Ultrasonography for the prediction of extension of trophoblastic infiltration into the tubal wall in ampullary pregnancy.

OBJECTIVE: Predictive factors of damage to the Fallopian tube may guide the treatment for patients with tubal pregnancy. The purpose of this study was to evaluate the predictive value of ultrasonographic findings in patients affected by ampullary pregnancy for the determination of the depth of trophoblastic infiltration into the tubal wall on histological examination. MATERIAL AND METHODS: 38 patients with ampullary pregnancy undergoing salpingectomy were enrolled into the study. The patients were divided into two subgroups depending on their transvaginal sonography (TVS) findings; either an ectopic gestational sac containing an embryo with cardiac activity or those with a tubal ring. The ampullary pregnancies were histologically classified according to the depth of infiltration of trophoblastic tissue into the tubal wall as follows: stage I: limited to mucosa; stage II: extension to the muscularis layer; stage III: complete infiltration of the tubal wall with or without rupture of the serosa. The association between findings on TVS and stage of trophoblastic invasion, serum beta-human chorionic gonodatropin (ß-hCG) levels was evaluated. RESULTS: Although there was no significant difference among two groups in terms of histological stage of trophoblastic infiltration (p = 0.257), patients in whom an embryo with cardiac activity had been identified were found to have higher percentage of stage II (47.8%) or stage III (8.7%) invasion. However, there was a significant difference in serum ß-hCG levels on the day of surgery among the two groups (p = 0.028). CONCLUSIONS: Ultrasonographic aspect of ampullary pregnancy is associated with depth of trophoblastic infiltration into the tubal wall and serum ß-hCG levels.

First trimester trophoblast and placental bed vascular volume measurements in IVF or IVF/ICSI pregnancies.

STUDY QUESTION: Are first trimester trophoblast volume (TV) and placental bed vascular volume (PBVV) different in IVF or IVF/ICSI pregnancies in comparison with spontaneously conceived pregnancies? SUMMARY ANSWER: Any possible abnormal placentation in IVF or IVF/ICSI pregnancies in comparison with spontaneously conceived pregnancies is not detected by a difference in PBVV or TV at an early gestational age (GA). WHAT IS KNOWN ALREADY: Assisted reproductive technology pregnancies have been associated with an increased risk of placenta-related adverse pregnancy outcomes. It is unclear whether these effects originate from infertility or from the technique itself. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study in which 154 pregnant patients qualified for participation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 154 pregnant patients, 84 conceived spontaneously and 70 conceived after IVF or IVF/ICSI. We determined the TV at 10 weeks GA by Virtual Organ Computer-aided AnaLysis measuring application and the PBVV at 12 weeks GA by the virtual reality operating system of BARCO I-Space in both subgroups. The investigators were blinded to the mode of conception during the measurements. Analysis was limited to singleton pregnancies with only one sac ever detectable. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in TV (mean 42.7, SD 15.9 versus mean 41.2, SD 13.9, P = 0.70) and PBVV (mean 27.6, SD 16.9 versus mean 24.8, SD 19.9, P = 0.20) between IVF or IVF/ICSI pregnancies and spontaneously conceived pregnancies. There was a significant correlation between TV and PBVV (rs = 0.283, P = 0.004). LIMITATIONS, REASONS FOR CAUTION: The limitations of the present study concern the small size of the study groups. WIDER IMPLICATIONS OF THE FINDINGS: IVF or IVF/ICSI does not seem to be associated with abnormal placentation. STUDY FUNDING/COMPETING INTERESTS: This study was financially supported by the Erasmus Trustfonds, the Meindert de Hoop foundation and the Fonds NutsOhra. No competing interests are declared.

Early first-trimester trophoblast volume in pregnancies that result in live birth or miscarriage.

OBJECTIVES: To assess the validity of trophoblast volume measurements on three-dimensional ultrasound (3D-US) with Virtual Organ Computer-aided AnaLysis (VOCAL(TM) ), to create reference values between 6 and 12 weeks of gestation and to compare trophoblast volume between pregnancies ending in miscarriage and those resulting in live birth. METHODS: In a prospective periconceptional cohort, we performed weekly 3D-US in 112 singleton pregnancies resulting in a non-malformed live birth and in 56 ending in miscarriage. Scans were performed between 6 and 12 weeks. Trophoblast volumes were calculated by subtracting the gestational sac volume from the volume of the total pregnancy. The interobserver and intraobserver agreement of measurements were determined to assess validity. Reference values were created for trophoblast volume in relation to crown-rump length and gestational age. RESULTS: A total of 722 3D-US examinations were available for offline VOCAL measurements, but measurements could be performed in only 53% of these due to non-targeted scanning and incomplete framing. Interobserver and intraobserver agreement for trophoblast volume measurements were excellent, with intraclass correlation coefficients > 0.97. Trophoblast volumes of pregnancies ending in miscarriage were significantly smaller (P < 0.01) than were those of pregnancies that resulted in live birth. Trophoblast growth in pregnancies ending in miscarriage was also reduced compared with that in pregnancies that resulted in live birth. CONCLUSION: VOCAL is a valid technique for measuring trophoblast volume during the early first trimester of pregnancy. Pregnancies ending in miscarriage have smaller trophoblast volumes as well as reduced trophoblast growth compared with those that result in live birth.

Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction.

Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero-placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the prediction of FGR offered by a model based on placental volume.

Free blastocyst and implantation stages in the European brown hare: correlation between ultrasound and histological data.

The European brown hare (Lepus europaeus) is the only species with superconception, whereby the maternal reproductive tract hosts two sets of conceptuses at different developmental stages. The embryonic development of the hare has not yet been described. To understand the mechanism of superconception, we studied oviduct transport and implantation stages by embryo flushing and live high-resolution ultrasound. Ultrasound data of implantation stages is correlated with histology. In the oviduct, a mucin coat is deposited on the zona pellucida. The blastocysts enter the uterine horns on Day 5, 1 day later than in the rabbit, and directly expand approximately threefold. Spacing is accompanied by peristaltic movement of the endometrium. The mucin coat disappears and the conceptuses attach. The yolk-sac expands in the blastocoel and syncytial knobs invade the antimesometrial endometrium. Maternal blood lacunae appear in the mesometrial endometrial folds, which are subsequently invaded by the syncytiotrophoblast. The haemochorial chorioallantoic placenta forms. The yolk-sac cavity is gradually replaced by the allantois and finally by the exocoel. The different reproductive strategies of the precocial hare and the altricial rabbit are discussed. We assume that the lagomorph-specific mucin coat and the hare-specific delay of the oviduct-uterine transition are prerequisites for superconception.

Screening for placenta accreta at 11-14 weeks of gestation.

OBJECTIVE: We sought to describe the potential value of 11-14 weeks' screening for placenta accreta (PA). STUDY DESIGN: Patients with a history of lower segment cesarean section were prospectively included between 11-13+6 weeks over a 1.5-year period. The first 258 were offered standard screening whereas the following 105 underwent screening for PA. Women were considered high-risk when the trophoblast overlapped the scar visualized by transvaginal ultrasound and low-risk otherwise. RESULTS: The group screened for PA did not differ from the nonscreened group for demographic characteristics. In all, 6 of 105 (5.8%) women were considered high-risk. In the nonscreened group, 1 case of PA was discovered during an elective repeat cesarean. In the screened population, 1 case of PA occurred in a high-risk patient allowing a conservative planned management at 35 weeks. CONCLUSION: At 11-14 weeks, ultrasound may help risk stratification for PA with a specific follow-up. Early recognition of patients at risk might improve the perinatal outcome of PA.

Exaggerated placental site mimicking placental site trophoblastic tumor: case report and literature review.

Exaggerated placental site is defined as a non-neoplastic trophoblastic lesion featuring exuberant infiltration into the endometrium and myometrium by intermediate trophoblasts and syncytiotrophoblasts. Exaggerated placental site can occur following normal or ectopic pregnancy, abortion, or hydatidiform mole. We encountered a case of reactive exaggerated placental site seven months following normal pregnancy that clinically mimicked placental site trophoblastic tumor. Few reports have described the clinical course, histopathology and differential diagnosis of exaggerated placental site; we present our patient's case together with histopathological observations and review of related literature.

Sonographic study of the decidua basalis in early pregnancy loss.

OBJECTIVES: To describe the sonographic findings in the decidua basalis layer in spontaneous early pregnancy loss and to compare them with those in normal pregnancy. METHODS: We reviewed 119 scans at 4-10 weeks' gestation from 110 patients who miscarried clinically at less than 13 weeks' gestation and 132 scans also at 4-10 weeks from 98 patients who had normal uncomplicated term pregnancies. The thickness and echogenicity of the decidua basalis layer were compared between pregnancies which suffered early loss and normal controls. RESULTS: Relative thinning of the decidua basalis was observed in cases of early pregnancy loss from 5-6 weeks onwards when compared with normal pregnancies. In embryonic pregnancies that subsequently miscarried, the decidua basalis did not show the rising trend in thickness that was observed in normal pregnancies. Shortly before and after embryonic demise, the decidua appeared relatively more echogenic compared with that in normal pregnancy and the placenta showed areas of hypoechogenicity. Embryonic demise was followed by disorganization of the decidual layer, which became difficult to recognize. Pregnancy with an empty sac showed a more gradual trend in the thinning of the decidua basalis, but the uniformity and echogenicity of the layer appeared to be relatively better preserved with time. CONCLUSION: The decidua basalis layer in pregnancies that are destined to miscarry in the first trimester differs sonographically from that in normal pregnancies. The sonographic differences are suggestive of a defective decidual-placental complex resulting from deficient trophoblastic invasion.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy.

OBJECTIVE: Predictive factors of damage to the Fallopian tube may guide the treatment of patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonography (TVS) in women with ampullary pregnancy. METHODS: Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 85 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. RESULTS: There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity had been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). CONCLUSIONS: In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring.

Sonographic study of the decidua basalis in the first trimester of pregnancy.

OBJECTIVES: To describe the sonographic appearance of the decidua basalis and its changes in the first trimester of pregnancy. METHODS: We reviewed images from 159 first-trimester ultrasound examinations in 105 women with uncomplicated pregnancies who later delivered at term. The appearance of the decidua basalis layer and the sonographic changes that it underwent, including in echogenicity and thickness, were analyzed with respect to gestational age. RESULTS: A distinct decidual layer could be identified consistently at 5-6 weeks' gestation and its thickness peaked at 6-7 weeks. It was seen inconsistently at 8-9 weeks and was not identifiable by 10 weeks. Its appearance changed over time, from a uniformly echogenic layer at 5-6 weeks to a heterogeneous echogenic layer at 7 weeks, corresponding to the histological evidence of trophoblast penetration. The layer then became less echogenic with time until it became unidentifiable. CONCLUSIONS: There is a window of opportunity in the first trimester for sonographic examination of the decidua. This may allow screening, at an early stage, for conditions that affect the decidua during pregnancy.

Occurrence and outcome of residual trophoblastic tissue: a prospective study.

OBJECTIVE: The purpose of this study was to evaluate the occurrence of residual trophoblastic tissue after miscarriage or delivery, to assess the diagnostic value of sonography with color Doppler examination in the detection of retained tissue, and to define in what cases expectant management may be an option. METHODS: We conducted a prospective observational study using sonography with color Doppler imaging in consecutive patients at routine follow-up after miscarriage or delivery. Expectant management was proposed in all patients with suspected retained tissue providing they were hemodynamically stable and in the absence of signs of infection. In case of surgical removal of retained tissue, the histologic examination was compared with the sonographic findings. RESULTS: In total, 1070 patients were assessed. In 67 patients (6.3%), sonographic and color Doppler examination showed retained tissue, and in 41 (61%) of them, curettage was performed. In all but 1 case, retained tissue was confirmed on histologic examination. Cases of retained tissue were more often seen after first-trimester (17%) or second trimester (40%) miscarriage, in the presence of abnormal uterine bleeding (57%), and with areas of enhanced myometrial vascularity (77.3%). CONCLUSIONS: Sonography with color Doppler examination is clinically useful to confirm or exclude residual trophoblastic tissue.

Uterine artery Doppler velocimetry at 11-14 weeks in singleton pregnancies conceived by assisted reproductive technology.

OBJECTIVE: Singleton pregnancies resulting from assisted reproductive technologies (ART) have an increased risk of preterm delivery, pre-eclampsia and intrauterine growth restriction. The aim of the present study was to determine whether first-trimester trophoblastic invasion, as assessed by uterine artery Doppler velocimetry, is different in singleton pregnancies resulting from ART compared to those conceived naturally. METHODS: Case-control study on 31 singleton ART pregnancies (26 in-vitro fertilization-embryo transfer, five intracytoplasmic sperm injection) and 62 matched pregnancies conceived spontaneously. Doppler velocimetry was performed at 11-14 weeks of gestation. RESULTS: The mean resistance index (coefficient of variation) was 0.70 (17%) and 0.70 (18%) in ART and controls, respectively (P = 0.92). The corresponding values for mean pulsatility index were 1.40 (44%) and 1.47 (44%) in ART and controls, respectively (P = 0.58). Pregnancies with no, unilateral or bilateral diastolic notches were 48%, 26%, 26% and 36%, 37%, 27%, in ART and controls, respectively (P = 0.43). CONCLUSION: There are no differences in uterine artery Doppler indices between pregnancies obtained by invasive ART and naturally conceived matched controls. This finding suggests that there is no major difference in trophoblastic invasion of the maternal spiral arteries between ART and spontaneous pregnancies.

Histological classification of chorionic villous vascularization in early pregnancy.

BACKGROUND: The objective of the study was to assess the reproducibility of a new classification for early pregnancy chorionic villous vascularization (Grade: I, normal; IIA, mild hypoplasia; IIB, severe hypoplasia and III, avascular) for routine microscopic examination in daily clinical practice. METHODS: In this observational study, four observers scored first trimester chorionic villous vascularization. Scoring was performed in microscopic slides of chorionic tissue obtained by D&C in 30 patients with early pregnancy loss due to empty sac (n = 10), fetal death (n = 10) and termination of pregnancy (n = 10) using the new classification. Ultrasonographic measurement of trophoblastic thickness (TT) at the implantation site was available in all patients and in a reference group of 100 ongoing singleton pregnancies. The vascularization score could therefore be related to the TT. RESULTS: The new classification resulted in a good-to-excellent agreement in histological scoring (0.73-0.90) between investigators (kappa 0.64-0.86). TT was not related to either vascularization or pregnancy outcome and only partly to hydropic degeneration. CONCLUSION: The vascularization scoring system is a simple, valid and effective method for assessment of chorionic villous vascularization. It is helpful in understanding the underlying cause of pregnancy loss, as the classification can distinguish between normal and abnormal embryonic development. We did not find either a relation between TT and pregnancy outcome or between TT and vascularization.

Sonographic versus clinical evaluation as predictors of residual trophoblastic tissue.

BACKGROUND: The study aims to compare the diagnostic accuracy of sonographic evaluation versus clinical estimation in women suspected to have retained trophoblastic fragments. METHODS: The study group consisted of 68 consecutive patients admitted to our department due to suspected residual trophoblastic tissue. Each woman underwent ultrasound and physical examination by expert clinicians. The clinicians performing the physical examination were not informed of the sonographic findings, and vice versa. RESULTS: Patients were divided into three subgroups: clinical suspicion only of residual trophoblastic tissue (n = 8), sonographic suspicion only (n = 44) and combined sonographic and clinical suspicion of residual trophoblastic tissue (n = 16). In the latter group, in 14 out of 16 women (87.5%) retained trophoblastic tissue was confirmed by histological examination, a significantly higher rate compared to ultrasonographic (45.5%, P < 0.002) or clinical suspicion only (62.5%, P = 0.07). The specificity and positive predictive value of the clinical examination were significantly higher compared to ultrasonographic evaluation (P < 0.05), while the sensitivity of the ultrasonographic evaluation was higher than the clinical estimation (P < 0.05). There was no statistically significant difference in the negative predictive value or in diagnostic accuracy between the two methods. CONCLUSIONS: Based on our current experience, it seems that the combination of both clinical and ultrasonographic evaluation is recommended before uterine curettage is performed, thus lowering the rate of unnecessary invasive procedures.

Risk factors for persistent trophoblastic activity after surgery for ectopic pregnancy.

BACKGROUND: The purpose of this study was to explore the value of preoperative ultrasound and human chorionic gonadotropin (hCG) monitoring to predict the occurrence of residual trophoblastic tissue after laparoscopic conservative surgery for tubal pregnancy. METHODS: During the period from January 1998 to December 1999 all 206 women undergoing treatment for ectopic pregnancy at the Karolinska hospital were included in the study. A vaginal ultrasound examination was performed and the ectopic size was measured. Serum-hCG levels were recorded preoperatively, and at days 1-2 and 14-21 after surgery. RESULTS: A diameter of 8 mm or less was observed in 13 of the 14 patients needing secondary treatment. The risk of second surgery if the finding at the preoperative ultrasound was larger than 8 mm was 1/73 resulting in a negative predictive value of 0.01. A considerable overlap in the hCG levels was found on days 1-2 after surgery between women with and without second surgery. CONCLUSIONS: Using a single cutoff point for hCG seems to be of little value as residual trophoblastic tissue can manifest itself at different times--early or late--during the postoperative period. Women with a small ectopic pregnancy as detected by preoperative vaginal ultrasound are at high risk of developing residual trophoblastic tissue. These patients should be considered by the surgeon and monitored with hCG levels until values decline and become undetectable. Management of patients with slowly but declining values can be conservative. If hCG levels are rising or do not decline, methotrexate (MTX) can be an alternative.

Human chorionic gonadotropin level as a predictor of trophoblastic infiltration into the tubal wall in ectopic pregnancy: a blinded study.

OBJECTIVE: To determine the relationship between gestational age, tubal ultrasonographic diameter, and serum hCG levels and different stages of trophoblastic infiltration of the tubal wall in ectopic pregnancy. DESIGN: Blinded prospective study. SETTING: University-based clinic in Italy. PATIENT(S): Thirty-seven consecutive patients with an ampullary ectopic pregnancy. INTERVENTION(S): Laparoscopic salpingectomy. MAIN OUTCOME MEASURE(S): Gestational age, diameter of the tubal mass as determined by transvaginal ultrasonography. and hCG level on the day of surgery. Ectopic pregnancy was classified according to the depth of trophoblastic infiltration: trophoblast limited to the tubal mucosa (stage I), extension to the tubal muscularis (stage II), or complete tubal wall infiltration up to the serosa discontinued by trophoblastic cells (stage III). RESULT(S): Fifteen patients (40.5%) had stage I tubal infiltration, 14 (37.8%) had stage II infiltration, and 8 (21.6%) had stage III infiltration. Gestational age and diameter of the tube did not differ among the three groups. The median hCG level was 1,710.5 mIU/mL (range, 113-5,635 mIU/mL) for patients with stage I infiltration. 4,690.0 mIU/mL (range, 150-21,531 mIU/mL) for patients with stage II infiltration, and 15,700.0 mIU/mL (range, 13,809-21,650 mIU/mL) for patients with stage III infiltration. All the patients with hCG levels > 6,000 mIU/mL had stage II or III invasion. CONCLUSION(S): These findings may explain why the conservative treatment of ectopic pregnancy is less successful in patients with high hCG levels than in patients with low levels. Use of radical procedures may be justified in the former group.

Implantation despite an extensive endometrial defect after hysteroscopic resection of symptom-free residual trophoblastic tissue 15 months after cesarean section.

Successful implantation occurred after embryo transfer in the presence of an extensive endometrial defect after hysteroscopic resection of residual trophoblastic tissue 15 months after cesarean section. At the end of hysteroscopic surgery the anterior uterine wall seemed smooth, although ultimately no endometrium was left in that part and in parts of the fundus. Thus implantation is possible even with extensive endometrial defects. Interesting facts in this case were, first, the long symptom-free period with residual trophoblastic tissue in the uterus, and, second, successful implantation, pregnancy, and delivery despite at least 30% of endometrial surface being irreversibly destroyed. We suggest hysteroscopic resection as the method of choice for exact and minimally traumatic removal of especially older residual trophoblastic tissue.

Sonohysterography for the diagnosis of residual trophoblastic tissue.

OBJECTIVE: To assess the efficacy, safety, and associated complications of sonohysterography for the diagnosis of residual trophoblastic tissue. METHODS: We conducted a prospective study of 23 consecutive patients admitted to our ultrasonography unit with clinical and ultrasonographic signs of retained intrauterine tissue. RESULTS: Twelve patients had hydrosonographic features suggestive of residual trophoblastic tissue (i.e., an intrauterine lesion not detachable from the uterine wall after instillation of saline), whereas in 11 cases the hydrosonographic findings were negative for retained tissue. Blood flow was detected within abnormal intrauterine masses in 4 of 12 patients with trophoblastic tissue, whereas it was not detected in any patient without retained tissue (P = .093). No complications were encountered during the procedure or the postprocedure period. None of the patients had anesthetic complications, perforation of the uterus, fluid overload, or any other surgical complication. All 12 patients underwent hysteroscopic removal of the suspected residual trophoblastic tissue, and histologic confirmation of residual trophoblastic tissue was obtained in all cases. CONCLUSIONS: Sonohysterography for detection and diagnosis of residual trophoblastic tissue is an accurate and safe procedure. Further studies comparing the efficacy of sonohysterography with that of diagnostic hysteroscopy are warranted.