Reproducibility of assessment of full-dilatation Cesarean section scar in women undergoing second-trimester screening for preterm birth.

OBJECTIVE: To assess the reproducibility of a standardized method of measuring the Cesarean section (CS) scar, CS scar niche and their position relative to the internal os of the uterine cervix by transvaginal ultrasound in pregnant women with a previous full-dilatation CS. METHODS: This was a prospective, single-center reproducibility study on women with a singleton pregnancy and a previous full-dilatation CS who underwent transvaginal ultrasound assessment of cervical length and CS scar characteristics at 14-24 weeks' gestation. The CS scar was identified as a hypoechogenic linear discontinuity of the myometrium at the anterior wall of the lower uterine segment or cervix. The CS scar niche was identified as an indentation at the site of the scar with a depth of at least 2 mm. The CS scar position was evaluated by measuring the distance to the internal cervical os. CS scar niche parameters, including its length, depth, width, and residual and adjacent myometrial thickness, were assessed in the sagittal and transverse planes. Qualitative reproducibility was assessed by agreement regarding visibility of the CS scar and niche. Quantitative reproducibility of CS scar measurements was assessed using three sets of images: (1) real-time two-dimensional (2D) images (real-time acquisition and caliper placement on 2D images by two operators), (2) offline 2D still images (offline caliper placement by two operators on stored 2D images acquired by one operator) and (3) three-dimensional (3D) volume images (volume manipulation and caliper placement on 2D images extracted by two operators). Agreement on CS scar visibility and the presence of a niche was analyzed using kappa coefficients. Intraobserver and interobserver reproducibility of quantitative measurements was assessed using Bland-Altman plots. RESULTS: To achieve the desired statistical power, 72 women were recruited. The CS scar was visualized in > 80% of images. Interobserver agreement for scar visualization and presence of a niche in real-time 2D images was excellent (kappa coefficients of 0.84 and 0.85, respectively). Overall, reproducibility was higher for real-time 2D and offline 2D still images than for 3D volume images. The 95% limits of agreement (LOA) for intraobserver reproducibility were between ± 1.1 and ± 3.6 mm for all sets of images; the 95% LOA for interobserver reproducibility were between ± 2.0 and ± 6.3 mm. Measurement of the distance from the CS scar to the internal cervical os was the most reproducible 2D measurement (intraobserver and interobserver 95% LOA within ± 1.6 and ± 2.7 mm, respectively). Overall, niche measurements were the least reproducible measurements (intraobserver 95% LOA between ± 1.6 and ± 3.6 mm; interobserver 95% LOA between ± 3.1 and ± 6.3 mm). There was no consistent difference between measurements obtained by reacquisition of 2D images (planes obtained twice and caliper placed), caliper placement on 2D stored images or volume manipulation (planes obtained twice and caliper placed). CONCLUSIONS: The CS scar position and scar niche in pregnant women with a previous full-dilatation CS can be assessed in the second trimester of a subsequent pregnancy using either 2D or 3D volume ultrasound imaging with a high level of reproducibility. Overall, the most reproducible CS scar parameter is the distance from the CS scar to the internal cervical os. The method proposed in this study should enable clinicians to assess the CS scar reliably and may help predict pregnancy outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A prospective study of ultrasound screening for molar pregnancies in missed miscarriages.

OBJECTIVE: To examine the relationship between ultrasound and histological features in the screening for molar changes in missed miscarriage. METHODS: A prospective cohort study was conducted on all missed miscarriages, with features suspicious of molar pregnancy, on transvaginal ultrasound and/or on histological examination over a 5-year period. All cases of molar pregnancy diagnosed histologically were examined and cross-referenced with cases diagnosed on ultrasound and with the supplementary report from the regional referral center. When available, maternal serum beta-human chorionic gonadotropin (hCG) levels were recorded. RESULTS: Fifty-one cases of suspected molar pregnancy were referred to the regional center for further histological opinion and follow-up, and five cases were subsequently excluded from the final analysis because of the diagnosis of hydropic abortion (HA). In 33 cases a molar pregnancy was suspected at the initial scan. Of these, 26 (78.8%) were confirmed on histology, resulting in a 56% detection rate using ultrasound alone. In 15 cases hCG results were available, of which nine were greater than two multiples of the median. CONCLUSIONS: The diagnosis of both complete (CHM) and partial (PHM) hydatidiform moles in first-trimester miscarriages is difficult. hCG is significantly higher in both CHM and PHM and, in conjunction with transvaginal ultrasound, could provide the screening test required to enable clinicians to counsel women more confidently towards non-surgical methods of management of their miscarriage, where histopathological examination is not available.

Human fetal nongonadal tissues contain human chorionic gonadotropin/luteinizing hormone receptors.

Human chorionic gonadotropin (hCG), a heterodimeric glycoprotein hormone produced in abundance by placental syncytiotrophoblasts, is preferentially secreted into maternal circulation. Fetal circulation also contains low levels of hCG that are probably derived from fetal kidney, liver, anterior pituitary gland, etc. In addition, the fetus has access to hCG present in exocoelomic and amniotic fluids. hCG has been found in a number of fetal tissues known to stimulate fetal adrenal and testicular steroidogenesis and is also thought to play a role in growth and differentiation of fetal tissues. This led us to test the hypothesis that fetal nongonadal tissues, as in the adult, may also contain hCG/LH receptors. This hypothesis was tested by immunocytochemistry, Western blotting, in situ hybridization, and RT-PCR. The results demonstrate that kidney, liver, pancreas, lung, small and large intestines, and adrenals contained hCG/LH receptors. Although the role of fetal nongonadal hCG/LH receptors is not known, they may mediate the pleiotropic actions of hCG in the growing human fetus.

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.

Detection of the immunoregulator p43-placental isoferritin in the human embryo and fetus.

Human placental isoferritin (PLF) is known to exert an immunosuppressive activity in vitro and is involved in the down-regulation of the maternal immune system during pregnancy. We have investigated the presence of PLF in the human embryo and early fetus and its secretion into amniotic fluid (AF) and fetal blood. Immunohistochemistry was performed on 25 normal embryos and fetuses, at 7-22 weeks gestation, using the CM-H9 monoclonal antibody (mAb), generated specifically against the human p43-PLF protein. The amount of p43 was measured in AF of 81 fetuses at 11-22 weeks and in the blood of 19 fetuses at 15-22 weeks by means of an enzyme-linked immunosorbent assay with the same mAb. Positive p43-PLF immunostaining was found from 7 weeks gestation in proximal tubules of the primitive nephron and macrophages of the liver sinusoids, blood vessels and mesenchymal tissue. In the AF samples, p43-PLF was first detected at week 15 gestation and thereafter steadily increased with advancing gestation whereas in fetal blood, p43-PLF was below or just above the lower limit of the assay. The gap between the first appearance of 43-PLF in embryonic tissue and its secretion into the amniotic fluid is probably linked to maturation of the renal function. The detection of the p43-PLF immunomodulator protein in macrophages at a very early stage of embryonic development and its very low concentration in fetal blood suggests that its immunoregulatory role is limited to the feto-maternal interface.

Diminished expression of placental isoferritin p43 component in first trimester abnormal pregnancies.

Human placental isoferritin (PLF) is a sub-type of human ferritin mainly composed of a 43 kD protein, which has an immunosuppressive activity and may be involved in the downregulation of the maternal immune system during pregnancy. The aim of this study was to evaluate the distribution of p43 in the placental tissue of abnormal first trimester pregnancies. Samples of villous and decidual tissues were collected between 7 and 12 weeks' gestation from 28 missed abortions and eight complete moles. Samples of placental tissue from 20 normal pregnancies of similar gestational age were used as controls. The localization of p43 was determined by immunohistochemical techniques using CM-H9 monoclonal antibody. Compared to controls, specific p43 immunoreactivity was low in the villous syncytiotrophoblast of missed abortions and absent from all villous cellular types in complete moles. These findings correlate well with the low level of maternal serum PLF found previously in early pregnancy failures and molar gestation. This suggests that PLF may be involved in the pathogenesis of early pregnancy disorders related to an abnormal placentation.

Localization of p43 placental isoferritin in human maternal-fetal tissue interface.

OBJECTIVE: Human placental isoferritin, which is composed of a 43-kd protein subunit, is exclusively reactive with the CM-H9 monoclonal antibody. The p43 exerts immunosuppressive activity during pregnancy. The aim of this study was to localize the expression of p43 in the maternal-fetal tissue interface during normal gestation. STUDY DESIGN: Villous tissues samples were collected between 5 and 20 weeks' gestation and at term from uncomplicated pregnancies. Immunohistochemical localization of p43 was performed with CM-H9 monoclonal antibody. RESULTS: During the first trimester p43 was highly expressed in syncytiotrophoblast, Hofbauer cells, and decidual macrophages. From 15 weeks' gestation onward expression in the syncytiotrophoblast was below the level of detection; however, p43 was demonstrated in villous Hofbauer cells and decidual macrophages throughout gestation. CONCLUSIONS: Expression of p43 was demonstrated on both sides of the maternal-fetal tissue interface, with localization dependent on gestational age. This may suggest its immunologic function throughout pregnancy. First-trimester syncytiotrophoblast displayed high p43 levels, which disappeared later on, whereas maternal serum p43 level continued to increase, which suggests an extraplacental source for p43.