Insulin-like growth factor binding proteins in a natural pre-ovulatory follicle from a woman with polycystic ovary syndrome.

Insulin-like growth factor binding protein (IGFBP) concentrations in the follicular fluid of ovarian follicles have been shown to correlate with dominance and atresia. IGFBP-2 and IGFBP-4 are increased in atresia, and IGFBP-3 is decreased in dominant follicles. The purpose of this study was to compare the IGFBP concentration in follicular fluid from a natural pre-ovulatory follicle of a woman with polycystic ovarian syndrome (PCOS) with other PCOS follicles and dominant follicles from normally cycling women. Follicular fluid was collected from 5-7 mm diameter follicles and a natural pre-ovulatory follicle from women with PCOS, and healthy and atretic follicles from normal women. The IGFBP profiles were analysed using Western ligand blotting. The IGFBP concentrations in the 5-7 mm diameter follicles from the polycystic ovaries containing a pre-ovulatory follicle were similar to those in follicles from other women with PCOS, and comparable with androgenic cohort follicles from normal women. In particular, the IGFBP-2 and IGFBP-4 concentrations were elevated significantly compared with the oestrogenic cohort follicles. The concentrations of all IGFBP detected in the follicular fluid from the PCOS pre-ovulatory follicle were significantly less than those of the 5-7 mm diameter follicles from the same subject. The IGFBP concentrations were within the range of normal dominant follicles, and IGFBP-2 and IGFBP-3 were at the lower end of the normal range. The results indicate that the PCOS pre-ovulatory follicle contained a normal pattern of IGFBP expression even though the other follicles exhibited a pattern typical of PCOS. These data support the hypothesis that decreased concentrations of IGFBP, in particular IGFBP-3, may be involved in selection of the dominant follicle, and that when a spontaneous pre-ovulatory follicle develops in PCOS, the underlying cause of the polycystic ovaries is not resolved but the rest of the ovary remains polycystic.

A new method and apparatus that prevents the rebreathing of expired carbon dioxide of sleeping neonates and infants.

This study was done to measure the effect on inspiratory carbon dioxide (CO2) levels of infants exposed to the infant Crib Air (ICA) apparatus, a novel device which circulates room air within the infant's crib. Twenty-one healthy, sleeping infants and neonates (mean age = 14.7 weeks) were studied in a prospective crossover trial. All infants were studied lying face down or with the face placed passively to the side in their cribs. Inspiratory CO2 levels were recorded over a 30 minute period by measuring the concentration of CO2 immediately adjacent to the infants' nose and mouth. During the first 15 minute period, the baseline concentration of inspiratory CO2 was recorded. The infants were then exposed to the ICA apparatus in their cribs for 15 minutes and the concentrations of inspiratory CO2 were measured. Mean inspiratory CO2 levels in infants lying face down decreased from 8.5 to 1.4 mm Hg after ICA exposure (P < 0.001). Infants studied with their face placed passively to the side experienced a similar decrease in inspired CO2 concentrations. We conclude that the level of inspired CO2 by sleeping infants can be significantly reduced by the ICA regardless of the position of the infant's head.

Insulin-like growth factor-binding proteins in healthy and atretic follicles during natural menstrual cycles.

An increasing body of evidence suggests a regulatory role for insulin-like growth factor-binding proteins (IGFBPs) in ovarian folliculogenesis. Although IGFBPs have been identified in the follicular fluid (FF) from women undergoing hyperstimulation for in vitro fertilization, little is known about the pattern of IGFBP expression during follicle development in natural menstrual cycles. The purpose of the present study was to determine the pattern of IGFBPs in the FF of healthy and atretic follicles during the follicular phase of natural menstrual cycles. FF was aspirated from follicles in normal ovaries of regularly cycling women. Dominant follicles were identified as the largest follicle in either ovary with an androstenedione to estradiol ratio in the FF of 4 or less. The androstenedione/estradiol ratio in atretic follicles was greater than 4. IGFBPs in the FF samples were analyzed by ligand blotting with [125I]IGF-II. The identities of the BPs measured by ligand blotting were confirmed by immunoblot and RIA analysis. IGFBP-3 concentrations decreased in healthy follicles as the follicular phase progressed. IGFBP-3 levels were significantly lower in dominant than healthy cohort follicles. IGFBP-2 was elevated in atretic follicles relative to that in healthy follicles. The levels of a 29-kilodalton BP comigrating with IGFBP-1 did not change significantly. IGFBP-4 was detected in only some of the atretic follicles. These experiments demonstrate that 1) at least four distinct IGFBPs are present in FF of women with natural unstimulated menstrual cycles; 2) IGFBP-3 in FF decreases during folliculogenesis, and 3) IGFBP-2 levels are elevated in atretic follicles. These data support the concept that IGFBPs may play important roles in regulating follicle selection and atresia.

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.

Insulin-like growth factor binding proteins in ovarian follicles from women with polycystic ovarian disease: cellular source and levels in follicular fluid.

The follicular fluid (FF) of human ovaries contains insulin-like growth factor binding proteins (IGFBPs) which may regulate the bioavailability of the IGFs. Previously we showed discrete changes in IGFBP concentrations in FF which correlated with the physiological state of the follicle. The purpose of the present study was to test the hypothesis that IGFBPs in FF may be increased in polycystic ovarian disease (PCO). FF was aspirated from PCO follicles and size matched healthy and atretic follicles from normal ovaries of naturally cycling women. The IGFBPs in FF samples were studied by ligand blot analysis with 125I-IGF-II and by immunoblot analysis using specific antisera to five human IGFBPs. Of six IGFBP bands in PCO FF, three were identified as IGFBP-2, IGFBP-3, and IGFBP-4. Bands (29K and 31K) were not identified by any of the five IGFBP antisera. The total IGF binding capacity was increased in PCO FF relative to normal healthy or atretic FF. IGFBP-3 was the predominant BP present in FF from PCO follicles as well as normal healthy and atretic follicles with no significant difference in any of the groups of follicles studied. IGFBP-2, IGFBP-4, and the 29K BP were present in smaller amounts, but there were significantly higher levels of each of these BPs in PCO follicles than in normal healthy follicles. Only IGFBP-4 was elevated in PCO follicles relative to normal atretic follicles indicating that the pattern of IGFBP expression in PCO FF was very similar to the pattern observed in atretic follicles. To determine the source of the IGFBPs in FF, granulosa or theca cells were cultured (up to 6 days) in serum-free medium. Ligand blot analysis of the conditioned medium revealed basal secretion of IGFBP-3 by both theca and granulosa cells. FSH inhibited granulosa cell IGFBP-3 production but increased the 29K BP in the medium. Transforming growth factor-beta stimulated basal IGFBP-3 secretion and reversed the FSH effects. Human CG (100 ng/mL) inhibited theca cell IGFBP-3 production but did not stimulate any other IGFBP. The results of our studies indicate that IGFBP-2, IGFBP-4, and the 29K BP are significantly increased in PCO FF and that gonadotropins and TGF-beta regulate the production of IGFBPs by human theca and granulosa cells.

Falloposcopic classification and treatment of fallopian tube lumen disease.

OBJECTIVE: To devise a diagnostic classification and scoring system for tubal lumen disease based on falloposcopy and to evaluate it against tuboplasty procedures and pregnancy outcomes. DESIGN: Prospective study approved by the hospital Institutional Review Board. SETTING: Academic tertiary infertility center. PATIENTS: Seventy-five women with hysterosalpingographic and laparoscopic evidence of endotubal disease had 112 tubes available for falloposcopic evaluation. INTERVENTION: Diagnostic and operative falloposcopy was performed, when indicated, using aquadissection, flexible wire cannulation, or direct balloon tuboplasty. RESULTS: The endotubal lumens were considered to be falloposcopically normal in 52 tubes (46%), to contain mild to moderate disease in 33 (29%), and severe to obstructive disease in 27 (25%) cases. Within a year of the procedure, 6 of the 28 women (21%) in whom at least 1 tube was normal conceived, in 2 of 22 (9%) with mild to moderate disease, and in 0 of 16 (0%) with severe endotubal disease. CONCLUSIONS: Falloposcopy provides a visual means of scoring endotubal disease and may be intrinsically therapeutic for dislodging intraluminal debris and breaking down filmy adhesions in normal or minimally diseased tubes. The presence of severe disease remains resistant to the use of current endotuboplasty treatments as reflected by poor pregnancy outcome, and such women should be provided the option of microsurgical tubal repair or in vitro fertilization and embryo transfer procedures.

Fluorometry of selenium in human hair, urine and blood. A single-tube process for submicrogram determination of selenium.

This communication introduces a special lyophilization process for selenium determination by fluorometric methods. It permits a small sample volume, with several modifications including a single test tube process. Samples and standard are lyophilized first, then digested with nitric-perchloric acid mixture in a heated sand bath. Selenium is complexed with 2,3-diaminonaphthalene and extracted by n-hexane in the same test tube. The n-hexane layer is transferred to a cuvette and measured fluorometrically. Selenium concentration in healthy children from Long Island (aged 5-18 years) was: hair 0.765 +/- 0.114 microgram/g (n = 52), urine 28.65 +/- 8.27 micrograms/g creatinine (n = 66), and serum 95.4 +/- 14.4 ng/ml (n = 44). The current literature reflects an increase in the role of selenium in human nutrition. Thus, a simple but reliable method for determination of selenium in biological materials is needed in the clinical and research laboratory.