A new definition of recurrent implantation failure on the basis of anticipated blastocyst aneuploidy rates across female age.

Objective: To present a definition of recurrent implantation failure that accounts for the effects of female age and anticipated blastocyst euploidy rates on cumulative implantation rates. Design: Mathematical modeling. Setting: Not applicable. Patient(s): Not applicable. Intervention(s): Mathematical modeling of cumulative implantation probability on the basis of published blastocyst euploidy rates across categories of female age. Main Outcome Measure(s): The number of blastocysts required to achieve 95% cumulative implantation probability under the assumption of the absence of any other factor affecting implantation. Result(s): When the euploidy status of the transferred embryo is unknown (i.e., not subjected to preimplantation genetic testing for aneuploidies), our simulation shows that no age category reaches 95% cumulative probability of implantation of at least one embryo until after transfer of seven blastocysts. The number of blastocysts required to reach the same threshold is higher for older patients. For example, women older than 38 years require transfer of more than 10 untested blastocysts for the upper range of predictive probability to meet the threshold of 95%. On the other hand, if the implantation rate for a euploid blastocyst is assumed to be 55%, then 4 blastocysts are enough to reach a cumulative probability rate greater than 95%, regardless of age. Conclusion(s): The term "recurrent implantation failure"should be a functional term guiding further management. We suggest that recurrent implantation failure should not be called until implantation failure becomes reasonably likely to be caused by factors other than embryo aneuploidy, the leading cause of implantation failure. We propose a new definition that factors in anticipated blastocyst euploidy rates across categories of female age, euploid blastocyst implantation rate, and a specified threshold of cumulative probability of implantation

Risk of pleural mm and residual asbestos burden in the lung: a retrospective case-control study

Introduction Results of Malignant Pleural Mesothelioma (MPM) occurrence (mortality and incidence) by cumulative exposure dose clearly showed a proportional relation of MPM risk with dose, confirmed among studies by fibre burden. We evaluated the association between residual fibre content and MPM risk by circumstance of asbestos exposure. Methods and materials Lung samples obtained from pleuropneumonectomies or autopsies (349 MPMs, and 41 controls) among subjects investigated for probability and circumstance of asbestos exposure were examined through Scanning Electron Microscopy; 291 cases had an occupational asbestos exposure, 38 MPMs a non-occupational exposure (familiar or environmental), whereas among 20 MPM an asbestos exposure was not identified. The MPM risk was evaluated by means of Odds Ratio (OR). Results The residual asbestos fibre burden was higher among MPMs occupationally exposed (Geometric Mean:2.10 Million fibres/gram of dried tissue; 95% CI:1.5–2.58) in comparison with non-occupational (GM:0.66 Mff/gdt; 95% CI:0.47–0.95) or with unknown exposures (GM:0.59 Mff/gdt; 95% CI:0.34– 1.03) and controls (GM:0.26 Mff/gdt; 95% CI:0.20–0.34). Among occupationally exposed, the MPM risk increased according to the asbestos fibre burden reaching an OR of 36.8 (95%CI:11.9–113.5) for concentrations higher than 1 Mff/g dt, compared to the reference level (<0.25 Mff/gdt). Higher ORs were observed at any concentration of amphibole fibres in comparison those for chrysotile fibres. Conclusions The MPM risk was strongly associated to the residual asbestos fibre lung burden. The MPM risk due to non-occupational exposure shows a magnitude comparable with that with unknown asbestos exposures. The residual lung burden of chrysotile is strongly influenced by clearance and time since exposures ceased

Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos

Objectives To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed. Methods The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either ‘definite’ or ‘probable’ or ‘possible’. Results The participants had finished working in asbestos exposure conditions more than 20 years ago (on average 26.1±11.0 years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities. Conclusions The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection

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

Peer review in medical journals: beyond quality of reports towards transparency and public scrutiny of the process

Published medical research influences health care providers and policy makers, guides patient management, and is based on the peer review process. Peer review should prevent publication of unreliable data and improve study reporting, but there is little evidence that these aims are fully achieved. In the blinded systems, authors and readers do not know the reviewers' identity. Moreover, the reviewers' reports are not made available to readers. Anonymous peer review poses an ethical imbalance toward authors, who are judged by masked referees, and to the medical community and society at large, in case patients suffer the consequences of acceptance of flawed manuscripts or erroneous rejection of important findings. Some general medical journals have adopted an open process, require reviewers to sign their reports, and links online pre-publication histories to accepted articles. This system increases editors' and reviewers' accountability and allows public scrutiny, consenting readers understand on which basis were decisions taken and by whom. Moreover, this gives credit to reviewers for their apparently thankless job, as online availability of signed and scored reports may contribute to researchers' academic curricula. However, the transition from the blind to the open system could pose problems to journals. Reviewers may be more difficult to find, and publishers or medical societies could resist changes that may affect editorial costs and journals' revenues. Nonetheless, also considering the risk of competing interests in the medical field, general and major specialty journals could consider testing the effects of open review on manuscripts regarding studies that may influence clinical practice

Parasitic myomas after laparoscopic surgery: an emerging complication in the use of morcellator? Description of four cases

Objective: To report the development of parasitic myomas after the use of a morcellator. Design: Retrospective study. Setting: Tertiary care referral center for the treatment of benign gynecologic pathologies. Patient(s): Women undergoing surgery for uterine fibroids. Intervention(s): Chart review. Main Outcome Measure(s): Presence of parasitic leiomyomas. Result(s): We identified four cases of parasitic myomas over the 3-year study period. Two out of the four were symptomatic. The prevalence of this complication, considering all women with whom the electric morcellator was used (n 1⁄4 423) was 0.9% (95% CI, 0.3–2.2%). Considering exclusively the women who underwent myomectomy (n 1⁄4 321), it was 1.2% (95% CI, 0.4–2.9%). Conclusion(s): Laparoscopic myomectomy with the use of a morcellator is associated with an increased risk of developing of parasitic myomas. A thorough inspection and washing of the abdominopelvic cavity at the end of the surgery should be performed to prevent this rare complication