The fetal larynx and pharynx: structure and development on two- and three-dimensional ultrasound.

OBJECTIVES: To present a systematic approach for evaluating the fetal pharynx and larynx based on two- and three-dimensional ultrasound (2D-US and 3D-US) modalities, describing the sonographic appearance and function of the fetal upper respiratory tract and measuring the anatomical components of the pharynx and larynx. METHODS: Gravidae presenting from the late first trimester to mid-gestation for routine booked examinations with structurally normal singleton fetuses of confirmed gestational age were enrolled. Transabdominal 2D-US was performed for anatomical and functional evaluation of the pharynx and larynx. Color Doppler was used to show fluid motion in the target area. 3D-US (Voluson® E6 with RAB-4-8-D transducer) scans of the fetal neck were acquired during fetal quiescence and in the absence of movements of the pharynx and larynx. Multiplanar reconstruction (MPR) in post-processing allowed adjustment of the volume to obtain the coronal plane. After a learning period to understand the sonographic anatomy of the target area, we measured the pharynx width and height, the upper, middle and lower larynx width and the larynx height. Render mode was applied for spatial evaluation of the target area. We developed a new methodological approach for structured evaluation of the fetal pharynx and larynx based on five spatial planes: posterior and anterior coronal planes and high, mid and low axial planes. RESULTS: We examined 582 fetuses during the second trimester of pregnancy; target anatomy was imaged successfully in 218 patients at 11-24 gestational weeks. Acquisition added approximately 1 min to examination time. Rates of successful visualization and measurements increased significantly as pregnancy progressed, being 23% (46/194) at 11-13 weeks, 29% (69/240) at 14-16 weeks, 35% (18/51) at 17-19 weeks and 88% (85/97) at 20-24 weeks (P < 0.01). Pharynx components identified were: the sphenoid bone, pterygoid processes, constrictor muscles, piriform recesses and uvula. Larynx components identified were: the epiglottis, aryepiglottic folds, corniculate cartilages, arytenoid cartilages, cricoid cartilage, thyroid cartilage and vocal cords. MPR showed the biconcave shape of the uvula, which may explain the 'equals sign' observed on 2D-US. We observed the bilateral mode of movements of the constrictor muscles, aryepiglottic folds and vocal cords, and the bidirectional fluid jet flows through the larynx. Scatterplots of measured structures vs gestational age were created. Pharynx width ranged from 0.11 to 0.93 (mean ± SD, 0.48 ± 0.17) cm; pharynx height ranged from 0.23 to 2.01 (mean ± SD, 0.94 ± 0.34) cm; upper larynx width ranged from 0.04 to 0.37 (mean ± SD, 0.15 ± 0.07) cm; middle larynx width ranged from 0.08 to 0.77 (mean ± SD, 0.34 ± 0.16) cm; lower larynx width ranged from 0.05 to 0.64 (mean ± SD, 0.24 ± 0.11) cm; and larynx height ranged from 0.20 to 1.83 (mean ± SD, 0.71 ± 0.31) cm. All measurements were positively correlated with gestational age. CONCLUSIONS: The fetal larynx and pharynx can be evaluated thoroughly using 2D- and 3D-US modalities. Knowledge of normal anatomy, function and biometry may prove useful in the evaluation of anatomical or functional pathology involving the fetal upper respiratory tract. Recognition of anatomical anomalies may enhance fetal intervention such as balloon placement in cases of diaphragmatic hernia.

Umbilical cord cysts in the second and third trimesters: significance and prenatal approach.

OBJECTIVES: This study was carried out to determine the prognosis, and the clinical approach, in fetuses with umbilical cord cysts, during the second and third trimesters of gestation, according to our experience and data in the current literature. METHODS: We identified 10 fetuses with umbilical cord cysts that were diagnosed during the second and third trimesters of pregnancy at three referral centers. All underwent detailed ultrasound evaluation at the time of diagnosis and during follow-up. Prenatal karyotype testing was offered to all women. A MEDLINE review of the literature published from 1980 to 2009 was carried out to identify previous studies and case reports of fetuses with umbilical cord cysts. RESULTS: In our series of 10 cases, significant additional abnormalities were observed in two during a detailed sonogram. In one case, trisomy 18 was diagnosed, leading to pregnancy termination, and in the other case a neonate with heart defects and a normal karyotype was born. These results differ from those reported in the literature, in which the association between second- and third-trimester umbilical cord cysts and fetal anomalies ranged from 38 to 100%. CONCLUSIONS: In our study, as in other publications, an association was found between the presence of second- and third-trimester umbilical cord cysts and fetal anomalies. The strong association between second- and third-trimester umbilical cord cysts and aneuploidy in the literature seems to be biased, mainly because of the tendency to report abnormal cases. When these findings are accompanied by additional sonographic abnormalities, the association with aneuploidy is clear and should be an indication for fetal karyotype testing.

Early second trimester transvaginal ultrasound anomaly scan does not cause adverse perinatal outcome.

OBJECTIVE: During an early second-trimester transvaginal ultrasound anomaly scan, pressure is applied to the uterus, and the fetus is often rotated manually to allow scanning of its various organs. This study was designed to determine if performing a transvaginal ultrasound anomaly scan during the early second trimester of pregnancy is associated with adverse perinatal outcome or cord entanglement. METHODS: During the 4.5year study period we prospectively collected cases of routine ultrasound scans at 14-17weeks gestation performed as anomaly screening, together with perinatal outcome. The study population consisted of 164 women who underwent a transvaginal approach, and the control population consisted of 224 women in which a transabdominal approach was used. Data on perinatal parameters was collected from delivery charts from the four local hospitals. RESULTS: There were more operative deliveries (vaginal or Cesarean) in the transvaginal scan group (32% vs. 23%, p=0.05). However, on multiple logistic regression analysis vaginal scans were not associated with increased operative delivery rates with an adjusted odds ratio of 1.47 and a 95% confidence interval of 0.85-2.54. There were no other clinically significant differences in perinatal outcomes, or in cord entanglement. CONCLUSIONS: Transvaginal ultrasound anomaly scan conducted in the early second trimester of pregnancy is a safe procedure for the fetus.

Low dose ketoconazole attenuates serum androgen levels in patients with polycystic ovary syndrome and inhibits ovarian steroidogenesis in vitro.

OBJECTIVE: To investigate the effects of a low-dose ketoconazole on ovarian steroidogenesis and on serum androgen levels in polycystic ovary syndrome (PCOS). DESIGN: In vitro, human granulosa-luteal cells were incubated with ketoconazole and radiolabeled steroid substrates, to follow their metabolic fate by thin-layer chromatography analysis. In vivo, normally cycling women (n = 7) in their luteal phase were administered one tablet of 200 mg ketoconazole at 8 A.M. Serum steroid levels, sampled basally and at 12 P.M., 4 P.M., and 8 A.M. the next morning, were compared with untreated control group (n = 7) values. Polycystic ovary syndrome women (n = 11) were similarly administered ketoconazole 6 to 10 days after occurrence of spontaneous menses. Adrenal origin of hyperandrogenemia was excluded by stimulation with ACTH and a normal basal DHEAS. The steroid diurnal variation was determined in the same patients a day before treatment. RESULTS: In vitro, ketoconazole selectively inhibited the key steroidogenic cytochromes, namely P450scc, P45017 alpha, and P450arom (IC50 = 0.5 to 1.0 microgram/mL). In vivo, in the luteal phase, ketoconazole transiently decreased serum values (mean +/- SE) of E2 (19.2% +/- 2.1%) and P (38.3% +/- 8.5%) within 4 to 8 hours. The same low-dose ketoconazole, administered to PCOS women, decreased serum values of androstenedione (17.6% +/- 4.7%), T (24.6% +/- 7.6%), and free T (30.7% +/- 7.7%). In contrast, 17 alpha-hydroxyprogesterone increased concomitantly (78.5% +/- 10.8%), suggesting a greater suppressibility of the P45017 alpha lyase activity. The E2 levels in PCOS patients were slightly elevated (29.1% +/- 5.6%), resulting in a 1.7- to 2.3-fold increase of the E2:T ratio. CONCLUSIONS: These findings suggest that a low-dose ketoconazole may facilitate a decreased intraovarian T:E2 ratio, which may prove favorable for follicular maturation in PCOS.

Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist.

OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.

[Operative laparoscopy in pregnancy].

The development of laparoscopic surgery in gynecology and general surgery has greatly advanced over the past decade, and recently has been successfully performed in pregnancy. In the English literature we found that of the 518 cases reported (mean age 32 years) the most common was for cholecystectomy (45%), followed by operations on the adnexae (34%), appendectomy (15%) and others (6%). To these we add 3 cases of cholecystectomy and 1 of an adnexal tumor. Of all the reported cases, 33% were performed in the 1st trimester, 56% in the 2nd and 11% in the 3rd. This review demonstrates a definite trend to laparoscopy in pregnancy. It appears to be safe when performed by experienced surgeons, but further studies addressing safety of laparoscopic surgery during pregnancy are needed to reach definitive conclusions.

Real-time spectral analysis of the fetal EEG: a new approach to monitoring sleep states and fetal condition during labor.

Adverse perinatal events affecting cerebral functions are a major cause of neonatal mortality, morbidity, and long-term neurologic deficit. Intrapartum fetal EEG, which records fetal brain electrical activity, provides a monitoring modality for evaluating the fetal CNS during labor. In this study, we describe a new approach to such monitoring that is based on real-time spectral analysis of the fetal EEG during labor. Fourteen pregnant women with uncomplicated term pregnancies who went into labor participated in the study. Two suction-cup electrodes were applied to the fetal scalp at the occipitoparietal or parietal region after rupture of membranes. Real-time spectral analysis was used to determine the frequency and amplitude of the fetal EEG signal. The spectral edge frequency (SEF) was calculated as the frequency below which 90% of the power in the power spectrum resides. The average EEG amplitude and the SEF were displayed using the density spectral array technique. Fetal heart rate and intrauterine pressure were also measured. Two fundamental EEG patterns were identified: high-voltage slow activity and low-voltage fast activity. The SEF was found to be an excellent index of cyclic EEG activity. Fetal heart rate demonstrated increased variability and an elevated baseline during low-voltage fast activity, whereas both parameters decreased during high-voltage slow activity. During episodes of variable decelerations in the fetal heart rate, a decrease in the SEF was observed, accompanied by an increased EEG voltage. The results obtained substantiate the presence of sleep cycles in the human fetus. This kind of cortical activity monitoring may enable rapid alertness to cerebral hypoxia and allow for prompt intervention, thereby decreasing the risk for birth asphyxia and subsequent brain damage.

Transvaginal ultrasonography in the diagnosis and treatment of infertility.

The use of transvaginal sonography (TVS) in the management of infertility is gaining increasing popularity. The improved resolution and better tissue textural differentiation afforded by TVS makes this technique useful in monitoring ovarian follicular growth, ovulation, and corpus luteum formation, and in evaluating the normal anatomy of the uterus and the cervix and their cyclic response to ovarian steroids. Adnexal and cul-de-sac abnormalities related to infertility can also be identified. TVS-guided procedures can be accurately and safely performed; transvaginal follicular aspiration, gamete or embryo transfer to the Fallopian tube, and fetal reduction are just a few of the procedures recently introduced to reproductive medicine.

Transvaginal ultrasonography-guided aspiration of gestational sacs for selective abortion in multiple pregnancy.

A method for selective termination of multiple pregnancy by means of transvaginal ultrasonography-guided aspiration of gestational sacs is described. This technique was applied successfully in two women in whom the number of embryos was reduced from four to two at 7 weeks' gestation.

Fetal hydrocephalus associated with maternal neurofibromatosis.

Neurofibromatosis (NF), an autosomal dominant inherited disorder affecting multiple organ systems, is rare among pregnant women. NF in pregnancy has been reported to be complicated by maternal hypertension, fetal intrauterine growth retardation and fetal wastage. A case of pregnancy associated with neurofibromatosis, complicated by pregnancy aggravated chronic hypertension, asymmetric intrauterine growth retardation and fetal hydrocephalus is described. Possible interrelations between those pathologies are discussed.

Onset of spontaneous labor and changes in E2 and progesterone levels--possible interrelation.

Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy. This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone (E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternal serum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 +/- 24.5 mg/ml verus 177.3 +/- 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor.

Ultrasonographic "endometrial three-layer" pattern: a unique finding in ectopic pregnancy.

Although diagnostic ultrasonography is playing an increasing role in the investigation of the patient with suspected ectopic pregnancy (EP), it has significant limitations in the very early stages of pregnancy. By sonographically exploring the intrauterine echoes in 45 cases of documented EP, we demonstrated a unique pattern in 28 cases (62.2%). A well-defined spheric structure forming an endometrial three-layer (ETL) pattern was seen, probably formed by a midline echo between the two adjacent edematous proliferative layers of the endometrium, the latter resembling the late proliferative endometrium. In 17 patients with a proved EP (37.8%), the ETL pattern was not demonstrated. However, the ETL was not demonstrated in all 40 cases of early intrauterine pregnancy and all 50 cases of miscarriage. These findings suggest a 100% specificity and a sensitivity of 62.2% for the ETL pattern in the diagnosis of EP.

First trimester selective reduction in multiple pregnancy guided by transvaginal sonography.

Transvaginal ultrasonography-guided fetal reduction was performed in 11 patients presenting with multiple pregnancies. Embryonic aspiration was carried out in 7 women at 7 to 8 weeks and in 4 patients fetal intrathoracic injection was performed at 9 to 11 weeks, menstrual age. Seven patients delivered healthy babies at greater than 35 weeks, 3 have delivered prematurely 15 to 17 weeks after the procedure with subsequent neonatal death of all sets of twins. We believe that our method overcomes the technical difficulties related to the transabdominal or transcervical approach and should be the method of choice for early selective abortion.

Prophylactic effect of the open vaginal vault method in reducing febrile morbidity in abdominal hysterectomy.

In a randomized study, we evaluated the efficacy of the "open vaginal vault" method of abdominal hysterectomy, when cefonicid is administrated preoperatively, in reducing postoperative febrile morbidity. The vaginal vault was left open in 72 patients and closed in 65 patients in control groups. No significant difference in postoperative febrile morbidity was noticed in the two groups.

Pregnancy and laparoscopic surgery.

We reviewed the English literature regarding laparoscopic surgery during pregnancy and found that of 518 reported procedures, the most common was cholecystectomy (45%), followed by adnexal surgery (34%), appendectomy (15%), and other operations (6%). We add six cases to this list; three cholecystectomies, an adnexal procedure, and two for abdominal pain. Thirty-three percent were performed in the first trimester, 56% in the second, and 11% in the third trimester. This review demonstrates a definite trend, indicating that laparoscopy in pregnancy appears to be safe when performed by experienced practitioners. (J Am Assoc Gynecol Laparosc 6(3):347-351, 1999)

Simultaneous detection of three common sexually transmitted agents by polymerase chain reaction.

OBJECTIVE: Human papillomaviruses, herpes simplex viruses, and Chlamydia trachomatis are very common infections of the genital tract. The purpose of our study was to develop a polymerase chain reaction-based assay for the simultaneous detection of these organisms from a single genital swab. STUDY DESIGN: To prove the technical feasibility of a simultaneous polymerase chain reaction assay for these organisms, a mixture of deoxyribonucleic acids extracted from cells infected by these three agents was amplified in the same tube with three different sets of primers corresponding to specific regions of the human papillomavirus genome, the herpes simplex virus 1 and 2 genomes, and the Chlamydia trachomatis plasmid, respectively. Then genital swabs from patients with suspected infection by one or more of these agents were assayed by polymerase chain reaction for the presence of herpes simplex virus, human papillomavirus, and Chlamydia trachomatis independently and simultaneously. Most of the samples were analyzed in parallel by other methods: herpes simplex virus by culture., Chlamydia trachomatis by culture and antigen staining, and human papillomavirus by the filter in situ hybridization method. RESULTS: Analysis of the polymerase chain reaction products amplified from the deoxyribonucleic acid mixture revealed three bands corresponding to the respective amplified region of each microorganism. A total of 391 genital swabs were assayed independently by polymerase chain reaction for the presence of herpes simplex virus (113 samples), human papillomavirus (200 samples), and Chlamydia trachomatis (78 genital swabs and four urethral swabs). Forty-nine were herpes simplex virus positive (47 by culture), 45 were human papillomavirus positive (43 by filter in situ hybridization), and one sample was positive for Chlamydia trachomatis, both by polymerase chain reaction and by culture. Ninety-two of the 391 samples were analyzed simultaneously by polymerase chain reaction for the presence of the three agents. The correlation between the results obtained independently and simultaneously was of the order of 100%: 29 were positive for herpes simplex virus, 16 were positive for human papillomavirus, and one was positive for Chlamydia trachomatis, in one sample we could detect both human papillomavirus and herpes simplex virus. CONCLUSIONS: The polymerase chain reaction simultaneous assay is a quick and efficient way of detecting herpes simplex virus, human papillomavirus, and Chlamydia trachomatis from a single genital swab. This method can greatly simplify the diagnostic procedures in the laboratory.