胰岛素样生长因子及胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系

目的　探讨胰岛素样生长因子 (IGF) Ⅰ、IGF Ⅱ和IGF结合蛋白 3(IGFBP 3)与胎儿生长的关系 ,以及IGF在胎儿生长受限 (FGR)发病中的作用。方法　选取 2 0例分娩FGR胎儿 (FGR组 )、10例分娩巨大儿 (巨大儿组 )及 2 0例分娩正常儿 (对照组 )的产妇 ,抽取 3组产妇分娩后肘静脉血及其新生儿脐静脉血 ,分离血清。采用放射免疫法和免疫放射法测定 3组产妇及其新生儿血清中IGF Ⅰ、IGF Ⅱ及IGFBP 3的水平。结果　 (1)FGR组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为(130 5± 2 6 0 ) μg/L、(2 40± 0 42 ) μg/L及(5 5 79± 848) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 6± 1 7) μg/L、(1 5 4± 0 31) μg/L及 (86 9± 183) μg/L。 (2 )巨大儿组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 9 7± 44 6 ) μg/L、(2 43± 0 2 5 ) μg/L及(5 5 6 2± 742 ) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 9 6± 2 3 9) μg/L、(2 19± 0 2 9) μg/L及(16 82± 130 )μg/L。(3)对照组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 7 9± 70 7) μg/L、(2 41± 0 36 )μg/L及 (5 5 86± 6 78) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 8 9     

Serum ferritin level as a marker of preterm labor.

Objective: To compare the serum ferritin levels in women with preterm labor (PTL) or preterm premature rupture of membranes with those in normal gravid women. Method: The study group consisted of 50 consecutive subjects with preterm labor and 49 subjects with preterm premature rupture of membranes (PROM). The control group consisted of 50 subjects matched with the study group for hemoglobin (Hb) and gestation who did not have PTL or preterm PROM. Serum ferritin levels were assayed in both the groups. Results: Mean serum ferritin levels in patients with preterm labor and preterm premature rupture of membranes were 23.24+/-12.13 ng/ml and 29.44+/-28.41 ng/ml, respectively. The mean serum ferritin in control subjects was 8.69+/-3.7 ng/ml. The difference was evaluated by Student's t-test and was found to be statistically significant. Conclusion: The serum ferritin level is significantly raised in pregnant women with preterm labor and preterm PROM.     

Maternal zinc and cord blood zinc, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels in small-for-gestational-age newborns

PURPOSE: To determine the relationship between maternal serum zinc (Zn) levels and birth weight of the offspring and their correlation with cord blood Zn, insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHOD: 22 term small-for-gestational-age (SGA) and 34 term appropriate-for-gestational-age (AGA) infants and their mothers were included. Maternal and cord blood Zn levels and cord blood IGF-1 and IGFBP-3 levels were measured. RESULTS: Eighteen percent of mothers had Zn deficiency (< 75 mcg/dl). No significant difference between IGF-1 and IGFBP-3 levels and birth weight of infants of the mothers with and without Zn deficiency was found. Maternal and neonatal Zn levels correlated (r = 0.38, p < 0.01). Mean IGF-1 and IGFBP-3 levels were significantly lower in the SGA group compared to the AGA group (42.3 +/- 16.8 ng/ml, 1.2 +/- 0.2 mcg/ml, and 62.4 +/- 22.7 ng/ml, 1.5 +/- 0.4 mcg/ml, p < 0.001). A correlation was found between birth weight, IGF-1 and IGFBP-3 levels, and weight gain of the mother during pregnancy (p < 0.01). CONCLUSIONS: Zn deficiency was not observed to be a risk factor for low birth weight. The significant difference between the SGA and AGA babies' IGF-1 and IGFBP-3 levels emphasizes function of the IGF system in intrauterine growth.     

Oral 17beta-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins.

OBJECTIVE: We evaluated the acute effects of low-dose oral estradiol and sequential progesterone on the insulin-like growth factor (IGF)/growth hormone (GH) axis, IGF-binding proteins (IGFBPs) 1 and 3, and plasma levels of sex hormone-binding globulin (SHBG) in postmenopausal subjects. STUDY DESIGN: Thirty healthy normal-weight women (mean age: 54.2 +/- 5.7 years) spontaneously postmenopausal for at least 6 months were enrolled. None had used hormone replacement therapy (HRT). Appropriate investigations excluded renal, glucose, lipid and coagulation abnormalities. Breast X-ray and endometrial ultrasound examinations excluded organic pathologies. They received oral cyclical HRT for 1 year, based on the administration of oral estradiol (1 mg/day) for 28 consecutive days plus progesterone (200 mg/day) from day 15 to day 28; out of the whole group, 15 subjects received progesterone orally (group A), while in 15 progesterone was administered transvaginally (group B). On the day before treatment (T0), on day 14 (T14) and on day 28 (T28) of the first cycle, plasma levels of estradiol, progesterone, SHBG, GH, IGF-I and -II, IGFBP-1 and -3, insulin and C-peptide were assayed in all patients. The same parameters were evaluated at T14 and T28 during the 12th month of treatment. RESULTS: At T14, we observed significant increases in the levels of estradiol (from 20 +/- 16 to 115 +/- 71 pg/ml, p < 0.001), SHBG (from 132 +/- 42 to 182 +/- 55 nmol/l, p < 0.001) and IGFBP-1 (from 92 +/- 57 to 127 +/- 87 ng/ml, p < 0.004), while the level of IGF-I decreased (from 197 +/- 138 to 129 +/- 85 ng/ml, p < 0.003). At T28, progesterone levels were significantly higher in the women receiving it orally than transvaginally (8.4 +/- 6.1 vs. 3.7 +/- 3.2 ng/ml, p < 0.025). However, while oral progesterone did not affect the estrogen-induced variations, transvaginal progesterone abrogated the increase in the levels of IGFBP-1. The levels of IGF-II, IGFBP-3, GH, glucose, C-peptide and insulin did not change at any time. At 1 year, the values maintained the same trends. The estrogen-induced variations of SHBG were correlated directly with those of estradiol (r = 0.48) and inversely with those of IGF-I (r = -0.424). CONCLUSIONS: Low-dose oral estradiol reduces plasma levels of IGF-I and increases IGFBP-1 and SHBG concentrations, while GH is unchanged. These effects, significant and immediate, lead us to hypothesize a direct action of estradiol on hepatocytes.     

胰岛素样生长因子I及其结合蛋白1对超排卵周期卵泡发育的影响

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Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations

OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. RESULTS: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/- 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.     

Unconjugated serum estriol in the prediction of preterm delivery

OBJECTIVE: The objective was to analyze the serum estriol levels among patients with sings and symptoms of preterm labor and/or preterm rupture of membranes. STUDY DESIGN: A prospective study included pregnant women with sings and symptoms of preterm labor. The main end point of the study was the delivery <28 days from testing. RESULTS: 196 patients were included. 116 patients were included in group I (idiopathic preterm labor), 37 patients in group II (PROM) and the control group (group III) consisted of 43 patients. The incidence of preterm delivery was 31% in group I; in the PROM group all the patients delivered preterm. The mean serum estriol levels in all groups were compared regarding delivery <28 days from testing. In group I patients that delivered <28 days had statistically higher serum level of E3 (14.5 ng/ml vs. 11.1 ng/ml, p = 0.03); in group II the mean E3 serum level did not differ significantly (12.5 ng/ml, p = 0.168). The detailed analysis revealed that significant difference was observed in patients tested after completed 30 wk of gestation (15.4 ng/ml vs 12,8 ng/ml, p = 0.043), but not in patients <30 wk of gestation (9,5 ng/ml vs. 10.0 ng/ml, p = 0.842). CONCLUSIONS: The serum level of E3 seems to have prognostic value in the diagnosis of preterm delivery among symptomatic patients after 30 week of gestation.     

The relationship among intrauterine growth, insulinlike growth factor I (IGF-I), IGF-binding protein-3, and bone mineral status in newborn infants

Insulinlike growth factors (IGFs) exert profound effects on somatic growth and cellular proliferation of many tissues and play an essential role in bone metabolism. The aim of this study was to investigate how fetal growth and bone mineralization correlate with IGF-I and IGF-binding protein-3 (IGFBP-3) levels of newborn infants and their mothers. In addition, we aimed to determine the predictive value of anthropometric measurements on variability in bone mineral status. Umbilical cord venous blood samples were obtained at delivery from 100 term newborn infants. Forty of the newborn infants had birthweights appropriate for gestational age (AGA), 30 were small for gestational age (SGA), and 30 were large for gestational age (LGA). Data were acquired using whole-body dual-energy X-ray absorptiometry scanner with a pediatric platform. Umbilical cord serum IGF-I concentrations were higher in LGA newborns ( P < 0.01), but lower in SGA newborns ( P < 0.01) than in AGA newborns. Umbilical cord serum IGFBP-3 concentrations in LGA newborns were significantly greater than in SGA and AGA newborns ( P < 0.01 and P < 0.01, respectively). Whole-body bone mineral density (WB BMD) was higher in LGA babies (0.442 +/- 0.025 g/cm2 [SD]; P < 0.01) but lower in SGA (0.381 +/- 0.027 g/cm 2; P < 0.0001) than in AGA babies (0.426 +/- 0.022 g/cm2). WB BMD and content (WB BMC) were correlated significantly with birthweight, birth height, head circumference, body mass index (BMI) of the infants; ponderal index and triceps skinfold thickness (reflecting fat stores) of the infants; cord serum IGF-I concentration, serum IGF-I concentration of the mothers; and fat mass, proportionate fat mass, weight, and BMI of the mothers. In contrast, WB BMC was also correlated positively with cord serum IGFBP-3 concentration and gestational age, and WB BMD was positively correlated with serum IGFBP-3 levels of the mothers. Umbilical cord serum IGF-I concentration of the infants was correlated significantly with the concentration of the mothers ( R = 0.232; P = 0.020). Umbilical cord serum IGF-I and IGFBP-3 concentrations were correlated significantly with the fat mass, gestational age, birthweight, birth height, head circumference, and BMI of the infants. Umbilical cord IGF-I concentration was also correlated with ponderal index and triceps skinfold thickness of the infants, maternal weight, BMI, and proportionate fat mass of the infants. Stepwise multiple regression analyses showed no significant relation between bone indices (WB BMD, WB BMC) and the infant's or mother's variations including serum IGF-I and IGFBP-3 concentrations. Birthweight and gestational age are related to bone indices. However, the present study does not provide support for the hypothesis that serum IGF-I and IGFBP-3 levels of infants and their mothers may play a major role in the regulation of bone metabolism in the developing skeleton.     

Insulin-like growth factor-binding protein 1 and insulin-like growth factor-binding protein 3 in pre-eclampsia

Objective To investigate circulating levels of insulin-like growth factor-binding protein 1 (IGFBP-1) and IGFBP-3 in the mother and the fetus in pregnancies complicated by pre-eclampsia, and the relationship between serum levels of IGFBPs and fetal birthweight.
Design A prospective study over an 18 month period.
Setting A tertiary care academic medical centre.
Participants Sixty-six pregnant women with pre-eclampsia (35 cases of mild/moderate pre-eclampsia and 31 cases of severe pre-eclampsia) and 78 nonpra-eclamptic pregnant women of matched gestational weeks and maternal ages.
Main outcome measures Serum concentrations of IGFBP-1 and IGFBP-3 at the time of delivery.
Results In pre-eclampsia associated with intrauterine growth retardation (IUGR), maternal and cord serum IGFBP-1 levels at the time of delivery were elevated. By contrast, circulating IGFBP-3 levels in both the mother and the fetus were lower in pre-eclampsia with IUGR than in nonpre-eclamptic pregnancy. However, there was no difference in serum IGFBP-1 and IGFBP-3 levels between pre-eclampsia without IUGR and nonpre-eclamptic pregnancy in both the mother and the fetus.
Conclusions In pre-eclampsia, elevated concentrations of circulating IGFBP-1 and decreased serum IGFBP-3 levels were observed in both the mother and the fetus. However, these changes may simply reflect low birthweight in pre-eclampsia.     

Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.     

Chronic intrauterine bleeding and fetal growth at less than 32 weeks of gestation

Placental hemosiderin deposition representing intrauterine bleeding at least 24-48 h before delivery is detected frequently in prematurity. The objective of this study was to assess incidence and site of histologic evidence of intrauterine bleeding in association with fetal growth in prematurity. Placentas of consecutive nonanomalous singleton liveborns delivered <32 weeks of gestation were studied for the presence of hemosiderin in decidua of the placental basal plate or extraplacental membranes (confirmed by Prussian blue stain). Cases of placenta previa, clinical abruption, or coagulopathy and cases in whom obstetric and neonatal gestational age assessment differed by >2 weeks were excluded. A single reviewer blinded to clinical data except for gestational age at delivery assessed the presence of decidual hemosiderin. Statistical analysis included ANOVA, and Mann-Whitney U test with p<0.05 considered significant. The study included 352 patients delivered for principal indication of premature rupture of membranes (PROM) or preterm labor (PTL) and 78 patients delivered for preeclampsia between 1989 and 1994. Mean birth weight percentiles for neonates delivered following PROM/PTL versus preeclampsia were: no decidual hemosiderin 42+/-25 versus 17.4 +/-25, extraplacental membrane hemosiderin 42+/-25 versus 9.2 +/-10, placental basal plate hemosiderin 42+/-25 versus 17+/-24, and hemosiderin in both sites 27+/-21 versus 6.4+/-10 (p = 0.02). Hemosiderin deposition in both placental basal plate and extraplacental decidua is associated with significantly lower mean birth weight percentiles in PROM/PTL at less than 32 weeks of gestation. We postulate that in these patients placental disruption which accompanies decidual bleeding may explain the relatively impaired fetal growth. In preeclampsia, hemosiderin depositions are not associated with further impaired fetal growth.     

Significance of detecting insulin-like growth factor binding protein-1 in cervicovaginal secretions: comparison with nitrazine test and amniotic fluid volume assessment

OBJECTIVES: The diagnosis of premature rupture of membranes (PROM) is sometimes challenging, and common diagnostic tests are of limited value in the diagnosis. We aimed to study the accuracy of detecting insulin-like growth factor binding protein-1 (IGFBP-1) in vaginal fluid by a rapid dipstick method in comparison with the nitrazine test and amniotic fluid index (AFI) and we studied the predictivity of these methods on the latency of pregnancy in patients with suspected PROM. MATERIAL AND METHOD: One hundred and fifty-one patients (36 definite PROM, 35 no PROM and 80 suspected PROM) at 20-42 weeks' gestation were included in the study. Patients with preterm labor and PROM, patients at <20 gestational weeks, and those with multiple pregnancies were excluded. IGFBP-1 in the cervicovaginal fluid was measured by a rapid dipstick method (PROM test). AFI was measured by the four-quadrant method and an AFI of <80 mm was considered as oligohydroamnios. RESULTS: The sensitivity, specificity and accuracy of the nitrazine test, the PROM test and AFI were 97, 16 and 56%, 97, 97 and 97% and 94, 91 and 92%, respectively. The nitrazine test results were affected by vaginal discharge but the PROM test results were not affected. Only a positive PROM test was associated with delivery within 7 days [odds ratio (OR) 12; 95% confidence interval (CI) 4.2-35, p < 0.001]. CONCLUSION: The dipstick method of detecting IGFBP-1 in the vaginal fluid is a rapid, reliable and noninvasive method. The PROM test is the most accurate diagnostic test and predictor of latency in patients with suspected PROM.     

Serum insulin-like growth factors in normal pregnancy and in pregnancies complicated by preeclampsia

BACKGROUND: Lower levels of insulin-like growth factor I (IGF-I) have been shown to be associated with preeclampsia and also with a reduced risk of breast cancer later in life. Lower levels of IGF before clinical signs of preeclampsia could be one possible mechanism in the etiology of preeclampsia as well as for the reduced risk of breast cancer associated with preeclampsia. We have prospectively investigated maternal serum levels of IGF-I, IGF-II, and the main binding protein insulin-like growth factor binding protein 3 (IGFBP-3) in women with and without preeclampsia. METHODS: We used maternal serum samples from a Swedish-Norwegian cohort study obtained in the 17th and 33rd gestational week from 30 women who subsequently developed preeclampsia and 128 women who did not develop preeclampsia. RESULTS: There were no significant differences in serum concentrations IGF-I and IGFBP-3 in the 17th or the 33rd week of gestation between women who developed preeclampsia or not. Compared with nonpreeclamptic women, preeclamptic women had significantly higher serum levels of IGF-II in week 33, but there was no difference in week 17. CONCLUSION: In women who developed preeclampsia, we found no support for the hypothesis that the disease was preceded by lower serum levels of IGF-I and IGF-II, or higher serum levels of IGFBP-3. However, among women who later developed preeclampsia, serum levels of IGF-II were significantly higher in the 33rd gestational week.     

Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: a 2-year, double-blind, placebo-controlled study

OBJECTIVE: To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio. DESIGN: A 2-year randomized, double-blind, placebo-controlled study. SETTING: Endocrinology outpatient department. PATIENT(S): Fifty-six postmenopausal, hysterectomized women. INTERVENTION(S): Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years. MAIN OUTCOME MEASURE(S): At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated. RESULT(S): Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was -32.5% (95% CI: -20.1; -44.8%) for CEE; -16.4% (95% CI: -3.6; -29.2%) for raloxifene at 150 mg/day; and -15.4% (95% CI: -1.0; -29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point. CONCLUSION(S): Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.     

The effect of estrogen level on glucose-induced changes in serum insulin-like growth factor binding protein-1 concentration.

OBJECTIVE: To investigate the regulation of insulin-like growth factor binding protein-1 (IGFBP-1) concentration during ovarian stimulation. DESIGN: A prospective study of patients undergoing in vitro fertilization treatment. SETTING: Infertility unit at the University Central Hospital of Oulu, a tertiary referral center. PATIENTS: Sixteen healthy, regularly menstruating lean tubal infertility patients. INTERVENTIONS: Oral glucose tolerance test was performed first in a hypoestrogenic state after suppression by long-term gonadotropin-releasing hormone (GnRH) agonist and, second, in a hyperestrogenic state after stimulation by human menopausal gonadotropins. MAIN OUTCOME MEASURES: Serum concentrations of IGFBP-1, insulin-like growth factor I (IGF-I), insulin and sex hormone-binding globulin were measured before and 2 hours after glucose administration. RESULTS: Before and after glucose administration, the serum IGFBP-1 concentrations were significantly higher in the hyperestrogenic state (estradiol [E2] level 3.5 +/- 0.57 nmol/L) after ovarian stimulation than in the GnRH-analogue-induced hypoestrogenic state before the gonadotropin treatment (E2 level 0.10 +/- 0.02 nmol/L). On both occasions glucose-induced hyperinsulinemia caused a significant decrease in the circulating IGFBP-1 levels, whereas the IGF-I levels remained unchanged. There was a significant correlation between E2 and the insulin-suppressed IGFBP-1 level. The sum of follicular diameters correlated positively with the serum IGFBP-1 concentration. CONCLUSIONS: Gonadotropin-induced hyperestrogenism is related to elevated serum IGFBP-1 levels, either via estrogen-stimulated synthesis or via increased contribution from multiple follicles. Glucose-induced hyperinsulinemia suppresses serum IBFBP-1 concentration equally both in the hypoestrogenic and hyperestrogenic states. Because of similar IGF-I levels, it is likely that the biological activity of IGF-I is different before and after gonadotropin stimulations.     

The importance of serum insulin-like growth factor-I level determination in the follow-up of patients with epithelial ovarian cancer.

PURPOSE OF INVESTIGATION: The aim of our study was to assess whether serum levels of serum insulin-like growth factor-I (IGF-I) could be used for the follow-up of the patients with epithelial ovarian cancer and to identify whether it was superior to serum CA 125. METHODS: Our study group consisted of 28 patients diagnosed with epithelial ovarian cancer who had initial high serum CA 125 levels and have received chemotherapy following the operation. Preoperatively and before each chemotherapy administration, serum CA 125 and IGF-I levels were measured. RESULTS: The mean value of preoperative serum CA 125 was 364.0 +/- 152.9 U/ml. Serum CA 125 levels decreased with chemotherapy (Spearman rs= - 0.641, p=0.000). The mean preoperative serum IGF-I concentration was 58.04 +/- 52.7 ng/ml, and it showed a slight increase with chemotherapy. (Spearman rs=0.3 18, p=0.001). We observed that there was a weak-moderate negative correlation between the two markers, and when chemotherapy was administered serum CA 125 levels which were initially high started to decrease while serum IGF-I levels showed a mild increase (Spearman rs= - 0.350, p=0.000). CONCLUSION: The measurement of serum IGF-I does not provide any additional benefit in monitoring the response of the disease to chemotherapy.     

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

OBJECTIVE: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). DESIGN: Retrospective data analysis of selective groups of patients. SETTING: A private IVF unit. PATIENT(S): Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. INTERVENTION(S): In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. MAIN OUTCOME MEASURE(S): Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle's E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). RESULT(S): In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S): Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.     

Maternal serum ferritin concentration in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD). METHODS: A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders. RESULTS: Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p < 0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522). CONCLUSIONS: Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.     

基质金属蛋白酶9及其组织抑制物1的水平变化与胎膜早破发病的关系

目的探讨母血、羊水、脐血中基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制物1(TIMP-1)的水平变化与胎膜早破发病的关系。方法采用双抗体夹心酶联免疫吸附法,动态检测58例胎膜早破患者(胎膜早破组)及38例正常孕妇(对照组)的母血、羊水、脐血中MMP-9及TIMP-1的水平,同时进行胎膜组织的病理检查,对合并绒毛膜羊膜炎的患者也进行相应的MMP-9及TIMP-1的水平检测。结果(1)胎膜早破组母血、脐血及羊水中MMP-9水平分别为(141·9±84·6)、(138·2±81·4)及(85·6±27·5)ng/L,其水平均明显高于对照组,两组比较,差异有统计学意义(P<0·05、P<0·05及P<0·01);胎膜早破组母血、羊水、脐血中TIMP-1水平分别为(378·1±220·2)、(44·6±24·0)及(257·2±98·8)ng/L,其水平均明显低于对照组,两组比较,差异有统计学意义(P<0·05、P<0·05及P<0·01)。(2)母血、羊水、脐血中MMP-9的水平随破膜时间的延长而升高,尤其破膜时间超过24h时升高更为明显;而TIMP-1则随破膜时间的延长而下降,尤其破膜时间超过24h时降低更为明显。(3)两组共合并绒毛膜羊膜炎患者15例,其中胎膜早破组13例(13/58,22%),绒毛膜羊膜炎患者的母血、脐血、羊水中MMP-9水平分别为(183·8±84·7)、(171·2±92·9)及(95·5±21·1)ng/L,其水平均明显高于非绒毛膜羊膜炎患者(81例),两者比较,差异有统计学意义(P<0·05、P<0·05及P<0·01)。绒毛膜羊膜炎患者的母血、羊水、脐血中TIMP-1水平分别为(269·7±144·4)、(32·1±16·6)及(210·6±81·9)ng/L,其水平均明显低于非绒毛膜羊膜炎患者,两者比较,差异有统计学意义(P<0·05、P<0·05及P<0·01)。(4)胎膜早破组的新生儿Apgar评分≤7分者,其母血、脐血、羊水中MMP-9水平分别为(234·4±79·4)、(222·1±120·1)及(108·5±42·2)ng/L,其水平均明显高于Apgar评分≥8分者,两者比较,差异有统计学意义(P<0·05、P<0·05及P<0·01);与之相反,胎膜早破组的新生儿Apgar评分≤7分者,母血、羊水、脐血中TIMP-1的水平分别为(225·3±121·7)、(25·2±15·8)及(181·7±135·2)ng/L,其水平均明显低于Apgar评分≥8分者,两者比较,差异有统计学意义(P<0·05、P<0·05及P<0·01)。结论MMP-9水平的异常升高及TIMP-1水平的显著下降,是胎膜早破发病的重要机制。MMP-9及TIMP-1的水平检测可作为一种新的生物学标志物用于胎膜早破并绒毛膜羊膜炎感染的诊断,尤其适用于亚临床感染状态的早期诊断,并有助于评估新生儿预后。     

Relationship of insulin-like growth factor-I and insulin-like growth factor binding proteins in umbilical cord plasma to preeclampsia and infant birth weight.

OBJECTIVE: To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS: Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS: Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP-1 was more than twice as high as in controls (both P <.01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION: Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease.