables of the First Trimester Combined Screening Test.

The modality of endometrial preparation for the transfer of frozen-thawed embryos may influence maternal and fetal adaptation to pregnancy and could thus impact the results of the first trimester combined screening test. We conducted a retrospective cross-sectional study on singleton pregnancies achieved by embryo transfer of a single frozen-thawed blastocyst, comparing two different endometrial preparation protocols: natural cycle (n = 174) and hormone replacement therapy (HRT) (n = 122). The primary outcome was the risk of preeclampsia at the first trimester combined screening test. Secondary endpoints included variable reflecting fetal cardiac function (nuchal translucency and fetal heart rate), maternal adaptation (median arterial blood pressure-MAP and uterine arteries pulsatility index-UtA-PI), and placentation (pregnancy associated plasma protein A and placental growth factor). The risk of early preeclampsia was comparable in the two groups (38% vs. a 28%, p = 0.12). However, women in the natural cycle group showed lower fetal heart rate (159 [155-164] vs. 164 [158-168], p = 0.002) and higher UtA-PI (0.96 [0.74-1.18] vs. 0.72 [0.58-0.90], p < 0.001). The frequency of a screening test at high risk for aneuploidies was similar. The modality of transfer of frozen-thawed embryos is associated with changes in the variables reflecting maternal and fetal cardiovascular function.

A systematic review and meta-analysis on alcohol consumption and risk of endometriosis: an update from 2012.

Endometriosis is a complex and chronic disease, whose multifactorial nature has encouraged a deep investigation on the role of lifestyle factors. A strong association between alcohol intake and endometriosis risk has already been shown. We aimed to confirm this association, considering the updated literature. 23 eligible studies were identified through comprehensive literature search of PubMed and EMBASE (May 2012-October 2021). A borderline statistical significance was found comparing any alcohol consumption with no consumption (unadjusted OR 1.14; 95% CI: 0.99-1.31, p = 0.06), in contrast with a previous meta-analysis. However, we confirmed the significant association between moderate alcohol intake and endometriosis (unadjusted OR 1.22, 95% CI: 1.03-1.45, p = 0.02), also performing a sensitivity analysis (unadjusted OR 1.27, 95% CI: 1.04-1.54). Our partly divergent evidence reflects the tough challenge of isolating the impact of specific factors on the natural history of multifactorial diseases. Indeed, on one hand alcohol could be adopted by patients as a self-management therapy and on the other, it could favor the disease, promoting positive feedback with inflammatory mediators and oxidative stress. Our study encourages further investigation on the role of modifiable lifestyle factors and highlights the opportunity to adopt them to prevent or at least limit endometriosis progression.

Peripheral mitochondrial DNA, telomere length and DNA methylation as predictors of live birth in in vitro fertilization cycles.

OBJECTIVE: To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate. DESIGN: Prospective cohort study. SETTING: Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. PATIENTS: 181 women aged 37-39 years who underwent IVF at a single-centre between January 2017 and December 2018. INTERVENTIONS: On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation. MAIN OUTCOME MEASURES: This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles. RESULTS: TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 ± 4.2 and 37.3 ± 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82-0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82-0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83-1.00, p = 0.048). CONCLUSION: DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success.

Inflammatory biomarkers in pregnant women with COVID-19: a retrospective cohort study.

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we have assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with COVID-19 and we have correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 62 (27.3%) pregnant women and 165 (72.7%) postpartum women, 21 (9.2%) patients received oxygen supplementation and 2 (0.9%) required admission to intensive care unit but none died. During hospitalization leukocytes (p < 0.001), neutrophils (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001) and C reactive protein (p < 0.001) decreased significantly, whereas lymphocytes (p < 0.001), platelets (p < 0.001) and ferritin (p = 0.001) increased. Lymphocyte values at admission were correlated with oxygen need, with a 26% higher risk of oxygen supplementation for each 1000 cells decreases. Overall, in obstetric patients hospitalized with COVID-19, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced lymphocyte values at admission.

CMR for Identifying the Substrate of Ventricular Arrhythmia in Patients With Normal Echocardiography.

OBJECTIVES: This study sought to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had echocardiography ruled out pathological findings. BACKGROUND: Approximately one-half of sudden cardiac deaths are attributable to malignant VA. Echocardiography is commonly used to identify SHD that is the most frequent substrate of VA. METHODS: A single-center prospective study was conducted in consecutive patients with significant VA, categorized as >1,000 but <10,000 ventricular ectopic beats [VEBs]/24 h; ≥10,000 VEBs/24 h; nonsustained ventricular tachycardia, sustained ventricular tachycardia, or a history of resuscitated cardiac arrest, and no pathological findings at echocardiography, requiring a clinically indicated CMR. Primary endpoint was CMR detection of SHD. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis. RESULTS: A total of 946 patients were enrolled (mean 41 ± 16 years of age; 64% men). CMR studies were used to diagnose SHD in 241 patients (25.5%) and abnormal findings not specific for a definite SHD diagnosis in 187 patients (19.7%). Myocarditis (n = 91) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 55), dilated cardiomyopathy (n = 39), ischemic heart disease (n = 22), hypertrophic cardiomyopathy (n = 13), congenital cardiac disease (n = 10), left ventricle noncompaction (n = 5), and pericarditis (n = 5). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.52 and 2.38, respectively) and sustained ventricular tachycardia (ORs: 2.67 and 2.23, respectively). CONCLUSIONS: SHD was able to be identified on CMR imaging in a sizable number of patients with significant VA and completely normal echocardiography. Chest pain and sustained ventricular tachycardia were the strongest predictors of positive CMR imaging results.

Plaque quantification by coronary computed tomography angiography using intravascular ultrasound as a reference standard: a comparison between standard and last generation computed tomography scanners.

AIMS: The emerging role of coronary computed tomography angiography (CCTA) as a non-invasive tool for atherosclerosis evaluation is supported by data reporting a good correlation between CCTA and intravascular ultrasound (IVUS) for plaque volume quantification. Aim of the present study was to evaluate whether a last generation CT-scanner may improve coronary plaque volume assessment using IVUS as standard-of-reference. METHODS AND RESULTS: From a registry of 1915 consecutive, all-comers, patients who underwent a clinically indicated IVUS evaluation we enrolled 59 patients who underwent CCTA with a 64-slice CT (Group 1) and 59 patients who underwent CCTA with whole-heart coverage CT scanner (Group 2). Patients who underwent CCTA with unfavourable heart rhythm were not excluded from the analysis. Image quality (4-point Likert scale) focused on plaque analysis was evaluated. Plaque volume quantification by CCTA was compared to IVUS. No difference in clinical characteristics was found between Group 1 and Group 2. Plaque volume quantification by CCTA was considered not feasible in 11 plaques of Group 1 and in 4 plaques of Group 2 (P = 0.09). Higher correlation for plaque volume quantification by CCTA vs. IVUS was demonstrated in Group 2 when compared with Group 1 (r = 0.9888 vs. 0.9499; P < 0.0001). The Bland-Altman analysis showed plaque volume overestimation by CCTA of 11.9 mm3 in Group 1 and 4 mm2 in Group 2 (P < 0.001). Effective radiation dose of CCTA was significantly lower in Group 2 vs. Group 1 (2.7 ± 0.9 vs. 8.1 ± 3.6 mSv, respectively; P < 0.001). CONCLUSIONS: CCTA using a new scanner generation showed to be an accurate non-invasive tool to assess and quantify coronary plaque volume.