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Objectives: To determine the normal values of α-fetoprotein (AFP) in amniotic fluid between the gestational ages of 11 and 13 weeks and compare these with previously published values. Methods: Amniotic fluid AFP was analyzed in 149 patients who had undergone amniocentesis between 11 ± 0 and 13 ± 6 weeks gestation as part of the pilot study of the Canadian Early and Mid-Trimester Amniocentesis Trial. Analysis was done using the Abbott IMX System (Abbott Laboratories Diagnostic Division, Abbott Park, Ill.). These values were then compared with previously published values. Results: There is a progressive and linear rise in the amniotic fluid AFP concentration from 11 to 13 weeks gestation. The differences between each of the three gestational ages were statistically significant at the 0.05 level. The values differed significantly from those obtained by Crandall et al. [Am J Obstet Gynecol 1989;160:1204–1206], which were also consistently higher. Conclusion: Although reference points for 11, 12 and 13 weeks have been established, there are limitations to their clinical application.

Prenatal genetic aneuploidy screening approaches are designed to identify pregnant patients at increased risk of having a fetus affected. Conventional prenatal screening has consisted in providing women a risk estimate of having a pregnancy affected with trisomy 21 or trisomy 18 based on maternal age and analysis of serum markers and ultrasound nuchal translucency (NT) measurement. In 2011, the introduction of cell-free DNA (cfDNA) based screening into clinical practice has provided new options for aneuploidy screening programs. Different protocols are currently in use, some that perform screening in the first trimester (combined first trimester screening), some in the second trimester (QUAD), some that integrate first and second trimester (serum integrated screening, integrated screening, sequential, or contingent screening). cfDNA screening can be implemented as a second tier / contingent screen or as a first tier screen and has the ability to detect chromosomal anomalies other than the common aneuploidies screened for by conventional screening. The choice of protocol will be based on local expertise and resources. Aneuploidy screening should also be offered to pregnant women with twin gestation although fewer validation studies in twins of the test being offered are available compared to studies done in singleton gestations. Professional societies and expert groups emphasize the need for pre-test and post-test counselling to ensure that women are making an informed decision. The general counselling points to be covered are similar regardless of the type of prenatal screening being offered. Prenatal screening programs should be implemented with resources that support patient and health care provider education, quality assurance of laboratory and NT services, access to genetic counselling services and diagnostic testing. The rapid pace of new developments in cfDNA screening for chromosomal anomalies brings new opportunities to enhance the performance of the screening but at the same time, challenges as the test menus are expanded and data is lacking as to the cost-effectiveness and clinical utility of implementing expanded panels.

Resume Objectif Analyser les donnees au sujet des autopsies foetales et perinatales, le processus d'obtention du consentement et les autres options de collecte de donnees a la suite d'un diagnostic prenatal de malformations non chromosomiques, ainsi qu'aider les cliniciens a offrir des services de counseling postnatal a propos du diagnostic foetal et des risques de recurrence.Criteres d'evaluation des resultats et de classifcation des recommandations, fondes sur ceux du Groupe d'etude canadien sur les soins de sante preventifsNiveaux de resultats*Categories de recommandations† I:Resultats obtenus dans le cadre d'au moins un essai comparatif convenablement randomise II-1:Resultats obtenus dans le cadre d'essais comparatifs non randomises bien concus II-2:Resultats obtenus dans le cadre d'etudes de cohortes (prospectives ou retrospectives) ou d'etudes analytiques cas-temoins bien concues, realisees de preference dans plus d'un centre ou par plus d'un groupe de recherche II-3:Resultats decoulant de comparaisons entre differents moments ou differents lieux, ou selon qu'on a ou non recours a une intervention Des resultats de premiere importance obtenus dans le cadre d'etudes non comparatives (par exemple, les resultats du traitement a la penicilline, dans les annees 1940) pourraient en outre fgurer dans cette categorie III:Opinions exprimees par des sommites dans le domaine, fondees sur l'experience clinique, etudes descriptives ou rapports de comites d'experts A.On dispose de donnees suffsantes pour appuyer la mesure clinique de prevention B.On dispose de donnees acceptables pour appuyer la mesure clinique de prevention C.Les donnees existantes sont contradictoires et ne permettent pas de formuler une recommandation pour ou contre l'usage de la mesure clinique de prevention; cependant, d'autres facteurs peuvent infuer sur la prise de decision D.On dispose de donnees acceptables pour deconseiller la mesure clinique de prevention E.On dispose de donnees suffsantes pour deconseiller la mesure clinique de prevention F.Les donnees sont insuffsantes (d'un point de vue qantitatif ou qualitatif) et ne permettent pas de formuler une recommandation; cependant, d'autres facteurs peuvent infuer sur la prise de decision Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W « Canadian Task Force on Preventive Health Care New grades for recommendations from the Canadian Task Force on Preventive Health Care », CMAJ, vol 169, 2003, p 207–8*La qualite des resultats signales dans les presentes directives cliniques a ete etablie conformement aux criteres d'evaluation des resultats presentes dans le Rapport du Groupe d'etude canadien sur les soins de sante preventifs†Les recommandations que comprennent les presentes directives cliniques ont ete classees conformement a la methode de classifcation decrite dans le Rapport du Groupe d'etude canadien sur les soins de sante preventif Issues Mieux conseiller les patientes et leur famille qui font face a un diagnostic prenatal d'anomalie foetale non chromosomique au sujet des autopsies foetales et perinatales. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en 2009 et en 2010, au moyen de mots cles adequats (« fetal autopsy », « postmortem », « autopsy », « perinatal postmortem examination », « autopsy protocol », « postmortem magnetic resonance imaging », « autopsy consent », « tissue retention », « autopsy evaluation »). Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Des publications additionnelles ont ete identifiees a partir des bibliographies de ces articles. Aucune restriction n'a ete imposee en matiere de date ou de langue. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Avantages, desavantages et couts La presente mise a jour renseigne les lecteurs au sujet (1) des avantages de la tenue d'une autopsie foetale ou perinatale, (2) du processus de consentement et (3) des solutions de rechange face au refus de la famille de proceder a une autopsie. Elle offre egalement une approche standardisee envers les autopsies foetales et perinatales, en mettant l'accent sur les prelevements additionnels pertinents, le cas echeant. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1).

Resume Objectif Offrir aux fournisseurs de soins de sante canadiens des donnees actuelles sur l'utilisation de l'amplification en chaine par polymerase fluorescente quantitative (QF-PCR) ou d'une technologie equivalente dans le diagnostic prenatal des anomalies chromosomiques fœtales. Options Au cours des dernieres decennies, le diagnostic prenatal des anomalies chromosomiques fœtales a repose sur l'analyse cytogenetique conventionnelle de cultures d'amniocytes, de villosites choriales ou de sang fœtal. Au cours des quelques dernieres annees, la validite clinique d'une nouvelle technique (la QF-PCR) pour ce qui est de la detection des aneuploidies courantes a ete signalee par un certain nombre de chercheurs. Cette technique dispose de l'avantage de fournir rapidement des resultats pour le diagnostic ou l'exclusion de l'aneuploidie en ce qui concerne les chromosomes 13, 18, 21, X ou Y II est maintenant possible de choisir d'avoir recours a une analyse chromosomique standard ou a la QF-PCR pour le diagnostic prenatal des anomalies chromosomiques (ou encore de mener ces deux tests), en fonction de l'indication clinique du depistage. Le present document analyse l'utilite clinique de la QF-PCR et formule des recommandations quant a son utilisation dans le cadre des soins offerts aux patientes canadiennes. Resultats Des recherches ont ete menees dans Medline et PubMed afin d'en tirer les articles publies en anglais entre janvier 2000 et decembre 2010 qui presentaient des donnees issues de la comparaison entre la QF-PCR et l'analyse cytogenetique standard des prelevements prenataux. Une deuxieme recherche a ete menee pour identifier les publications en anglais qui offraient des resultats d'analyses cytogenetiques menees sur des prelevements prenataux chez des femmes exposees a un risque accru d'aneuploidie fœtale en raison de leur âge, de resultats anormaux a la suite du depistage prenatal ou de marqueurs faibles echographiques fœtaux semblant indiquer un risque accru d'aneuploidie. Ces publications ont ete incluses lorsqu'elles offraient des renseignements detailles sur les anomalies detectees, peu importe si un depistage rapide de l'aneuploidie avait ete mene. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises et aux etudes observationnelles pertinentes. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Les directives cliniques precedemment publiees par la Societe des obstetriciens et gynecologues du Canada au sujet du depistage prenatal ont egalement ete analysees dans le cadre de l'elaboration de la presente directive clinique. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau). Avantages, desavantages et couts La presente directive clinique fait la promotion du recours a un test ADN rapide de depistage de l'aneuploidie chez les femmes exposees a un risque accru de connaitre une grossesse affectee par une aneuploidie courante. La mise en oeuvre d'un tel test aura l'avantage de fournir rapidement des resultats precis aux femmes exposees a un risque accru de syndrome de Down, de trisomie 13, de trisomie 18, d'aneuploidie ou de triploidie des chromosomes sexuels. Elle favorisera egalement une meilleure utilisation des ressources laboratoires et la reduction des couts lies au diagnostic prenatal. Cependant, un faible pourcentage de grossesses presentant une anomalie chromosomique potentiellement significative sur le plan clinique, bien que detectables au moyen de methodes cytogenetiques conventionnelles, passeront inapercues au moment de la mise en oeuvre de la QF-PCR. Recommandations 1. La QF-PCR est un moyen fiable de detecter les trisomies et devrait remplacer l'analyse cytogenetique conventionnelle lorsque le depistage prenatal n'est mene qu'en raison d'un risque accru d'aneuploidie affectant les chromosomes 13, 18, 21, X ou Y. Comme pour tout autre test, les services de counseling pretest devraient comprendre une discussion sur les avantages et les limites de ce test. Au cours de la periode initiale d'utilisation, l'offre d'une formation aux fournisseurs de soins de sante s'averera necessaire. (II-2A) 2. L'analyse cytogenetique conventionnelle et la QF-PCR devraient toutes deux etre mises en oeuvre dans tous les cas de diagnostic prenatal demande en raison de la constatation echographique d'une anomalie foetale (y compris une mesure accrue de la clarte nucale > 3,5 mm) ou de la presence d'un remaniement chromosomique familial. (II-2A) 3. Le suivi cytogenetique des resultats de QF-PCR indiquant des trisomies 13 et 21 est recommande pour ecarter la presence possible de translocations robertsoniennes hereditaires. Toutefois, la decision de mettre en oeuvre, pour tous les cas, une culture d'appoint qui permettrait la tenue d'un depistage cytogenetique traditionnel (lorsque cela s'avererait indique en raison de donnees cliniques ou de laboratoire additionnelles) devrait etre prise par chacun des centres offrant le depistage, en fonction de l'experience et des ressources cliniques et de laboratoire locales. (III-A) 4. D'autres technologies de detection rapide de l'aneuploidie etant en mesure d'offrir un rendement semblable ou ameliore (pour ce qui est de la detection des trisomies 13, 18 et 21, et de l'aneuploidie des chromosomes sexuels) pourraient en venir a remplacer la QF-PCR. (III-A)

To review the effect of assisted human reproduction (AHR) on perinatal outcomes, to identify areas requiring further research with regard to birth outcomes and AHR, and to provide guidelines to optimize obstetrical management and counselling of prospective Canadian parents.This document compares perinatal outcomes of different types of AHR pregnancies with each other and with those of spontaneously conceived pregnancies. Clinicians will be better informed about the adverse outcomes that have been documented in association with AHR, including obstetrical complications, adverse perinatal outcomes, multiple gestations, structural congenital abnormalities, chromosomal abnormalities, and imprinting disorders.Published literature was retrieved through searches of MEDLINE and the Cochrane Library from January 2005 to December 2012 using appropriate controlled vocabulary and key words (assisted reproduction, assisted reproductive technology, ovulation induction, intracytoplasmic sperm injection, embryo transfer, and in vitro fertilization). Results were not restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies; studies of all designs published in English from January 2005 to December 2012 were reviewed, and additional publications were identified from the bibliographies of these articles. Searches were updated on a regular basis and incorporated in the guideline to August 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. There is increasing evidence that infertility or subfertility is an independent risk factor for obstetrical complications and adverse perinatal outcomes, even without the addition of assisted human reproduction. (II-2) 2. The relative risk for an imprinting phenotype such as Silver-Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman syndrome is increased in the assisted reproduction population, but the actual risk for one of these phenotypes to occur in an assisted pregnancy is estimated to be low, at less than 1 in 5000. The exact biological etiology for this increased imprinting risk is likely heterogeneous and requires more research. (II-2) Recommendations 1. All men with severe oligozoospermia or azoospermia (sperm count5 million/hpf) should be offered genetic/clinical counselling, karyotype assessment for chromosomal abnormalities, and Y-chromosome microdeletion testing prior to in vitro fertilization with intracytoplasmic sperm injection. (II-2A) 2. All men with unexplained obstructive azoospermia should be offered genetic/clinical counselling and genetic testing for cystic fibrosis prior to in vitro fertilization with intracytoplasmic sperm injection. (II-2A) 3. Multiple pregnancy is the most powerful predictive factor for adverse maternal, obstetrical, and perinatal outcomes. Couples should be thoroughly counselled about the significant risks of multiple pregnancies associated with all assisted human reproductive treatments. (II-2A) 4. The benefits and cumulative pregnancy rates of elective single embryo transfer support a policy of using this protocol in couples with good prognosis for success, and elective single embryo transfer should be strongly encouraged in this population. (II-2A) 5. To reduce the incidence of multiple pregnancy, health care policies that support public funding for assisted human reproduction, with regulations promoting best practice regarding elective single embryo transfer, should be strongly encouraged. (II-2A) 6. Among singleton pregnancies, assisted reproductive technology is associated with increased risks of preterm birth and low birth weight infants, and ovulation induction is associated with an increased risk of low birth weight infants. Until sufficient research has clarified the independent roles of infertility and treatment for infertility, couples should be counselled about the risks associated with treatment. (II-2B) There is a role for closer obstetric surveillance of women who conceive with assisted human reproduction. (III-L) 7. There is growing evidence that pregnancy outcomes are better for cryopreserved embryos fertilized in vitro than for fresh embryo transfers. This finding supports a policy of elective single embryo transfer for women with a good prognosis (with subsequent use of cryopreserved embryos as necessary), and may reassure women who are considering in vitro fertilization. (II-2A) 8. Women and couples considering assisted human reproduction and concerned about perinatal outcomes in singleton pregnancies should be advised that (1) intracytoplasmic sperm injection does not appear to confer increased adverse perinatal or maternal risk over standard in vitro fertilization, and (2) the use of donor oocytes increases successful pregnancy rates in selected women, but even when accounting for maternal age, can increase the risks of low birth weight and preeclampsia. (II-2B) 9. Any assisted reproductive technology procedure should be prefaced by a discussion of fetal outcomes and the slight increase in the risk of congenital structural abnormalities, with emphasis on known confounding factors such as infertility and body mass index. (II-2B) 10. In pregnancies achieved by artificial reproductive technology, routine anatomic ultrasound for congenital structural abnormalities is recommended between 18 and 22 weeks. (II-2A) 11. Pregnancies conceived by intracytoplasmic sperm injection may be at increased risk of chromosomal aberrations, including sex chromosome abnormalities. Diagnostic testing should be offered after appropriate counselling. (II-2A) 12. The possible increased risk for late onset cancer due to gene dysregulation for tumour suppression requires more long-term follow-up before the true risk can be determined. (III-A) 13. The clinical application of preimplantation genetic testing in fertile couples must balance the benefits of avoiding disease transmission with the medical risks and financial burden of in vitro fertilization. (III-B) 14. Preimplantation screening for aneuploidy is associated with inconsistent findings for improving pregnancy outcomes. Any discussion of preimplantation genetic screening with patients should clarify that there is no adequate information on the long-term effect of embryo single cell biopsy. (I-C).

Objective: To determine the incidence and etiology of prenatally diagnosed microcephaly. Methods: Retrospective review of 10 years at a tertiary obstetrical hospital. The study population consisted of 21 infants with confirmed prenatal and postnatal microcephaly. Results: There were 8 different definite/probable etiologies identified (viral, monochorionic twinning, genetic syndrome, neural tube defect, abnormal karyotype, hypoxic insult, constitutional). Conclusions: Retrospective study indicates the commonest etiologies for prenatal microcephaly are in utero infection, monochorionic twin insult, rare genetic syndrome and chromosomal anomalies.

Objective: Our purpose was to evaluate the knowledge of folic acid and its use preconceptionally in women of British Columbia. Methods: The study was conducted at British Columbia Women’s Hospital in Vancouver, Canada, between April 15 and June 15, 1999. Pregnant women and women in the postpartum period were asked to complete a survey on folic acid. Results: In total, 1,004 women completed the questionnaire during the study period. Seventy-one percent of the women knew that vitamins could help prevent birth defects. Of those, 76.3% identified folic acid as the one vitamin specifically associated with reduction of birth defects. It was identified that 49.4% of all women took vitamins prior to pregnancy. Conclusions: Women in the population studied were relatively well informed about the benefits of folic acid, but less than 50% of them took vitamins prior to conception.

systemic lupus erythematosus (SLE) in pregnancy is associated with increased maternal and fetal morbidity including fetal loss, growth restriction, and maternal hypertension. Pregnancy complications are more frequent and more severe when conception occurs in patients with lupus nephritis or antiphospholipid antibodies, or during a period of active disease. Lupus flares occur in the majority of pregnancies and often involve the renal and haematologis systems. They tend to be mild to moderate and are treatable with medical therapy, primarily glucocorticoids. Neonatal lupus syndrome is a rare complication of maternal SLE. It is associated with transplacental passage of anti-Ro and/or anti-La antibodies, resulting in cutaneous, haematologic, and cardiac manifestations. Cardiac involvement is common in this syndrome, manifesting as complete congenital heart block due to destruction of the fetal conduction system by antibodies. Antepartum steroid use may be useful in treatment or prevention of congenital heart block. With optimal prenatal care and fetal antepartum surveillance, patients with SLE may have successful, although high risk, pregnancies.

A 58-year-old post-menopausal women was a surrogate mother. She developed severe pre-eclampsia at 35 weeks of pregnancy and was delivered by Caesarean section. Postmenopausal motherhood is a controversial subject. The risk of obstetrical complications (gestational hypertension and diabetes) is high in women over 50. Their care is complex and should be multidisciplinary.

Twenty years after midtrimester genetic amniocentesis was first used, first trimester invasive prenatal procedures were introduced. Chorionic villous sampling presents some disadvantages that entitled many centers to look into an alternative for first trimester diagnosis. Early amniocentesis (EA) can be performed effectively, as shown over the years in many observational studies and partially randomized and randomized trials. Recently, a multicenter randomized trial (Canadian Early and Midtrimester Amniocentesis Trial) reported a higher total pregnancy loss, a significant increased incidence of musculoskeletal foot deformities, a significant increased culture failure rate, and an increased postaminiocentesis rate of leakage in the EA group compared with midtrimester amniocentesis. These results concerning EA procedures from 11w +0 to 12w +6 should be included in any pre-EA counseling. However, further trials have started to evaluate EA procedures between 13w +0 to 14w +6 .

Cytogenetic results from a large multicentre randomized controlled study of 2108 amniotic fluids obtained at 11+0–12+6 weeks (EA) and 1999 fluids at 15+0–16+6 weeks (MA) were compared. There was no statistically significant difference in the rate of chromosome abnormalities (EA =1.9 per cent; MA=1.7 per cent) or level III mosaicism (EA=0.2 per cent; MA= 0.2 per cent) between the groups. Level I and Level II mosaicism occurred more frequently in MA. Maternal cell contamination was not significantly different between the groups, but maternal cells only were analysed from one bloody EA fluid. The number of repeat amniocenteses because of cytogenetic problems was 2.2 per cent in the EA group compared with only 0.3 per cent in the MA group. On average, culture of EA fluids required one day more than MA fluids. Although both culture success (97.7 per cent) and accuracy (99.8 per cent) were high for patients randomized to the EA group, routine amniocentesis prior to 13 weeks’ gestation is not recommended for clinical reasons including an increased risk of fetal loss and talipes equinovarus. Copyright © 1999 John Wiley & Sons, Ltd.

The goal of thalassemia screening is the identification, prior to the conception or birth of an affected child, of couples where both partners are thalassemia carriers. When both partners are identified as carriers for alpha- or beta-thalassemia, the risk of having a fetus who is homozygous or compound heterozygous for the abnormal gene is 25%. A study was performed to identify whether routine screening for thalassemia is indicated for the Chinese population in British Columbia (BC). In a population of 783 subjects, studied either prospectively or retrospectively, 5.0% were alpha-thalassemia carriers and 1.7% were beta-thalassemia carriers. In addition, a review of all BC cases of prenatal diagnosis for thalassemia over a 6-year period indicated that 26% of couples were identified as alpha-thalassemia carriers because of a second or third trimester diagnosis of fetal hydrops, and 17% of couples referred for beta-thalassemia already had an affected child. The experience with prenatal diagnosis shows that a significant proportion of at-risk couples are not identified prior to or early in a pregnancy. The prevalence of carriers for thalassemia would warrant a program of education and routine screening for this condition in the BC Asian population.

Purpose The invasive nature of vaginal sonography, recently introduced as an improved diagnostic method for imaging the contents of the pregnant uterus, has provoked discussion about patient preference for female sonographers. This study examined whether patients had a gender preference for the sonographer who would conduct such an examination. Methods Over 3 months, a written survey was given to pregnant women to complete anonymously while waiting for their scheduled sonographic examination. The survey covered gender preference for the sonographer and education, ethnicity, and previous experience with the procedure. Surveys were turned in by 1,002 pregnant women. Results Of the women whose survey responses were analyzed, 62% preferred a female sonographer. The principal reason given for this preference was comfort with the same gender. The majority of respondents were 25–40 years old, married, white, and multiparous. The level of education varied widely. Conclusions These findings point to a need to seek consumer input when new technology is introduced, to provide women with choices where possible, and to ensure that they have access to information about those choices. © 1999 John Wiley & Sons, Inc. J Clin Ultrasound 27:15–19, 1999.

Purpose This study was done to produce enhanced fetal biometry charts and graphs presenting percentile values as a function of fetal age. Methods The relationships between the ultrasound measurements of 10 fetal parameters and menstrual age were determined by a cross-sectional study. Data were obtained from 508 to 790 fetuses. Anatomic structures were scanned and measured 3 times during 1 routine sonographic examination. The study group consisted of 1,396 Caucasian women who had normal singleton fetuses with confirmation of menstrual dates by sonography before 14 weeks and for whom complete pregnancy outcome information was available. For each of the 10 parameters, percentile curves were derived for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles. Results Ready-to-use fetal measurement charts and graphs are presented in a format giving the percentile values as a function of fetal age. There were no significant differences between male and female fetuses. Conclusions These fetal biometry charts and graphs, obtained from a North American Caucasian population, enhance previously published data. © 1998 John Wiley & Sons, Inc. J Clin Ultrasound 26:433–453, 1998.

Objective To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Options Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new cytogenetic technologies and embryo-stage biopsy. Outcomes Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies. Evidence Published literature was retrieved through searches of The Cochrane Library and Medline in April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods, fertilization in vitro) and key words (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, and embryo selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. (Table 1) Benefits, harms, and costs This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The major harms and costs identified are those of assisted reproductive technologies. Summary Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening is being proposed to improve the effectiveness of in vitro fertilization by screening for embryonic aneuploidy. Though FISH-based PGS showed adverse effects on IVF success, emerging evidence from new studies using comprehensive chromosome screening technology appears promising.

Resume Objectif Offrir aux fournisseurs de soins de maternite et a leurs patientes des lignes directrices factuelles contemporaines en ce qui concerne les services de counseling traitant des risques et des avantages maternels propres a la tenue des interventions diagnostiques prenatales orientees par echographie (et/ou des techniques permettant l'etablissement d'un diagnostic genetique) necessaires dans les cas ou il a ete etabli pendant la periode prenatale que la grossesse serait exposee a des risques, ainsi qu'en ce qui concerne la prise de decisions subsequentes quant a la prise en charge de la grossesse (questions abordant des aspects tels que le niveau du fournisseur de soins obstetricaux, la surveillance prenatale, le lieu ou devraient se derouler les soins et l'accouchement, et la decision de poursuivre ou d'interrompre la grossesse). La presente directive clinique se limite aux services de counseling traitant des risques et des avantages maternels, et aux decisions en matiere de prise en charge de la grossesse pour les femmes qui necessitent (ou qui envisagent) la mise en oeuvre d'une intervention ou d'une technique effractive orientee par echographie aux fins de l'etablissement d'un diagnostic prenatal. Population de patientes Femmes enceintes identifiees, a la suite de la mise en oeuvre de protocoles etablis de depistage prenatal (taux seriques maternels ± imagerie, resultats d'analyse de l'ADN acellulaire indiquant des risques eleves, resultats anormaux au moment de l'imagerie foetale diagnostique ou antecedents familiaux de troubles hereditaires), comme etant exposees a un risque accru d'anomalie genetique foetale. Ces femmes pourraient necessiter ou demander des services de counseling au sujet des risques et des avantages pour la grossesse de la tenue d'une intervention effractive orientee par echographie visant a determiner l'etiologie, le diagnostic, et/ou la pathologie de possibles anomalies foetales.

Objective: to make recommendations about chromosamal aneuploidy, congenital malformations, and pregnancy loss in twin gestations to physicians providing prenatal care. Options: invasive prenatal testing (amniocentesis, chorionic villus sampling, cordocentesis), non-invasive testing (ultrasound, maternal serum screening) Outcomes: informed choice regarding invasive and non-invasive prenatal testing in twin gestations. Evidence: informatian obtained from well-designed cohort or case control analytic studies from more than one centre. Values: evidence-based methods and review of the literature were used. Benefits, risks, and costs: the collective risks of chromosomal aneuploidy in one of the fetuses in a twin pair is hypothetically increased. A woman who will be 32 years of age at the estimated date of delivery (EDD) with a twin gestation has a similar risk of a liveborn neonate with a chromosomal anomaly as a woman who will be 35 years of age at her EDD with a singleton pregnancy. For the total study group, the incidence of aneuploidy and pregnancies delivered at less than 28 weeks was 5.2 percent and 9.5 percent, respectively. Selective termination is a management option for a twin pregnancy with an abnormal fetus. Monozygotic twin pregnancies are at an increased risk for discordant malformations. Recommendation: a woman with a twin pregnancy has an increased risk that one or both twins will have chromosomal aneuploidy if the woman attains a maternal age of 32 on the expected date of delivery. This fetal chromosomal risk corresponds to the risk for a maternal age of 35 with a singleton pregnancy. A woman with a twin pregnancy should be made aware of this increased fetal chromosomal risk and be given a choice of invasive (amniocentesis, chorionic villus sampling, cordocentesis) or non-invasive (ultrasound, maternal serum screening) prenatal diagnosis and should be informed of the advantages, disadvantages, and risks of each choice. Procedure loss rates in twins are estimated at one percent while total pregnancy loss rates are increased due to background twin risks. Detailed ultrasound examination is required because of the increased risks of discordant malformation in monozygotic twins with normal chromosomes. Selective termination could be offered as a management option for a patient with an abnormal fetus in a twin pregnancy. Validation: no specific recommendations other than literature conclusions are available for twin gestations. Quality of evidence: II-2. Classification of recommendation: B.

Fetal cells that circulate in maternal peripheral blood (PB) during pregnancy offer a potential source of nucleated fetal material for noninvasive prenatal diagnosis. Fluorescence-activated cell sorting was used to target two populations of fetal cells: nucleated erythroid cells (NECs; CD71/glycophorin-A+ CD45lo-int CD34−) and hematopoietic progenitor cells (CD34+ cells; CD34++ CD71/glycophorin-A− CD45int). Fetal cells were detected by fluorescence in situ hybridization (FISH) using directly conjugated chromosome X and Y probes in 65% (13 of 20) of the maternal PBs (fetal karyotype 46,XY). The frequency of fetal cells isolated from the NEC and CD34+ fractions was, respectively, 0 to 14 and 0 to 7 cells per 2 × 107 previously frozen maternal cells (≈20 mL of blood). In nonfrozen samples, the yield and recovery of fetal cells was moderately improved. Culturing the CD34+ sorted fractions in serum-free media with cytokines improved the quality of the FISH preparations and resulted in a slight expansion in detectable fetal cells. The frequency of fetal cells isolated from cultured CD34+ fractions was 0 to 35 and 0 to 93 cells per 2 × 107 previously frozen and nonfrozen maternal PB cells, respectively. These results document the isolation, characterization, and enumeration of fetal cells from the maternal periphery that appear to be present in most, but not all, samples analyzed.

Objective To provide a review of published studies on the use of cell-free fetal DNA in maternal plasma for the non-invasive diagnosis of Down syndrome, trisomy 18, and trisomy 13. Evidence: PubMed was searched for articles published between 2006 and October 2012, using appropriate key words (e.g., non-invasive prenatal diagnosis, Down syndrome, cell-free fetal DNA, aneuploidy screening). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to October 31, 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The studies reviewed were classified according to criteria described by the Canadian Task Force on Preventive Health Care, and the recommendations for practice were ranked according to this classification (Table 1).

Early amniocentesis (EA) for prenatal diagnosis at less than 14 weeks gestation is becoming more common. The number of randomized studies are small and have not had the power to determine the accuracy and safety of the procedure when compared to chorionic villus sampling or mid-trimester amniocentesis. Procedures at 11+0 to 12+6 weeks should be considered experimental. This review discusses the ethics, embryology, and clinical experience in obtaining samples for cytogenetics, amniotic fluid alpha fetoprotein (AFP), and acetylcholinesterate (AChE) estimation. The procedure and cytogenetic failures, spontaneous and therapeutic pregnancy losses, and congenital anomalies associated with early amniocentesis will be described.

Early amniocentesis at less than 14 weeks gestation is becoming more common in prenatal diagnosis populations. Randomized studies are minimal and have not had the power to determine the accuracy and safety of the procedure compared to chorionic villus sampling or mid-trimester amniocentesis. Procedures at 11+0-12+6 weeks should be considered experimental. This clinical review considers the ethics, embryology, and clinical experience (cytogenetics, AFP, AChE, procedure and cytogenetic failures, spontaneous and therapeutic pregnancy losses, congenital anomalies) of early amniocentesis.

ots cles : Carrier screening, prenatal screening, autosomal ecessive disorder, autosomal dominant disorder, X-linked disorder, halassemia, hemoglobinopathy, cystic fibrosis, Duchenne/Becker uscular dystrophy, Fragile X, spinal muscular atrophy, Tay-Sachs isease, Bloom syndrome, Canavan disease, familial ysautonomia, Fanconi anemia, Gaucher disease, glycogen torage disease, mucolipidosis, Niemann-Pick, maple syrup urine isease, Walker-Warburg, hemophilia A, hemophilia B, invasive renatal testing, perinatal autopsy

To provide the physician with an overview of common genetic conditions that should be considered during a women's annual gynaecological assessment to determine the patient's risk or to initiate specific testing or referral to another subspecialty service, depending on personal or family history.This genetic information can be used for patient education and possible disease and/or mutation screening or diagnosis.The use of this genetic information may allow improved risk-benefit assessment and management at the annual gynaecological examination.Studies published in English up to and including May 2010 were retrieved through searches of PubMed and the Cochrane Library, using appropriate controlled vocabulary (gynaecological diagnosis, genetic inheritance) and key words (genetic risk, genetic mutation, inheritance, family history, uterus, ovary, endometrial, vagina, colon, gastric, renal, breast, cardiac, thrombophilia, diabetes, epilepsy, leiomyomata uteri). Other literature sources were identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The levels of evidence are not adequate for evidence-based recommendations to be made.This committee opinion will enhance the use of new genetic knowledge and its application to the annual gynaecological care of women. Risk management and diagnostic opportunities for genetic gynaecological conditions will be improved. A more complete understanding of genetic conditions may increase anxiety and psychological stress for women and their families.Society of Obstetricians and Gynaecologists of Canada.The levels of evidence are not adequate for evidence-based recommendations to be made.

To correlate maternal and fetal outcomes of pregnancies affected by preterm premature rupture of membranes (PPROM) at24 weeks' gestational age with the amount of residual amniotic fluid as determined by sonographic evaluation.We searched the local maternal-fetal medicine database for the records of all women with PPROM prior to 24 completed weeks of pregnancy. The quantity of residual amniotic fluid determined by ultrasound was recorded and women were separated into two groups: (A) deepest vertical pocket (DVP) ≥ 1 cm, or (B) DVP1 cm (severe oligohydramnios). Hospital chart review was undertaken to determine latency to delivery, perinatal death, and maternal complications. Data were analyzed using Fisher exact and Wilcoxon-Mann-Whitney U tests.We identified 31 subjects, of whom nine elected termination of pregnancy (6 in group A, 3 in group B). Six of 10 subjects in group A had a live delivery without neonatal death, whereas only one of 12 subjects in group B had a live delivery (P = 0.020). Additional complications included placental abruption in 63% in group A and 45% in group B, chorioamnionitis in 50% and 70%, respectively, and postpartum endometritis in 0% and 9%, respectively. None of these differences were statistically significant. There were no cases of maternal sepsis or maternal death in either group. Group A was associated with a later GA at delivery (27.5 weeks vs. 23 weeks, P = 0.07), with the GA at rupture of the membranes similar for both groups.These results indicate that a higher level of residual amniotic fluid after periviable PPROM is associated with fetal survival and increased latency to delivery without an increase in maternal complications. This information will be valuable in counselling pregnant women with PPROM24 weeks.

To provide Canadian health care providers with current information on the use of quantitative fluorescent polymerase chain reaction (QF-PCR) or equivalent technology in the prenatal diagnosis of fetal chromosomal abnormalities.Over the last few decades, prenatal diagnosis of fetal chromosomal abnormalities has relied on conventional cytogenetic analysis of cultured amniocytes, chorionic villi, or fetal blood. In the last few years, the clinical validity of a newer technique, QF-PCR, to detect the common aneuploidies has been reported by a number of investigators. This technique has the advantage of providing rapid results for the diagnosis or exclusion of aneuploidy in chromosomes 13, 18, 21, X or Y. It is now possible to choose standard chromosome analysis or QF-PCR for the prenatal diagnosis of chromosomal abnormalities, or to perform both tests, depending on the clinical indication for testing. This document reviews the clinical utility of QF-PCR and makes recommendations for its use in the care of Canadian patients.Medline and PubMed were searched for articles published in English between January 2000 and December 2010 that presented data on the use of QF-PCR versus standard cytogenetic analysis of prenatal samples. A second search was done to identify publications in English that provided results of cytogenetic analysis performed on prenatal samples for women at an increased risk of fetal aneuploidy because of maternal age, abnormal prenatal screening results, or fetal soft ultrasound markers suggestive of an increased risk of aneuploidy. Publications were included if they provided detailed information on the abnormalities detected, regardless of whether or not rapid aneuploidy screening was undertaken. Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).This guideline promotes the use of a rapid aneuploidy DNA test for women at increased risk of having a pregnancy affected by a common aneuploidy. This will have the benefit of providing rapid and accurate results to women at increased risk of fetal Down syndrome, trisomy 13, trisomy 18, sex chromosome aneuploidy or triploidy. It will also promote better use of laboratory resources and reduce the cost of prenatal diagnosis. However, a small percentage of pregnancies with a potentially clinically significant chromosomal abnormality will remain undetected by QF-PCR but detectable by conventional cytogenetics. Recommendations 1. QF-PCR is a reliable method to detect trisomies and should replace conventional cytogenetic analysis whenever prenatal testing is performed solely because of an increased risk of aneuploidy in chromosomes 13, 18, 21, X or Y. As with all tests, pretest counselling should include a discussion of the benefits and limitations of the test. In the initial period of use, education for health care providers will be required. (II-2A) 2. Both conventional cytogenetics and QF-PCR should be performed in all cases of prenatal diagnosis referred for a fetal ultrasound abnormality (including an increased nuchal translucency measurement3.5 mm) or a familial chromosomal rearrangement. (II-2A) 3. Cytogenetic follow-up of QF-PCR findings of trisomy 13 and 21 is recommended to rule out inherited Robertsonian translocations. However, the decision to set up a back-up culture for all cases that would allow for traditional cytogenetic testing if indicated by additional clinical or laboratory information should be made by each centre offering the testing according to the local clinical and laboratory experience and resources. (III-A) 4. Other technologies for the rapid detection of aneuploidy may replace QF-PCR if they offer a similar or improved performance for the detection of trisomy 13, 18, 21, and sex chromosome aneuploidy. (III-A).

To review the literature with respect to the use of diagnostic ultrasound in the management of twin pregnancies. To make recommendations for the best use of ultrasound in twin pregnancies.Reduction in perinatal mortality and morbidity and short- and long-term neonatal morbidity in twin pregnancies. Optimization of ultrasound use in twin pregnancies.Published literature was retrieved through searches of PubMed and the Cochrane Library in 2008 and 2009 using appropriate controlled vocabulary (e.g., twin, ultrasound, cervix, prematurity) and key words (e.g., acardiac, twin, reversed arterial perfusion, twin-to-twin transfusion syndrome, amniotic fluid). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date restrictions. Studies were restricted to those with available English or French abstracts or text. Searches were updated on a regular basis and incorporated into the guideline to September 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The evidence collected was reviewed by the Diagnostic Imaging Committee of the Society of Obstetricians and Gynaecologists of Canada, with input from members of the Maternal Fetal Medicine Committee and the Genetics Committee of the SOGC. The recommendations were made according to the guidelines developed by The Canadian Task Force on Preventive Health Care (Table 1).The benefit expected from this guideline is facilitation and optimization of the use of ultrasound in twin pregnancy. SUMMARY STATEMENTS: 1. There are insufficient data to make recommendations on repeat anatomical assessments in twin pregnancies. Therefore, a complete anatomical survey at each scan may not be needed following a complete and normal assessment. (III) 2. There are insufficient data to recommend a routine preterm labour surveillance protocol in terms of frequency, timing, and optimal cervical length thresholds. (II-2) 3. Singleton growth curves currently provide the best predictors of adverse outcome in twins and may be used for evaluating growth abnormalities. (III) 4. It is suggested that growth discordance be defined using either a difference (20 mm) in absolute measurement in abdominal circumference or a difference of 20% in ultrasound-derived estimated fetal weight. (II-2) 5. Although there is insufficient evidence to recommend a specific schedule for ultrasound assessment of twin gestation, most experts recommend serial ultrasound assessment every 2 to 3 weeks, starting at 16 weeks of gestation for monochorionic pregnancies and every 3 to 4 weeks, starting from the anatomy scan (18 to 22 weeks) for dichorionic pregnancies. (II-1) 6. Umbilical artery Doppler may be useful in the surveillance of twin gestations when there are complications involving the placental circulation or fetal hemodynamic physiology. (II-2) 7. Although many methods of evaluating the level of amniotic fluid in twins (deepest vertical pocket, single pocket, amniotic fluid index) have been described, there is not enough evidence to suggest that one method is more predictive than the others of adverse pregnancy outcome. (II-3) 8. Referral to an appropriate high-risk pregnancy centre is indicated when complications unique to twins are suspected on ultrasound. (II-2) These complications include: 1. Twin-to-twin transfusion syndrome 2. Monoamniotic twins gestation 3. Conjoined twins 4. Twin reversed arterial perfusion sequence 5. Single fetal death in the second or third trimester 6. Growth discordance in monochorionic twins. Recommendations 1. All patients who are suspected to have a twin pregnancy on first trimester physical examination or who are at risk (e.g., pregnancies resulting from assisted reproductive technologies) should have first trimester ultrasound performed. (II-2A) 2. Every attempt should be made to determine and report amnionicity and chorionicity when a twin pregnancy is identified. (II-2A) 3. Although the accuracy in confirmation of gestational age at the first and second trimester is comparable, dating should be done with first trimester ultrasound. (II-2A) 4. Beyond the first trimester, it is suggested that a combination of parameters rather than a single parameter should be used to confirm gestational age. (II-2C) 5. When twin pregnancy is the result of in vitro fertilization, accurate determination of gestational age should be made from the date of embryo transfer. (II-1A) 6. There is insufficient evidence to make a recommendation of which fetus (when discordant for size) to use to date a twin pregnancy. However, to avoid missing a situation of early intrauterine growth restriction in one twin, most experts agree that the clinician may consider dating pregnancy using the larger fetus. (III-C) 7. In twin pregnancies, aneuploidy screening using nuchal transluscency measurements should be offered. (II-2B) 8. Detailed ultrasound examination to screen for fetal anomalies should be offered, preferably between 18 and 22 weeks' gestation, in all twin pregnancies. (II-2B) 9. When ultrasound is used to screen for preterm birth in a twin gestation, endovaginal ultrasound measurement of the cervical length should be performed. (II-2A) 10. Increased fetal surveillance should be considered when there is either growth restriction diagnosed in one twin or significant growth discordance. (II-2A) 11. Umbilical artery Doppler should not be routinely offered in uncomplicated twin pregnancies. (I-E) 12. For defining oligohydramnios and polyhydramnios, the ultrasonographer should use the deepest vertical pocket in either sac: oligohydramnios when2 cm and polyhydramnios when8 cm. (II-2B).

To give health care providers information about the genetic information that can be used as part of health surveillance for women undergoing a pre-conception evaluation for genetic risk assessment and possible genetic screening or testing.This genetic information can be used for patient education and possible prenatal testing.The use of this genetic information may allow improved risk-benefit assessment for pre-conception counselling for individual patients and their families.PubMed or Medline and the Cochrane Database were searched in November 2009, using appropriate key words (pre-conception, genetic disease, maternal, family history, genetic health risk, genetic health surveillance, prenatal screening, prenatal diagnosis, birth defects, and teratogen). Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, and national and international medical specialty societies.The benefits for the patient and her family include understanding of possible genetic risk and enhanced pregnancy outcomes. The harm includes increased anxiety or psychological stress associated with the possibility of identifying genetic risks.The evidence obtained was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS AND SUMMARY STATEMENTS: A review of the current literature does not provide enough information for this committee opinion to present evidence-based recommendations.

Resume Objectif Analyser le risque d'infection in utero attribuable aux interventions effractives prenatales chez les femmes qui presentent des infections par le virus de l'hepatite B, le virus de l'hepatite C et/ou le virus de l'immunodeficience humaine (VIH). Issues Morbidite et mortalite foetales et neonatales. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans Medline, CINAHL et The Cochrane Library au moyen d'un vocabulaire controle (p. ex. « amniocentesis », « chorionic villus sampling », « cordocentesis », « fetal and neonatal infection ») et de mots cles (p. ex. « hepatitis B », « hepatitis C », « HIV ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles publies en anglais ou en francais entre 2002 et 2012 (les etudes publiees entre 1966 et 2002 ont deja fait l'objet d'une analyse dans le cadre de la directive clinique n° 123). Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en fevrier 2014. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau). Recommandations 1.Pour l'evaluation du risque prenatal chez les femmes infectees par le virus de l'hepatite B, le virus de l'hepatite C et/ou le virus de l'immunodeficience humaine, il est recommande d'utiliser des methodes non effractives qui font appel a des tests comptant une sensibilite elevee et un faible taux de faux positif (comme le depistage serique combine [ou non] a la mesure de la clarte nucale, l'echographie anatomique et le depistage prenatal moleculaire non effractif). (III-B) 2.Dans le cas des femmes infectees par le virus de l'hepatite B, le virus de l'hepatite C et/ou le virus de l'immunodeficience humaine qui doivent subir une amniocentese, aucun effort ne devrait etre menage pour faire en sorte d'eviter d'inserer l'aiguille au travers du placenta ou tres pres de ce dernier. (II-2B) 3.Nous ne disposons que de peu de donnees au sujet des autres interventions effractives prenatales diagnostiques et therapeutiques; nous devrions donc proceder a l'analyse des risques et des avantages de telles interventions avant de les utiliser. (III-C) 4.Le taux d'infection neonatale par le virus de l'hepatite B qui est attribuable a l'amniocentese peut atteindre jusqu'a 1,4 % chez les nouveau-nes issus de meres seropositives pour l'antigene de surface de l'hepatite B. Toutefois, le taux d'infection neonatale attribuable a l'amniocentese chez les nouveau-nes issus de meres seropositives pour l'antigene e de l'hepatite B pourrait atteindre pas moins de 16 %. Bien que l'on n'ait constate aucune difference significative sur le plan statistique en matiere de taux d'infection entre les nouveau-nes exposes a l'amniocentese et ceux qui ne l'ont pas ete, au sein de ces deux populations maternelles, le fait de connaitre l'etat serologique de la mere quant a l'antigene e de l'hepatite B pourrait se reveler utile au moment de lui offrir des renseignements au sujet des risques associes a l'amniocentese. (II-2A) 5.Chez les femmes infectees par le virus de l'hepatite C, la tenue d'une amniocentese ne semble pas entrainer une hausse significative du risque de transmission verticale; quoi qu'il en soit, les femmes devraient etre avisees que tres peu d'etudes se sont adequatement penchees sur une telle possibilite. (II-2C) La tenue d'autres recherches a ce sujet est recommandee. (III-L) 6.Chez les femmes infectees par le virus de l'immunodeficience humaine qui font l'objet d'un traitement antiretroviral combine, l'amniocentese ne semble pas entrainer une hausse significative du risque de transmission verticale, particulierement lorsque la charge virale est indetectable; quoi qu'il en soit, les femmes devraient etre avisees que nous ne disposons que de peu de donnees sur le sujet. (II-2B) 7.Chez les femmes qui ne font pas l'objet d'un traitement antiretroviral combine, la tenue d'une amniocentese entraine la hausse du risque de transmission verticale. Dans la mesure du possible, l'administration d'un traitement antiretroviral combine devrait etre entamee et la tenue de l'amniocentese devrait etre differee jusqu'a ce que la charge virale devienne indetectable. Les autres aspects de la prise en charge devraient etre personnalises en consultation avec des specialistes en maladies infectieuses et des obstetriciens. (III-B)

Objective The reproductive and gynecologic outcomes for women after the pregnancy complicated by open maternal-fetal surgery (OMFS) were evaluated. Study Design The retrospective review identified 93 women with OMFS from a single institution (1996–2007). Consent and questionnaires were sent to women. Institutional review board approval was obtained from the Committee for Protection of Human Subjects. Results The total return rate was 57.3%. Total pregnancies reported were 47, with 36 delivering after 20 weeks' gestation. The uterine dehiscence and rupture rates were 14% and 14%, respectively. Fetal anomalies occurred in 4 subsequent pregnancies. Normal conception occurred in 98% of subsequent pregnancies. Gynecologic issues were reported by 8 women, with infertility, abdominal pain, and ovarian and uterine factors. Conclusion The reproductive outcomes of uterine dehiscence (14%) and rupture (14%) in a subsequent pregnancy continue to be a major counseling issue for OMFS. Fertility and gynecologic factors do not appear to be increased for women undergoing OMFS.

To review the techniques and indications of preimplantation genetic testing, including preimplantation genetic diagnosis and screening.Limited to an introductory discussion about the genetic aspects of preimplantation reproductive techniques.This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies.The Cochrane Library and Medline were searched for articles relating to preimplantation testing that were published from 1990 to February 2008, using the following terms: preimplantation genetic diagnosis, preimplantation genetic screening, and in vitro fertilization. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and from national and international medical specialty societies.This update is a consensus of the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. The recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care.This update educates readers about new genetic concepts, directions, and technology. The major harms and costs identified are those of assisted reproductive technologies.The Society of Obstetricians and Gynaecologists of Canada.Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening has been proposed to improve the effectiveness of in vitro fertilization in women of advanced maternal age or in couples with recurrent miscarriage or implantation failure, but the benefits of this approach are debated.The recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. 1. Before preimplantation genetic diagnosis is performed, genetic counselling must be provided to ensure that patients fully understand the risk of having an affected child, the impact of the disease on an affected child, and the benefits and limitations of all available options for preimplantation and prenatal diagnosis. (III-A) 2. Couples should be informed that preimplantation genetic diagnosis can reduce the risk of conceiving a child with a genetic abnormality carried by one or both parents if that abnormality can be identified with tests performed on a single cell. (II-2B) 3. Invasive prenatal testing to confirm the results of preimplantation genetic diagnosis is encouraged because the methods used for preimplantation genetic diagnosis have technical limitations that include the possibility of a false negative result. (II-2B) 4. Before preimplantation genetic screening is performed, thorough education and counselling must be provided to ensure that patients fully understand the limitations of the technique, the risk of error, and the lack of evidence that preimplantation genetic screening improves live-birth rates. (III-A) 5. Available evidence does not support the use of preimplantation genetic screening as currently performed to improve live-birth rates in patients with advanced maternal age, recurrent implantation failure, or recurrent pregnancy loss. (I-D).

To determine the prenatal evolution/natural history and postnatal outcome of fetuses diagnosed with a neural tube defect (NTD) lacking the Arnold-Chiari-II malformation (ACM II).This retrospective study reviewed 16 fetuses evaluated with ultrasound (US) and MRI at a single referral center from 1/2000 to 8/2007. Follow-up studies and available postnatal outcomes were reviewed.Postpartum diagnosis was terminal myelocystoceles 7/16 (44%); myelomeningoceles (MMCs) 3/16 (19%); lipomyelomeningoceles 2/16(13%); and thoracic myelocystocele 1/16 (6%). Three patients (19%) were lost to follow-up or termination of pregnancy. Two prenatally diagnosed 'closed' NTD were postnatally found to be MMCs. Three of the myelocystoceles had additional omphalocele, bladder extrophy, imperforate anus and spinal defect (OEIS complex). For the total cohort, impaired lower extremity function was seen in 38%, impaired bladder function in 64%, and ventriculoperitoneal shunting in 8%. Four fetuses with a myelocystocele developed hindbrain herniation in the third trimester of pregnancy. The preterm delivery rate was 38%. Five of eight (63%) neonates with postnatally diagnosed myelocystoceles had mothers with a body mass index over 30.Prenatal differentiation between closed and open NTD is not always possible. Postnatal outcome of isolated myelocystocele and MMC seems to be more favorable than for an NTD with ACM II (shunt requirement). Incontinence is the major childhood morbidity. Maternal obesity may be a risk factor for closed NTDs.

OBJECTIVES: The objectives are to analyze the outcomes of fetal interventions for fetal limb abnormalities associated with amniotic band syndrome (ABS), to compare the outcome with the known natural history, and to establish selection criteria for fetal intervention. MATERIAL AND METHODS: In a Medline search, six cases of prenatal fetoscopic interventions for ABS were found. An unpublished case was added. RESULTS: Review of the seven cases of treated ABS in utero suggests that abnormal, but present blood flow at Doppler distal to the area constricted by the band may optimally identify cases suitable for fetal surgery. We propose a prenatal classification in stages of cases of ABS based on ultrasound and Doppler findings. Premature rupture of membranes (PROM) occurred in five patients (71%). The median gestational age (GA) at delivery was 34.8 weeks (range 32 to 39). The median time between procedure and PROM was 6 weeks (range 4 days to 14.3 weeks). The median time between procedure and delivery was 11.8 weeks (range 5-17). CONCLUSION: The use of a uniform prenatal classification of cases of ABS may allow a more precise correlation of prenatal findings and postnatal outcome.

To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders).To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada.The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care.The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC).Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder for which prenatal diagnosis is possible. Ideally, screening should be done pre-conceptionally. However, for a significant proportion of patients, the screening will occur during the pregnancy, and the time constraint for obtaining screening results may result in psychological distress. This guideline does not include a cost analysis.1. Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A) 2. Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This investigation should include quantitation of HbA2 and HbF. In addition, if there is microcytosis(mean cellular volume80 fL) and/or hypochromia (mean cellular hemoglobin27 pg) in the presence of a normal hemoglobin electrophoresis or high performance liquid chromatography the patient should be investigated with a brilliant cresyl blue stained blood smear to identify H bodies. A serum ferritin (to exclude iron deficiency anemia) should be performed simultaneously. (III-A) 3. If a woman's initial screening is abnormal (e.g., showing microcytosis or hypochromia with or without an elevated HbA2, or a variant Hb on electrophoresis or high performance liquid chromatography) then screening of the partner should be performed. This would include a complete blood count as well as hemoglobin electrophoresis or HPLC, HbA2 and HbF quantitation,and H body staining. (III-A) 4. If both partners are found to be carriers of thalassemia or an Hb variant, or of a combination of thalassemia and a hemoglobin variant, they should be referred for genetic counselling. Ideally,this should be prior to conception, or as early as possible in the pregnancy. Additional molecular studies may be required to clarify the carrier status of the parents and thus the risk to the fetus. (II-3A) 5. Prenatal diagnosis should be offered to the pregnant woman/couple at risk for having a fetus affected with a clinically significant thalassemia or hemoglobinopathy. Prenatal diagnosis should be performed with the patient's informed consent. If prenatal diagnosis is declined, testing of the child should be done to allow early diagnosis and referral to a pediatric hematology centre, if indicated. (II-3A) 6. Prenatal diagnosis by DNA analysis can be performed using cells obtained by chorionic villus sampling or amniocentesis. Alternatively for those who decline invasive testing and are at risk of hemoglobin Bart's hydrops fetalis (four-gene deletion alpha-thalassemia), serial detailed fetal ultrasound for assessment of the fetal cardiothoracic ratio (normal0.5) should be done in a centre that has experience conducting these assessments for early identification of an affected fetus. If an abnormality is detected, a referral to a tertiary care centre is recommended for further assessment and counselling. Confirmatory studies by DNA analysis of amniocytes should be done if a termination of pregnancy is being considered. (II-3A) 7. The finding of hydrops fetalis on ultrasound in the second or third trimester in women with an ethnic background that has an increased risk of alpha-thalassemia should prompt immediate investigation of the pregnant patient and her partner to determine their carrier status for alpha-thalassemia. (III-A) VALIDATION: This guideline has been prepared by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the Board of Directors of the CCMG and the Executive and Council of the SOGC.

To review the obstetrical outcomes associated with abnormally elevated or decreased level of one or more of the most frequently measured maternal serum marker analytes used in screening for aneuploidy. To provide guidance to facilitate the management of pregnancies that have abnormal levels of one of more markers and to assess the usefulness of these markers as a screening test.Perinatal outcomes associated with abnormal levels of maternal serum markers analytes are compared with the outcomes of pregnancies with normal levels of the same analytes or the general population.The Cochrane Library and Medline were searched for English-language articles published from 1966 to February 2007, relating to maternal serum markers and perinatal outcomes. Search terms included PAPP-A (pregnancy associated plasma protein A), AFP (alphafetoprotein), hCG (human chorionic gonadotropin), estriol, unconjugated estriol, inhibin, inhibin-A, maternal serum screen, triple marker screen, quadruple screen, integrated prenatal screen, first trimester screen, and combined prenatal screen. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key individual studies on which the recommendations are based are referenced. Supporting data for each recommendation are summarized with evaluative comments and references. The evidence was evaluated using the guidelines developed by the Canadian Task Force on Preventive Health Care.The evidence collected was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada.The benefit expected from this guideline is to facilitate early detection of potential adverse pregnancy outcomes when risks are identified at the time of a maternal serum screen. It will help further stratification of risk and provide options for pregnancy management to minimize the impact of pregnancy complications. The potential harms resulting from such practice are associated with the so called false positive (i.e., uncomplicated pregnancies labelled at increased risk for adverse perinatal outcomes), the potential stress associated with such a label, and the investigations performed for surveillance in this situation. No cost-benefit analysis is available to assess costs and savings associated with this guideline. SUMMARY STATEMENTS: 1. An unexplained level of a maternal serum marker analyte is defined as an abnormal level after confirmation of gestational age by ultrasound and exclusion of maternal, fetal, or placental causes for the abnormal level. (III) 2. Abnormally elevated levels of serum markers are associated with adverse pregnancy outcomes in twin pregnancies, after correction for the number of fetuses. Spontaneous or planned mutifetal reductions may result in abnormal elevations of serum markers. (II-2) RECOMMENDATIONS: 1. In the first trimester, an unexplained low PAPP-A (0.4 MoM) and/or a low hCG (0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) In the second trimester, an unexplained elevation of maternal serum AFP (2.5 MoM), hCG (3.0 MoM), and/or inhibin-A (or =2.0 MoM) or a decreased level of maternal serum AFP (0.25 MoM) and/or unconjugated estriol (0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) 2. Pregnant woman with an unexplained elevated PAPP-A or hCG in the first trimester and an unexplained low hCG or inhibin-A and an unexplained elevated unconjugated estriol in the second trimester should receive normal antenatal care, as this pattern of analytes is not associated with adverse perinatal outcomes. (II-2A) 3. The combination of second or third trimester placenta previa and an unexplained elevated maternal serum AFP should increase the index of suspicion for placenta accreta, increta, or percreta. (II-2B) An assessment (ultrasound, MRI) of the placental-uterine interface should be performed. Abnormal invasion should be strongly suspected, and the planning of delivery location and technique should be done accordingly. (III-C) 4. A prenatal consultation with the medical genetics department is recommended for low unconjugated estriol levels (0.3 MoM), as this analyte pattern can be associated with genetic conditions. (II-2B) 5. The clinical management protocol for identification of potential adverse obstetrical outcomes should be guided by one or more abnormal maternal serum marker analyte value rather than the false positive screening results for the trisomy 21 and/or the trisomy 18 screen. (II-2B) 6. Pregnant woman who are undergoing renal dialysis or who have had a renal transplant should be offered maternal serum screening, but interpretation of the result is difficult as the level of serum hCG is not reliable. (II-2A) 7. Abnormal maternal uterine artery Doppler in association with elevated maternal serum AFP, hCG, or inhibin-A or decreased PAPP-A identifies a group of women at greater risk of IUGR and gestational hypertension with proteinuria. Uterine artery Doppler measurements may be used in the evaluation of an unexplained abnormal level of either of these markers. (II-2B) 8. Further research is recommended to identify the best protocol for pregnancy management and surveillance in women identified at increased risk of adverse pregnancy outcomes based on an abnormality of a maternal serum screening analyte. (III-A) 9. In the absence of evidence supporting any specific surveillance protocol, an obstetrician should be consulted in order to establish a fetal surveillance plan specific to the increased obstetrical risks (maternal and fetal) identified. This plan may include enhanced patient education on signs and symptoms of the most common complications, increased frequency of antenatal visits, increased ultrasound (fetal growth, amniotic fluid levels), and fetal surveillance (biophysical profile, arterial and venous Doppler), and cervical length assessment. (III-A) 10. Limited information suggests that, in women with elevated hCG in the second trimester and/or abnormal uterine artery Doppler (at 22-24 weeks), low-dose aspirin (60-81 mg daily) is associated with higher birthweight and lower incidence of gestational hypertension with proteinuria. This therapy may be used in women who are at risk. (II-2B) 11. Further studies are recommended in order to assess the benefits of low-dose aspirin, low molecular weight heparin, or other therapeutic options in pregnancies determined to be at increased risk on the basis of an abnormal maternal serum screening analyte. (III-A) 12. Multiple maternal serum markers screening should not be used at present as a population-based screening method for adverse pregnancy outcomes (such as preeclampsia, placental abruption, and stillbirth) outside an established research protocol, as sensitivity is low, false positive rates are high, and no management protocol has been shown to clearly improve outcomes. (II-2D) When maternal serum screening is performed for the usual clinical indication (fetal aneuploidy and/or neural tube defect), abnormal analyte results can be utilized for the identification of pregnancies at risk and to direct their clinical management. (II-2B) Further studies are recommended to determine the optimal screening method for poor maternal and/or perinatal outcomes. (III-A).

To review the molecular genetic techniques currently available for rapid prenatal diagnosis of fetal aneuploidy, as well as those still under investigation.Limited to introductory discussion of rapid aneuploidy detection methods.Medline was searched for articles related to the topic that were published after 1992. This document represents an abstraction of the information.This update was prepared by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.This update provides information about methods of rapid aneuploidy detection using molecular techniques and the evidence supporting their use in prenatal diagnosis. These methods are reliable and cost-effective for detecting the targeted fetal aneuploidies, but are limited in their ability to detect non-aneuploid chromosome abnormalities, some of which are clinically significant.

Omphalocele is one of the most common abdominal wall defects seen in the prenatal period. Once this diagnosis is confirmed, it is important to check the fetal karyotype and thoroughly assess the fetus for other malformations. Prenatal management involves serial assessment of fetal growth and prenatal testing to ensure fetal well-being. Closure of the abdominal wall and replacement of organs into the abdominal cavity can be done directly if the omphalocele is small or in a staged manner if the omphalocele is large. Successful outcomes for these neonates can be optimized with a multidisciplinary team approach to prenatal and postnatal management.