National Canadian Survey on the Management of Noneuploid Embryos.

OBJECTIVE: To comprehensively describe current preimplantation genetic testing for aneuploidy (PGT-A) practices and management of non-euploid embryos in Canada. METHODS: This was a cross-sectional study utilizing an online survey distributed by email to all medical directors of fertility clinics with independent in vitro fertilization (IVF) embryology laboratories. The survey was designed to determine practice patterns regarding PGT-A usage; PGT-A reference laboratory, platform, and thresholds for classifying embryos; and management of embryos classified as mosaic, inconclusive, or aneuploid. RESULTS: Twenty-five medical directors (69%) participated in the survey. The majority of clinics (91%) offered PGT-A screening, with 45% of clinics offering PGT-A as routine screening. The majority of clinics (90%) that offered PGT-A received mosaicism data; 61% of these clinics had transferred mosaic embryos, and 94% would transfer mosaic embryos. Clinics that performed ≥1000 IVF cycles annually were more likely to have transferred mosaic embryos (100% vs. 45.5%; P = 0.043). The mean percentage of IVF cycles using PGT-A was lower in clinics that had transferred mosaic embryos (12.3% vs. 30.4%; P = 0.033). Only 1 clinic had transferred an aneuploid embryo, but 2 other clinics would consider this option. The majority of clinics (61%) that receive mosaicism data would recommend noninvasive prenatal testing (NIPT) following mosaic embryo transfer, with 22% of clinics indicating that this would be the only genetic test offered. CONCLUSION: We report significant practice variation in PGT-A and management of non-euploid embryos across Canada and highlight areas where consensus should be encouraged.

Preimplantation genetic testing for aneuploidy: A Canadian Fertility and Andrology Society Guideline.

The objective of this guideline from the Canadian Fertility and Andrology Society is to synthesize the evidence on preimplantation genetic testing for aneuploidies (PGT-A) using trophectoderm biopsy and 24-chromosome analysis and to provide clinical recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. To date, randomized controlled trials have been limited to good-prognosis patients who were able to generate two or more blastocysts for biopsy. In this specific population the GRADE analysis of PGT-A shows an increase in the implantation rate and ongoing pregnancy or delivery rate per transfer. Clearly, it is difficult to generalize from this subgroup of patients to the infertility population at large. As a result, the application of PGT-A should be individualized, and patient factors such as age and ability to generate embryos will influence decision-making. Comprehensive patient counselling and informed consent are imperative before undertaking PGT-A. Potential benefits must be weighed against the costs and limitations of the technology, including the risk of embryo damage, false positives, false negatives and the detection of embryonic mosaicism. Future research is required, especially with regard to the use of PGT-A in poorer prognosis patients, and with respect to reporting outcomes per cycle start and cumulatively per retrieval.

Opinion de comité no 406 : Dépistage prénatal après FIV avec test génétique préimplantatoire des aneuploïdies.

OBJECTIFS: Examiner l'approche du dépistage génétique prénatal et du diagnostic des anomalies chromosomiques dans les grossesses conçues par fécondation in vitro à la suite d'un test génétique préimplantatoire des aneuploïdies. PROFESSIONNELS CONCERNéS: Omnipraticiens, médecins de famille, obstétriciens, sages-femmes, infirmières, spécialistes en médecine fœto-maternelle, spécialistes en fertilité, conseillers en génétique, généticiens et autres professionnels de la santé qui participent au dépistage prénatal. POPULATION CIBLE: Toute personne ou tout couple dont la grossesse est issue d'une fécondation in vitro et dont l'embryon a préalablement été soumis à un dépistage génétique préimplantatoire des aneuploïdies. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Medline, PubMed et Cochrane Library pour extraire la littérature publiée au plus tard en septembre 2018. DÉCLARATIONS SOMMAIRES.

Committee Opinion No. 406: Prenatal Testing After IVF With Preimplantation Genetic Testing for Aneuploidy.

OBJECTIVE: To review the approach to prenatal genetic screening and diagnosis for chromosomal abnormalities in pregnancies conceived through in vitro fertilization and following preimplantation genetic testing for aneuploidy. INTENDED USERS: General practitioners, family physicians, obstetricians, midwives, nurses, maternal-fetal medicine specialists, fertility specialists, genetic counsellors, geneticists, and other health care providers involved in prenatal screening. TARGET POPULATION: All individuals or couples who conceivd through in vitro fertilization and underwent preimplantation genetic testing for aneuploidy. EVIDENCE: Literature published in or before September 2018 was retrieved through searches of Medline, PubMed, and the Cochrane Library. SUMMARY STATEMENTS.

Fertility patients' use and perceptions of online fertility educational material.

BACKGROUND: Online educational information is highly sought out by patients with infertility. This study aims to assess patient-reported usage and helpfulness of fertility educational material on a clinic website and social media accounts. METHODS: Educational material was created on common fertility topics in text and video format and posted on the clinic website and social media accounts. At the first consultation for infertility, patients were provided with a postcard directing them to material online. At the first follow-up appointment, patients were invited to fill out a survey assessing whether patients viewed the online educational material and if they found the information helpful. RESULTS: 98.4% (251/255) of patients completed the survey, of which 42.6% (106/249) looked at the online material. Of those who viewed the online information, 99.1% (115/116) found the information helpful or somewhat helpful and 67.6% (73/108) found reading the material online better prepared them for making fertility decisions at their doctor's appointment. CONCLUSION: Patients found online fertility information on the clinic website and social media accounts useful for making fertility treatment decisions. Providing online educational material has the potential to improve patient care by empowering patients with the knowledge to make more informed treatment decisions, and improving the quality of the time spent with the physician.

Expanding Urgent Oncofertility Services for Reproductive Age Women Remote from a Tertiary Level Fertility Centre by Use of Telemedicine and an On-site Nurse Navigator.

The objective of this study was to examine a 1-year pilot program aimed at increasing access to fertility preservation (FP) information and services for reproductive-age women newly diagnosed with cancer at a centre geographically remote from a tertiary fertility clinic. An oncofertility nurse navigator (ONN) position was created within the regional cancer centre with the goals of (1) improving local physician knowledge of FP and FP services and (2) improving patient access to FP counselling and services. The ONN identified all women diagnosed with cancer requiring treatment that could impact their fertility and discussed FP options with them and their physicians. As part of a comprehensive program aimed at facilitating access to FP services, the ONN arranged consultations with fertility specialists via telemedicine and coordinated satellite cycle monitoring with a local gynaecologist in order to minimize travel. Patients were surveyed about their reproductive plans, decision-making around FP and experiences with the program. Physicians were surveyed about their engagement with FP services, barriers to FP access and satisfaction with the program. Twenty-two women were eligible for FP during the year-long pilot program. All participated in the study. The most common diagnoses were breast and cervical cancer. At the time of diagnosis, 36.4% of women had no biological children and 68.2% did not desire (more) children. Four women had an FP consultation, and two proceeded with oocyte or embryo cryopreservation. At the end of the pilot program, more physician respondents often or always discussed FP with their patients, stated they frequently refer for FP consultations and stated their patients could obtain FP services in a timely fashion. An ONN within a cancer centre remote from tertiary fertility care can enable access to FP services with minimal need for travel by using local gynaecologic expertise and telemedicine.

A Critical Appraisal of Fertility and Menstrual Tracking Apps for the iPhone.

OBJECTIVE: This study sought to review and appraise Apple App Store applications (apps) designed for menstrual cycle tracking, ovulation prediction, and other topics related to fertility or the management of infertility. METHODS: The Apple App Store was systematically searched using the keywords "period tracker," "menstrual tracker," "fertility," "ovulation," "IVF," and "in vitro fertilization." Apps were downloaded after being screened against pre-defined inclusion criteria. Included apps were independently reviewed by two authors. Data were extracted, and an app quality score (AQS) was calculated according to a premade rubric. Apps were assessed on the basis of their general features, menstrual cycle tracking and prediction features, infertility-related features, and usability. RESULTS: A total of 140 apps were included in the final analysis, of which 90 (64.3%) were free. The average AQS was 32.5%. There was no significant difference in AQS between free and paid apps (31.5% vs. 34.2%; P = 0.491). A total of 62 (44.3%) apps made dynamic cycle predictions on the basis of cumulatively input data. Thirty-one apps (22.1%) contained serious inaccuracies in content, tools, or both. Only 25 apps (17.9%) contained information or functions specifically related to infertility or its management. CONCLUSION: Some high-quality menstrual cycle tracking apps are available; however, many more are of low quality, and users should be wary of relying on their predictions to avoid pregnancy or to maximize chances of conception. Few apps specifically address the needs of patients struggling with infertility.

Joint SOGC-CCMG Opinion for Reproductive Genetic Carrier Screening: An Update for All Canadian Providers of Maternity and Reproductive Healthcare in the Era of Direct-to-Consumer Testing.

OBJECTIVE: This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document. INTENDED USERS: All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. TARGET POPULATION: Fertile, sexually active females and their fertile, sexually active male partners who are either planning a pregnancy or are pregnant (preferably in the first trimester of pregnancy, but any gestational age is acceptable). OPTIONS: Women and their partners will be able to obtain appropriate genetic carrier screening information and possible diagnosis of AR, AD, or XL disorders (preferably pre-conception), thereby allowing an informed choice regarding genetic carrier screening and reproductive options (e.g., prenatal diagnosis, preimplantation genetic diagnosis, egg or sperm donation, or adoption). OUTCOMES: Informed reproductive decisions related to genetic carrier screening and reproductive outcomes based on family history, ethnic background, past obstetrical history, known carrier status, or genetic diagnosis. SOGC REPRODUCTIVE CARRIER SCREENING SUMMARY STATEMENT (2016): Pre-conception or prenatal education and counselling for reproductive carrier screening requires a discussion about testing within the three perinatal genetic carrier screening/diagnosis time periods, which include pre-conception, prenatal, and neonatal for conditions currently being screened for and diagnosed. This new information should be added to the standard reproductive carrier screening protocols that are already being utilized by the most responsible maternity provider through the informed consent process with the patient. (III-A; GRADE low/moderate) SOGC OVERVIEW OF RECOMMENDATIONS QUALITY AND GRADE: There was a strong observational/expert opinion (quality and grade) for the genetic carrier literature with randomized controlled trial evidence being available only for the invasive testing. Both the Canadian Task Force on Preventive Health Care quality and classification and the GRADE evidence quality and grade are provided. EVIDENCE: MEDLINE; PubMed; government neonatal screening websites; key words/common reproductive genetic carrier screened diseases/previous SOGC Guidelines/medical academic societies (Society of Maternal-Fetal Medicine [SMFM]; American College of Medical Genetics and Genomics; American College of Obstetricians and Gynecologists [ACOG]; CCMG; Royal College Obstetrics and Gynaecology [RCOG] [UK]; American Society of Human Genetics [ASHG]; International Society of Prenatal Diagnosis [ISPD])/provincial neonatal screening policies and programs; search terms (carrier screening, prenatal screening, neonatal genetic/metabolic screening, cystic fibrosis (CF), thalassemia, hemoglobinopathy, hemophilia, Fragile X syndrome (FXS), spinal muscular atrophy, Ashkenazi Jewish carrier screening, genetic carrier screening protocols, AR, AD, XL). SEARCH PERIOD: 10 years (June 2005-September 2015); initial search dates June 30, 2015 and September 15, 2015; completed final search January 4, 2016. Validation of articles was completed by primary authors RD Wilson and I De Bie. BENEFITS, HARMS, AND COST: Benefits are to provide an evidenced based reproductive genetic carrier screening update consensus based on international opinions and publications for the use of Canadian women, who are planning a pregnancy or who are pregnant and have been identified to be at risk (personal or male partner family or reproductive history) for the transmission of a clinically significant genetic condition to their offspring with associated morbidity and/or mortality. Harm may arise from having counselling and informed testing of the carrier status of the mother, their partner, or their fetus, as well as from declining to have this counselling and informed testing or from not having the opportunity for counselling and informed testing. Costs will ensue both from the provision of opportunities for counselling and testing, as well as when no such opportunities are offered or are declined and the birth of a child with a significant inherited condition and resulting morbidity/mortality occurs; these comprise not only the health care costs to the system but also the social/financial/psychological/emotional costs to the family. These recommendations are based on expert opinion and have not been subjected to a health economics assessment and local or provincial implementation will be required. GUIDELINE UPDATE: This guideline is an update of four previous joint SOGC-CCMG Genetic Screening Guidelines dated 2002, 2006, 2008, and 2008 developed by the SOGC Genetic Committee in collaboration with the CCMG Prenatal Diagnosis Committee (now Clinical Practice Committee). 2016 CARRIER SCREENING RECOMMENDATIONS.

Alloimmune Red Blood Cell Antibodies: Prevalence and Pathogenicity in a Canadian Prenatal Population.

OBJECTIVE: The goals of this study were to determine the prevalence and relative frequencies of red blood cell antibodies in a Canadian prenatal population, and to evaluate the fetal and neonatal outcomes of affected pregnancies. METHODS: We conducted a retrospective review of pregnancies that screened positive for red cell antibodies between 2006 and 2010. The following antibodies were included: anti-D, -C, -c, -E, -e, -Fya, -Fyb, -Jka, and-Jkb. Cases of anti-Kell as the sole antibody were excluded. Fetal and neonatal outcome data were then collected and analyzed. RESULTS: The population prevalence of a positive antibody screen was 0.36%. Anti-E was the most frequent antibody at 48.5%, followed by anti-c and anti-Jka. Anti-D made up 6.8% of cases, but had significantly higher titres and was responsible for the majority of severely affected fetuses. Sixteen cases in our series experienced severe adverse fetal or neonatal outcomes. All severe outcomes occurred in cases that had a maximum titre of ≥ 8. CONCLUSION: Despite the decreasing incidence of anti-D alloimmunization, anti-D remains responsible for the majority of severe cases of hemolytic disease of the fetus and newborn.

Objectif : Cette étude avait pour objectif de déterminer la prévalence et la fréquence relative des anticorps anti-érythrocytaires au sein d'une population prénatale canadienne, et d'évaluer les issues fœtales et néonatales des grossesses affectées. Méthodes : Nous avons mené une analyse rétrospective portant sur les grossesses qui ont obtenu des résultats positifs au dépistage des anticorps anti-érythrocytaires entre 2006 et 2010. Les anticorps suivants ont été inclus : anti-D, -C, -c, -E, -e, -Fya, -Fyb, -Jka et -Jkb. Les cas où l'anti-Kell constituait le seul anticorps ont été exclus. Des données sur les issues fœtales et néonatales ont par la suite été recueillies et analysées. Résultats : La prévalence populationnelle de l'obtention d'un résultat positif au dépistage des anticorps a été de 0,36 %. L'anti-E a été l'anticorps le plus fréquent à 48,5 %, suivi de l'anti-c et de l'anti-Jka. Bien que l'anti-D n'ait constitué que 6,8 % des cas, ses titres étaient considérablement accrus et il a été à l'origine de la majorité des cas de fœtus gravement affecté. Dans le cadre de notre série, seize cas ont connu des issues indésirables fœtales ou néonatales graves. Toutes les issues graves ont été constatées dans les cas qui présentaient un titre maximum de ≥ 8. Conclusion : Malgré l'incidence décroissante de l'allo-immunisation anti-D, l'anti-D demeure à l'origine de la majorité des cas graves de maladie hémolytique du fœtus et du nouveau-né.

Tumor microsatellite instability in early onset gastric cancer.

Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. Genetic factors are implicated, including DNA mismatch repair (MMR) deficiency manifested as tumor microsatellite instability (MSI). However, a standardized panel of markers and a definition of low-versus-high level MSI in GC are lacking. We examined a population-based cohort of early onset (or=3 markers MSI+/MSI-high) demonstrated MMR protein deficiency. Three novel hMLH1 mutations (two germline frameshift and one somatic nonsense) were also found. The only significant clinicopathological associations were increased tumor size in MSI+ cases (P=0.04) and Lauren histotype (P=0.006) and tumor grade (P=0.007) in MSI-high cases. Tumor size, location, depth, nodal status, and Ming subtype were significant prognostic variables. Therefore, we propose a new definition of high-level MSI based on unifying characteristics of instability of more than or equal to three of six mononucleotide markers and loss of MMR protein expression.