Recurrent Fetal Anophthalmia Caused by retinoids acid gene 6 mutations: Correlation between prenatal ultrasonography, magnetic resonance imaging, and pathology.

OBJECTIVE: Anophthalmia is an extreme form on the spectrum of anophthalmia-microphthalmia (A/M) syndrome. Most articles define fetal microphthalmia by an ocular diameter (OD) less than fifth percentile. Diagnosis of fetal microphthalmia using only orbital measurements such as interocular distance (IOD), and OD may neglect the presence or morphology of the fetal lens, hence failing to identify abnormalities of the fetal globe. CASE REPORT: We hereby present a case of isolated fetal anophthalmia in two consecutive pregnancies from the same mother. Both fetuses presented as full-sized globes with absence or small size of lens under fetal ultrasound examination. Magnetic resonance imaging and pathology of the second fetus further revealed a thorough view of the underdeveloped globes. Whole exon sequencing (WES) analysis for the parents-fetus trio revealed compound heterozygous mutations of the retinoids acid gene 6 (STRA6). CONCLUSION: Detailed examination for intraocular structures including fetal lens, in addition to orbital measurements by ultrasound is crucial for diagnosis of diseases in the A/M spectrum.

Prenatal Diagnosis of Fetal Congenital Mesoblastic Nephroma and Neonatal Follow-up.

We describe a case of fetal congenital mesoblastic nephroma (CMN) who was diagnosed with ultrasound at 32 weeks of gestation; after delivery, the neonate received left radical nephrectomy, and pathology report confirmed the diagnosis. All cross-sectional imaging studies, such as ultrasonography, computed tomography (CT) scanning, and magnetic resonance imaging, may help to define the organ of origin and the relationship to the ipsilateral kidney. To our knowledge, this is the first case of fetal CMN who was diagnosed in the third trimester and then with a live-born baby in Taiwan. The prenatal examination such as three-dimensional ultrasound and CT image was performed to help us for prenatal diagnosis.

Prenatal sonographic diagnosis of single umbilical artery: Emphasis on the absent side and its relation to associated anomalies.

OBJECTIVE: To determine the absent side of a single umbilical artery (SUA) and to evaluate whether associated anomalies are related to the side of the missing artery in a Taiwanese population. MATERIALS AND METHODS: We retrospectively studied SUA fetuses from our computer database of fetal ultrasound in a tertiary medical center in Southern Taiwan. All cases were diagnosed as SUA prenatally using conventional scanners of two- and three-dimensional (2D and 3D, respectively) ultrasound, as well as color, power, and high-definition Doppler. The absent side of UA and associated anomalies were analyzed. RESULTS: From September 2006 to November 2011, 31 fetuses with SUA were diagnosed prenatally by ultrasound and all were enrolled for this series. The incidence was estimated to be 1:556 (0.18% = 31/17,086). The mean maternal age was 29.2 years (range, 15-36 years) and the mean fetal age was 30.0 weeks of gestation (range 18-36 weeks). Notably, the left-absent UA was detected in 16/31 (52%) fetuses, compared with the right-absent UA in 15/31 (48%) cases. In addition, congenital anomalies were noted prenatally in 2/16 (13%) fetuses with left-absent UA and in 3/15 (20%) fetuses with right-absent UA. CONCLUSION: In SUA fetuses, the absence of UA appears to occur equally at each side. Moreover, this study showed no significant difference between either side of missing UA and associated anomalies after statistical examination.

Prenatal ultrasonography and postnatal follow-up of a case of McKusick-Kaufman syndrome.

OBJECTIVE: McKusick-Kaufman syndrome (MKS) is a rare autosomal recessive syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). It is very difficult to diagnose MKS prenatally because of overlapping manifestations and associated anomalies with other syndromes. Herein, we present a case of MKS with prenatal ultrasound illustrating a fetal abdominal cystic mass. CASE REPORT: A 33-year-old woman, gravida 3 para 2, was referred to our obstetrics clinic at 34 weeks' gestation for fetal abdominal cyst detected by prenatal ultrasound. Our ultrasound illustrated a fetal abdominal cystic mass with two communicating components (suspected HMC) and polydactyly involving both hands and feet. At birth, the gross appearance revealed abdominal distention, vulva edema, and PAP. MKS was highly suspected. Abdominal computed tomography (CT) at 3 days of life showed HMC with a transverse vaginal septum. At 3 months of age, she received colpotomy and vaginal reconstruction to relieve the abdominal distension by HMC. Then she accepted corrections of PAP of both hands and feet at 8 months and 10 months. At 5 years of age, her body and mental development did not show any retardation. Pediatric ophthalmologic examination revealed no specific findings. Given the above evidences, the diagnosis of MKS was finally made at 5 years of age. CONCLUSION: Rare syndromes like MKS may need early comprehensive evaluations and consultations. Although prenatal diagnosis might be impossible for MKS, prenatal awareness by fetal ultrasound is very helpful to assist early management and maternal transfer. The final diagnosis and appropriate management of MKS requires the collaboration of obstetricians, geneticists, pediatricians, and ophthalmologists as soon as abnormal signs are detected in utero.

Prenatal diagnosis of fetal gastroschisis using three-dimensional ultrasound: comparison between the 20th and 21st centuries.

OBJECTIVE: In order to compare the trends and improvements of prenatal diagnosis of gastroschisis, we herein retrospectively reviewed our cases of fetal gastroschisis detected by three-dimensional ultrasound (3D US) between the two centuries. MATERIALS AND METHODS: We reviewed our computer database of prenatal diagnosis on gastroschisis in National Cheng Kung University Hospital from October 1994 to November 2011. All the fetuses were initially scanned by two-dimensional (2D) US to locate the region of interest (ROI). Then, the 3D probe was used to scan all the ROI systematically and mechanically, and all the images were stored on laser discs for further 3D visualization and reconstruction. To compare the characteristics at prenatal diagnosis of gastroschisis between the 20th and 21st centuries in our hospital, the Chi-square test and Student t test were used. The p values less than 0.05 and 0.1 were considered statistically significant. RESULTS: In total, 26 fetuses with gastroschisis were depicted by 3D US in utero (10 cases were diagnosed in the 20th century and 16 cases in the 21st century). The ranges of gestational age at prenatal diagnosis of gastroschisis by 3D US in the 20th century were between 14 and 34 weeks (mean: 21.6 weeks) and between 14 and 33 weeks (mean: 21.9 weeks) in the 21st century. Moreover, seven cases (70%) were diagnosed before the third trimester in the 20th century, whereas 13 cases (81%) were diagnosed before the third trimester in the 21st century. CONCLUSION: Although without statistical significance, higher prenatal diagnosis rate before the third trimester in the 21st century was noted. The improvement of 3D US has remarkable advantages in adding novel visual depiction of a 3D lesion of a 3D fetus in 3D US after reconstruction and thus assists substantially in prenatal diagnosis, genetic consultation, and perinatal management of gastroschisis.

Prenatal diagnosis of fetal omphalocele by ultrasound: a comparison of two centuries.

UNLABELLED: An omphalocele, a fetal abdominal defect, is a very important congenital anomaly. Prenatal diagnosis of fetal omphalocele is crucial to clinical management. OBJECTIVE: To investigate the accuracy of prenatal diagnosis for fetal omphalocele, we undertook a retrospective and consecutive analysis of our ultrasound database between January 1994 and December 2011. MATERIALS AND METHODS: In total, ultrasound (US) detected 52 fetuses with an omphalocele in utero. RESULTS: The incidence of fetal omphalocele is estimated as 1:1249 (0.08%). We also compared the gestational age at US diagnosis between the two centuries. In the 20(th) century, 22 cases of omphalocele were detected: four (18%) cases at first trimester, 17 (77%) cases at second trimester, and 1 (5%) case at third trimester. In the 21(st) century, 30 cases of omphalocele were detected: 13 (43%) cases at first trimester, 15 (50%) cases at second trimester, and two (7%) cases at third trimester. The gestational age at diagnosis of omphalocele is significantly earlier in the 21(st) century than in the last century. CONCLUSION: With the advancement and improvement in US equipment, the early detection of fetal omphalocele is feasible, which will substantially contribute to fetal wellbeing.

Using Akaike information criterion and minimum mean square error mode in compensating for ultrasonographic errors for estimation of fetal weight by new operators.

OBJECTIVES: The accuracy of ultrasound (US) measurements is operator dependent. In order to decrease the operator-dependent errors in estimated fetal weight (EFW), a model selection analysis was undertaken to select significant compensation weighting factors on ultrasonographic parameters to support artificial neural network (ANN), and thus to enhance the accuracy of fetal weight estimation. MATERIALS AND METHODS: In total, 2127 singletons were examined by prenatal US within 3 days before delivery for ANN development, and another 100 cases were selected from new operators for evaluation. First, correlation analysis was used to analyze the differences between the prenatal and postnatal parameters. Second, Akaike information criterion (AIC) was used to determine the number of database partition and optimal weightings for compensating the input parameters of the ANN model. Finally, minimum mean squared error (MMSE) mode was utilized to determine the optimal EFW. RESULTS: EFW of the proposed compensation model using AIC and MMSE showed mean absolute percent error of 5.1 ± 3.1% and mean absolute error of 158.9 ± 96.2 g. When comparing the accuracy of EFW, our model using AIC and MMSE was superior to those conventional EFW formulas (all p < 0.05). CONCLUSION: We proved that performing the parameter compensation (by AIC) and model compensations (by MMSE) for the ANN model can improve EFW accuracy. Our AIC-MMSE model of EFW will contribute to the improvement of accuracy when adding new US datasets measured by new operators.

Prenatal diagnosis of fetal congenital cystic adenomatoid malformation of the lung using three-dimensional ultrasound: comparison between the 20th and 21st centuries.

OBJECTIVE: Congenital cystic adenomatoid malformation of the lung (CCAML) is one of the most common lung lesions diagnosed prenatally. In order to compare the trends and improvements of prenatal diagnosis of CCAML, we herein retrospectively reviewed our cases of fetal CCAML detected by three-dimensional ultrasound (3-D US) between two centuries. MATERIALS AND METHODS: We reviewed our computer database of prenatal diagnosis of CCAML in National Cheng Kung University Hospital from October 1994 to November 2011. All of the fetuses were initially scanned by two-dimensional (2-D) US to locate the region-of-interest (ROI). Then, the 3-D probe was used to scan all of the ROI systematically and mechanically, and the images were stored in the laser discs for further 3-D visualization and reconstruction. To compare the characteristics at prenatal diagnosis of CCAML between the 20th and 21st centuries in our hospital, Chi-square tests were undertaken. A p value <0.05 was considered as statistically significant. RESULTS: In total, 58 fetuses with CCAML were depicted by 3-D US in utero (12 cases were diagnosed in the 20th century and 46 cases in the 21st century). The ranges of gestational age at prenatal diagnosis of CCAML by 3-D US in the 20th century were between 15 and 36 weeks (mean=24 weeks), and were between 16 and 31 weeks (mean=22 weeks) in the 21st century. Moreover, nine cases (75%) were diagnosed at the second trimester in the 20th century, whereas 44 cases (96%) were diagnosed at the second trimester in the 21st century. CONCLUSION: The advancement of 3-D US has remarkable advantages in adding novel visual depiction of a 3-D lesion of a 3-D fetus in 3-D US after reconstruction, and thus assists substantially in the prenatal diagnosis and genetic consultation of CCAML. Furthermore, the trend analysis in this series showed a significantly earlier gestational age at prenatal diagnosis of CCAML in the 21st century than that in the 20th century.

Three-dimensional ultrasound in the prenatal diagnosis of osteogenesis imperfecta.

OBJECTIVE: Fetal osteogenesis imperfecta (OI) is a heterogeneous group of collagen disorders characterized by bone fragility, blue sclerae, deafness, and dentinogenesis imperfecta. Ultrasonography is acknowledged as a reliable diagnostic modality for the prenatal diagnosis of OI, especially type II. In the past, two-dimensional (2D) ultrasound (US) has been applied as the mainstay of prenatal diagnosis of OI. In this series, we report our work of detecting OI using three-dimensional (3D) US. MATERIAL AND METHODS: We reviewed our computer database of prenatal diagnosis of OI at the National Cheng Kung University Hospital from April 1996 to July 2010. All the cases were scanned by 2D and 3D US. In total, six cases of fetal OI were diagnosed. RESULTS: Compared with 2D US, 3D US can detect fetal OI precisely, and provide additional vivid illustration after various modes of reconstruction that 2D US cannot. CONCLUSION: In conclusion, 3D US may contribute significantly to the detection of OI in utero and provide a novel visual depiction of this defect after reconstruction. The technique may thus substantially assist in prenatal diagnosis as well as consultations for fetal OI.

Glucosamine-induced insulin resistance in ovariectomized rats is relevant to decreasing the expression of glucose transport protein subtype 4 in the skeletal muscle and in increasing the size of pancreatic islets.

OBJECTIVE: Glucosamine (GlcN) is a popular nutritional supplement used to treat osteoarthritis in postmenopausal women. Postmenopausal women are at higher risk of type 2 diabetes mellitus and metabolic syndrome because of ovarian hormone deficiency. We used ovariectomized (OVX) rats as the model to investigate whether GlcN would induce insulin resistance (IR) in OVX rats and the underlying mechanisms. METHODS: The rats were divided into four groups: (1) sham-operated group (SHAM), (2) SHAM with GlcN treatment (SHAM + GlcN), (3) OVX group, (4) OVX with GlcN treatment (OVX + GlcN). Intraperitoneal (IP) GlcN was given at 12 weeks after the surgical procedure for 2 weeks. The IP glucose tolerance test (IPGTT) was performed to measure plasma glucose and insulin and to calculate the clinical homeostasis model assessment-IR (HOMA-IR) and glucose-insulin index. Western blot analysis for the detection of glucose transport protein subtype 4 expression in the skeletal muscle and histopathological examination of the changes in pancreatic islets were also performed. RESULTS: Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and HOMA-IR were elevated more significantly in this group. In addition, plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN group after IP glucose injection, implying that IR was induced by GlcN only in female rats without the protection of ovarian hormone. In addition, we found that treatment with GlcN decreased the expression of glucose transport protein subtype 4 in the skeletal muscle and induced pancreatic islet hyperplasia only in OVX rats. CONCLUSIONS: The results demonstrate that female rats do not develop IR upon GlcN treatment except after ovariectomy. Those who take GlcN after menopause or bilateral oophorectomy should watch their blood glucose level closely, especially after meals.

Efficient fetal size classification combined with artificial neural network for estimation of fetal weight.

OBJECTIVES: A novel analysis was undertaken to select a significant ultrasonographic parameter (USP) for classifying fetuses to support artificial neural network (ANN), and thus to enhance the accuracy of fetal weight estimation. METHODS: In total, 2127 singletons were examined by prenatal ultrasound within 3 days before delivery. First, correlation analysis was used to determine a significant USP for fetal grouping. Second, K-means algorithm was utilized for fetal size classification based on the selected USP. Finally, stepwise regression analysis was used to examine input parameters of the ANN model. RESULTS: The estimated fetal weight (EFW) of the new model showed mean absolute percent error (MAPE) of 5.26 ± 4.14% and mean absolute error (MAE) of 157.91 ± 119.90 g. Comparison of EFW accuracy showed that the new model significantly outperformed the commonly-used EFW formulas (all p < 0.05). CONCLUSION: We proved the importance of choosing a specific grouping parameter for ANN to improve EFW accuracy.

Prenatal diagnosis of fetal multicystic dysplastic kidney in the era of three-dimensional ultrasound: 10-year experience.

OBJECTIVE: To demonstrate the usefulness of three-dimensional (3D) ultrasound in prenatal diagnosis of fetal multicystic dysplastic kidney (MCDK) disease. METHODS: In our previous study, we demonstrated that using 3D ultrasound in conjunction with traditional two-dimensional (2D) ultrasound can facilitate the diagnosis of MCDK. In this study, we followed all the MCDK cases diagnosed in our center in the recent decade (from 2002 to 2011) and compared the results with the data collected in the prior decade (from 1995 to 2002). RESULTS: Between 2002 and 2011, a total of 39 cases with fetal MCDK diagnosed by 2D and 3D ultrasound were retrospectively analyzed. The average gestational age when the diagnosis of MCDK was made was 23.6 weeks of gestation (95% confidence interval: 22.09-25.09). The Pearson chi-square test revealed a borderline nonsignificant difference statistically in the categorized gestational age at diagnosis (p = 0.052) as compared to the gestational age in the prior study. The average amniotic fluid index in fetuses with unilateral and bilateral MCDK was 16.76 ± 3.34 and 4.78 ± 5.82, respectively (p < 0.001). MCDK was not found to be associated with gestational age or chromosomal anomalies in our study. CONCLUSION: The surface-rendering mode of 3D ultrasound is very useful in prenatal diagnosis and counseling for MCDK.

Thanatophoric dysplasia: role of 3-dimensional sonography.

PURPOSE: Fetal thanatophoric dysplasia (TD) is a lethal skeletal dysplasia. Therefore, antenatal diagnosis of TD is mandatory in routine obstetrical care. However, because TD is relatively rare, prenatal detection is not an easy task. In the past, 2-dimensional (2D) sonography had been applied as the mainstay of prenatal diagnosis of TD. In this series, we report our work of detecting TD using 3-dimensional (3D) sonography. METHODS: We reviewed our computer database of prenatal diagnosis of TD in National Cheng Kung University Hospital from May 1995 to June 2006. All the cases were scanned using 2D and 3D sonography. In total, 9 cases of fetal TD were diagnosed. RESULTS: 3D sonography can detect fetal TD and provide additional vivid illustration after various modes of reconstruction that 2D sonography cannot afford. CONCLUSION: 3D sonography may contribute significantly to the detection of TD in utero and provide a novel visual depiction of this defect after reconstruction. Thus, 3D sonography may assist substantially in prenatal diagnosis as well as consultation.

Clinical suppression of precocious puberty with cetrorelix after failed treatment with GnRH agonist in a girl with gonadotrophin-independent precocious puberty.

This report presents the case of a 7-year-old girl with gonadotrophin-independent precocious puberty treated with cetrorelix [gonadotrophin-releasing hormone (GnRH) antagonist] after poor response to GnRH agonist therapy was observed in the endocrinology outpatient clinic. Uterine and ovarian morphology returned to within the normal prepubertal range after GnRH antagonist was injected subcutaneously. Vaginal bleeding stopped completely. The effects of GnRH antagonist treatment were comparable to those of GnRH agonist. The potential advantage of GnRH antagonists would be a clinically significant direct effect on the ovary, if it exists, and GnRH antagonists should be available for use in such children.

Prenatal diagnosis of fetal acrania using three-dimensional ultrasound.

Fetal acrania is uniformly lethal and termination is suggested whenever the diagnosis is made. Traditionally, the diagnostic tool was 2-D ultrasound (US). In this series, we report our work of detecting acrania using 3-D US. We reviewed our medical records of prenatal diagnosis on fetal acrania in National Cheng Kung University Hospital from May 1997 to December 2002. All the cases were scanned by a 3-D US scanner. In total, 29 cases of fetal acrania were diagnosed. The range of gestational age at prenatal diagnosis by US was between 11 and 21 weeks and 44% were depicted in the first trimester. Among them, 93.1% were isolated findings, and one was associated with trisomy 18. Comparing with previous literature, 3-D US can detect fetal acrania as early as 2-D US, and it also can provide additional vivid illustration after various modes of reconstruction, which 2-D US cannot. In conclusion, 3-D US may contribute to early detection of fetal acrania and provide a novel visual depiction of this defect after reconstruction; thus, assists substantially in diagnosis as well as consultation.

Effects of laparoscopic ovarian drilling on young adult women with polycystic ovarian syndrome.

STUDY OBJECTIVE: To assess changes in serum hormone levels and ovarian stromal blood flow after laparoscopic ovarian drilling (LOD) in young adult women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, nonrandomized study (Canadian Task Force classification II-1). SETTING: Tertiary care, major teaching hospitals. PATIENTS: Anovulatory young women with PCOS who were resistant to clomiphene citrate. INTERVENTION: Laparoscopic ovarian drilling. MEASUREMENTS AND MAIN RESULTS: To evaluate the endocrinological effects of LOD, serum leptin, insulin-like growth factor-1, estrone (E1), and estradiol were measured before and after ovarian drilling in the early follicular phase. Three-dimensional transabdominal power Doppler examinations were performed to determine the effects of LOD. Serum leptin was correlated with body mass index (BMI) before LOD. Levels of BMI, fasting blood sugar, and leptin were higher and LH, LH/FSH, and the sugar/insulin ratio were lower in the obese group. There were significant decreases in the free androgen index, and total testosterone, luteinizing hormone (LH), and LH/follicle-stimulating hormone (FSH) levels, and a significant increase in sex hormonebinding globulin (SHBG) concentration in the 3 months after the operation. The vascularization index and vascularization flow index of the intraovarian stroma significantly decreased after treatment. Reversed correlations between leptin and LH, LH/FSH, E1, thyroid-stimulating hormone, and SHBG were noted 3 months after the operation compared with levels obtained before the operation. CONCLUSIONS: Treatment of young adult women with PCOS using LOD did not influence leptin levels but changed the ovarian stromal blood flow dynamics during short-term follow-up. The surgical procedure may be beneficial both to endocrine profiles and to intraovarian stromal flow in patients with PCOS.

Quantification of ovarian stromal Doppler signals in poor responders undergoing in vitro fertilization with three-dimensional power Doppler ultrasonography.

OBJECTIVE: This was a prospective comparative clinical study to test the hypothesis that the decreased ovarian sensitivity to gonadotropins observed in women embarking on an in vitro fertilization (IVF) treatment may be due to changes in ovarian stromal blood flow. STUDY DESIGN: Three-dimensional (3D) power Doppler ultrasonographic indexes were used to quantify ovarian stromal blood flow and vascularization in poor responders. Forty patients undergoing an IVF cycle were collected and divided into two groups, a poor responder group (n=17) (estradiol <600 pg/mL or < or =3 oocytes retrieved) and normal responder group (n=23), based on their response to a standard down-regulation protocol for controlled ovarian stimulation. During ovarian stimulation, on the day of administration of human chorionic gonadotropin (HCG), patients underwent hormonal (serum E2), ultrasonographic (follicular number and diameter), and 3D power Doppler (ovarian stromal blood flow) evaluation. RESULTS: Compared with poor responders, the serum estradiol levels on the day of administration of HCG, the number of follicles more than 14 mm, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate were significantly higher in normal responders. The Vascularization Index, Flow Index, and Vascularization Flow Index were significantly lower (P<.05) in the poor responder (0.13+/-0.11, 30.89+/-10.35, and 0.05+/-0.04, respectively) compared with the women with a normal response (1.20+/-1.10, 43.88+/-7.77, and 0.61+/-0.57, respectively). CONCLUSION: The 3D power Doppler indexes of ovarian stromal blood flow in poor responders was significantly lower than normoresponders. This may help to explain the poor response during HCG administration in controlled ovarian stimulation.