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Viruses Oct 2023Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options.
METHODS
Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review.
RESULTS
A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = -0.479, 95% CI = -0.977 to 0.019, = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV).
CONCLUSIONS
The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options.
Topics: Pregnancy; Infant; Female; Humans; Pregnancy Complications, Infectious; Cytomegalovirus Infections; Amniocentesis; Infectious Disease Transmission, Vertical
PubMed: 38005820
DOI: 10.3390/v15112142 -
Ultrasound in Obstetrics & Gynecology :... Feb 2023Cytomegalovirus (CMV) DNA is detectable in the amniotic fluid collected by amniocentesis in cases in which the fetus has been infected. However, cases of congenital... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Cytomegalovirus (CMV) DNA is detectable in the amniotic fluid collected by amniocentesis in cases in which the fetus has been infected. However, cases of congenital neonatal CMV infection with a negative amniocentesis result have also been reported in the literature. The aim of the present study was to compare pregnancies with a negative amniocentesis result to those with a positive amniocentesis result in terms of incidence of fetal insult and long-term sequelae.
METHODS
Observational studies that included pregnant women with CMV infection who underwent amniocentesis and that reported their results together with neonatal and/or long-term outcomes of the offspring were included. The risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. The rate of severe symptoms at birth, defined as neurological symptoms or multiorgan involvement at birth, and the rate of severe sensorineural hearing loss (SNHL) and/or neurodevelopmental impairment at follow-up were the main outcomes of the study. The secondary outcome was the rate of pregnancy termination due to the presence of CMV-associated central nervous system (CNS) findings or multiorgan involvement on ultrasound/magnetic resonance imaging (MRI).
RESULTS
Seven studies were included in the systematic review and meta-analysis. The pooled false-negative rate of amniocentesis was 8.0% (95% CI, 5.0-13.0%). The pooled rate of severe symptoms at birth was 0.0% (95% CI, 0.0-1.0%; I = 0%) in fetuses with a negative amniocentesis result and 22.0% (95% CI, 11.0-38.0%; I = 75%) in those with a positive amniocentesis result. The pooled odds ratio (OR) was 0.03 (95% CI, 0.01-0.10; I = 0%). The pooled rate of severe SNHL and/or neurodevelopmental impairment at follow-up in fetuses with a negative amniocentesis result was 0.0% (95% CI, 0.0-1.0%; I = 0%) and, in those with a positive amniocentesis result, it was 14.0% (95% CI, 7.0-26.0%; I = 64%). The pooled OR was 0.04 (95% CI, 0.01-0.14; I = 0%). The pooled rate of pregnancy termination due to the presence of CMV-associated CNS findings or multiorgan involvement on ultrasound/MRI was 0.0% (95% CI, 0.0-2.0%; I = 0%) in fetuses with a negative amniocentesis result and 20.0% (95% CI, 10.0-36.0%; I = 82%) in those with a positive amniocentesis result. The pooled OR was 0.03 (95% CI, 0.01-0.08; I = 0%). A subgroup analysis including only pregnancies with primary CMV infection and a sensitivity analysis including only prospective studies were carried out, showing very similar results to those of the main analysis.
CONCLUSION
A negative amniocentesis result in pregnant women with CMV infection ensures lack of fetal insult and long-term sequelae to the child, even if transmission has occurred. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Child; Pregnancy; Infant; Female; Humans; Amniocentesis; Pregnancy Complications, Infectious; Prospective Studies; Cytomegalovirus; Cytomegalovirus Infections; Infectious Disease Transmission, Vertical; Observational Studies as Topic
PubMed: 36412976
DOI: 10.1002/uog.26128 -
Diagnostics (Basel, Switzerland) Nov 2021The primary methods for prenatal diagnosis of Clubfoot are ultrasound (US) and magnetic resonance imaging (MRI). An ultrasound is performed between the 1st trimester and... (Review)
Review
The primary methods for prenatal diagnosis of Clubfoot are ultrasound (US) and magnetic resonance imaging (MRI). An ultrasound is performed between the 1st trimester and the 28th week of pregnancy and it is reported to be used as a diagnostic method alone or in combination with MRI. So far, an international consensus on the most effective screening method has not been reached. This systematic review and meta-analysis were performed to establish the most effective and reliable exam for prenatal diagnosis of Clubfoot. The literature search was conducted using a PIOS-approach from May 2021 to June 2021. Studies reporting cases of prenatal diagnosis of Clubfoot made through US and MRI conducted from January 2010 to June 2021 were included in the study and reviewed by 2 authors. The 23 selected studies included 2318 patients. A total of 11 of the studies included details on the accuracy, while the rest were used to obtain information about the primary methodology utilized. In all the selected studies, US was used as the primary diagnostic instrument. Thirteen of the studies used the US exclusively, while three used MRI in addition to US and seven performed karyotyping after US diagnosis. The US has been shown to be the instrument of choice for the prenatal diagnosis of Clubfoot. International guidelines for an ultrasonography classification of congenital clubfoot are required to reduce the inter-variability accuracy of this procedure.
PubMed: 34943470
DOI: 10.3390/diagnostics11122235 -
PloS One 2021Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in...
Current practices of management of maternal and congenital Cytomegalovirus infection during pregnancy after a maternal primary infection occurring in first trimester of pregnancy: Systematic review.
INTRODUCTION
Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in many countries.
OBJECTIVES
This systematic review aims to provide the state of the art on current practices concerning management of maternal and congenital CMV infection during pregnancy, after maternal primary infection (PI) in first trimester of pregnancy.
DATA SOURCES
Electronically searches on databases and hand searches in grey literature.
STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS
Primary outcome was listing biological, imaging, and therapeutic management interventions in two distinct populations: population 1 are pregnant women with PI, before or without amniocentesis; population 2 are pregnant women with congenitally infected fetuses (after positive amniocentesis). Secondary outcome was pregnancy outcome in population 2.
RESULTS
Out of 4,134 studies identified, a total of 31 studies were analyzed, with 3,325 pregnant women in population 1 and 1,021 pregnant women in population 2, from 7 countries (Belgium, France, Germany, Israel, Italy, Spain and USA). In population 1, ultrasound (US) examination frequency was 0.75/month, amniocentesis in 82% cases, maternal viremia in 14% and preventive treatment with hyperimmune globulins (HIG) or valaciclovir in respectively 14% and 4% women. In population 2, US examination frequency was 1.5/month, magnetic resonance imaging (MRI) in 44% cases at 32 weeks gestation (WG), fetal blood sampling (FBS) in 24% at 28 WG, and curative treatment with HIG or valaciclovir in respectively 9% and 8% patients.
CONCLUSIONS
This systematic review illustrates management of maternal and congenital CMV during pregnancy in published and non-published literature, in absence of international consensus.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019124342.
Topics: Amniocentesis; Cytomegalovirus; Cytomegalovirus Infections; Disease Management; Female; Fetal Diseases; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prenatal Diagnosis
PubMed: 34860861
DOI: 10.1371/journal.pone.0261011 -
PloS One 2020Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of...
BACKGROUND
Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework.
METHODS
We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework.
RESULTS
Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events.
CONCLUSION
Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.
Topics: Female; GRADE Approach; Humans; Immunologic Factors; Postnatal Care; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rh-Hr Blood-Group System
PubMed: 32913362
DOI: 10.1371/journal.pone.0238844 -
Experimental and Therapeutic Medicine Sep 2020Fetal goitrous hypothyroidism is a rare condition associated with important obstetrical, neonatal complications, and neurodevelopmental impairments. Prenatal treatment...
Fetal goitrous hypothyroidism is a rare condition associated with important obstetrical, neonatal complications, and neurodevelopmental impairments. Prenatal treatment remains controversial, and the risk to benefit ratio must be accurately assessed and considered for individualized management. The objective of this review was to evaluate the feasibility, safety, and effectiveness of the conservative treatment of fetal goitrous hypothyroidism. In total, 25 reports that met our inclusion criteria were selected and the management of 38 cases was analyzed. Prenatal diagnosis consisted mainly of ultrasonographic findings. Fetal thyroid status was assessed by cordocentesis. Prenatal treatment varied widely in terms of levothyroxine (LT4) route of administration, dosage, number of injections, and frequency. Although different regimens and routes of administration were proposed, they seem to have similar results regarding fetal goiter reduction and thyroid status at birth. At birth, most babies had hypothyroidism, but the long-term follow-up indicated a normal psycho-neuromotor development. Our data confirm the feasibility of conservative treatment with LT4 for fetal goitrous hypothyroidism. Further studies are needed to determine the optimal management of this disorder.
PubMed: 32765729
DOI: 10.3892/etm.2020.8794 -
Acta Obstetricia Et Gynecologica... Nov 2020Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of... (Comparative Study)
Comparative Study Meta-Analysis
INTRODUCTION
Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of emergency cerclage vs expectant management on maternal and perinatal outcomes, and to assess the current status of evidence.
MATERIAL AND METHODS
A search was conducted from 1 June 2019 until 1 September 2019 and eligible studies were identified in the MEDLINE, Scopus, Cochrane and US clinical trials registry without limitations concerning the publication dates and languages. Randomized controlled trials (RCTs), non-RCTs and observational studies comparing emergency cerclage with no cerclage/expectant management, in women presenting with painless cervical dilatation were included.
RESULTS
The electronic search yielded 3607 potential studies, of which 38 were fully reviewed and 12 observational studies (1021 participants) were included. Cerclage was superior to expectant management for the primary outcomes of preterm birth before 28 and 32 gestational weeks, OR 0.25 (95% CI 0.16-0.39, five studies, N = 392, I = 41%, low quality) and 0.08 (95% CI 0.02-0.29, four studies, N = 176, I = 51%, low quality), respectively. Cerclage was also superior to expectant management for the secondary outcomes of fetal loss OR 0.26 (95% CI 0.12-0.56, 8 studies, N = 455, I = 46%, very low-quality), pregnancy prolongation in days mean difference 47.45 (95% CI 39.89-55.0, 12 studies, N = 1027 I = 86%, very low quality), gestational age at birth in weeks mean difference 5.68 (95% CI 4.69-6.67, 9 studies, N = 892, I = 73%, very low quality), admission to neonatal intensive care OR 0.21 (95% CI 0.07-0.70, two studies, N = 79, I = 36%, very low quality) and neonatal death OR 0.12 (95% CI 0.04-0.34, five studies, N = 130, I = 0%, very low quality). There were no differences between cerclage and expectant management concerning premature rupture of membranes during or after the procedure OR 0.68 (95% CI 0.31-1.48, two studies, N = 155, I = 85%, very low quality) and chorioamnionitis OR 1.14 (95% CI 0.31-4.25, three studies, N = 88, I = 33%, very low quality).
CONCLUSIONS
Emergency cerclage in pregnant women with painless cervical dilatation seems to decrease preterm births, prolong the pregnancy, and decrease the neonatal deaths and fetal losses, but does not increase the risk of chorioamnionitis and premature rupture of membranes. Despite the extremely favorable estimates for cerclage, the results should be viewed with caution because, as a result of the lack of randomized control trials, the quality of evidence is low to very low.
Topics: Cerclage, Cervical; Emergencies; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Intensive Care, Neonatal; Pregnancy; Premature Birth; Treatment Outcome; Uterine Cervical Incompetence; Watchful Waiting
PubMed: 32757297
DOI: 10.1111/aogs.13968 -
Ultrasound in Obstetrics & Gynecology :... Nov 2020To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. (Meta-Analysis)
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.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Female; Fetal Death; Humans; Odds Ratio; Pregnancy; Pregnancy, Twin; Risk Factors
PubMed: 32632979
DOI: 10.1002/uog.22143 -
Obstetrics and Gynecology May 2020To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome...
OBJECTIVE
To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome abnormalities.
DATA SOURCES
Systematic searches were performed in 27 databases, including ClinicalTrials.gov, from inception to July 1, 2019, for articles with the keywords "Zika," "prenatal," "ultrasound," and "amniocentesis."
METHODS OF STUDY SELECTION
A total of 3,049 unique records were identified. Two reviewers independently assessed titles, abstracts, and full texts for relevance; 84 articles met the inclusion criteria. These articles describe 402 mother-fetus or mother-neonate dyads; 385 were included in the review of prenatal ultrasound examination, and 56 in the review of amniocentesis (39 in both).
TABULATION, INTEGRATION, AND RESULTS
Among 195 fetuses with congenital Zika syndrome findings on prenatal ultrasound examination, postnatal congenital Zika syndrome abnormalities were reported for 153 (78%; 95% CI 7-84%). High proportions of microcephaly (76%; 95% CI 69-82%) and brain abnormalities (78%; 95% CI 69-86%) were confirmed postnatally. Among 190 fetuses without congenital Zika syndrome findings on prenatal ultrasound examination, 17% (95% CI 12-24%) had congenital Zika syndrome abnormalities identified postnatally. Structural congenital Zika syndrome abnormalities were identified postnatally in approximately equal proportions among dyads with and without Zika virus RNA detected in an amniotic fluid specimen (68% and 67%; 95% CI 52-82% and 95% CI 38-88%). In six pregnancies, Zika virus RNA was detected in amniotic fluid but not in a subsequent amniocentesis specimen.
CONCLUSION
Prenatal ultrasound examination frequently detects structural findings associated with Zika virus infection; however, not all abnormalities are detected, and some may represent transient findings. As with other congenital infections, prenatal detection may vary with timing of infection, timing of ultrasound examination, technical expertise, and severity of abnormalities. The detection of Zika virus RNA in amniotic fluid in the included studies did not predict the risk for congenital Zika syndrome abnormalities in these cases, and clearance of Zika virus RNA from amniotic fluid appears possible after maternal infection. Diagnostic testing for Zika virus infection remains a shared decision between patients and clinicians, and more data are needed to define clinical predictors that will inform these decisions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42018080959.
Topics: Adult; Amniocentesis; Female; Fetal Diseases; Humans; Pregnancy; Ultrasonography, Prenatal; Young Adult; Zika Virus; Zika Virus Infection
PubMed: 32282593
DOI: 10.1097/AOG.0000000000003829 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an... (Comparative Study)
Comparative Study 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 I 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%; I = 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%; I = 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%; I = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I = 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.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Chromosome Aberrations; Embryo Loss; Female; Gestational Age; Humans; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 31124209
DOI: 10.1002/uog.20353