Wrongful birth and wrongful life lawsuits in obstetrics and gynecology.

Developments in preconception and prenatal technologies have led to undeniable advances in how health-care providers screen and treat patients. Despite these advances, at any point errors can occur leading to misdiagnosis or a missed diagnosis. In some instances, the missed information can lead to the birth of a child with health issues where short of the error, the decision to avoid conception or terminate the pregnancy might have been made. When these lapses unfold, there exists the potential for a wrongful birth or wrongful life lawsuit to ensue. While these 2 actions are based on the same set of events, they are distinct legal claims with varying degrees of judicial permissibility. Global legal acceptability of wrongful birth and life lawsuits tends to resemble patterns in the United States. Analyzing prior wrongful birth and wrongful life claims can reveal common trends in events leading to these types of lawsuits, as well as an understanding of their potential outcomes. A familiarity with wrongful birth and wrongful life lawsuits demonstrates how these cases are unique from other forms of prenatal or birth injury tort lawsuits and can provide insights to common shortcomings in clinical practice. Applying these lessons to clinical practice highlights key approaches towards limiting the risk of certain errors leading to wrongful birth and wrongful life lawsuits, with the goal of health-care providers offering high quality health care.

A Low-Cost, High-Fidelity Simulator for Transabdominal Chorionic Villus Sampling.

INTRODUCTION: Chorionic villus sampling (CVS) remains essential for first-trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use. METHODS: We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily available materials costing less than $10 and can be refrigerated and re-used to train maternal-fetal medicine fellows in CVS. RESULTS: All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for 3 months and dozens of simulated procedures each without any apparent qualitative degradation in performance. DISCUSSION/CONCLUSION: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS.

Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

Pregnancy outcome of confined placental mosaicism: meta-analysis of cohort studies.

OBJECTIVE: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls. DATA SOURCES: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved. STUDY ELIGIBILITY CRITERIA: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture. METHODS: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I2 statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319). RESULTS: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I2=72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I2=0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I2= 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed. CONCLUSION: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Majority of transferred mosaic embryos developed healthy live births revealed by a preclinical study using embryonic morphology assessment and noninvasive PGT-A on cell-free DNA in blastocoel fluid.

PURPOSE: This preclinical study aimed to evaluate whether using transferred mosaic embryos (primarily selected by embryonic morphology assessment (EMA) and compared by the noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) on cell-free DNA in blastocoel fluid (BF)) increases the rates of clinical pregnancies (CPs) and healthy live births (HLBs) and to investigate whether niPGT-A could provide valuable genetic information for the EMA-selected transferred mosaic embryos. METHODS: This study collected 215 blastocyst culture samples and 182 BF samples. Cell-free DNA from the BF was amplified and examined by next-generation sequencing-based niPGT-A. All 182 patients underwent EMA. However, only 147 underwent in vitro fertilization and embryo transfer, and only 113 clinical outcomes were followed up. Comprehensive chromosome screening for the chorionic villus sampling of spontaneous miscarriages and noninvasive prenatal testing for ongoing pregnancies were also performed. RESULTS: The implantation rate was 77.55% in 147 transferred high-quality embryos selected by EMA. Among 113 CPs, 16 led to spontaneous miscarriage (14.16%), and 97 resulted in HLBs (85.84%). According to the niPGT-A results for 113 patients with clinical outcomes, 80.4% had CP (euploid, 20.54%; single aneuploid, 1.79%; mosaic chromosome aneuploid and/or segmental aneuploid, 58.04%). Of all the mosaic aneuploids, 90.76% were false positive, transforming to euploid. CONCLUSIONS: Transferred EMA-selected embryos showed higher implantation rates. The niPGT-A of BF provided valuable genetic status ("-ploid") information, which helped reduce aneuploid-induced implantation failure and miscarriage, thereby increasing the CP and HLB rates. Additionally, majority of the transferred embryos with complex/chaotic mosaic aneuploid would likely develop HLBs.

Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing.

Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22−13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.

First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

OBJECTIVE: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy. METHODS: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis. RESULTS: CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%). CONCLUSIONS: Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Mosaicism for copy number variations in the placenta is even more difficult to interpret than mosaicism for whole chromosome aneuploidy.

OBJECTIVE: To compare mosaicisms in prenatal chorionic villus samples (CVSs) with corresponding postpartum placental samples. METHOD: We collected placentas from 15 consecutive cases of mosaicism detected in CVSs and obtained five standardized samples on each placenta after delivery. All pre- and postnatal placental samples were uncultured and analyzed by high-resolution chromosomal microarray. RESULTS: Ten cases of mosaicism for whole chromosome aneuploidy (mWC) and five cases with mosaicism for (sub)chromosomal copy number variations (mCNVs) were included. In 5/10 mWC cases and in 4/5 mCNV cases the prenatally detected aberration was confirmed in the postpartum placenta. Three postpartum placentas revealed various complex aberrations differing from the prenatal results: (1) mosaicisms for different deletions/duplications on 9p and 9q in all samples (prenatal: mosaic 5.3 Mb duplication on 9p24), (2) different regions with deletions/duplications/loss of heterozygosity on 1p in all samples (prenatal: mosaic 2.3 Mb 1p36 duplication), and (3) mosaicism for a duplication on 5q and a deletion on 6p in one out of five samples (prenatal: mosaic trisomy 7). CONCLUSION: CNVs constitute a complex subgroup in placental mosaicism. Counseling of these couples after chorionic villus sampling should not focus on the specific CNV involved, but on the nature of mosaicism and the option of amniocentesis and ultrasound.

Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive Diagnostic Testing for Fetal Chromosomal Abnormalities.

The Korean Society of Maternal Fetal Medicine proposed the first Korean guideline on prenatal aneuploidy screening and diagnostic testing, in April 2019. The clinical practice guideline (CPG) was developed for Korean women using an adaptation process based on good-quality practice guidelines, previously developed in other countries, on prenatal screening and invasive diagnostic testing for fetal chromosome abnormalities. We reviewed current guidelines and developed a Korean CPG on invasive diagnostic testing for fetal chromosome abnormalities according to the adaptation process. Recommendations for selected 11 key questions are: 1) Considering the increased risk of fetal loss in invasive prenatal diagnostic testing for fetal genetic disorders, it is not recommended for all pregnant women aged over 35 years. 2) Because early amniocentesis performed before 14 weeks of pregnancy increases the risk of fetal loss and malformation, chorionic villus sampling (CVS) is recommended for pregnant women who will undergo invasive prenatal diagnostic testing for fetal genetic disorders in the first trimester of pregnancy. However, CVS before 9 weeks of pregnancy also increases the risk of fetal loss and deformity. Thus, CVS is recommended after 9 weeks of pregnancy. 3) Amniocentesis is recommended to distinguish true fetal mosaicism from confined placental mosaicism. 4) Anti-immunoglobulin should be administered within 72 hours after the invasive diagnostic testing. 5) Since there is a high risk of vertical transmission, an invasive prenatal diagnostic testing is recommended according to the clinician's discretion with consideration of the condition of the pregnant woman. 6) The use of antibiotics is not recommended before or after an invasive diagnostic testing. 7) The chromosomal microarray test as an alternative to the conventional cytogenetic test is not recommended for all pregnant women who will undergo an invasive diagnostic testing. 8) Amniocentesis before 14 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 9) CVS before 9 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 10) Although the risk of fetal loss associated with invasive prenatal diagnostic testing (amniocentesis and CVS) may vary based on the proficiency of the operator, the risk of fetal loss due to invasive prenatal diagnostic testing is higher in twin pregnancies than in singleton pregnancies. 11) When a monochorionic twin is identified in early pregnancy and the growth and structure of both fetuses are consistent, an invasive prenatal diagnostic testing can be performed on one fetus alone. However, an invasive prenatal diagnostic testing is recommended for each fetus in cases of pregnancy conceived via in vitro fertilization, or in cases in which the growth of both fetuses differs, or in those in which at least one fetus has a structural abnormality. The guidelines were established and approved by the Korean Academy of Medical Sciences. This guideline is revised and presented every 5 years.

Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey.

INTRODUCTION: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. METHODS: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. RESULTS: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. CONCLUSION: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Evaluation of the High Resolution Melting Approach for Detection of ß-Thalassemia Gene Mutations.

ß-Thalassemia (ß-thal), an autosomal recessive hemoglobinopathy, is one of the most common genetic disorders in Pakistan. Awareness of this disease, genetic counseling, extended family carrier screening and prenatal diagnosis (PND) are helpful in prevention and control. Currently, direct DNA sequencing and multiple amplification refractory mutation system-polymerase chain reaction (MARMS-PCR) are the methods used to detect ß-thal mutations, the latter being the most widely used. This study aimed to evaluate PCR-high resolution melting (PCR-HRM) analysis for the detection of most common ß-thal mutations that are found in Pakistan. This study was designed to identify the ß-thal mutations using PCR-HRM analysis in a total of 90 samples [blood and chorionic villus sampling (CVS)]. These samples were first screened for routine mutations by MARMS-PCR and then evaluated by PCR-HRM analysis. The results of PCR-HRM analyses were further confirmed by direct DNA sequencing and all analyses interpreted the same results in all 90 samples. Eleven cases (36.6%) were detected to carry IVS-I-5 (G>C) (HBB: c0.92 + 5G>C), six cases (20.0%) with frameshift codons (FSC) 41/42 (-TTCT) (HBB: c.126_129delCTTT), five cases (16.0%) were diagnosed with codon 15 (G>A) (HBB: c.47G>A), three cases (10.0%) were found with codon 30 (G>C) (HBB: c.93G>C), one case was diagnosed with FSC 16 (-C) (HBB: c.51delC), one with IVS-I-1 (G>T) (HBB: c0.92 + 1G>T) and one with codon 5 (-CT) (HBB: c.17_18delCT). The PCR-HRM analysis represents a less tedious and more useful method for the detection of ß-globin gene mutations.

Fetal Genetic Diagnosis by Chorionic Villus Sampling: Evaluation of the Five-Year Experience from a Single Center.

OBJECTIVE: We summarized our five-year chorionic villus sampling (CVS) experience with indications, detected chromosomal abnormalities and pregnancy outcomes. Materials and Methods: This retrospective study examined 552 patients underwent CVS for prenatal diagnosis between 2014 and 2018. Results: The most frequent patients undergoing CVS indications were abnormal aneuploidy screening results, increased nuchal translucency, and cystic hygroma/edema. Of 552 CVS, 385 were normal, 141 abnormal. Eight were contaminated with maternal cells, 4 were mosaics, in 12 the culture failed, and in 2 there was inadequate sampling. The most frequent chromosomal abnormalities were trisomy 21, trisomy 18 and 45,X. Of 246 followed pregnancies, there were 165 live-births (67,1%), 58 pregnancy terminations (23,6%), and 23 pregnancy losses (9,3%). There were 5 procedure-related losses (2%), 3 of which were chromosomally normal. Conclusion: Although significant advances have been made in noninvasive methods such as NIPT, CVS is still a reliable technique for cytogenetic diagnosis in early gestation.

Chorionic villus sampling experience of a reference perinatal medicine center.

AIM: To share the chorionic villus sampling (CVS) experience of a single surgeon in our institution. METHODS: This retrospective study consists of CVS cases performed between 2000 and 2018. A total of 66 types of indications were classified under two main categories, the screening group (SG) and the inherited disease group (IDG). The SG and IDG were compared in terms of clinical characteristics of the patients, Beksaç obstetrics index (BOI), timing of CVS in terms of gestational week, and complications and termination of pregnancy (TOP) rate. RESULTS: CVS was performed at 656 women, 69 and 587 of whom were included in the SG and IDG, respectively. CVS indications of the SG were determined as advanced maternal age, high risk in combined test, fetal anomaly suspicion in ultrasonography, and increased nuchal translucency in 23, 23, 14 and 9 cases, respectively. On the other hand, CVS indications of the IDG were hereditary disorders related to hematological, muscular, and metabolic systems for 233, 179, and 116 cases, respectively. Furthermore, 32 patients had a single-gene disorder and 14 had a neurodegenerative disease. According to the results of CVS, 359 fetuses were found to be normal (54.73%), while 205 (31.25%) and 92 (14.02%) fetuses were found to be disorder-positive or carriers, respectively. Two hundred pregnant women accepted TOP. Eight (1.2%) pregnancies ended with abortion after CVS. Statistically significant differences were observed in BOI and TOP rate between SG and IDG (p: 0.042 and 0.013). CONCLUSION: Hereditary disorders were the most common CVS indications and the acceptance of TOP was significantly higher in this group.

Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center.

STUDY QUESTION: Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father's semen parameters? SUMMARY ANSWER: The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers' sperm parameters. WHAT IS KNOWN ALREADY: Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. STUDY DESIGN, SIZE, DURATION: We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. MAIN RESULTS AND THE ROLE OF CHANCE: An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7-4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3-4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96-1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm.Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6-1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm.The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04-1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration <15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14-3.78), sperm concentration <5 million/ml (AOR 1.9; 95% CI 1.05-3.45) and total sperm count <10 million (AOR 1.97; 95% CI 1.04-3.74). LIMITATIONS, REASONS FOR CAUTION: We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing.The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: N/A.

Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls. RESULTS: Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS. CONCLUSION: The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Riesgo de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas en un embarazo de gemelos: revisión sistemática y metaanálisis OBJETIVO: Evaluar la tasa de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas (BVC) en un embarazo de gemelos. MÉTODOS: Se hizo una búsqueda en las bases de datos MEDLINE, EMBASE y Cochrane de estudios que habían reportado complicaciones relacionadas con el procedimiento después de una amniocentesis o una BVC en un embarazo de gemelos. El resultado primario fue la tasa de pérdida del feto relacionada con el procedimiento. Los resultados secundarios fueron la pérdida del feto producida antes de las 24 semanas de gestación y la pérdida del feto producida dentro de las 4 semanas posteriores al procedimiento. Se utilizaron metaanálisis cara a cara para comparar cada resultado directamente, entre las mujeres que se sometieron a una amniocentesis y las que no se sometieron a ella, y entre las mujeres que se sometieron a una BVC y las que no se sometieron a ella, así como para calcular las diferencias de riesgo (DR) combinadas entre las mujeres expuestas y las no expuestas a cada procedimiento agresivo. Además, se utilizaron los metaanálisis de proporciones para estimar las tasas combinadas de cada uno de los tres resultados en las mujeres que se sometieron a amniocentesis o a BVC y en los controles. RESULTADOS: Se incluyeron 16 estudios (3.419 embarazos de gemelos sometidos a un procedimiento agresivo y 2.517 no sometidos). Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos sometidos y no sometidos a amniocentesis mostraron un mayor riesgo de pérdida general del feto en total en los sometidos a amniocentesis (Razón de Momios (RM), 1,46 (P=0,04); DR, 0,013 (P=0,04)), mientras que no hubo diferencias en el riesgo de pérdida del feto antes de las 24 semanas de gestación (RM, 1,59 (P=0,06); DR, 0,010 (P=0,11)) ni en el de las 4 semanas posteriores al procedimiento (RM, 1,38 (P=0,3); DR, 0,003 (P=0,8)). En general, la tasa conjunta de pérdida del feto fue del 2,4% (IC 95%, 1,4-3,6%) en los embarazos de gemelos sometidos a amniocentesis, en comparación con el 2,4% (IC 95%, 0,9-4,6%) en los que no se sometieron a amniocentesis. Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos que se sometieron y que no se sometieron a una BVC no mostraron diferencias significativas ni en la pérdida del feto en total (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)) ni en la pérdida del feto antes de las 24 semanas de gestación (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)). En general, la tasa combinada de pérdida del feto fue del 2,0% (IC 95%, 0,0-6,5%) de los embarazos de gemelos sometidos a BVC, comparada con el 1,8% (IC 95%, 0,3-4,2%) de los que no se sometieron a BVC. CONCLUSIÓN: El riesgo de pérdida del feto tras la amniocentesis y la BVC en gemelos es menor que lo reportado en el pasado y la tasa de pérdida del feto antes de las 24 semanas de gestación, o dentro de las 4 semanas posteriores al procedimiento, no difiere de la del riesgo de contexto en los embarazos de gemelos que no se someten a pruebas prenatales agresivas. Estos datos pueden servir de guía para el asesoramiento prenatal de los embarazos de gemelos que se someten a procedimientos agresivos.

New approach for estimating risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). CONCLUSIONS: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Nuevo enfoque para estimar el riesgo de aborto después de una biopsia de vellosidades coriónicas OBJETIVO: Estimar el riesgo de aborto asociado con la biopsia de vellosidades coriónicas (BVC). MÉTODOS: Se trata de un estudio retrospectivo de cohorte de mujeres que acudieron a un examen ecográfico de rutina entre las 11+0 y las 13+6 semanas de gestación a una de entre un total de ocho centros de medicina fetal en España, Bélgica y Bulgaria, entre julio de 2007 y junio de 2018. En el estudio se incluyeron dos poblaciones: 1) todos los embarazos con feto único sometidos a evaluación del primer trimestre en el Hospital Clínico Universitario Virgen de la Arrixaca de Murcia (España), a las que no se les hizo una BVC (grupo no BVC); y 2) todos los embarazos con feto único sometidos a BVC tras la evaluación del primer trimestre en uno de los ocho centros participantes (grupo BVC). Se excluyeron los embarazos diagnosticados con anomalías genéticas o defectos fetales importantes antes o después del nacimiento, los que resultaron en una interrupción y los que más tarde se sometieron a amniocentesis durante el embarazo. Para estimar la relación entre la BVC y el aborto espontáneo se utilizó el pareamiento por puntaje de propensión (PPP). Se comparó el riesgo de aborto de los grupos BVC y no BVC después del pareamiento PPP (razón 1:1). Este procedimiento creó dos grupos comparables en los que las características de la madre y el embarazo que se asocian con la BVC estaban equilibradas, de manera similar a cómo funciona la aleatorización en un ensayo clínico aleatorizado. RESULTADOS: La población de estudio consistió en 22.250 embarazos en el grupo no BVC y 3.613 en el grupo BVC. La incidencia de abortos en el grupo BVC (2,1%; 77/3.613) fue significativamente mayor que en el grupo no BVC (0,9% (207/22.250); P<0,0001). El algoritmo del PPP emparejó 2.122 BVC con 2.122 casos no BVC, de los cuales 40 (1,9%) y 55 (2,6%) embarazos en los grupos BVC y no BVC, respectivamente, resultaron en un aborto espontáneo (razón de momios (RM), 0,72 (IC 95%, 0,48-1,10); P=0,146). Se encontró una interacción significativa entre el riesgo de aborto espontáneo después de una BVC y el riesgo de aneuploidía, lo que sugiere que el efecto de la BVC en el riesgo de aborto espontáneo difiere según las características del contexto. Concretamente, cuando el riesgo de aneuploidía es bajo, el riesgo de aborto después de una BVC aumenta (RM, 2,87 (IC 95%, 1,13-7,30)) y cuando el riesgo de aneuploidía es alto, paradójicamente el riesgo de aborto después de una BVC se reduce (RM, 0,47 (IC 95%, 0,28-0,76)), presumiblemente debido al diagnóstico prenatal y a la interrupción de embarazos con aneuploidías importantes que, de otro modo, hubieran provocado un aborto espontáneo. Por ejemplo, en una paciente para quien el riesgo de aneuploidía es de 1 entre 1000 (0,1%), el riesgo de aborto después de la BVC aumenta al 0,3% (0,2 puntos porcentuales más alto). CONCLUSIONES: El riesgo de aborto espontáneo en las mujeres que se someten a una BVC es aproximadamente un 1% mayor que el de las mujeres a las que no se les hace, aunque este exceso de riesgo no se atribuye únicamente al procedimiento agresivo sino, en cierta medida, a las características demográficas y del embarazo de cada paciente. Después de tener en cuenta estos factores de riesgo y limitar el análisis a los embarazos de bajo riesgo, la BVC parece triplicar aproximadamente el riesgo de aborto en comparación con el riesgo de fondo de la paciente. Aunque se trata de un aumento sustancial en términos relativos, en los embarazos sin factores de riesgo de aborto, después de una BVC el riesgo de aborto sigue siendo bajo y similar, o ligeramente superior, al de la población en general. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Guideline No. 409: Intrauterine Fetal Diagnostic Testing in Women with Chronic Viral Infections.

OBJECTIVE: This revised guideline provides updated information for the care of women with chronic viral infections who require intrauterine fetal diagnostic testing. TARGET POPULATION: Women with chronic viral infections who are pregnant or planning a pregnancy. OPTIONS: Non-invasive screening tests for diagnosis: maternal serum placental analytes with or without nuchal translucency, sonography, maternal serum cell-free placental DNA; and intrauterine fetal diagnostic testing: amniocentesis, chorionic villus sampling, cordocentesis. OUTCOMES: The recommendations in this guideline have the potential to decrease or eliminate morbidity and mortality in women with chronic viral infections and their infants, which is associated with significant health and economic outcomes. EVIDENCE: Published literature was retrieved through searches of PubMed, guidelines of national societies (Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, other international societies), and the Cochrane Library using appropriate controlled vocabulary (amniocentesis, chorionic villus sampling, cordocentesis, procedure pregnancy loss risk, viral vertical transmission, fetal and neonatal infection) and keywords (maternal infection or exposure, hepatitis B, hepatitis C, human immunodeficiency virus). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials (if available), and observational case-control studies or case series from 2012 to 2019 published in English or French. Studies from 1966 to 2002 were previously reviewed in the SOGC guideline No. 123: Amniocentesis and Women with Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus, and those from 2002 to 2012 were previously reviewed in the SOGC guideline No. 309: Prenatal Invasive Procedures in Women With Hepatitis B, Hepatitis C, and/or Human Immunodeficiency Virus Infections. Updated literature searches were completed regularly through August 2019 and were incorporated into this guideline. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: The intended users are maternity care providers and women with chronic viral infections. This guideline provides information to educate and counsel these women, and to offer them reproductive options. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis.

OBJECTIVES: To estimate the procedure-related risks of miscarriage following chorionic villus sampling (CVS) and amniocentesis in a large unselected screened population, and to determine whether these risks are consistent with those reported in systematic reviews and meta-analyses. METHODS: This was a retrospective cohort study carried out on data obtained from a large fetal medicine unit in the UK between January 2009 and May 2018. We included all women with singleton pregnancy who booked for pregnancy care at our unit before 20 weeks' gestation, after excluding those with multiple pregnancy, major fetal defect, pregnancy termination and loss to follow-up. We estimated the risk of miscarriage in women who underwent a CVS or amniocentesis as well as in those who did not have an invasive procedure. The procedure-related risk of miscarriage was estimated as risk difference (95% CI) between the two groups. Univariate and multivariate regression analyses were used to derive odds ratios (95% CI) and determine which maternal and pregnancy characteristics provided a significant contribution in the prediction of miscarriage and whether CVS or amniocentesis provided a significant independent contribution. RESULTS: During the study period, 45 120 singleton pregnancies were booked for pregnancy care at our hospital, of which 1546 had an invasive procedure. We excluded 1429 (3.2%) pregnancies due to fetal defects, termination of pregnancy or missing outcomes. Of the 43 691 pregnancies included in the study population, 861 underwent CVS and 375 amniocentesis. In pregnancies that underwent CVS, the risk of miscarriage was 1.5% (13/861), compared with 1.2% (476/39 152) in pregnancies that had first-trimester combined screening and did not have an invasive procedure (P = 0.437). In pregnancies that underwent an amniocentesis, the risk of miscarriage was 0.8% (3/375), compared with 1.2% (491/42 463) in those that did not undergo an invasive procedure (P = 0.520). Univariate and multivariate regression analysis demonstrated that there was no significant contribution in the prediction of the risk of miscarriage from CVS (P = 0.399 and P = 0.592, respectively) or amniocentesis (P = 0.543 and P = 0.550, respectively). The risk of procedure-related loss attributed to CVS was 0.29% (95% CI, -0.53 to 1.12%) and that following amniocentesis was -0.36% (95% CI, -1.26 to 0.55%), which was not significantly different from the risk in women who did not have any procedure. CONCLUSIONS: The procedure-related risks of miscarriage following CVS and amniocentesis in our study are considerably lower than those currently quoted and are consistent with the estimates of such risks reported by systematic reviews and meta-analyses. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis.

OBJECTIVE: To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis. METHODS: A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I2 statistic. Egger's bias was estimated to assess reporting bias in published studies. RESULTS: The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I2 = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I2 = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I2 = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I2 = 0%). CONCLUSIONS: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Riesgo de aborto después de una amniocentesis o una biopsia de vellosidades coriónicas: revisión sistemática de bibliografía y metaanálisis actualizado OBJETIVO: Estimar el riesgo de aborto relacionado con el procedimiento de la amniocentesis o la biopsia de vellosidades coriónicas (BVC) mediante una revisión sistemática de bibliografía y un metaanálisis actualizado. MÉTODOS: Se realizó una búsqueda en MEDLINE, EMBASE y The Cochrane Library para identificar estudios que reportaron sobre complicaciones después de una BVC o amniocentesis. Se consideraron elegibles para su inclusión los estudios controlados de gran tamaño que reportaron datos sobre la pérdida del embarazo antes de las 24 semanas de gestación. Se estableció contacto con los autores de los estudios cuando fue necesario para identificar datos adicionales necesarios. Se introdujeron en tablas de contingencia los datos de los casos que se sometieron a un procedimiento invasivo y controles y se estimó el riesgo de aborto para cada estudio. Las estadísticas resumen basadas en un modelo de efectos aleatorios se calcularon después de tener en cuenta la ponderación para cada estudio incluido en la revisión sistemática. El riesgo de aborto relacionado con cada procedimiento se estimó como una diferencia de riesgo ponderada de las estadísticas resumen para los casos y controles. Los análisis de subgrupos se realizaron de acuerdo con la similitud en los niveles de riesgo de anomalías cromosómicas entre los grupos de prueba invasiva y de control. La heterogeneidad se evaluó mediante el test estadístico I2 . Se estimó el sesgo de Egger para evaluar el sesgo de información reportada en los estudios publicados. RESULTADOS: La búsqueda electrónica arrojó 2943 citas potenciales, de las cuales se seleccionaron para su inclusión en la revisión sistemática 12 estudios controlados para la amniocentesis y siete para la BVC. Después de los 63723 procedimientos de amniocentesis sucedieron un total de 580 abortos, lo que resultó en un riesgo ponderado de pérdida de embarazo del 0,91% (IC 95%, 0,73-1,09%). En el grupo de control hubo 1726 abortos en 330469 embarazos, con una tasa de pérdida del 0,58% (IC 95%, 0,47-0,70%). El riesgo ponderado de aborto relacionado con el procedimiento de amniocentesis fue del 0,30% (IC 95%, 0,11-0,49%; I2  = 70,1%). Después de 13011 procedimientos de BVC se produjeron un total de 163 abortos, lo que resultó en un riesgo de pérdida de embarazo del 1,39% (IC 95%, 0,76-2,02%). En el grupo de control hubo 1946 abortos en 232680 embarazos, lo que supuso una tasa de pérdida del 1,23% (IC 95%, 0,86-1,59%). El riesgo ponderado de aborto relacionado con el procedimiento de BVC fue de 0,20% (IC 95%, -0,13-0,52%; I2  = 52,7%). Sin embargo, cuando se consideraron los estudios que incluyeron sólo mujeres con perfiles de riesgo similares para la anomalía cromosómica en los grupos de intervención y control, el riesgo relacionado con el procedimiento de la amniocentesis fue de 0,12% (IC 95%, -0,05-0,30%; I2  = 44.1%) y para el MVC fue de -0,11% (IC 95%, -0,29-0,08%; I2  = 0%). CONCLUSIONES: Los riesgos de aborto relacionados con el procedimiento de la amniocentesis y la BVC son menores que los actualmente mencionados a las mujeres. El riesgo parece ser insignificante cuando estas intervenciones se compararon con grupos de control del mismo perfil de riesgo.