Intrauterine sonographic assessments of embryonic heart diameter

Our purpose was to evaluate embryonic heart diameter in early first- trimester pregnancy using intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer. A total of 40 women about to undergo therapeutic abortion from 6-9.9 weeks gestational age and one abnormal pregnancy with fetal hydrops at 9 weeks were studied with a specially developed catheter-based high- resolution real-time miniature (2.4 mm outer diameter) ultrasound transducer (20 MHz). A curvilinear relationship was found between the menstrual age and embryonic heart diameter (R2 = 95.7%), and a normal range of embryonic heart diameter for estimating the growth of the embryonic heart during early first-trimester pregnancy was generated. A normogram of menstrual age as predicted by embryonic heart diameter was also established. There was a good curvilinear correlation between embryonic heart diameter and crown-rump length (R2 = 90.1%). The embryonic heart diameter/crown-rump length ratio rapidly decreased from week 6 to week 7, and remained almost constant thereafter. Embryonic heart diameter (5.2 mm) in the case of fetal hydrops at 9 weeks was above the normal range. These results may provide an additional method of estimating gestational age in the early first trimester of pregnancy. In this limited series, a single case of embryonic heart enlargement was demonstrated, suggesting its potential use in the detection of embryonic congestive heart failure.      

The fetal gallbladder morphology and morphometry by microdissection

Most studies of the fetal gallbladder have been performed using ultrasonography. The identification of the fetal gallbladder and the presence of gallstones have been determined this way. The purpose of this study was to investigate the morphology and morphometry of the actual fetal gallbladder by microdissection and to examine its internal features and content. Eighty-nine formalin-embalmed fetuses of CR age 35mm to 342mm, i.e. 10 weeks to 36 weeks gestational age (GA), were studied by hepatic evisceration. The fetal gallbladder was examined in-situ in its bed, in relation to the umbilical vein, the anterior hepatic margin and its protrusion below the inferior hepatic surface of the liver. After excision, the form, length and diameters of the gallbladder were determined and its internal surface, lumen and content also examined. The mean length of the fetal gallbladder for the gestational ages studied ranged from 2.21mm (10 weeks GA) to 281.6mm (32 weeks GA) the mean fundal diameter ranged from 0.4mm (one specimen only) to 9.42.4mm for the same period, while the infundibular width ranged from 0.41mm (one specimen only) to 9.01.6mm, and the antero-posterior diameter at the fundus ranged from 0.90.3mm to 9.03.3mm for the same period. The parameters of the gallbladder for the period examined showed a curvilinear increase in size and were consistent with the ultrasonographic studies. The distance of the fetal gallbladder from the umbilical vein was variable and, as the gallbladder lengthened, the fundus encroached the anterior hepatic margin towards 34 weeks. A descent of the gallbladder from an “intra-hepatic” position early in fetal life to a sub-hepatic position later was clearly evident. The gallbladder wall was thick in early fetal life (10–13 weeks GA) and contained crumbly debris. Bile staining occurred at 14 weeks gestational age and the mucosa took on the normal appearance with the bile having an adult colour and consistency at 20 weeks GA.     

The fetal gallbladder: morphology and morphometry by microdissection

Most studies of the fetal gallbladder have been performed using ultrasonography. The identification of the fetal gallbladder and the presence of gallstones have been determined this way. The purpose of this study was to investigate the morphology and morphometry of the actual fetal gallbladder by microdissection and to examine its internal features and content. Eighty-nine formalin-embalmed fetuses of CR age 35 mm to 342 mm, i.e. 10 weeks to 36 weeks gestational age (GA), were studied by hepatic evisceration. The fetal gallbladder was examined in-situ in its bed, in relation to the umbilical vein, the anterior hepatic margin and its protrusion below the inferior hepatic surface of the liver. After excision, the form, length and diameters of the gallbladder were determined and its internal surface, lumen and content also examined. The mean length of the fetal gallbladder for the gestational ages studied ranged from 2.21 mm (10 weeks GA) to 281.6 mm (32 weeks GA); the mean fundal diameter ranged from 0.4 mm (one specimen only) to 9.42.4 mm for the same period, while the infundibular width ranged from 0.41 mm (one specimen only) to 9.01.6 mm, and the antero-posterior diameter at the fundus ranged from 0.90.3 mm to 9.03.3 mm for the same period. The parameters of the gallbladder for the period examined showed a curvilinear increase in size and were consistent with the ultrasonographic studies. The distance of the fetal gallbladder from the umbilical vein was variable and, as the gallbladder lengthened, the fundus encroached the anterior hepatic margin towards 34 weeks. A descent of the gallbladder from an "intra-hepatic" position early in fetal life to a sub-hepatic position later was clearly evident. The gallbladder wall was thick in early fetal life (10-13 weeks GA) and contained crumbly debris. Bile staining occurred at 14 weeks gestational age and the mucosa took on the normal appearance with the bile having an adult colour and consistency at 20 weeks GA.     

Case Report: First established pregnancy and birth after ovarian stimulation with recombinant human follicle stimulating hormone (Org 32489)

This case report describes the first established pregnancy andbirth after ovarian stimulation with Org 32489, pure recombinanthuman follicle stimulating hormone (recFSH, Organon International).A patient with tubal infertility participated in an open efficacystudy of recFSH evaluating the efficacy of combined gonadotrophin-releasinghormone (GnRH)agonist/recFSH treatment in women undergoing in-vitrofertilization (IVF) and embryo transfer. Ovarian stimulationwas induced by recFSH in association with buserelin (Suprecur^®,4 x 150 µg/day) using a short protocol. After 9 days ofrecFSH treatment (75 IU/day), six pre-ovulatory follicles (15mm) were observed and 10 000 IU human chorionic gonadotrophinwere administered. Nine mature oocytes were retrieved by oocytepuncture and after IVF, three embryos were replaced in the uterus.A viable singleton intra-uterine pregnancy was revealed at agestational age of 7 weeks. The pregnancy progressed normallyand ended with a vaginal delivery at a gestational age of 39.5weeks. A healthy girl was born and paediatric examination didnot demonstrate any abnormality.     

Ultrasonographic estimation of fetal gestational age by fetal kidney length

Introduction: Fetal kidney length vs biparietal diameter (BPD) and femur length (FL) were comparatively evaluated and the role of fetal kidney length in estimating gestational age was determined in the second and third trimesters. Materials and methods: The study was carried out on 199 women with singleton uncomplicated pregnancies attending the outdoor patient department (OPD) for routine ultrasound fetal biometry. Fetal kidney length was measured biweekly, between 18 weeks and 38 weeks of gestation. Linear regression models for estimation of gestational age were derived from biometric indices (BPD and FL) and kidney length. Result: The earliest age at which fetal kidney could be seen sonographically was the 18th week of gestation with the mean kidney length of 12 ± 1.31 mm. The mean sonographic kidney length at the 38th week of gestation was 40.4 ± 1.71 mm, indicating that the mean fetal kidney length increases as pregnancy progresses from 18 weeks to 38 weeks of gestation. Conclusion: The best linear regression model for estimating fetal gestational age is femur length, kidney length, and biparietal diameter in that order, with standard error of ±3.85 days, ±8.04 days, and ±8.75 days, respectively.     

Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements.

In-utero assessment of the internal female genitalia is important for determination of fetal gender in fetuses with suspected genital tract anomalies. We therefore measured fetal uterine transverse width and circumference from 19 weeks of gestation until term, using transvaginal and transabdominal high-resolution ultrasound techniques in order to establish nomograms. A prospective, cross-sectional study on 180 normal singleton pregnancies was performed. Data were obtained for 140 normal fetuses. The mean +/- SD uterine width and circumference were 12.9 +/- 4.1 mm (95% confidence interval 12.1-13.7), and 40.2 +/- 12.5 mm (95% confidence interval 37.9-42.5) respectively. Uterine size as a function of gestational age was expressed by the regression equations: uterine width (mm) = 12.9 + 0.7 x gestational age (weeks), and uterine circumference (mm) = 40.2 + 2.1 x gestational age. The correlation coefficients, r = 0.885 and r = 0.888, for uterine width and circumference, by gestational age respectively, were highly statistically significant (P < 0.001). A nomogram of uterine width and circumference per gestational week, and the 95% prediction limits were defined. The present data offer baseline measurements of the fetal uterus that may allow intrauterine assessment of the female genital tract and associated fetal gender.     

胎儿心、肝和肾长度预测胎儿发育的可行性探讨

目的探讨南方地区胎儿期体质发育数据,为影像诊断、孕期保健等提供参考数据。方法对741例引产胎儿的肝脏、心脏、肾脏的长度及体重进行测量性分析。结果①胎儿的肝脏、心脏、肾脏的长度及体重增长速率与胎龄增加呈正相关。肝脏长度在24周前、33～37周间变化明显,心脏长度在25周后加速均匀增长,肾脏长度在28周前、33～37周间变化明显与体重增长速度比较一致,29～32周为体重变化敏感期。②胎儿体重与肝心肾脏长度间以及孕周与肝心肾脏长度存在线性关系,其中体重分别与心、肝脏长度间的线性关系较强,肝、心、肾脏长度对胎儿体重和孕周的预测效果较好。结论可考虑利用肝、心、肾脏长度对胎儿体重(间接反映发育状况)进行预测。     

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.     

Fetal erythropoiesis and parvovirus B19]

Target cells for the human parvovirus B19 include erythroid progenitors located in the bone marrow in adults and in the liver in fetuses of 12 to 30 weeks gestational age. The main manifestations of fetal parvovirus B19 infection seem to be related to lysis of the erythroid progenitors which causes non immune hydrops fetalis with severe anemia, congestive heart failure, generalized edema and death. The exact incidence of human parvovirus B19 infection during pregnancy remains unclear.     

Transvaginal injection of potassium chloride and methotrexate for the treatment of tubal pregnancy with a live fetus.

A case of ectopic pregnancy with a gestational sac in the right tube of 25 mm diameter and beating fetal heart was treated conservatively by transvaginal, ultrasonically guided injection of potassium chloride and methotrexate. Serum levels of beta-human chorionic gonadotrophin returned to normal in 42 days and the tubal mass collapsed gradually and resolved in 7 weeks.     

Three-dimensional intrauterine sonography in the early first-trimester of human pregnancy: preliminary study

Our purpose was to visualize normal embryonal surface anatomic structures using three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer in the early first trimester of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age were studied by means of 3D intrauterine sonography with a specially developed catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). This imaging system can provide conventional 2D intrauterine sonographic images and can also generate within seconds high-quality 3D images in the surface and transparent mode. At week 8, prominent forehead was evident, and upper and lower limbs and midgut herniation were clearly depicted. At week 9, fingers and toes were depicted as small digital rays, and the sacral tail protruded caudally. The midline cranial ectodermal cleft was also identified. At week 10, embryonic face and fingers were clearly shown. 3D intrauterine sonography provides a novel means for visualizing of surface anatomic structures of the human embryo in utero. These results suggest that 3D intrauterine sonography can become an important modality in future embryological research and in detection of embryonic developmental disorders in the early first-trimester pregnancy.      

Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody.

Seventeen women with recurrent fetal loss associated with anti-phospholipid antibody were treated by prednisolone and low-dose aspirin (PSL/ASP) therapy from the early gestational period. The success rate of pregnancy in the treated patients was significantly higher than that in 12 untreated patients of similar background, including age, number of previous fetal losses and anti-cardiolipin titre (76.5 versus 8.3%, P less than 0.01). The degree of fetal growth retardation evident in previous pregnancies was also improved by the therapy, suggesting that PSL/ASP itself has a beneficial effect against placental damage. These clinical improvements were accompanied by a reduction in anti-phospholipid antibody titre, especially that of anti-phosphatidylserine antibody (anti-PS), to within the normal range within 8 weeks after PSL/ASP administration in most of the treated patients. There was no reduction of antibody titre in the untreated patients during pregnancy. It was concluded that PSL/ASP therapy, when started in the early gestational period (prior to 8 weeks gestation), was effective for the achievement of successful pregnancy and the prevention of fetal growth retardation and that the anti-PS titre was a good clinical marker for evaluating the effect of PSL/ASP therapy.     

Intrauterine sonographic measurement of embryonic brain vesicle

Our purpose was to evaluate embryonic brain vesicle measurements using intrauterine sonography in early first-trimester pregnancy. Fifty-one women about to undergo therapeutic abortion from 7-9.9 weeks gestational age were studied with a specially developed flexible catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). Length, width and height of telencephalon, diencephalon, mesencephalon and rhombencephalon were measured. The normal range of embryonic brain vesicle measurements for each day of pregnancy was determined. Curvilinear relationships were found between the menstrual age and telencephalon height (r(2) = 71.2%), diencephalon length (r(2) = 39. 6%), width (r(2) = 39.4%) and height (r(2) = 48.3%) and mesencephalon length (r(2) = 59.0%) respectively. Linear relationships were found between the menstrual age and telencephalon width (r(2) = 41.4%), mesencephalon height (r(2) = 58.7%) and rhombencephalon length (r(2) = 44.9%), width (r(2) = 56.8%) and height (r(2) = 35.5%) respectively. Telencephalon length and mesencephalon width were constant throughout menstrual age. These results suggest that intrauterine sonography provides accurate embryonic brain measurements in utero. Moreover, intrauterine sonography may become an important modality in future embryological research and in detection of embryonic brain developmental disorders in early first-trimester pregnancy.     

Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: association with pathological findings

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a prospective case-control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty-four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR-positive and PCR-negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death.     

A clinical and epidemiological study of human parvovirus B19 infection in fetal hydrops using PCR southern blot hybridization and chemiluminescence detection

Ninety-eight samples from 80 cases of spontaneous abortions after fetal death or hydrops fetalis from 12,000 pregnant women were examined using PCR. DNA was extracted from amniotic fluid, fetal blood, ascitic fluid and fetal biopsies or placenta specimens using QIA amp kits (QIAGEN). A 270-bp length fragment located within the B19 gene NS1 was amplified using PCR followed by electrophoresis and southern-blot hybridization assay using a horseradish peroxidase-labelled probe and chemiluminescence detection. This assay was able to detect 1 to 10 DNA copies in a 10 |gml sample. Parvovirus B19 was identified in 11 cases (14% of fetal hydrops; 1 case for 1,100 pregnancies). Amniotic fluid was the most common and reliable sample to assess the diagnosis. Gestational age ranged from 17 to 28 weeks (mean 23 weeks). IgM antibodies were detected in 3 maternal sera, 2 patients of which reported an exposure to B19 infection during pregnancy. In 2 cases, intrauterine blood transfusions led to the cessation of symptoms and to birth of normal babies. J. Med. Virol. 54:140–144, 1998. © Wiley-Liss, Inc.     

Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan

A national collaborative study was conducted in Japan to evaluate the clinical course and the sequelae of patients with hydatidiform mole coexistent with twin live fetus (HMTF). Seventy-two cases of HMTF were diagnosed based on gross appearance and histopathological criteria. In 18 cases, the molar parts were cytogenetically confirmed to be of androgenetic origin (complete mole). The overall incidence of persistent trophoblastic tumour (PTT) in patients with HMTF was 30.6%, and it increased to 50.0% in the 18 patients with proven androgenetic complete mole coexistent with twin live fetus (CHMTF). Among these patients, the mean gestational age at termination of pregnancy or delivery in those who developed PTT (n = 9) and those who did not (n = 9) were 20.6 and 19.4 weeks respectively. The incidence of severe maternal complications was significantly higher in patients who subsequently developed PTT (P < 0.05). The rate of subsequent development of PTT in patients with CHMTF was found to be considerably higher than in a previous study of patients with single complete mole (50 and 12.5% respectively). However, since the risk of malignancy is unchanged with advancement of gestational age, continued pregnancy may be allowed in patients with HMTF provided that severe maternal complications are controlled and fetal karyotype and development are normal.     

Placental Transport of Maternal Immunoglobulin G

PROBLEM: How does the placental transport of immunoglobulin G (IgG) vary with gestational age? METHOD OF STUDY: MEDLINE was searched for the appearance of “pregnancy” and “IgG” in the title or abstract from 1966 up to 1995. All publications were reviewed for any kind of IgG data from the fetus and the mother and “known” gestational age. In total, 96 publications from the MEDLINE search fulfilled the search criteria. Seven of ninety-six publications contained IgG and gestational age data from the fetus and/or the mother. Five other publications that fulfilled the same criteria were also available and were also included. RESULTS: Fetal serum IgG concentrations were found to increase with gestational age according to the formula: fetal IgG = 13.564 ? 1.094* gestational age (GA) + 0.026* GA² (R² = 0.877). The fetomaternal (f/m) ratio was also found to increase with gestational age according to the formula: f/m IgG = 0.399 ? 0.059* GA + 0.003* GA² ? 2.065* 10^—5* GA³ (R² = 0.831). CONCLUSIONS: The fetal IgG concentrations exceed maternal IgG concentrations after the 35th week of pregnancy. The fetal IgG concentrations are extremely low in the beginning of pregnancy, they exceed 2.5 g/L at >25 pregnancy weeks, and they reach 5 g/L at pregnancy week 30.     

Is there a human fetal gallbladder contractility during pregnancy?

The purpose of this study was to evaluate whether human fetal gallbladder contractility exists in the second half of pregnancy. Ultrasound examinations were performed on 54 normal pregnant women from 20 to 40 weeks of gestation. Fetal gallbladder volume was monitored every 30 min from 08:00 to 18:00 h in each patient. Maximum gallbladder volume was related linearly with gestational age between 20 and 32-35 weeks of gestation, after which a plateau was observed. Minimum gallbladder volume was unchanged throughout gestation. Functional capacity (maximum volume - minimum volume) of the fetal gallbladder increased linearly with advancing gestation until 32-35 weeks gestation, and thereafter was constant. Contractility rate [(maximum volume - minimum volume/maximum volume)x100] increased curvilinearly with advancing gestation (R(2) = 30.7%, P < 0.0001). The daily change in fetal gallbladder volume showed a typical sinusoidal pattern, and the contractility cycle of gallbladder volume was unchanged during pregnancy (3.1 +/- 0.6 h). These results suggest that there is an apparent gallbladder contractility in human fetuses in utero, and that maternal meals seem not to affect the volume of the fetal gallbladder. Further study is needed to clarify the physiological role of fetal gallbladder contractility during pregnancy.     

Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization

BACKGROUND: Maternal serum HCG (MSHCG) is higher when the fetus is a female than when it is male. This has been demonstrated in the second and third trimesters of pregnancy, and recently at 10-14 weeks gestation. In this study we assessed whether this gender-related difference can be detected as early as week 3 post-fertilization. METHODS: The IVF setting was chosen because it provides precise dating of gestational age and early sonography for the number of gestational sacs. The study included 347 IVF cycles from 335 patients. Only pregnancies with a single implanted embryo that resulted in a single live birth of known gender were included. MSHCG was measured on days 14-20 post-fertilization, and levels were expressed as gestational age-corrected multiples of the median (MoMs). The log10 MSHCG MoMs were compared according to fetal gender. RESULTS: MSHCG levels were significantly higher (18.5%) in week 3 post-fertilization in the presence of a female fetus (P < 0.0002). CONCLUSION: Because a fetal gender-related difference in MSHCG can be demonstrated as early as week 3 post-fertilization, the difference may be attributed to placental factors and not to the effects of the fetal hypothalamic-hypophyseal-gonadal axis.     

Secretory endometrial protein PP14 in women with early pregnancy bleeding.

The decidualized endometrium produces secretory proteins of which secretory endometrial protein PP14 is the major product during the first trimester of pregnancy. The protein is secreted into the uterine lumen as well as into the peripheral blood. The purpose of this study was to examine whether decidual function, evaluated by the serum concentration of PP14, was different in women with early pregnancy bleeding compared to normal pregnant women. A reference range for serum PP14 was established on the basis of single samples from 236 normal pregnant women with ultrasonically confirmed gestational age. All the women were delivered of a normal child at term. The study comprised 128 pregnant women admitted because of vaginal bleeding between 6 and 18 weeks gestation. At ultrasonography, intrauterine fetal heart activity was either present or was confirmed at a subsequent examination. No difference was found in the serum level of PP14 compared to that in normal pregnancies, but women with vaginal bleeding and depressed PP14 levels appeared to have a 5-fold higher risk of preterm delivery than women with bleeding and normal PP14 levels.