Comparison of transdermal versus oral estradiol on endometrial receptivity

OBJECTIVE: To compare the effects of oral micronized E2 with transdermal E2 on endometrial receptivity in women undergoing oocyte donation. DESIGN: Prospective, randomized, crossover trial. Serum E2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and beta-3-integrin expression. SETTING: University-based donor oocyte program. PATIENTS: Twenty-seven patients presenting for donor oocytes. MAIN OUTCOME MEASURES: Endometrial histology and beta-3-integrin expression. RESULTS: The endometrial glandular histology in women given oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E2. Seventy percent of women given oral E2 displayed a lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag. Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on transdermal E2. CONCLUSION: The supraphysiologic serum E2 levels associated with oral micronized E2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.     

Ultrastructural aspects of endometrium in infertile women with septate uterus

OBJECTIVES: To evaluate the endometrial surface morphology in patients with septate uterus and primary infertility in an attempt to throw light on the question of whether endometrial anomalies are involved in the pathogenesis of infertility in women with mullerian malformations. DESIGN: Endometrial biopsies were performed in eight women with septate uterus and primary infertility during hysteroscopy scheduled in the preovulatory phase of the cycle (when a follicle > 17 mm was identified by ultrasonography and E2 levels were >200 pg/mL [conversion factor to SI unit, 3.671]). Two samples were obtained from each patient, one from endometrium covering the septum and the other from endometrium lining the lateral wall of the uterus. All specimens were examined by scanning electron microscopy. MAIN OUTCOME MEASURES: The number of glandular ostia, the ciliated:nonciliated cell ratio, and the number of cilia on ciliated cells were analyzed in endometrial specimen from both the covering of the septum and the corresponding uterine lateral wall. RESULTS: In five patients septal endometrium showed the following defective preovulatory changes with respect to endometrium of the lateral uterine wall: a reduced number of glandular ostia, irregular nonciliated cells with rare microvilli, incomplete ciliogenesis on ciliated cells, and decrease in the ciliated:nonciliated cell ratio (1:52 +/- 11 versus 1:21 +/- 8). CONCLUSIONS: Our results indicate a decrease in the sensitivity of endometrium covering the septa of malformed uteri to preovulatory hormonal changes. This could play a role in the pathogenesis of primary infertility in patients with septate uterus.     

Localization by indirect immunofluorescence of nitric oxide synthase in mouse and human spermatozoa

OBJECTIVE: To determine and compare the concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (FGF) in the peritoneal fluid of women with and without endometriosis. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with university medical school. PATIENTS: Forty-two women with endometriosis and 34 women without endometriosis confirmed by laparoscopy. MAIN OUTCOME MEASURES: Epidermal growth factor and basic FGF concentrations were determined by highly sensitive enzyme immunoassays using monoclonal antibodies. RESULT: Approximately 50% of the PF samples had EGF concentrations of > 0.4 pg/mL (conversion factor to SI unit, 0.17) and 90% had basic FGF concentrations of > 1 pg/mL (conversion factor to SI unit, 0.058). Concentrations of EGF or basic FGF in PF did not differ significantly between the two groups. In normal women, there was a significant correlation between EGF and basic FGF during the luteal phase. In women with endometriosis, EGF levels were higher during the luteal phase, but there was no correlation of either EGF or basic FGF levels with the severity of endometriosis. CONCLUSIONS: The concentrations of EGF and basic FGF were highly variable in the PF of women with or without endometriosis and did not differ significantly. The concentrations were so low that neither EGF nor basic FGF in PF could bind to its receptor.     

Elevation of the serum bilirubin diconjugate fraction provides an early marker for cholestasis in the rat

OBJECTIVES: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. DESIGN: Historical cohort study. SETTING: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. PATIENT(S): Criteria for inclusion were oocyte recipients age < or = 40 years, FSH > 18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. RESULT(S): The ages of the donors to groups I and II were comparable (31.1 +/- 16.7 versus 29.8 +/- 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 +/- 2.1 versus 8.6 +/- 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E2 on the day of hCG administration (2,356 +/- 826 versus 1,847 +/- 843 pg/mL; conversion factor to SI unit, 3,671), number of oocytes retrieved (25 +/- 14 versus 22 +/- 13), number of embryos transferred (4.4 +/- 2.1 versus 4.0 +/- 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). CONCLUSION(S): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.     

Seasonal changes in pituitary function: amplification of midfollicular luteinizing hormone secretion during the dark season

OBJECTIVE: To analyze the effect of season on the pulsatility of gonadotropin secretion in women living in an area with a large annual variability in daylight length. DESIGN: A prospective study. Pulse studies were carried out in each subject during both the dark and light season. SETTING: The gynecologic endocrine research unit of the University Central Hospital of Oulu. PARTICIPANTS: Eleven ovulatory, healthy women volunteering for the study. INTERVENTIONS: Serum samples were collected at 10-minute intervals for 6 hours on days 7 to 9 of the cycle. MAIN OUTCOME MEASURES: Serum LH and FSH concentrations were measured and the data were analyzed with an algorithm computer-based program. RESULTS: The mean area of LH pulses analyzed was significantly higher during the dark season than the light season (49.1 +/- 3.1 versus 38.5 +/- 1.7 mIU/mL; conversion factor to SI unit, 1.00), while in the amplitude (1.9 +/- 0.1 versus 1.8 +/- 0.1 mIU/mL), number of pulses (5.2 +/- 0.3 versus 4.4 +/- 0.6), and the mean level (9.6 +/- 0.5 versus 9.4 +/- 0.9 mIU/mL) the difference did not reach statistical significance. The number (5.2 +/- 0.5 versus 5.2 +/- 0.4,), amplitude (1.0 +/- 0.05 versus 1.1 +/- 0.07 mIU/mL; conversion factor to SI unit, 1.00), area (29.9 +/- 2.4 versus 29.6 +/- 3.1 mIU/mL), and the mean level of FSH (5.4 +/- 0.6 versus 6.0 +/- 0.8 mIU/mL) during the dark and light seasons were identical, showing no seasonal variability. CONCLUSIONS: The results indicate increased pituitary LH secretion in the midfollicular phase during the dark season that may be related to increased melatonin secretion and decreased ovarian activity at this time of the year.     

Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome

OBJECTIVE: To evaluate the outcomes of IVF and the incidence of ovarian hyperstimulation syndrome (OHSS) after discontinuing gonadotropin therapy in patients at risk of developing OHSS by delaying hCG administration until a drop in serum E2 levels was observed. DESIGN: Retrospective study. SETTING: IVF program at a university center. INTERVENTIONS: Gonadotropin administration was withheld in 22 patients (group 1) when their serum E2 level was > or = 3,000 pg/mL (conversion factor to SI unit, 3.671). Patients continued GnRH analogue injections daily, and hCG was administered when serum E2 levels dropped to < or = 3,000 pg/mL. Outcomes were compared with 26 patients (group 2) in whom embryo transfer was canceled and all embryos cryopreserved for transfer during a subsequent unstimulated cycle. MAIN OUTCOME MEASURES: Outcomes of IVF and incidence of OHSS were compared in both groups of patients. In group 1, follicular and hormonal parameters before and after the coasting interval were compared in pregnant versus nonpregnant patients. In addition, serum hormonal profiles were evaluated daily during the coasting period to determine the effects of gonadotropin withdrawal. RESULTS: Although the mean number of oocytes retrieved was significantly higher in group 2, fertilization rates, miscarriage rates, delivery rates/stimulation cycle, and the incidence of OHSS did not differ significantly between the two groups. CONCLUSION: Withholding gonadotropin administration is an effective alternative to prevent the development of severe OHSS in a high-risk population. Although the risk of cancellation cannot be completely eliminated, this strategy can provide a high pregnancy rate without the need to repeat multiple frozen-thawed cycles.     

Relationship of preoperative serum CA-125 to survival in epithelial ovarian carcinoma

BACKGROUND: Epithelial carcinoma of the ovary has the highest death rate of any gynecologic malignancy in the developed world. The antigen CA-125 has been used over the past decade as a tumor marker for epithelial ovarian cancer and other cancers of coelomic epithelium. The object of this study was to see if the degree of elevation of preoperative CA-125 was related to length of survival in patients with epithelial ovarian carcinoma. METHODS: Eighty-two consecutive patients diagnosed with epithelial ovarian carcinoma were evaluated for their initial preoperative CA-125 level, time to recurrence, length of survival and level of primary debulking as well as International Federation of Gynecologists and Obstetricians stage, grade and histology. Ovarian tumors of low malignant potential were not included in the study. All patients had their initial surgery performed by one surgeon. RESULTS: Decreased length of survival was related to the degree of elevation of CA-125 prior to initial exploratory laparotomy (P = .047). The mean initial CA-125 for patients surviving five years or more (15 patients) was 899 U/mL, with an SD of +/- 1,880 U/mL, while the CA-125 for patients surviving less than five years (67 patients) was 1,978 U/mL, with an SD of +/- 1,852 U/mL (P = .02). Increased stage of disease at initial laparotomy showed a relationship to increased CA-125 (P < .0001). CONCLUSION: In epithelial ovarian carcinoma, high preoperative serum levels of CA-125 predict decreased length of survival.     

Elevated serum progesterone levels during pituitary suppression may signify adrenal hyperandrogenism

OBJECTIVE: To investigate whether elevated serum P levels after pituitary down-regulation signify adrenal enzyme defects or hyperandrogenism. DESIGN: Prospective study. SETTING: Assisted reproduction unit in a university medical center. PATIENT(S): Two hundred twenty-seven IVF patients treated by the long down-regulation protocol. INTERVENTION(S): Oral dexamethasone (DEX) administration if P level exceeded 0.8 ng/mL (conversion factor to SI unit, 3.180) after pituitary suppression. MAIN OUTCOME MEASURE(S): Serum concentrations of P, E2, LH, DHEAS, and 17 alpha-hydroxyprogesterone and ACTH stimulation tests. RESULT(S): In eight patients (3.5%), serum P levels exceeded 0.8 ng/mL and E2 and LH levels confirmed pituitary down-regulation. Mean DHEAS levels in the patients in this group were significantly higher than in the other patients. All eight patients demonstrated a significant decrease in serum P level after DEX administration. In five patients the ACTH stimulation test suggested an adrenal defect. Five pregnancies were achieved after the addition of DEX to the treatment protocol. CONCLUSION(S): High serum P levels after pituitary down-regulation appear to be of adrenal origin and may be the first indication of an adrenal enzyme defect. Further investigation such as an ACTH stimulation test is recommended, followed by treatment with DEX if indicated.     

Insulin-like growth factor-I in men with idiopathic osteoporosis

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 +/- 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.     

Effects of raloxifene in a guinea pig model for leiomyomas

OBJECTIVE: Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol. STUDY DESIGN: To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography. RESULTS: On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment. CONCLUSIONS: Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.     

Active transforming growth factor-beta in wound repair: determination using a new assay

The increase in serum FSH that accompanies female reproductive aging occurs before changes in estradiol (E2). A decrease in negative feedback from inhibin A (a product of the dominant follicle and corpus luteum) and/or inhibin B (secreted by developing follicles) may explain the rise in FSH with age. To test the hypothesis that decreases in inhibin A or inhibin B occur at an age at which the first increase in follicular phase FSH is evident, daily blood samples were obtained across the menstrual cycle from younger (<35 yr; n = 23) and older (35-46 yr; n = 21) cycling women. These cross-sectional studies were complemented by longitudinal data in 3 women studied at a 10-yr interval. In the early follicular phase, mean inhibin B was lower in older cycling women (88 +/- 7 vs. 112 +/- 10 pg/mL; P < 0.05) and FSH was higher (13.0 +/- 0.5 vs. 11.2 +/- 0.7 IU/L in older vs. younger, respectively; P < 0.04). In the mid- and late follicular phases, inhibin B was also lower in the older women (117 +/- 9 vs. 146 +/- 10 and 85 +/- 8 vs. 117 +/- 11 pg/mL; P < 0.04), whereas E2 was higher (105 +/- 14 vs. 68 +/- 5 and 240 +/- 27 vs. 163 +/- 9 pg/mL; P < 0.02), and no differences in FSH were observed in the two groups at these times. In women studied longitudinally, FSH and inhibin B varied inversely in the follicular phase. In the early luteal phase, mean inhibin B was lower in the older group (64 +/- 6 vs. 94 +/- 12 pg/mL; P < 0.03), and FSH was higher (12.5 +/- 1.0 vs. 9.7 +/- 0.6 IU/L; P < 0.03). In the mid- and late luteal phases, inhibin B was also lower in older subjects (21 +/- 2 vs. 33 +/- 5 and 22 +/- 2 vs. 36 +/- 6 pg/mL; P < 0.02). No difference in inhibin A, E2, or progesterone was observed across the luteal phase, between the two groups. However, in all subjects studied longitudinally, increased age was associated with a decrease in inhibin A, inhibin B, and progesterone in the absence of changes in E2. Our conclusions were: 1) reproductive aging is accompanied by decreases in both inhibin B and inhibin A; 2) the decrease in inhibin B precedes the decrease in inhibin A and occurs in concert with an increase in E2, suggesting that inhibin B negative feedback is the most important factor controlling the earliest increase in FSH with aging; 3) these studies suggest that the decrease in inhibin B is the earliest marker of the decline in follicle number across reproductive aging.     

Direct activation of human peritoneal mesothelial cells by heat-killed microorganisms

OBJECTIVE: The aim of the study was to determine if human peritoneal mesothelial cells (HPMCs) can be activated directly by bacterial products contained in preparations of heat-killed Escherichia coli and staphylococci. SUMMARY BACKGROUND DATA: It has been shown recently that cytokine-activated HPMCs produce the inflammatory mediators, interleukin-1, interleukin-6, interleukin-8, and macrophage chemotactic protein-1. Studies concerning the effects of bacterial products on HPMCs are scarce and have not yielded conclusive results. METHODS: Growth-arrested HPMC monolayers were prepared from cell suspensions obtained by enzymatic disaggregation of small pieces of omentum. They were incubated for 24 hours with heat-killed E. coli (ATCC 25922), heat-killed staphylococci (ATCC 25933), or E. coli lipopolysaccharide, and the release of various cytokines in the culture media was measured by radioimmunoassays or enzyme-linked immunosorbent assays. Results were expressed as mean +/- standard error of the mean in picograms per milliliter of supernatant and analyzed with the Wilcoxon test; p values of less than 0.05 were considered significant. RESULTS: Baseline production of interleukin-6, interleukin-8, the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES), and macrophage chemotactic protein-1 varied widely from one omental preparation to the other. E. coli increased the release of these mediators: from 1206 +/- 316 pg/mL to 8480 +/- 2189 pg/mL for interleukin-6, from 285 +/- 58 pg/mL to 3164 +/- 1053 pg/mL for interleukin-8, from 7 +/- 5 pg/mL to 684 +/- 264 pg/mL for RANTES, and from 2212 +/- 346 pg/mL to 7726 +/- 1473 pg/mL for macrophage chemotactic protein-1. Heat-killed staphylococci did not alter significantly the production of RANTES or macrophage chemotactic protein-1 but increased the production of the two other cytokines from 1325 +/- 389 pg/mL to 2206 +/- 523 pg/mL for interleukin-6 and from 318 +/- 70 pg/mL to 819 +/- 265 pg/mL for interleukin-8. CONCLUSIONS: The authors' results show that HPMCs are able to react to a direct stimulation with heat-killed microbes. They suggest that HPMCs, as well as resident macrophages, participate actively in the initiation and possibly in the modulation of intraperitonen inflammatory reactions.     

Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.     

Evaluation of serum creatine kinase levels in ectopic pregnancy

OBJECTIVE: To analyze whether increased serum creatine kinase (CK) levels are useful in early detection of ectopic pregnancy (EP). DESIGN: Prospective cohort study. SETTING: Patients in a university-based reproductive endocrinology and infertility practice. PATIENTS: Infertile women who achieved clinical pregnancy. INTERVENTIONS: Serum CK with isoenzymes levels were drawn after sonographic evaluation in patients achieving clinical pregnancy. MAIN OUTCOME MEASURES: Comparison of serum CK levels in patients with EP versus those with normal and abnormal intrauterine pregnancy (IUP), both separately and together as one group. RESULTS: There was no significant difference in mean total CK levels for patients with EP (82.25 +/- 81.39 IU/L; conversion factor to SI unit, 1.00) versus normal IUP (62.54 +/- 44.79 IU/L), abnormal IUP (55.15 +/- 3.46 IU/L), or all IUP (60.87 +/- 40.72 IU/L). The mean gestational ages were similar in all three groups: EP, 46.78 +/- 6.65 days; normal IUP, 47.56 +/- 8.29 days; and abnormal IUP, 47.86 +/- 13.30 days. CONCLUSION: Serum CK levels do not help to predict EP for infertility patients achieving conception. To assist in preventing maternal morbidity, a more discriminative test is needed to identify this condition early in gestation.     

Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant

BACKGROUND: To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea, as well as its significance in monitoring therapy and follow-up. METHODS: One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospectively studied for serum CA-125 concentration. For those with advanced endometriosis receiving danazol treatment after conservative surgery, CA-125 was also determined every month during medication and once every 12 months after treatment. RESULTS: The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1% and 87.5% respectively. Elevated CA-125 (>35 U/ml) was noted in 65/75 cases (86.70%) with advanced endometriosis, but in only 15/56 patients (26.8%) with minimal and mild endometriosis. Although there were significantly higher CA-125 levels in unmarried women, and a negative correlation (r=-0.1970, p=0.0284) between CA-125 and parity, there was no statistical difference in incidence of endometriosis by the status of marriage or parity. Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment, even though they tested with normal CA-125 levels (<35 U/ml) at that time. Fifteen patients had elevated CA-125 levels before and one year after therapy, and were confirmed with recurrence of endometriosis by laparoscopy. Nine women with elevated CA-125 levels before treatment, were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy. CONCLUSION: For endometriosis, CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels. It is not an effective screening tool for patients with dysmenorrhea, or for monitoring therapy. There was no significant correlation between the development of endometriosis and reproductive factors.     

Premature progesterone elevation spares blastulation but not pregnancy rates in in vitro fertilization with coculture

OBJECTIVE: To clarify whether embryo development to the blastocyst stage may be affected by premature P elevation during controlled ovarian hyperstimulation (COH) for IVF-ET with embryo coculture. DESIGN: Retrospective study. SETTING: Tertiary care infertility center. PATIENT(S): One hundred thirty-one women undergoing 153 IVF-ET cycles with embryo coculture. INTERVENTION(S): Patients underwent COH with GnRH agonist and hMG. Embryos were cocultured up to the blastocyst stage. According to plasma P levels on the day of hCG, two groups were defined: low P (P < or = 0.9 ng/mL; conversion factor to SI unit, 3.180) and high P (P > 0.9 ng/mL). MAIN OUTCOME MEASURE(S): Blastulation (number of blastocysts/number of noncavitating embryos x 100) and pregnancy rates (PRs). RESULT(S): Blastulation rates were similar in the low and high P groups (51% and 48%, respectively). Moreover, patients included in the high P groups achieved significantly lower clinical and ongoing PRs (12% versus 29% and 7% versus 25%, respectively). CONCLUSION(S): The lack of difference in blastulation rates between the groups further supports the hypothesis that premature P elevation does not alter oocyte and embryo quality. Hence, the observed decrease in PRs is likely to reflect impaired endometrial receptivity in the high P group.     

Estrogen-mediated neuroprotection after experimental stroke in male rats

BACKGROUND AND PURPOSE: We have previously shown that 17beta-estradiol reduces infarction volume in female rats. The present study determined whether single injection or chronic implantation of estrogen confers neuroprotection in male animals with middle cerebral artery occlusion (MCAO) and whether there is an interaction with endogenous testosterone. METHODS: Male Wistar rats were treated with 2 hours of reversible MCAO. In protocol 1, acute versus chronic estrogen administration was examined in groups receiving the following: Premarin (USP) 1 mg/kg IV, immediately before MCAO (Acute, n=13, plasma estradiol=171+/-51 pg/mL); 7 days of 25 microg (E25, n=10, 10+/-3 pg/mL) or 100 microg 17beta-estradiol (E100, n=12, 69+/-20 pg/mL) by subcutaneous implant; or saline (SAL, n=21, 3+/-1 pg/mL). Laser-Doppler flowmetry was used to monitor the ipsilateral parietal cortex throughout the ischemic period and early reperfusion. At 22 hours of reperfusion, infarction volume was determined by 0 2,3,5-triphenyltetrazolium chloride staining and image analysis. In protocol 2, rats were castrated to deplete endogenous testosterone and then treated with estradiol implants: castration only (CAST, n= 13, estradiol=5+/-2 pg/mL), sham-operated (SHAM, n= 10, 4+/-2 pg/mL), estradiol implant 25 microg (CAST+E25, n=16, 7+/-2 pg/mL) or 100 microg (CAST+E100, n=14, 77+/-14 pg/mL). RESULTS: Cortical infarct volumes were reduced in all estrogen-treated groups: Acute (21+/-4% of ipsilateral cortex), E25 (12+/-5%), and E100 (12+/-3%) relative to SAL (38+/-5%). Caudate infarction was similarly decreased: Acute (39+/-7% of ipsilateral striatum), E25 (25+/-7%), and E100 (34+/-6%) relative to SAL (63+/-4%). Castration did not alter ischemic outcome; cortical and caudate infarction (percentage of respective ipsilateral regions) were 37+/-5% and 59+/-5% in CAST and 39+/-7% and 57+/-5% in SHAM, respectively. Estrogen replacement reduced infarction volume in castrated animals in cortex (19+/-4% in CAST+E25 and 12+/-4% in CAST+E100) and in caudate (42+/-6% in CAST+25 and 20+/-7% in CAST + 100). Laser-Doppler flowmetry results during ischemia and reperfusion was not different among groups. CONCLUSIONS: Both acute and chronic 17beta-estradiol treatments protect male brain in experimental stroke. Testosterone availability does not alter estradiol-mediated tissue salvage after MCAO.     

Effects of low-dose recombinant human insulin-like growth factor-I on insulin sensitivity, growth hormone and glucagon levels in young adults with insulin-dependent diabetes mellitus

Despite recent interest in the therapeutic potential of recombinant human insulin-like growth factor-I (rhIGF-I) in the treatment of diabetes mellitus, its mechanism of action is still not defined. We have studied the effects of low-dose bolus subcutaneous rhIGF-I (40 microg/kg and 20 microg/kg) on insulin sensitivity, growth hormone (GH) and glucagon levels in seven young adults with insulin-dependent diabetes mellitus (IDDM) using a randomized double-blind placebo-controlled crossover study design. Each was subjected to a euglycemic clamp (5 mmol/L) protocol consisting of a variable-rate insulin infusion clamp (6:00 PM to 8:00 AM) followed by a two-dose hyperinsulinemic clamp (insulin infusion of 0.75 mU x kg(-1) x min(-1) from 8 to 10 AM and 1.5 mU x kg(-1) x min(-1) from 10 AM to 12 noon) incorporating [6,6 2H2]glucose tracer for determination of glucose production/utilization rates. Following rhIGF-I administration, the serum IGF-I level (mean +/- SEM) increased (40 microg/kg, 655 +/- 90 ng/mL, P < .001; 20 microg/kg, 472 +/- 67 ng/mL, P < .001; placebo, 258 +/- 51 ng/mL). Dose-related reductions in insulin were observed during the period of steady-state euglycemia (1 AM to 8 AM) (40 microg/kg, 48 +/- 5 pmol/L, P = .01; 20 microg/kg, 58 +/- 8 pmol/L, P = .03; placebo, 72 +/- 8 pmol/L). The mean overnight GH level (40 microg/kg, 9.1 +/- 1.4 mU/L, P = .04; 20 microg/kg, 9.6 +/- 2.0 mU/L, P = .12; placebo, 11.3 +/- 1.7 mU/L) and GH pulse amplitude (40 microg/kg, 18.8 +/- 2.9 mU/L, P = .04; 20 microg/kg, 17.0 +/- 3.4 mU/L, P > .05; placebo, 23.0 +/- 3.7 mU/L) were also reduced. No differences in glucagon, IGF binding protein-1 (IGFBP-1), acetoacetate, or beta-hydroxybutyrate levels were found. During the hyperinsulinemic clamp conditions, no differences in glucose utilization were noted, whereas hepatic glucose production was reduced by rhIGF-I 40 microg/kg (P = .05). Our data demonstrate that in subjects with IDDM, low-dose subcutaneous rhIGF-I leads to a dose-dependent reduction in the insulin level for euglycemia overnight that parallels the decrease in overnight GH levels, but glucagon and IGFBP-1 levels remain unchanged. The decreases in hepatic glucose production during the hyperinsulinemic clamp study observed the following day are likely related to GH suppression, although a direct effect by rhIGF-I cannot be entirely discounted.     

Age-related reduction in glucose elimination is accompanied by reduced glucose effectiveness and increased hepatic insulin extraction in man

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled i.v. glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (i.v. tolerance index, 1.31 +/- 0.10 vs. 1.70 +/- 0.12% min-1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 +/- 0.07 vs. 0.70 +/- 0.08 (pmol/L)min-2/(mmol/L), P = 0.026), lower SG, 0.017 +/- 0.002 vs. 0.025 +/- 0.002 min-1, P = 0.004), and higher HE (81.3 +/- 2.4 vs. 73.2 +/- 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P < 0.001) and negatively with HE (r = -0.54, P < 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 +/- 18 vs. 66 +/- 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.     

The effects of chronic ill health and treatment with sulphasalazine on fertility amongst men and women with inflammatory bowel disease in Leicestershire

Our aim was to investigate the effect of GnRH-agonist (GnRH-a) induced suppression of plasma sex steroids on serum GH, insulin like growth factor-I (IGF-I) and insulin levels after an oral glucose load (OGTT) in women with polycystic ovary syndrome (PCOS). Serum insulin, GH and IGF-I levels during a 75-g 4-h OGTT were measured in 3 nonobese and 7 obese hyperandrogenic women with PCOS and normal glucose tolerance before and after 10 weeks of treatment with the GnRH-a triptorelin (3,75 mg im every 28 days). Basal estrogen and androgen levels were also measured at time 0 of the first and the second OGTT. After the therapy serum estrogens and androgens were significantly suppressed. Body weight remained unchanged. Basal GH significantly increased after the treatment while fasting IGF-I and insulin levels decreased from (mean +/- SE) 349.3 +/- 31.8 to 278.7 +/- 33.2 ng/mL and from 22.4 +/- 4.1 to 18.8 +/- 4.4 microU/mL, respectively. The insulin response to OGTT (area under curve) was also reduced (from 16,017 +/- 2598 to 11,736 +/- 2317 microU/mL/240 min). Our results suggest that the GnRH-a induced suppression of ovary secretion may modify the serum GH and IGF-I levels and the insulin response to an OGTT in women with PCOS.