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Objective: To describe the feasibility of an ultrasound-guided repositioning technique for partially expelled intrauterine devices (IUDs) without use of sedation., Methods: This was a descriptive feasibility study of patients with a partially expelled IUD managed in our outpatient clinic from January 2016 to February 2020. The partially expelled IUDs (vertical arm extending partially or entirely through the cervical canal) were repositioned at the uterine fundus using Hartmann alligator forceps under ultrasound guidance. Paracervical or intracervical anesthesia and prophylactic antibiotics were not used. Data related to the procedure and 6-month follow-up were extracted from patient medical records. The primary outcome was the success rate of the repositioning procedure, defined as ultrasound confirmation of the entire IUD located above the internal os. Secondary outcomes included the retention and expulsion rates of the repositioned IUD at 6 months after the procedure and description of complications., Results: We included data from 55 women with a partially expelled IUD (35 levonorgestrel IUDs and 20 copper IUDs) referred for repositioning. Ultrasound-guided repositioning of the IUD was successful in 51 (92.7%) cases, while the procedure was not completed in four patients due to pain. Of the 55 procedures, 48 (87.3%) were performed by obstetrics and gynecology trainees under the supervision of a senior specialist. Among the 51 successfully repositioned IUDs, nine (17.6%) were expelled within 6 months after the procedure and six patients were lost to follow-up. No uterine perforation or infection-related complications occurred within 6 months of the procedure., Conclusion: The ultrasound-guided repositioning technique appears to be a safe and feasible approach for partially expelled IUDs. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To compare the reported rate of any congenital anomaly and perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer using a pairwise meta-analysis and to evaluate the same outcomes following fresh-blastocyst, frozen-blastocyst, fresh-cleavage or frozen-cleavage embryo transfer using a network meta-analysis., Methods: A literature search was performed in PubMed, Scopus and CENTRAL and registers for ongoing studies, from inception to February 2022, for randomized controlled trials (RCTs) with any sample size and observational studies including at least 100 live births per group, comparing the rates of any congenital anomaly and perinatal outcome of pregnancy following fresh/frozen embryo transfer at cleavage (day 2-3) vs blastocyst (day 5-7) stage. Risk ratios (RRs) along with their 95% CIs were pooled via a random-effects model meta-analysis. Within a frequentist network meta-analysis framework, outcomes of all four treatment modalities (i.e. fresh-blastocyst, fresh-cleavage, frozen-blastocyst, frozen-cleavage) were compared further. Any congenital anomaly constituted the primary outcome, whereas preterm delivery (delivery < 37 weeks), low birth weight (LBW; < 2500 g), gender of the neonate (male), perinatal death and healthy neonate (defined as liveborn neonate, delivered at term, weighing ≥ 2500 g, surviving for at least 28 days postbirth and without any congenital anomaly) were considered as secondary outcomes. Subgroup analyses by plurality (liveborn singleton vs multiple pregnancy) were conducted in the pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for non-randomized studies. Certainty of evidence was assessed using GRADE., Results: Through the literature search, 550 studies were retrieved and 33 were included in the systematic review. We found no significant difference in the risk for any congenital anomaly between blastocyst- and cleavage-stage transfer (RR, 0.80 (95% CI, 0.63-1.03); 10 studies; n = 192 442; I 2  = 85.5%). An increased probability of a male neonate was observed following blastocyst- vs cleavage-stage transfer (RR, 1.07 (95% CI, 1.06-1.09); 18 studies; n = 227 530; I 2  = 32.7%). No significant differences in other secondary outcomes or significant subgroup differences between liveborn singletons and multiple pregnancies were observed. The network meta-analysis showed a significantly lower risk for LBW following frozen-blastocyst vs fresh-blastocyst (RR, 0.76 (95% CI, 0.60-0.95)) or fresh-cleavage (RR, 0.74 (95% CI, 0.59-0.93)) transfer. Frozen-blastocyst transfer was associated with an increased risk for perinatal death compared with the fresh-cleavage method (RR, 2.06 (95% CI, 1.10-3.88)). The higher probability of a male neonate following blastocyst transfer remained evident in the network comparisons. All outcomes were assessed to be of very-low certainty of evidence., Conclusions: Current very-low certainty of evidence shows that there may be little-to-no difference in the risk for congenital anomaly or adverse perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer, although there was a slightly increased probability of a male neonate following blastocyst transfer. When considering cryopreservation, frozen-blastocyst transfer was associated with a reduction in the risk for LBW compared with both fresh-transfer modalities, and fresh-cleavage transfer may be associated with a reduction in the risk for perinatal death compared with frozen-blastocyst transfer. High-quality RCTs with separate data on fresh and frozen cycles and consistent reporting of culture conditions and freezing methods are mandatory. Individual participant data meta-analyses are required to address the substantial inconsistency resulting from current aggregate data approaches. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To summarize in a systematic review the current evidence regarding definitions, diagnosis, prevalence, etiology, clinical relevance and impact of surgical treatment for T-shaped uterus not related to diethylstilbestrol (DES) exposure, and to highlight areas on which future research should focus., Methods: A search of PubMed, Scopus and EMBASE was performed on 9 April 2020 using the search terms 't-shaped OR t-shape OR infantile OR (lateral indentation) OR (diethylstilbestrol OR DES) AND (uterus OR uterine OR uteri) AND (anomaly OR anomalies OR malformation OR malformations)'. Additionally, the reference lists of the included studies were searched manually for other relevant publications. All studies presenting data on T-shaped uterus not associated with DES exposure and including at least 10 women were considered eligible. Studies regarding DES-related T-shaped uterus were excluded because DES has not been used since 1971. There were no restrictions on language, date of publication or status of publication., Results: Of 2504 records identified by the electronic search, 20 studies were included in the systematic review. The majority of studies were of poor quality. In 11 of 16 studies reporting on the diagnosis of T-shaped uterus, the diagnostic method used was three-dimensional ultrasound. There is no consensus on the definition of T-shaped uterus, but the most cited criteria (4/16 studies) were of the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy (ESHRE/ESGE; 2013). The prevalence of T-shaped uterus varied from 0.2% to 10% in the four included studies reporting such data. With respect to etiology (except for DES), T-shaped uterus was considered a primary condition in three studies and secondary to adhesions in five and adenomyosis in one. T-shaped uterus was related to worse reproductive outcome based on subfertility (nine studies), miscarriage (seven studies), preterm delivery (two studies), ectopic pregnancy (one study) and repeat implantation failure (seven studies). Of the 12 studies that reported on the effects of surgical treatment of T-shaped uterus by hysteroscopic metroplasty, some mentioned an improvement in pregnancy rate (rates ranging from 49.6% to 88%; eight studies), live-birth rate (rates ranging from 35.1% to 76%; seven studies) and term-delivery rate (four studies) and a reduction in miscarriage (rates ranging from 7% to 49.6%; five studies) and ectopic pregnancy (one study). However, the evidence is of very low quality with serious/critical risk of bias toward overestimating the intervention effect. Some authors reported no complications related to the procedure, while others mentioned persistence of the dysmorphism (rates ranging from 1.4% to 11%; three studies), bleeding (1.3%; one study), infection (2.6%; one study) and adhesions (11.1% and 16.8%; two studies)., Conclusions: The prevalence, etiology and clinical relevance, with respect to reproductive outcome, of T-shaped uterus remain unclear and there is no consensus on the definition and diagnostic method for this condition. Expectant management should be considered the most appropriate choice for everyday practice until randomized controlled trials show a benefit of intervention. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: Pouch of Douglas (POD) obliteration can be predicted with a high degree of certainty and reproducibility using the dynamic transvaginal ultrasound (TVS) sliding-sign technique. So far, studies on POD obliteration prediction have focused on tertiary-care populations with high prevalence of endometriosis; however, POD obliteration may exist in individuals with asymptomatic endometriosis or other conditions. Our primary aim was to determine the prevalence of a negative sliding sign, representing POD obliteration, in a cohort of patients undergoing TVS for any gynecological indication., Methods: This was a prospective observational study of consecutive women with an indication for gynecological TVS, conducted at a high-volume ultrasound practice between July and August 2018. Clinical and surgical history, indication for TVS and TVS findings were documented. The prevalence of TVS-confirmed POD obliteration, determined by interpretation of the sliding sign, was calculated for the entire cohort and for the subgroups of women with and without risk factors for endometriosis. High risk for endometriosis was defined as having (1) a TVS referral for endometriosis-like pelvic pain or endometriosis specifically and/or (2) clinical symptoms or signs suggestive of endometriosis. Low risk was defined as the absence of these characteristics., Results: During the study period, 1043 consecutive women underwent TVS. After excluding those who underwent transabdominal ultrasound, had a history of hysterectomy or with missing data, 909 women were analyzed. The prevalence of a negative sliding sign in the entire cohort was 47/909 (5.2%). A negative sliding sign was observed in 22/639 (3.4%) women with a low risk for endometriosis and 25/243 (10.3%) of those with a high risk for endometriosis (difference in proportions, 6.9% (95% CI 2.8-10.9%); P < 0.001)., Conclusions: We have demonstrated an overall prevalence of a negative sliding sign, suggesting POD obliteration, of 5.2% (or 1/20) in women seeking TVS for a gynecological indication. The prevalence of negative sliding sign in low-risk women is not negligible (3.4% or 1/29 women). These women are most likely to have asymptomatic endometriosis or another important etiology of POD obliteration. The prevalence of a negative sliding sign is approximately three-times higher in women with signs and/or symptoms of endometriosis (10.3% vs 3.4%). Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts., Methods: This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated., Results: According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle ≤ 130° (sensitivity, 80%; specificity, 96%; LR+, 21.3; LR-, 0.21), lateral indentation depth ≥ 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle ≤ 40° (sensitivity, 80%; specificity, 87.5%; LR+, 6.4; LR-, 0.23). Most of the experts diagnosed the uterus as being T-shaped in 0% (0/56) of cases when none of these three criteria was met, in 10% (2/20) of cases when only one criterion was met, in 50% (5/10) of cases when two of the three criteria were met, and in 93% (13/14) of cases when all three criteria were met., Conclusions: The diagnosis of T-shaped uterus is not easy; the agreement among experts was only moderate and the judgement of individual experts was commonly insufficient for accurate diagnosis. The three sonographic measurements with cut-offs that we identified (lateral internal indentation depth ≥ 7 mm, lateral indentation angle ≤ 130° and T-angle ≤ 40°) had good diagnostic test accuracy and fair-to-moderate reliability and, when applied in combination, they provided high post-test probability for T-shaped uterus. In the absence of other anomalies, we suggest considering a uterus to be normal when none or only one criterion is met, borderline when two criteria are met, and T-shaped when all three criteria are met. These three CUME criteria for defining T-shaped uterus may aid in determination of its prevalence, clinical implications and best management and in the assessment of post-surgical morphologic outcome. The CUME definition of T-shaped uterus may help in the development of interventional randomized controlled trials and observational studies and in the diagnosis of uterine morphology in everyday practice, and could be adopted by guidelines on uterine anomalies to enrich their classification systems. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To estimate the differences in frequency of diagnosis of septate uterus using three different definitions and determine whether these differences are significant in clinical practice, and to examine the association between diagnosis of septate uterus, using each of the three definitions, and infertility and/or previous miscarriage as well as the cost of allocation to surgery., Methods: This was a secondary analysis of data from a prospective study of 261 consecutive women of reproductive age attending a private clinic focused on the diagnosis and treatment of congenital uterine malformations. Reanalysis of the datasets was performed according to three different means of defining septate uterus: following the recommendations of the American Society for Reproductive Medicine (ASRM), a 2016 update of those of the American Fertility Society from 1988 (ASRM-2016: internal fundal indentation depth ≥ 1.5 cm, angle of internal indentation < 90° and external indentation depth < 1 cm); following the recommendations of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE/ESGE), published in 2013 and reaffirmed in 2016 (ESHRE/ESGE-2016: internal fundal/uterine indentation depth > 50% of uterine-wall thickness and external indentation depth < 50% of uterine-wall thickness, with uterine-wall thickness measured above interostial/intercornual line); and using a definition published last year which was based on the decision made most often by a group of experts (Congenital Uterine Malformation by Experts; CUME) (CUME-2018: internal fundal indentation depth ≥ 1 cm and external fundal indentation depth < 1 cm). We compared the rate of diagnosis of septate uterus using each of these three definitions and, for each, we estimated the association between the diagnosis and infertility and/or previous miscarriage, and anticipated the costs associated with their implementation using a guesstimation method., Results: Although 32.6% (85/261) of the subjects met the criteria for one of the three definitions of septate uterus, only 2.7% (7/261) of them were defined as having septate uterus according to all three definitions. We diagnosed significantly more cases of septate uterus using ESHRE/ESGE-2016 than using ASRM-2016 (31% vs 5%, relative risk (RR) = 6.7, P < 0.0001) or CUME-2018 (31% vs 12%, RR = 2.6, P < 0.0001) criteria. We also observed frequent cases that could not be classified definitively by ASRM-2016 (gray zone: neither normal/arcuate nor septate; 6.5%). There were no significant differences (P > 0.05) in the prevalence of septate uterus in women with vs those without infertility according to ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) or CUME-2018 (11% vs 12%). Septate uterus was diagnosed significantly more frequently in women with vs those without previous miscarriage according to ASRM-2016 (11% vs 3%; P = 0.04) and CUME-2018 (22 vs 10%; P = 0.04), but not according to ESHRE/ESGE-2016 (42% vs 28%; P = 0.8) criteria. Our calculations showed that global costs to the healthcare system would be highly dependent on the criteria used in the clinical setting to define septate uterus, with the costs associated with the ESHRE/ESGE-2016 definition potentially being an extra US$ 100-200 billion over 5 years in comparison to ASRM-2016 and CUME-2018 definitions., Conclusions: The prevalence of septate uterus according to ESHRE/ESGE-2016, ASRM-2016 and CUME-2018 definitions differs considerably. An important limitation of the ASRM classification, which needs to be addressed, is the high proportion of unclassifiable cases originally named, by us, the 'gray zone'. The high rate of overdiagnosis of septate uterus according to ESHRE/ESGE-2016 may lead to unnecessary surgery and therefore unnecessary risk in these women and may impose a considerable financial burden on healthcare systems. Efforts to define clinically meaningful and universally applicable criteria for the diagnosis of septate uterus should be encouraged. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The rate of maternal and perinatal complications increases after 39 weeks' gestation in both unselected and complicated pregnancies. The aim of this study was to synthesize quantitatively the available evidence on the effect of elective induction of labor at 39 weeks on the risk of Cesarean section, and on maternal and perinatal outcomes., Methods: PubMed, US Registry of Clinical Trials, SCOPUS and CENTRAL databases were searched from inception to August 2018. Additionally, the references of retrieved articles were searched. Eligible studies were randomized controlled trials of singleton uncomplicated pregnancies in which participants were randomized between 39 + 0 and 39 + 6 gestational weeks to either induction of labor or expectant management. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool. The overall quality of evidence was assessed according to the GRADE guideline. Primary outcomes included Cesarean section, maternal death and admission to the neonatal intensive care unit (NICU). Secondary outcomes included operative delivery, Grade-3/4 perineal laceration, postpartum hemorrhage, maternal infection, hypertensive disease of pregnancy, maternal thrombotic events, length of maternal hospital stay, neonatal death, need for neonatal respiratory support, cerebral palsy, length of stay in NICU and length of neonatal hospital stay. Pooled risk ratios (RRs) were calculated using random-effects models., Results: The meta-analysis included five studies (7261 cases). Induction of labor was associated with a decreased risk for Cesarean section (moderate quality of evidence; RR 0.86 (95% CI, 0.78-0.94); I 2  = 0.1%), maternal hypertension (moderate quality of evidence; RR 0.65 (95% CI, 0.57-0.75); I 2  = 0%) and neonatal respiratory support (moderate quality of evidence; RR 0.73 (95% CI, 0.58-0.95); I 2  = 0%). Neonates born after induction weighed, on average, 81 g (95% CI, 63-100 g) less than those born after expectant management. No significant effects were found for the other outcomes with the available data. The main limitation of our analysis was that the majority of data were derived from a single large study. A second limitation arose from the open-label design of the studies, which may theoretically have affected the readiness of the attending clinician to resort to Cesarean section., Conclusions: Elective induction of labor in uncomplicated singleton pregnancy at 39 weeks' gestation is not associated with maternal or perinatal complications and may reduce the need for Cesarean section, risk of hypertensive disease of pregnancy and need for neonatal respiratory support. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

This Consensus Opinion summarizes the main aspects of several techniques for performing ovarian antral follicle count (AFC), proposes a standardized report and provides recommendations for future research. AFC should be performed using a transvaginal ultrasound (US) probe with frequency ≥ 7 MHz. For training, we suggest a minimum of 20-40 supervised examinations. The operator should be able to adjust the machine settings in order to achieve the best contrast between follicular fluid and ovarian stroma. AFC may be evaluated using real-time two-dimensional (2D) US, stored 2D-US cine-loops and stored three-dimensional (3D) US datasets. Real-time 2D-US has the advantage of permitting additional maneuvers to determine whether an anechoic structure is a follicle, but may require a longer scanning time, particularly when there is a large number of follicles, resulting in more discomfort to the patient. 2D-US cine-loops have the advantages of reduced scanning time and the possibility for other observers to perform the count. The 3D-US technique requires US machines with 3D capability and the operators to receive additional training for acquisition/analysis, but has the same advantages as cine-loop and also allows application of different imaging techniques, such as volume contrast imaging, inversion mode and semi-automated techniques such as sonography-based automated volume calculation. In this Consensus Opinion, we make certain recommendations based on the available evidence. However, there is no strong evidence that any one method is better than another; the operator should choose the best method for counting ovarian follicles based on availability of resources and on their own preference and skill. More studies evaluating how to improve the reliability of AFC should be encouraged. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To assess the level of agreement between experts in distinguishing between septate and normal/arcuate uterus using their subjective judgment when reviewing the coronal view of the uterus from three-dimensional ultrasound. Another aim was to determine the interobserver reliability and diagnostic test accuracy of three measurements suggested by recent guidelines, using as reference standard the decision made most often by experts (Congenital Uterine Malformation by Experts (CUME))., Methods: Images of the coronal plane of the uterus from 100 women with suspected fundal internal indentation were anonymized and provided to 15 experts (five clinicians, five surgeons and five sonologists). They were instructed to indicate whether they believed the uterus to be normal/arcuate (defined as normal uterine morphology or not clinically relevant degree of distortion caused by internal indentation) or septate (clinically relevant degree of distortion caused by internal indentation). Two other observers independently measured indentation depth, indentation angle and indentation-to-wall-thickness (I:WT) ratio. The agreement between experts was assessed using kappa, the interobserver reliability was assessed using the concordance correlation coefficient (CCC), the diagnostic test accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) and the best cut-off value was assessed using Youden's index, considering as the reference standard the choice made most often by the experts (CUME)., Results: There was good agreement between all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri according to CUME; European Society of Human Reproduction and Embryology (ESHRE)-European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%) defined 80 septate and 20 normal/arcuate uteri, while American Society for Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and angle < 90°), 82 normal/arcuate (depth < 10 mm and angle > 90°) and 13 uteri that could not be classified (referred to as the gray-zone). The agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the three measurements, the interobserver reproducibility of indentation depth (CCC, 0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95% CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test accuracy of these three measurements using CUME as reference standard was very good, with AUC between 0.96 and 1.00. The best cut-off values for these measurements to define septate uterus were: indentation depth ≥ 10 mm, indentation angle < 140° and I:WT ratio > 110% ., Conclusions: The suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus while that of ASRM underestimates this prevalence, leaving in the gray-zone most of the uteri that experts considered as septate. We recommend considering indentation depth ≥ 10 mm as septate, since the measurement is simple and reliable and this criterion is in agreement with expert opinion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To identify, appraise and summarize the available data concerning the impact of human papilloma virus (HPV) infection on reproductive outcome following in-vitro fertilization (IVF)., Methods: We searched for studies in PubMed, EMBASE, Scopus, Lilacs and the Cochrane Central Register of Controlled Trials from inception to March 2017. Any type of HPV infection assessed through polymerase chain reaction, subfertility factors and IVF indications and protocols were considered. Our primary outcomes were live birth/ongoing pregnancy and miscarriage, while secondary outcomes included clinical and laboratory parameters. We planned subgroup analyses according to the status of cervical cytology and presence of infection in the male partner. We assessed the relative risk (RR), using a random-effects model; heterogeneity was assessed using the I 2 statistic. Quality of the evidence was evaluated using the recommendations of the GRADE Working Group., Results: From the 14 studies eligible for inclusion, quantitative data from 10, evaluating 299 women with HPV infection and 2049 women without HPV infection, were included in the analysis. The pooled results showed no significant difference between HPV-infected and non-infected women in rates of live birth/ongoing pregnancy (RR, 1.16 (95% CI, 0.88-1.53); I 2  = 0%; six studies, 983 women), clinical pregnancy (RR, 1.06 (95% CI, 0.74-1.54); I 2  = 61%; eight studies, 1173 women) or miscarriage (RR, 1.58 (95% CI, 0.93-2.69); I 2  = 8%; six studies, 290 clinical pregnancies). The overall quality of the evidence was very low, downgraded two levels because of serious limitations of the included studies (observational studies) and imprecision. In contrast, pooled results in the subgroup analysis based on the presence of infection in the male partner showed significant differences in rates of live birth/ongoing pregnancy (RR, 0.43 (95% CI, 0.23-0.82); I 2  = 0%; three studies, 429 participants; P = 0.01) and miscarriage (RR, 3.70 (95% CI, 1.94-7.05); I 2  = 0%; two studies, 90 participants; P < 0.0001)., Conclusions: The available evidence is still inadequate to enable us to draw firm conclusions regarding the effect of HPV infection in women on the most important reproductive outcomes following IVF; however, it suggests that the effect is not large for rates of live birth/ongoing pregnancy and clinical pregnancy. When infection is present in the male partner, it seems that there is a negative effect on live birth/ongoing pregnancy rate and an increase in miscarriage rate, a finding that should be interpreted with caution, owing to the very low quality of evidence supporting it. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the available evidence comparing effectiveness of ovarian stimulation (OS) using clomiphene citrate (CC) and/or letrozole (LTZ) to reduce follicle-stimulating hormone (FSH) consumption compared with standard OS., Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared reproductive outcomes following in-vitro fertilization. We searched 11 electronic databases and hand-searched the reference lists of included studies and related reviews. We stratified the results, separating studies according to the oral agent used (CC or LTZ) and the characteristics of the included women (expected poor ovarian response or other women). When combining the results of the included studies, we assessed the relative risk (RR) for live birth, clinical pregnancy, miscarriage and cycle cancelation, the Peto odds ratio (OR) for ovarian hyperstimulation syndrome (OHSS) and mean difference (MD) for the number of oocytes retrieved and FSH consumption., Results: A total of 22 studies were included in the review. Considering women with expected poor ovarian response, the available evidence suggested that using CC to reduce FSH consumption during OS provided similar rates of live birth (RR, 0.9 (95% CI, 0.6-1.2), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.4), moderate-quality evidence); the use of LTZ did not cause a relevant change in the number of oocytes retrieved (MD, -0.4 (95% CI, -0.9 to 0.1), high-quality evidence). Considering the studies evaluating other women, the available evidence suggested that using CC to reduce FSH consumption during OS reduced the number of oocytes retrieved (MD, -4.6 (95% CI, -6.1 to -3.0), high-quality evidence) and risk of OHSS (Peto OR, 0.2 (95% CI, 0.1-0.3), moderate-quality evidence), while results were similar for rates of live birth (RR, 0.9 (95% CI, 0.7-1.1), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.1), high-quality evidence). The quality of the evidence was low or very low for other outcomes., Conclusion: The use of CC to reduce FSH consumption in women with expected poor ovarian response has the advantage of providing similar reproductive outcomes with reduced costs. For the other women, the use of CC for reducing FSH consumption has the additional advantage of reducing OHSS, but also reduces the total number of oocytes retrieved. More studies are needed to evaluate the effect of LTZ for the same purpose. Future studies should focus on cumulative pregnancy per oocyte retrieval, patient dissatisfaction and agreement to repeat the cycle if not pregnant, which are important outcomes for clinical decisions. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self-selection after activation of the embryonic genome on day 3. Conversely, the in-vitro environment is likely to be inferior to that in vivo, and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo. Our objective was to identify, appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage-stage embryo transfer., Methods: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the transfer of blastocysts (days 5-6) with the transfer of cleavage-stage embryos (days 2-3) in women undergoing in-vitro fertilization or intracytoplasmic sperm injection. The last electronic searches were run on 1 August 2016. Abstracts and studies with a mean difference between the two study groups of > 0.5 for the number of embryos transferred were excluded., Results: We screened 1187 records and assessed 33 potentially eligible studies. Twelve studies were included, comprising a total of 1200 women undergoing blastocyst transfer and 1218 undergoing cleavage-stage embryo transfer. We observed low-quality evidence of no significant difference of blastocyst transfer on live birth/ongoing pregnancy (relative risk (RR), 1.11 (95% CI, 0.92-1.35), 10 RCTs, 1940 women, I 2  = 54%), clinical pregnancy (RR, 1.10 (95% CI, 0.93-1.31), 12 RCTs, 2418 women, I 2  = 64%), cumulative pregnancy (RR, 0.89 (95% CI, 0.67-1.16), four RCTs, 524 women, I 2  = 63%) and miscarriage (RR, 1.08 (95% CI, 0.74-1.56), 10 RCTs, 763 pregnancies, I 2  = 0%). There was moderate-quality evidence of a decrease in the number of women with surplus embryos after the blastocyst-stage embryo transfer (RR, 0.78 (95% CI, 0.66-0.91)). Overall, the quality of the evidence was limited by the quality of the included studies and by unexplained inconsistency across studies., Conclusions: Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice. As the quality of the evidence for the primary outcomes is low, additional well-designed RCTs are still needed before robust conclusions can be drawn. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS)., Methods: A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage., Results: We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS., Conclusion: There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto., Resultados: Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0,95 (IC 95%, 0,84-1,08)), o de embarazos confirmados ecográficamente (RR: 1,02 (IC 95%, 0,91-1,15)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1,28 (IC 95%, 1,01-1,63)) y de embarazos confirmados ecográficamente (RR: 1,26 (IC 95%, 1,04-1,53)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1,03 (IC 95%, 0,80-1,34)) y las tasas de embarazos confirmados ecográficamente (RR: 0,99 (IC 95%, 0.81-1,22)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0,54 (IC 95%, 0,39-0,77)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0,63 (IC 95%, 0,49-0,80)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the accuracy of three-dimensional (3D) transvaginal sonographic (TVS) parameters in predicting the evolution of a pregnancy of unknown location (PUL)., Methods: This was a prospective observational study performed at the early pregnancy unit of a university hospital from September 2008 to June 2012. Women with a positive pregnancy test without any signs of intra- or extrauterine pregnancy at their first TVS examination were considered eligible and a 3D dataset containing the entire uterus was acquired. An experienced observer analyzed all 3D datasets for assessment of the following parameters: endometrial thickness, volume, mean gray-scale index and asymmetry. Women were followed until they were classified as having: (i) non-visualized pregnancy loss (NVPL); (ii) intrauterine pregnancy (IUP); or (iii) ectopic pregnancy or persistent PUL. We compared the values of the TVS parameters across the three groups. We also assessed the area under the receiver-operating characteristics curve of the 3D-TVS parameters in comparison to that for serum β-human chorionic gonadotropin (β-hCG) ratio (48 h/baseline) to predict PUL outcome. We then evaluated whether combining the 3D-TVS parameters with serum β-hCG ratio improved the predictive accuracy for PUL outcome by performing a logistic regression analysis., Results: During the study period 4939 consecutive pregnant women presented at the unit for their initial TVS examination and 325 (7%) were classified as having a PUL, of whom 161 women were enrolled and had a 3D scan of the uterus. However, 19 were excluded because of incomplete follow-up. Data from 142 women with PUL were therefore included in the analysis and the outcomes of these women were: NVPL in 98 (69%), IUP in 27 (19%) and ectopic pregnancy + persistent PUL in 14 + 3 = 17 (12%). Endometrial thickness, endometrial volume and the proportion of women with asymmetric endometrial shape differed significantly between the outcome groups. Endometrial thickness and volume could be used as reasonable predictors of both NVPL and IUP, whereas asymmetric endometrial shape and mean gray-scale index could be used as reasonable predictors of IUP only. The best single parameter to predict PUL outcomes was the β-hCG ratio. Regression analysis demonstrated that endometrial volume and endometrial shape asymmetry added significantly to the β-hCG ratio in predicting IUP but not NVPL., Conclusions: 3D-TVS markers have a low diagnostic accuracy in predicting PUL outcome. The addition of endometrial volume and shape asymmetry improves the accuracy of the β-hCG ratio in predicting IUP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Essure® has been tested as an alternative treatment for hydrosalpinx before embryo transfer (ET) in women undergoing assisted reproduction techniques. However, the persistence of a foreign body inside the uterine cavity might have a negative impact on the outcome of pregnancy. The present systematic review aimed at identifying, appraising and summarizing the available evidence regarding the effectiveness and safety of using Essure prior to ET for women with hydrosalpinx., Methods: We searched for studies in PubMed, Scopus, CENTRAL, Web of Science and ClinicalTrials.gov and the reference lists of eligible studies. All studies including at least 10 women with hydrosalpinx who received Essure, any other intervention or no treatment prior to ET were considered eligible. Study selection, data extraction and evaluation of the risk of bias were performed independently by two authors. Study outcomes were miscarriage per clinical pregnancy, singleton preterm birth per singleton live birth and live birth/ongoing pregnancy and clinical pregnancy per ET. The pooled results for each outcome and intervention were summarized as proportions with their respective 95% CIs, using a random-effects model., Results: Our electronic search of databases was performed on 7 November 2015, and 26 studies with 43 study arms were considered eligible: eight study arms evaluating Essure; seven assessing tubal aspiration; seven appraising effects of no treatment; 12 evaluating salpingectomy; two assessing tubal division; and seven evaluating tubal occlusion. When compared with women who had no intervention, women with Essure had a higher clinical pregnancy rate per ET (36% (95% CI, 0-43%) vs 13% (95% CI, 9-17%)). When compared with women who had other interventions, women with Essure had a higher miscarriage rate per clinical pregnancy (38% (95% CI, 27-49%) vs 15% (95% CI, 10-19%))., Conclusions: The available evidence suggests that, although Essure prior to ET in women with hydrosalpinx improves the chance of achieving a clinical pregnancy compared with no intervention, it is associated with a higher rate of miscarriage when compared with the other interventions. Although this evidence is based on observational studies, we believe that salpingectomy should be the first option for women who are eligible for videolaparoscopy. However, it is still premature to make recommendations for women who are not eligible for surgery, and randomized controlled trials are needed to clarify which is the best treatment alternative in such a scenario. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess perinatal outcomes and intrauterine complications following fetal intervention for congenital heart disease (CHD)., Methods: A systematic review and meta-analysis were performed following an electronic search of PubMed and Scopus databases (last searched August 2015). Perinatal outcomes that were assessed included fetal death, live birth, preterm delivery < 37 weeks' gestation and neonatal death. Intrauterine complications that were assessed included bradycardia requiring treatment and hemopericardium requiring drainage. Estimated proportions were reported as mean (95% CI). Inconsistency was assessed using the I 2 statistic., Results: An electronic search identified 2279 records, of which 29 studies (11 retrospective cohort and 18 case reports) were considered eligible for analysis. Fetal death after treatment of CHD by aortic valvuloplasty was reported in three studies, with a rate of 31% (95% CI, 9-60%), after pulmonary valvuloplasty in one study, with a rate of 25% (95% CI, 10-49%), after septoplasty in one study, with a rate of 14% (95% CI, 6-28%) and after pericardiocentesis and/or pericardioamniotic shunt placement in 24 studies, with a rate of 29% (95% CI, 18-41%). Bradycardia requiring treatment was reported after aortic valvuloplasty in two studies, with a rate of 52% (95% CI, 16-87%), after pulmonary valvuloplasty in one study, with a rate of 44% (95% CI, 23-67%), and after septoplasty in one study, with a rate of 27% (95% CI, 15-43%)., Conclusions: Current evidence on the effectiveness of prenatal intervention for CHD derives mostly from case reports and a few larger series; no study was randomized. Although the results of the meta-analysis are encouraging in terms of perinatal survival, they should be interpreted with caution when comparing with procedures performed after delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess and compare the rate of procedure-related complications after intrauterine treatment of spina bifida by endoscopic surgery and by open fetal surgery., Methods: Systematic literature searches in PubMed and SCOPUS databases were performed on 20 September 2015 to identify randomized controlled trials and observational studies on treatment of human spina bifida by endoscopic or open fetal surgery techniques. Only studies with ≥ 10 cases that were published in or after 2000 were included in the meta-analysis in order to reduce the risk of bias. Primary outcomes (complete dehiscence, focal dehiscence and/or markedly thin hysterotomy scar; preterm delivery < 34 weeks; mean gestational age at delivery) and secondary outcomes (oligohydramnios, prelabor rupture of membranes, placental abruption, chorioamnionitis and perinatal death) were assessed for both techniques. Precision of the estimated proportions was evaluated with 95% CIs. Inconsistency was assessed using the I(2) statistic., Results: The search identified 1080 records that were examined based on title and abstract, of which 28 full-text articles were examined completely for eligibility. Nine records were excluded because cases were also described in other studies, leaving 19 records for analysis. When comparing endoscopic vs open fetal surgery, the rate of complete dehiscence, focal dehiscence and/or markedly thin hysterotomy scar was, respectively, 1% (95% CI, 0-4%) vs 26% (95% CI, 12-42%); preterm delivery < 34 weeks was 80% (95% CI, 41-100%) vs 45% (95% CI, 38-53%); oligohydramnios was 39% (95% CI, 9-75%) vs 14% (95% CI, 7-24%); prelabor rupture of membranes was 67% (95% CI, 12-100%) vs 38% (95% CI, 26-50%); and perinatal death was 14% (95% CI, 1-38%) vs 5% (95% CI, 3-8%)., Conclusion: Open fetal surgery for spina bifida seems to show lower rates of procedure-related complications than does endoscopic surgery, but the rate of hysterotomy scar complications is high after open surgery. Because of the low quality of evidence, the conclusions should be interpreted with caution. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To compare the effects of dydrogesterone and progesterone for luteal-phase support (LPS) in women undergoing assisted reproductive techniques (ART)., Methods: We performed a systematic review to identify relevant randomized controlled trials (RCTs) by searching the following electronic databases: Cochrane CENTRAL, PubMed, Scopus, Web of Science, ClinicalTrials.gov, ISRCTN Registry and WHO ICTRP., Results: The last search was performed in October 2015. Eight RCTs were considered eligible and were included in the review and meta-analyses. There was no relevant difference between oral dydrogesterone and vaginal progesterone for LPS with respect to rate of ongoing pregnancy (risk ratio (RR), 1.04 (95% CI, 0.92-1.18); I(2) , 0%; seven RCTs, 3134 women), clinical pregnancy (RR, 1.07 (95% CI, 0.93-1.23); I(2) , 34%; eight RCTs, 3809 women) or miscarriage (RR, 0.77 (95% CI, 0.53-1.10); I(2) , 0%; seven RCTs, 906 clinical pregnancies). Two of the three studies reporting on dissatisfaction of treatment identified lower levels of dissatisfaction among women using oral dydrogesterone than among women using vaginal progesterone (oral dydrogesterone vs vaginal progesterone capsules: 2/79 (2.5%) vs 90/351 (25.6%), respectively; oral dydrogesterone vs vaginal progesterone gel: 19/411 (4.6%) vs 74/411 (18.0%), respectively). The third study showed no difference in dissatisfaction rate (oral dydrogesterone vs vaginal progesterone capsules: 8/96 (8.3%) vs 8/114 (7.0%), respectively)., Conclusions: Oral dydrogesterone seems to be as effective as vaginal progesterone for LPS in ART cycles, and appears to be better tolerated . Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To identify, evaluate and summarize the available evidence regarding the effectiveness and safety of administering a gonadotropin releasing hormone (GnRH) agonist during the luteal phase in women undergoing assisted reproductive techniques., Methods: In this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) comparing the addition of a GnRH agonist during the luteal phase, compared with standard luteal-phase support. We searched seven electronic databases and hand-searched the reference lists of included studies and related reviews. Our primary outcome was live birth or ongoing pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy per randomized woman, miscarriage per clinical pregnancy, adverse perinatal outcome and congenital malformations., Results: The evidence from eight studies examining 2776 women showed a relative risk (RR) for live birth or ongoing pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when excluding the studies that did not report live birth and those at high risk of bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73-1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to explain the observed heterogeneity. The quality of the evidence was deemed to be very low: it was downgraded because of the limitation of the included studies, imprecision, inconsistency across the studies' results, and suspicion of publication bias. None of the included studies reported adverse perinatal outcomes or congenital malformations., Conclusions: There is evidence that adding GnRH agonist during the luteal phase improves the likelihood of ongoing pregnancy. However, this evidence is of very low quality and there is no evidence for adverse perinatal outcome and congenital malformations. We therefore believe that including this intervention in clinical practice would be premature., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To examine and compare the reproducibility of measurement of first- and second-trimester uterine artery pulsatility index (UtA-PI) using transabdominal (TAS) and transvaginal (TVS) ultrasound., Methods: This was an observational study including women ≥ 18 years of age, with a singleton pregnancy, in the first trimester (between 11 + 0 and 13 + 6 weeks' gestation) or second trimester (between 20 and 26 weeks' gestation). UtA-PI and angle of insonation were assessed by two observers (one with 15 and the other with 3 years of experience) using both TAS and TVS. The more experienced observer performed two scans alternated by the other observer. The acquisitions were completely independent and the observers were blinded to each other and to their own measurements. Reproducibility of the measurements by TVS and TAS was assessed using the concordance correlation coefficients (CCCs), intraclass correlation coefficients (ICCs) and limits of agreement (LoA)., Results: We analyzed data from 97 women in the first trimester and 96 in the second trimester. The mean ± SD UtA-PI was significantly higher when measured using TVS, compared with TAS, in both the first (1.60 ± 0.49 vs 1.52 ± 0.63, respectively; P = 0.03) and second (1.07 ± 0.33 vs 0.96 ± 0.32, respectively; P < 0.001) trimesters. The median angle of insonation was significantly lower when using TVS, compared with TAS, in both the first (8.0° (interquartile range (IQR), 2.5-16.3°) vs 12.5° (IQR, 2.5-20.0°), respectively; P = 0.04) and second (10.0° (IQR, 4.5-16.5°) vs 17.5° (IQR, 5.0-27.9°), respectively; P < 0.001) trimesters. Both ultrasound techniques had similar reproducibility: the intraobserver CCC ranged from 0.93 to 0.95 and the interobserver CCC ranged from 0.81 to 0.86; and the ICCs of both techniques were highly comparable (the intraobserver LoA was approximately ± 20-30% and the interobserver LoA was approximately ± 30-40%)., Conclusions: When measuring UtA-PI, assessment by TVS provides higher values and better insonation angle compared with TAS. The reproducibility of the ultrasound methods in both first and second trimesters of pregnancy was comparable and should not be considered as good. Future studies examining technical improvements with the aim of increasing the reproducibility of this technique should be encouraged., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To examine whether endometrial thickness and the presence of endometrioma are independent predictors of clinical pregnancy rate or simply associated with poor ovarian response (POR)., Methods: This was a retrospective cohort study assessing the first cycle of all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a university hospital in Brazil between January 2011 and December 2012. Only the first cycle of each woman within the study period was considered. Women over 40 years of age and those who used clomiphene citrate during controlled ovarian stimulation (COS) or did not undergo embryo transfer were excluded from analysis. POR was defined as ≤ three oocytes retrieved and a thin endometrium was defined as endometrial thickness ≤ 7.0 mm on the day of human chorionic gonadotropin (hCG) administration. We performed a multiple regression analysis to identify which of the following parameters were independent predictors of clinical pregnancy: age, number of oocytes retrieved, endometrial thickness or the presence of endometrioma., Results: Within the study period, 787 women began COS, but 270 were excluded from analysis. Among the 517 women analyzed, those who achieved pregnancy were younger and yielded more oocytes. The proportion of POR was higher in women with a thin endometrium (17/57 (29.8%) vs 80/460 (17.4%); P = 0.03) and in women with endometrioma (15/39 (38.5%) vs 82/478 (17.2%); P = 0.002). The results of regression analysis showed that only age and the number of oocytes retrieved were independent predictors of pregnancy. Additionally, we observed higher clinical pregnancy rates in women with a thin endometrium from whom ≥ seven oocytes were retrieved (11/25 (44.0%)) compared to women with normal endometrial thickness (99/241 (41.1%)). Considering only women from whom ≥ four oocytes were retrieved, we observed reasonable pregnancy rates in those with a thin endometrium (14/40 (35.0%)) and in those with endometrioma (9/24 (37.5%))., Conclusion: Both a thin endometrium and the presence of endometrioma are associated with POR but are not important independent predictors of clinical pregnancy. Good pregnancy rates can be observed when these conditions are present in women with a good ovarian response., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate whether the antral follicle count (AFC) is underestimated in the presence of an endometrioma., Methods: This was a retrospective cohort study assessing all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at our clinic between January 2011 and December 2012 who had both ovaries and unilateral endometrioma. The primary outcome of the study was the difference between AFC and the number of oocytes retrieved per ovary., Results: Within the study period 787 women underwent IVF/ICSI at our clinic. Sixty of these women had at least one endometrioma, but 23 were excluded from the analysis as six had only one ovary and 17 had bilateral endometriomas. Therefore a total of 37 women were included in this study and analysis. Compared with the contralateral ovaries, ovaries with an endometrioma were significantly larger in volume (median, 10.3 (interquartile range (IQR), 4.7-18.9)  cm(3) vs median, 3.6 (IQR, 2.7-6.5)  cm(3); P < 0.001) and presented a significantly lower AFC (median, 3.0 (IQR, 1.0-6.0) vs median, 5.0 (IQR, 2.0-6.5); P = 0.001). However, the median number of oocytes retrieved was similar (P = 0.60) between ovaries with an endometrioma (2.0 (IQR, 0.5-5.0)) and the contralateral ovaries (2.0 (IQR, 0.0-4.0)). Accordingly, the median difference between AFC and number of oocytes retrieved was significantly smaller (P = 0.005) for ovaries with an endometrioma (0.0 (IQR, -1.0 to 1.5) than for those without (2.0 (IQR, 0.0-4.0))., Conclusions: Although the AFC is reduced in ovaries with an endometrioma, the number of oocytes retrieved is similar, suggesting that the AFC is underestimated in such ovaries. We believe that this is a consequence of an impaired ability to detect small follicles in the presence of an endometrioma., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To examine the quality of methods used and the accuracy of the interpretation of agreement in existing studies that examine the reliability of ultrasound measurements and judgments in obstetrics and gynecology., Methods: A systematic search of MEDLINE was performed on 25 March 2014, looking for studies that examined the reliability of ultrasound measurements and judgments in obstetrics and gynecology with evaluation of concordance (CCC) or intraclass (ICC) correlation coefficients or kappa as a main objective., Results: Seven hundred and thirty-three records were examined on the basis of their title and abstract, of which 141 full-text articles were examined completely for eligibility. We excluded 29 studies because they did not report CCC/ICC/kappa, leaving 112 studies that were included in our analysis. Two studies reported both ICC and kappa and were counted twice, therefore, the number used as the denominator in the analyses was 114. Only 16/114 (14.0%) studies were considered to be well designed (independent acquisition and blinded analysis) and to have interpreted the results properly. Most errors occurring in the studies are likely to overestimate the reliability of the method examined., Conclusions: The vast majority of published studies examined had important flaws in design, interpretation and/or reporting. Such limitations are important to identify as they might create false confidence in the existing measurements and judgments, jeopardizing clinical practice and future research. Specific guidelines aimed at improving the quality of reproducibility studies that examine ultrasound methods should be encouraged., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To identify, appraise and summarize the current evidence regarding the pathophysiology, staging, prediction and prevention of ovarian hyperstimulation syndrome (OHSS)., Methods: Two comprehensive systematic reviews were carried out: one examined methods of predicting either high ovarian response or OHSS and the other examined interventions aimed at reducing the occurrence of OHSS. Additionally, we describe the related pathophysiology and staging criteria., Results: Seven studies examining methods of predicting OHSS and eight more examining methods of predicting high ovarian response to controlled ovarian stimulation were included. Current evidence shows that the best methods of predicting high response are antral follicle count and anti-Müllerian hormone levels, and that a high ovarian response (examined by the number of large follicles, estradiol concentration or the number of retrieved oocytes) is the best method of predicting the occurrence of OHSS. Ninety-seven randomized controlled trials examining the effect of several interventions for reducing the occurrence of OHSS were included. There was high-quality evidence that replacing human chorionic gonadotropin by gonadotropin-releasing hormone agonists or recombinant luteinizing hormone, and moderate-quality evidence that antagonist protocols, dopamine agonists and mild stimulation, reduce the occurrence of OHSS. The evidence for the effect of the other interventions was of low/very low quality. Additionally, we identified and described 12 different staging criteria., Conclusions: There are useful predictive tools and several preventive interventions aimed at reducing the occurrence of OHSS. Acknowledging and understanding them are of crucial importance for planning the treatment of, and, ultimately, eliminating, OHSS while maintaining high pregnancy rates., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To summarize the current evidence on the effect of using ultrasound (US) guidance during embryo transfer (ET)., Methods: In this systematic review, we included randomized controlled trials examining the effect of the use of US guidance during ET; data from studies using the same catheter type in study arms were not pooled with the results from studies that used different catheter types., Results: Twenty-one studies were included in the quantitative analysis: 18 compared 'US guidance' with 'clinical touch', of which one was subsequently excluded from the quantitative meta-analysis owing to a lack of available data, three studies compared transvaginal US guidance with transabdominal US guidance, and one study compared 'hysterosonometry before ET' with US guidance. Comparison of the use of US guidance with clinical touch, in studies that used the same catheter type in the study arms, indicated a benefit of using US guidance during ET on the rates of live birth (relative risk (RR), 1.48 (95% CI, 1.16-1.87)), based on two studies involving 888 women with moderate-quality evidence, and on the rates of clinical pregnancy (RR, 1.32 (95% CI, 1.18-1.46)), based on 13 studies involving 3641 women with high-quality evidence. However, when comparing the use of US guidance with clinical touch in studies that used different catheter types, the results suggest that using US guidance during ET has no effect on the rates of reproductive outcome: live birth (RR, 0.99 (95% CI, 0.83-1.19)), based on one study involving 1649 women with moderate-quality evidence; clinical pregnancy (RR, 1.04 (95% CI, 0.89-1.21)), based on five studies involving 2949 women with moderate-quality evidence. The estimates for the rate of miscarriage and for the other identified comparisons were imprecise., Conclusions: The available evidence suggests that there is a benefit of using US guidance during ET. However, both US-guided transfer and clinical touch should be considered acceptable, as the benefit of US is not large and should be balanced against the increased cost and need to change the catheter type. More studies are required before conclusions can be drawn regarding the effect of other techniques on reproductive outcome., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To identify, appraise and summarize the available evidence regarding the effectiveness and safety of time-lapse embryo monitoring on the main outcomes of assisted reproductive techniques., Methods: In this systematic review and meta-analysis, we included only randomized controlled trials (RCTs) comparing time-lapse embryo imaging with standard embryo monitoring. Our primary outcomes were live births (efficacy) and congenital abnormalities (safety). The secondary outcomes were clinical pregnancy, ongoing pregnancy and miscarriage., Results: Two RCTs were considered eligible, and their data were extracted and included in a meta-analysis. In both studies embryos were transferred at the blastocyst stage. No studies reported rates of live birth or congenital abnormalities. Our estimates were not sufficiently precise to identify whether time-lapse monitoring provided a small benefit, no effect or minor harm on rates of clinical pregnancy (relative risk (RR), 1.05 (95% CI, 0.80-1.38)) or ongoing pregnancy (RR, 1.05 (95% CI, 0.76-1.45)), based on two studies involving 138 women with moderate-quality evidence. Considering the available data, we were unable to determine whether the intervention poses substantial benefit, no effect or substantial harm in the risk of miscarriage (RR, 0.95 (95% CI, 0.30-2.99)), based on two studies involving 76 clinical pregnancies with low-quality evidence., Conclusions: Time-lapse embryo imaging is unlikely to have a large effect on the chance of achieving clinical and/or ongoing pregnancy when transferring embryos at the blastocyst stage. More studies are required to improve the quality of the current evidence and also to examine whether this intervention is useful when transferring embryos at the cleavage stage., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate whether the presence or severity of endometriosis affects the outcome of assisted reproductive techniques (ART)., Methods: In this systematic review, all studies comparing the outcome of ART in women with and those without endometriosis, or at different stages of the disease, were considered eligible. We used either risk ratio (RR) or mean difference (MD) and their 95%CIs for comparisons. The primary outcome was live birth; the secondary outcome was clinical pregnancy. Miscarriage and the number of oocytes retrieved were examined as additional outcomes., Results: We included 92 studies in the review and 78 in the meta-analysis: 20,167 women with endometriosis were compared with 121,931 women without endometriosis, and 1703 women with Stage-III/IV endometriosis were compared with 2227 women with Stage-I/II endometriosis. The following results were observed for the comparison of women with endometriosis vs women without endometriosis: live birth, RR = 0.99 (95%CI, 0.92-1.06); clinical pregnancy, RR = 0.95 (95%CI, 0.89-1.02); miscarriage, RR = 1.31 (95%CI, 1.07-1.59); number of oocytes retrieved, MD = -1.56 (95%CI, -2.05 to -1.08). The following results were observed for the comparison of women with Stage-III/IV vs Stage-I/II endometriosis: live birth, RR = 0.94 (95%CI, 0.80-1.11); clinical pregnancy, RR = 0.90 (95%CI, 0.82-1.00); miscarriage, RR = 0.99 (95%CI, 0.73-1.36); number of oocytes retrieved, MD = -1.03 (95%CI, -1.67 to -0.39)., Conclusions: Women with endometriosis undergoing ART have practically the same chance of achieving clinical pregnancy and live birth as do women with other causes of infertility. No relevant difference was observed in the chance of achieving clinical pregnancy and live birth following ART when comparing Stage-III/IV with Stage-I/II endometriosis. The quality of the evidence for the additional examined outcomes was very low, not allowing meaningful conclusions to be drawn., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)