Managing patients with suspected postpartum retained products of conception using a novel sonographic classification.

BACKGROUND: Suspicion of retained products of conception (RPOC) often arises after delivery and still poses a diagnostic and management challenge. PURPOSE: To prospectively evaluate a sonographic classification for the management of patients with suspected RPOC after delivery. MATERIAL AND METHODS: Based on grayscale and Doppler ultrasound parameters, patients were classified into high, moderate, or low probability of RPOC. For the low and moderate probability groups, an ultrasound follow-up at the end of the puerperium was recommended. For the high probability group, a follow-up examination was conducted 10-14 days after the first ultrasound, and patients with persistent high probability findings were referred for surgical intervention. RESULTS: The sample was composed of 215 patients at risk of RPOC. Of these, 100, 93, and 22 patients were classified as having a low, moderate, or high probability of RPOC, respectively. Rates of RPOC were 55%, 2%, and 2% in the high, moderate, and low probability categories, respectively. When the categorization was based on the most recent ultrasound obtained during the puerperium, the adjusted RPOC prevalence rates were 71% in the high, 6% in the moderate, and 0% in the low probability groups. CONCLUSION: This study confirms the effectiveness of our sonographic classification for managing patients with suspected RPOC after delivery. In all three categories, it is recommended to adhere to a conservative management protocol in clinically stable women until the end of the puerperium. This approach provides good predictability for RPOC and can reduce unnecessary surgical interventions.

Tissue stiffness at the human maternal-fetal interface.

STUDY QUESTION: What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and placenta? SUMMARY ANSWER: The stiffness of decidua basalis, the site of placental invasion, was an order of magnitude higher at 103 Pa compared to 102 Pa for decidua parietalis, nonpregnant endometrium and placenta. WHAT IS KNOWN ALREADY: Mechanical forces have profound effects on cell behavior, regulating both cell differentiation and migration. Despite their importance, very little is known about their effects on blastocyst implantation and trophoblast migration during placental development because of the lack of mechanical characterization at the human maternal-fetal interface. STUDY DESIGN, SIZE, DURATION: An observational study was conducted to measure the stiffness of ex vivo samples of human nonpregnant secretory endometrium (N = 5) and first trimester decidua basalis (N = 6), decidua parietalis (N = 5), and placenta (N = 5). The stiffness of the artificial extracellular matrix (ECM), Matrigel®, commonly used to study migration of extravillous trophoblast (EVT) in three dimensions and to culture endometrial and placental organoids, was also determined (N = 5). PARTICIPANTS/MATERIALS, SETTING, METHODS: Atomic force microscopy was used to perform ex vivo direct measurements to determine the stiffness of fresh tissue samples. Decidua was stained by immunohistochemistry (IHC) for HLA-G+ EVT to confirm whether samples were decidua basalis or decidua parietalis. Endometrium was stained with hematoxylin and eosin to confirm the presence of luminal epithelium. Single-cell RNA sequencing data were analyzed to determine expression of ECM transcripts by decidual and placental cells. Fibrillin 1, a protein identified by these data, was stained by IHC in decidua basalis. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that decidua basalis was significantly stiffer than decidua parietalis, at 1250 and 171 Pa, respectively (P < 0.05). The stiffness of decidua parietalis was similar to nonpregnant endometrium and placental tissue (250 and 232 Pa, respectively). These findings suggest that it is the presence of invading EVT that is driving the increase in stiffness in decidua basalis. The stiffness of Matrigel® was found to be 331 Pa, significantly lower than decidua basalis (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Tissue stiffness was derived by ex vivo measurements on blocks of fresh tissue in the absence of blood flow. The nonpregnant endometrium samples were obtained from women undergoing treatment for infertility. These may not reflect the stiffness of endometrium from normal fertile women. WIDER IMPLICATIONS OF THE FINDINGS: These results provide direct measurements of tissue stiffness during the window of implantation and first trimester of human pregnancy. They serve as a basis of future studies exploring the impact of mechanics on embryo implantation and development of the placenta. The findings provide important baseline data to inform matrix stiffness requirements when developing in vitro models of trophoblast stem cell development and migration that more closely resemble the decidua in vivo. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Centre for Trophoblast Research, the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z), the Medical Research Council (MR/P001092/1), the European Research Council (772426), an Engineering and Physical Sciences Research Council Doctoral Training Award (1354760), a UK Medical Research Council and Sackler Foundation Doctoral Training Grant (RG70550) and a Wellcome Trust Doctoral Studentship (215226/Z/19/Z).

Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology.

STUDY QUESTION: Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy? SUMMARY ANSWER: Microvascular filling of the IVS was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed. WHAT IS KNOWN ALREADY: During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester. STUDY DESIGN, SIZE, DURATION: Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was observed from 7 weeks with progressive disintegration thereafter. Of note, microvascular flux rate did not progressively increase until 13 weeks, which suggests that resistance to maternal flow in the early placenta may be mediated more proximally by myometrial radial arteries that begin remodeling at the end of the first trimester. LIMITATIONS REASONS FOR CAUTION: Gestational age was determined by crown-rump length measurements obtained by transvaginal ultrasound on the day of contrast-enhanced imaging studies, which may explain the variability in the earliest gestational age samples due to the margin of error in this type of measurement. WIDER IMPLICATIONS OF THE FINDINGS: Our comprehensive in situ histological analysis, in combination with the use of an in vivo imaging modality that has the sensitivity to permit visualization of microvascular filling, has allowed us to reveal new evidence in support of increasing blood flow to the IVS from 6 weeks of gestation. Histologic review suggested the mechanism may be blood flow through capillary-sized channels that form through the loosely cohesive 'plugs' by 7 weeks gestation. However, spiral artery remodeling on its own did not appear to explain why there is significantly more blood flow at 13 weeks gestation. Histologic studies suggest it may be related to radial artery remodeling, which begins at the end of the first trimester. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests.

Accuracy of first-trimester ultrasound in diagnosis of intrauterine pregnancy prior to visualization of the yolk sac: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound in predicting the location of an intrauterine pregnancy before visualization of the yolk sac is possible. METHODS: This was a systematic review conducted in accordance with the PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library for relevant citations. Studies were selected in a two-stage process and their data extracted by two reviewers. Accuracy measures were calculated for each ultrasound sign, i.e. gestational sac, double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac. Individual study estimates were plotted in summary receiver-operating characteristics curves and forest plots for examination of heterogeneity. The quality of included studies was assessed. RESULTS: Seventeen studies including 2564 women were selected from 19 959 potential papers. Following meta-analysis, the presence of a gestational sac on ultrasound examination was found to predict an intrauterine pregnancy with a sensitivity of 52.8% (95% CI, 38.2-66.9%) and specificity of 97.6% (95% CI, 94.3-99.0%). The corresponding performance of the double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac were: 81.8% (95% CI, 68.1-90.4%) and 97.3% (95% CI, 76.1-99.8%); 66.1% (95% CI, 58.9-72.8%) and 100% (95% CI, 91.0-100%); 79.9% (95% CI, 73.0-85.7%) and 97.1% (95% CI, 89.9-99.6%); and 42.2% (95% CI, 27.7-57.9%) and 100% (95% CI, 54.1-100%), respectively. CONCLUSION: Visualization of a gestational sac, double decidual sac sign, intradecidual sign or chorionic rim sign increases the probability of an intrauterine pregnancy but is not as accurate for diagnosis as the detection of the yolk sac. However, the findings were limited by the small number and poor quality of the studies included and heterogeneity in the index test and reference standard.

First-trimester reference ranges for decidual thickness and its relation to progesterone levels.

AIMS: The present study aimed to provide normal reference ranges for decidual thickness measured ultrasonographically in healthy first-trimester pregnancies and to evaluate whether there was a relationship between decidual thickness and serum progesterone levels. METHODS: Decidual thickness of 173 women with a healthy gestation between 6+0 and 9+6 weeks was measured ultrasonographically and serum progesterone concentration was determined. Distribution of decidual thickness at each gestational week and its relation with serum progesterone levels was evaluated. RESULTS: Mean decidual thickness was 6.8, 5.7, 5.5, and 6.1 mm at 6th, 7th, 8th, and 9th gestational weeks, respectively. Decidual thickness showed a mild negative correlation with gestational week (ρ=-0.207, P=0.006) and a mild positive correlation with serum progesterone concentrations (ρ=0.191, P=0.021). CONCLUSION: The present study provided normal reference ranges for decidual thickness in healthy pregnancies in the first trimester. The association found between decidual thickness and progesterone levels might shed light on further studies investigating the predictive factors of pregnancy loss and might lead to changes in the management of threatened miscarriage.

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.

Analysis of the frequency of type 2 innate lymphoid cells and regulatory T cells in abortion-prone mice.

Recurrent spontaneous abortion (RSA) is the most common pregnancy related complication, affecting 1-5 % of pregnancies. Despite hormonal, genetic and anatomical factors that result in abortion, impairment of immune response at the feto-maternal interface during the first trimester of pregnancy is also one of the main causes of RSA. In the present study, we evaluated the frequency of blood and uterine group 2 innate lymphoid cells (ILC2s), their subsets and regulatory T cells (Tregs) in CBA/J × DBA/2 J as an abortion-prone model compared to normal pregnant (NP) mice using immunophenotyping. Results indicated that the percentages of ILC2s were significantly decreased in the AP group compared to the NP group at mid-gestation (P ≤ 0.01). Moreover, the percentages of both blood and uterine nILC2s were increased in NP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively), while iILC2s significantly increased in AP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively). Tregs were reduced in AP mice at both early and mid-gestation stages (P ≤ 0.01). Overall, our findings suggest that the changes in blood and uterine ILC2s might be associated with abortion in mice.

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.

Placenta accreta in the first trimester of pregnancy: sonographic findings.

In a case of histologically confirmed placenta increta, decidual protrusion into the myometrium was observed sonographically at 6 weeks' gestation, corresponding to placental protrusion from a disrupted placental-uterine wall interface seen in the later part of the first and second trimester. It is hypothesized that the histologic finding of decidual scarcity in placenta accreta is not a cause but rather an end result of the recruitment of trophoblasts across the decidual-placental interface in a maternal attempt at healing and/or repair in the presence of uterine injury, disease, or malformation that accounts for the associated factors and course of the condition.

A Case of Bilateral Decidualized Endometriomas during Pregnancy: Radiologic-pathologic Correlation.

Clinical differentiation between decidualized endometrioma and malignant transformation still poses difficulties as both are intracystic vascularized excrescences of an endometrial cyst and exhibit similar characteristics on color-flow Doppler sonography. This is a characteristic sonographic finding associated with ovarian cancer, but MRI can provide further information about mural excrescences that can aid in their differential diagnosis; for example, the signal of decidualized endometriomas is isointense with the placenta within the uterus on all sequences and the apparent diffusion coefficient is higher than that of malignant mural nodules. Thus, MRI should be an aid in deciding whether to intervene during pregnancy. However, considering that it is not yet possible to clearly differentiate decidualized endometriomas from ovarian cancer, surgery or watchful observation may still be needed to exclude the possibility of malignancy.

Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling.

Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternal-fetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNK-endothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-α expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired.

Determination of intervillous flow in early pregnancy.

The process of placentation in the macaque has been extensively studied and found to resemble closely that observed in the human. In this model, histopathologically, intervillous flow is anticipated from week 3 post-conception. We set out to document the nature and onset of intervillous flow in the macaque in vivo using colour Doppler imaging (CDI), colour Doppler energy (CDE) and pulsed-wave Doppler (PWD). Pregnant females were assessed between 15-50 days gestation (term = 165 days) with an Acuson 128/XP10 high-resolution ultrasound scanner, using a 7-MHz linear array probe. The placenta, subjacent decidua and myometrium were assessed using CDI and CDE. Specific regions of flow were interrogated using PWD; the resulting flow velocity waveforms were stored and quantified using conventional Doppler indices. B-mode sonography was able to demonstrate the well-defined placental-decidual interface observed in this species; CDI and CDE clearly visualized the uteroplacental vasculature. Spiral arteries were followed to their point of discharge into the intervillous space, and PWD at these sites obtained a characteristic flow velocity waveform. The indices obtained confirmed a flow of low resistance and pulsatility throughout the gestation studied. Flow within the intervillous space was noted from day 20 of gestation.

Human decidual production of hepatocyte-growth factor is not influenced by trophoblastic invasion in vivo.

OBJECTIVE: To evaluate and compare production of hepatocyte growth factor (HGF) from human first-trimester implantation-site decidua (decidua basalis) and nonimplantation site decidua (decidua parietalis), and hence to determine whether human trophoblast invasion in vivo is associated with increased decidual HGF production. DESIGN: Controlled prospective study. SETTING: University hospital-based study. PATIENT(S): Ten women undergoing first-trimester termination of singleton pregnancy for psychosocial reasons without preexisting medical or gynecologic diseases. INTERVENTION(S): Decidual samples surgically excised and processed for paraffin-embedded immunohistochemistry and for reverse transcription-polymerase chain reaction (RT-PCR) studies. MAIN OUTCOME MEASURE(S): Protein and mRNA production in decidua basalis and decidua parietalis by immunohistochemistry and RT-PCR, respectively. RESULT(S): No statistically significant difference was found between decidua basalis and decidua parietalis in HGF protein or mRNA production. Immunohistochemical analysis (n = 9) showed a mean score of 3.28 +/- 2.37 for decidua basalis and 3.61 +/- 2.66 for decidua parietalis. Semiquantitative analysis of HGF mRNA expression between the two sites showed no statistically significant difference (n = 10) CONCLUSION(S): Human decidual production of HGF is not influenced by trophoblastic invasion in vivo.

Radiographical and histological evaluation of canine decidual reaction induced by intralumenal injection of bouillon solution mixed with or without barium sulfate.

Radiographical examination of the canine uterus intralumenally injected with barium solution revealed that barium was gradually condensed, segmented and distributed equally along the lumen like embryos in early pregnant uterus. Histological examination of the uterus intralumenally injected with bouillon solution alone showed a remarkable fish net- or tree branch-like growth of superficial glands towards the uterine lumen. The uterus injected with barium in bouillon solution induced two different histological changes: One consisted of cystic glandular hyperplasia in the whole endometrium, which was a so-called Swiss cheese endometrium, and the other was composed of a fish net- or tree branch-like growth in the superficial layer accompanied with cystic glandular hyperplasia in the basal layer. The latter represented endometrial differentiation into spongy layer, supraglandular layer and basal glandular layer, being similar to that during normal early placentation. These findings suggest that clotted barium in bouillon solution has stimulating effects on the uterus similar to those of embryos.

[Sonographic diagnosis of ectopic pregnancy: optimal strategy?]. / Diagnostic échographique des grossesses extra-utérines. La sémiologie de base: comment optimiser les performances de l'échographie?

AIM AND METHODS: The diagnostic algorithms of ectopic pregnancy (EP) include sonographic procedures. Diagnostic sensitivity is low because the procedure is operator-dependent and each clinical aspect of EP is variable. We analyzed results of standardized ultrasound procedures performed within the framework of a detailed analysis of clinical findings. RESULTS: The sonographic procedure must be performed within the framework of an overall analysis including laboratory results (hCG level), examination of the decidua, localization of the corpus luteum, and careful detailed examination of adnexa. Hematosalpinx is pathognomonic of EP and is observed in 80% of cases. When diagnosis is doubtful, a second ultrasound procedure should be performed 48 hours later before undertaking laparoscopic diagnosis. CONCLUSION: The diagnostic sensitivity of ultrasonography has been consistently high in published series, undoubtedly because the studies were performed in referral centers highly experienced in diagnostic ultrasound.

[Vaginal bleeding and premature contractions during pregnancy in uterus bicornis with expulsion of a decidual polyp]. / Ausstossung eines Deziduapolypen aus dem nichtgraviden Uterushorn bei einer Schwangerschaft mit Uterus bicornis.

Diagnosis and clinical course of a rare case are described, and the importance of prenatal ultrasound diagnostic is discussed.

Decidualization of ovarian endometriosis during pregnancy mimicking malignancy.

OBJECTIVE: The purpose of this series is to present deciduosis (the formation of extrauterine decidua) as one of the differential diagnoses of a malignant tumor during pregnancy. METHODS: Two cases are described in which pregnant patients had a pelvic tumor. The lesions, which were diagnosed in the early second trimester, consisted of complex masses with an extensive blood supply and had a sonographic appearance of a malignant tumor. The high suspicion for malignancy necessitated surgical intervention. RESULTS: During surgery, the lesions were observed to be of an ovarian origin with papillary excrescences covering their exterior. The lesions were excised and sent for histologic examination. The results showed a markedly decidualized endometriotic cyst in both cases. CONCLUSIONS: This phenomenon is a diagnostic challenge and should be considered in the differential diagnosis of a malignant mass during pregnancy.

The intradecidual sign: is it reliable for diagnosis of early intrauterine pregnancy?

OBJECTIVE: Our aim was to determine the accuracy of the intradecidual sign for the diagnosis of intrauterine pregnancy and the exclusion of ectopic pregnancy. CONCLUSION: The intradecidual sign reliably excludes the presence of an ectopic pregnancy. The sensitivity for diagnosis of an intrauterine pregnancy increases when human chorionic gonadotropin levels are equal to or greater than 2,000 mIU/mL or the mean sac diameter is equal to or greater than 3 mm. It is of utmost importance to visualize this sign on multiple views with an unchanging appearance.