Sonographic demonstration of brain injury in fetuses with severe red blood cell alloimmunization undergoing intrauterine transfusions.

OBJECTIVE: To assess sonographically brain anatomy in fetuses with severe anemia due to red blood cell alloimmunization undergoing intrauterine intravascular transfusions. METHODS: Multiplanar neurosonography was performed in seven consecutive hydropic fetuses undergoing intrauterine transfusions (mean gestational age 22 +/- 2.5 weeks; mean hemoglobin concentration at the first transfusion 2.3 +/- 1.0 g/dL). RESULTS: Abnormal cerebral findings were identified in four out of seven fetuses. An intracerebellar hemorrhage developed in two fetuses after the first transfusion and one fetus that had severe brain edema before the first transfusion was later found to have cystic periventricular leukomalacia. In one fetus unilateral ventriculomegaly was noted after the first transfusion. Two fetuses were terminated. The remaining pregnancies had an uneventful course, the infants were delivered between 34 and 36 gestational weeks and were alive and well at the time of writing. Prenatal diagnosis of brain injury was always confirmed except for the case with ventriculomegaly that underwent spontaneous intrauterine resolution. CONCLUSIONS: Fetuses with extreme anemia due to red blood cell alloimmunization can be salvaged by intrauterine transfusion. In some of these cases brain injury may occur prenatally, and the risk seems to be particularly high when the hemoglobin concentration at the time of the first transfusion is

Erythropoietin course in newborns with Rh hemolytic disease transfused and not transfused in utero.

This study reports the Hb, erythropoietin (Epo), and reticulocyte course at different postnatal ages (range, 8-83 d) of 56 blood samples from 30 newborns (range, one or two blood samples from each newborn) with erythroblastosis fetalis (18 intrauterine transfused (IUTd) and 12 non-IUTd). Hb, Epo, and reticulocyte values were not statistically different in IUTd and non-IUTd cases. As age increased, decreasing Hb values and increasing Epo levels were observed. The reticulocyte count was relatively low in all but six cases. There was an inverse correlation between Epo and Hb (r = -55, p < 0.001), but no correlation was found between Hb and reticulocytes or between Epo and reticulocytes. When groups were formed on the basis of Hb levels, anemic newborns showed higher serum Epo than did nonanemic patients (p < 0.02). In the present study we found a significant increase in Epo levels in anemic newborns without a rise in the reticulocyte count. These results suggest that other mechanisms, rather than low Epo production, could be involved in the pathogenesis of this anemia. Persisting anti-D antibodies, probably at a medullary level, may destroy erythrocyte precusors, leading to anemia with a low reticulocyte count.

Different gonadotropin and leuprorelin ovulation induction regimens markedly affect follicular fluid hormone levels and folliculogenesis.

OBJECTIVES: To clarify the endocrine mechanisms underlying the outcome of different ovulation induction regimens with gonadotropins and GnRH agonists (GnRH-a). DESIGN: Prospective study. SETTING: Reproductive Endocrinology Center, University of Bologna. PATIENTS: Forty eumenorrheic women randomly assigned to four groups of 10 subjects each. INTERVENTIONS: Ovulation induction regimens: group A, purified FSH only; group B, purified FSH and flare-up GnRH-a; group C, purified FSH and long GnRH-a; and group D, hMG and long GnRH-a. MAIN OUTCOME MEASURES: Pelvic ultrasound and hormone levels in daily serum samples and in follicular fluid drawn immediately before hCG administration. RESULTS: Exogenous gonadotropin dose did not differ among groups. Group B had fewer preovulatory follicles than group C. Group B had higher serum LH, FSH, E2, P, T, and follicular fluid LH, E2, T, and alpha-inhibin than groups C and/or D. Groups C and D did not differ. CONCLUSIONS: Long GnRH-a regimens improved follicle yield and the endocrine milieu in spite of comparable exogenous gonadotropin dose and lower serum FSH and thus appear to be preferable in assisted reproduction. Reduced folliculogenesis found in flare-up GnRH-a regimens could be mediated by the atretic effects of high intraovarian androgens. Efficacy of purified FSH and hMG was comparable.

Long-term follow-up and final height in girls with central precocious puberty treated with luteinizing hormone-releasing hormone analogue nasal spray.

OBJECTIVE: To evaluate clinical, hormonal, and auxologic features in a group of girls with central precocious puberty during and after long-term treatment with luteinizing hormone-releasing hormone analogue nasal spray. DESIGN: Clinical survey, before-after trial. SETTING: Pediatric Clinic, Endocrinological Center, University of Bologna (Italy). PATIENTS: Forty-one girls with central precocious puberty were treated for 28 months (range, 12 to 60 months); 25 of them discontinued therapy at a mean chronological age of 10.0 +/- 0.9 years and were followed up for 25 months (range, 6 to 50 months). Twelve patients achieved adult height. INTERVENTION: Buserelin acetate (D-Ser [TBU] LHRH A1-9EA) nasal spray; 1800 micrograms/d subdivided into six intranasal administrations of 300 micrograms each. MEASUREMENTS/MAIN RESULTS: Basal follicle-stimulating hormone, peak gonadotropin values (fluoro-immunoenzymatic method, Eurogenetics, Tessenderlo, Belgium; sensitivity was 0.5 IU/L for luteinizing hormone and 1 IU/L for follicle-stimulating hormone), and estradiol (radioimmunoassay method, DPC Kit, Los Angeles, Calif; sensitivity was 11.01 pmol/L) were significantly suppressed (P < .0001) as of the third month of treatment and increased significantly (P < .01) to pretreatment levels 6 months after discontinuation of therapy. Uterine and mean ovarian volumes, which were stable throughout treatment, appeared significantly higher (P < .05) than before treatment at only 6 months after stopping therapy. In patients with more advanced bone age (according to Greulich and Pyle) at onset of treatment, we observed a more significant improvement of SD score for height (Tanner). Mean adult height in our patients was 159.5 +/- 6.1 cm, and the variables that were significantly associated with final height were height age/bone age ratio at onset and target height (according to Tanner). CONCLUSIONS: Long-term buserelin treatment administered nasally is effective because of completeness of inhibition, quick reversibility after treatment is stopped, and lack of side effects. Its auxologic results are different depending on bone age advancement at onset, which represents a predictor of "therapeutic success." Further follow-up would be useful.

A feasibility study of ovarian cancer screening: does fine-needle aspiration improve ultrasound specificity?

AIMS AND BACKGROUND: The prognosis for ovarian cancer patients depends on the stage at diagnosis. As a prerequisite for any proposed procedure for ovarian cancer screening, high levels of specificity should be obtained using combinations of tests. Based on preliminary data from an ongoing feasibility study, this report is focused on the possible gain in specificity provided by fine-needle aspiration of occult ovarian masses detected by ultrasound. METHODS: Ultrasonography was used as a basic test, and fine-needle aspiration was obtained from selected patients. Those with (a) positive aspiration cytology or histology, (b) complex or solid masses showing volume increase, (c) complex or irregular masses and inadequate samples, and (d) recurrent cystic lesions were operated on. RESULTS: A total of 3541 asymptomatic patients 50-69 years of age underwent ultrasonography, and 98 were selected for fine-needle aspiration. Of these, 19 (positivity rate 19/3541 or 0.5%) were operated on. Two ovarian cancer cases (FIGO Stage II and III) were detected (detection rate 2/3541 or 0.6 x 1,000; positive predictive value 2/19 or 10.5%). Specificity was 3443/3539 or 97.3% for ultrasound alone and 3522/3539 or 99.5% for the procedure as a whole. Surgical exploration for relapses of benign cysts reduced by some 50% the potential gain in positive predictive value provided by aspiration cytology compared with ultrasound alone. CONCLUSIONS: Although fine-needle aspiration has improved the performance of ultrasound, this 2-level procedure does not appear to achieve acceptable levels of specificity.

Uterine development and endocrine relationships after menarche.

Uterine volume and ovarian/uterine ratio during the first 6 postmenarchal years in 143 women were compared with an adult control group. Plasma gonadotropins and sex steroids were also correlated with uterine volume in adolescents. Uterine volume increased progressively and correlated positively with advancing postmenarchal (r = 0.24; p less than 0.05) and chronologic (r = 0.23; p less than 0.05) age. However, normal adult uterine volume was not yet reached by the highest postmenarchal (6 years) and chronologic (18 years) age. The ovarian/uterine ratio decreased gradually with increasing postmenarchal age but was always higher (0.22) than that of control subjects (0.12). Uterine volume correlated positively with plasma estradiol (r = 0.25; p less than 0.05) and dehydroepiandrosterone (r = 0.22; p less than 0.05) and its sulfate (r = 0.22; p less than 0.05) levels. This study indicates that the uterus continues to grow after menarche in conjunction with increasing hormone levels.

Endocrine and ovarian parameters at various frequencies of ovulation in adolescents.

We assessed ovarian and endocrine function in 86 adolescents over a six month period. Postmenstrual estrone (E1) and estradiol-17 beta (E2) levels, premenstrual FSH levels and pre- and postmenstrual LH, testosterone (T) and androstenedione (A) levels decreased as the frequency of ovulation increased, while premenstrual E2, progesterone (P) and 17 alpha-hydroxyprogesterone levels increased. Both right and left ovarian volume and the per cent of multifollicular ovaries decreased with an increase in the frequency of ovulation. In the premenstrual phase P values correlated significantly with frequency of ovulation for FSH (r = -0.43: P less than 0.001), LH (r = -0.36: P less than 0.01), T (r = -0.31: P less than 0.05) and A (r = -0.26: P less than 0.05). Our data suggest that in the postmenarcheal period the progressive loss of immature endocrine and ovarian characteristics (high LH, FSH, and androgen levels and enlarged, multifollicular ovaries) is linked to an increasing number of ovulations. Progesterone plays a major role in the development of cyclic function characteristic of adult maturity.

Pelvic ultrasonography in girls with precocious puberty, congenital adrenal hyperplasia, obesity, or hirsutism.

Real-time ultrasonography of the pelvic organs was performed on 151 girls with various complete and incomplete forms of precocious puberty, 20 girls with congenital adrenal hyperplasia, 20 with hirsutism, 18 with obesity, and 133 age-matched normal girls. Uterine and ovarian volumes were calculated and the ovarian morphologic picture was classified as homogeneous, nonhomogeneous (less than three small cystic areas), microcystic (four or more small cystic areas less than 9 mm in diameter), follicular (at least one cystic area greater than 9 mm), and macrocystic (large cystic area greater than 20 mm). Ultrasound imaging allowed an easy distinction between true precocious puberty and premature thelarche or idiopathic premature adrenarche. It was also helpful in the diagnosis of transient sexual precocity, although in these cases the differential diagnosis of precocious puberty can be difficult. In postmenarcheal patients with congenital adrenal hyperplasia, ultrasound study showed a low uterine volume and, frequently, a macrocyst in the ovary. In hirsute girls and in a few obese patients, ovaries had an increased volume and a microcystic structure, similar to those in polycystic ovary syndrome. Pelvic ultrasonography can be useful not only in diagnosing disorders in sexual development but also for greater understanding of the pathogenesis of these and other disorders.

Intravascular intrauterine transfusion for severe erythroblastosis fetalis using different techniques.

Over a 3-year period, 44 ultrasound-guided intravascular transfusions were performed between 18 and 32 weeks on 15 patients with severe erythroblastosis fetalis due to Rh immunization. In 4 fetuses, the first transfusion was performed before 20 weeks, in 6 between 20 and 25 weeks and in the remaining 5 between 25 and 31 weeks. Eight of the 15 fetuses were hydropic at the time of referral. Five transfusions were done in the intrahepatic umbilical vein, 6 were simple transfusions via percutaneous umbilical cord puncture, and 33 were partial exchange. There were 4 intrauterine deaths before 26 weeks, despite successfully performed transfusions: 3 of these fetuses were severely hydropic, while in the remaining fetus hydrops had been reversed in utero. Following delivery by cesarean section at 32 weeks of gestation, 1 of the neonates developed respiratory distress syndrome and died 17 h after birth. The overall survival rate was 67% (10 of 15 cases): 4 of the 8 hydropic fetuses (50%) and 6 of the 7 nonhydropic fetuses (83%) were alive at birth and survived the perinatal period. Three of the 5 losses occurred among the first 4 cases, while in the last 11 cases the survival rate increased to 82% (9 of 11).