Heavy traffic analysis of open processing networks with complete resource pooling: asymptotic optimality of discrete review policies

We consider a class of open stochastic processing networks, with feedback routing and overlapping server capabilities, in heavy traffic. The networks we consider satisfy the so-called complete resource pooling condition and therefore have one-dimensional approximating Brownian control problems. We propose a simple discrete review policy for controlling such networks. Assuming 2+\epsilon moments on the interarrival times and processing times, we provide a conceptually simple proof of asymptotic optimality of the proposed policy.Comment: Published at http://dx.doi.org/10.1214/105051604000000495 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist

Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (rFSH) molecule containing a hybrid beta subunit, which provides a plasma half-life of ∼65 hours while maintaining its pharmocodynamic activity. A single injection of corifollitropin alfa can replace daily FSH injections for the first week of ovarian stimulation for in vitro fertilization. Stimulation can be continued with daily FSH injections if the need arises. To date, more than 2500 anticipated normoresponder women have participated in clinical trials with corifollitropin alfa. It is noteworthy that one-third of women did not require additional gonadotropin injections and reached human chorionic gonadotropin criterion on day 8. The optimal corifollitropin dose has been calculated to be 100 μg for women with a body weight ≤60 kg and 150 μg for women with a body weight >60 kg, respectively. Combination of corifollitropin with daily gonadotropin-releasing hormone antagonist injections starting on stimulation day 5 seems to yield similar or significantly higher numbers of oocytes and good quality embryos, as well as similar ongoing pregnancy rates compared with women stimulated with daily rFSH injections. Stimulation characteristics, embryology, and clinical outcomes seem consistent with repeated corifollitropin-stimulated assisted reproductive technologies cycles. Multiple pregnancy or ovarian hyperstimulation syndrome rates with corifollitropin were not increased over daily FSH regimen. The corifollitropin alfa molecule does not seem to be immunogenic and does not induce neutralizing antibody formation. Drug hypersensitivity and injection-site reactions are not increased. Incidence and nature of adverse events and serious adverse events are similar to daily FSH injections. Current trials do not provide information regarding use of corifollitropin alfa in anticipated hyper- and poor responders to gonadotropin stimulation. Although corifollitropin alfa is unlikely to be teratogenic, at the moment data on congenital malformations is missing

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

Systematic review of native and graft-related aortic infection outcome managed with orthotopic xenopericardial grafts

International audienceObjective: Limited data are available on the use of xenopericardium in the treatment of native and graft-related aortic infections. The aim of this review was to assess outcomes of neoaortic reconstruction using xenopericardium in this challenging group of patients.Methods: Studies involving xenopericardial graft reconstruction to treat native and aortic graft infections were systematically searched and reviewed (Embase, Medline, and Cochrane databases) for the period of January 2007 to December 2017.Results: A total of 4 studies describing 71 patients treated for aortic graft (n = 54) and native aortic (n = 17) infections were included; 25 patients (35%) were operated on in an acute setting. The technical success rate was 100%. The mean 30-day mortality was 25% (range, 7.7%-31%). Only one death (1.4%) was linked to the operator-made pericardial tube graft (acute postoperative bleeding from proximal anastomosis). Septic multiorgan failure was the most common cause of perioperative death (72% [13/18]). Among the 53 patients who survived, only 3 presented with recurrent infection (5.7%), so 70.4% of patients were alive after intervention without evidence of infection (50/71). During follow-up, 2 false aneurysms (3.7% [2/53]), 1 early rupture (1.4% [1/71]), and 2 cases (3.7% [2/53]) of late rupture were reported. Other causes of late deaths unrelated to the aortic xenopericardial repair were not reported in the different series. The early reintervention rate was 1.4% (1/71), treated by open repair for rupture. The late reintervention rate was 7.5% (4/53) with thoracic endovascular aortic repair in three patients (one false aneurysm and two ruptures) and open repair in one patient (one false aneurysm). There were no cases of early or late graft thrombosis. One-year mortality rate was 38% but only 4.2% were related to the aortic repair using orthotopic xenopericardium (one early and two late ruptures).Conclusions: These data confirm the high morbidity of native and graft-related aortic infections and provide insight into the results of orthotopic xenografts as a treatment alternative. Larger series and longer follow-up will be required to compare the role of operator-made pericardial tube graft with other treatment options in infected fields

Double homemade fenestrated stent graft for total endovascular aortic arch repair.

International audienceThe aim of this retrospective analysis was to evaluate the outcomes of physician-modified double fenestrated stent grafts for total endovascular aortic arch repair: one proximal large fenestration for the brachiocephalic trunk and the left common carotid artery and one distal fenestration for the left subclavian artery (LSA)

A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe

STUDY QUESTION: How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY: With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN, SIZE, DURATION: A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS, SETTING, METHODS: The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE: By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA: N/A LIMITATIONS, REASONS FOR CAUTION: Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS: The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations.Peer reviewe

SARS-CoV-2, fertility and assisted reproduction

BACKGROUND In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. OBJECTIVE AND RATIONALE This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. SEARCH METHODS PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. OUTCOMES From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. WIDER IMPLICATIONS This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research.The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.Peer reviewe