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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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.     

Cotreatment with growth hormone, after pituitary suppression, for ovarian stimulation in in vitro fertilization: a randomized, double-blind, placebo-control trial.

OBJECTIVE: To explore the effect of cotreatment with growth hormone (GH) for ovarian stimulation after pituitary suppression. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Specialist Reproductive Endocrine and In Vitro Fertilization (IVF) Unit. PATIENTS, PARTICIPANTS: Twenty-five IVF patients who had responded suboptimally in a previous treatment cycle. A subgroup of 18 patients were found to have ultrasound (US) findings of polycystic ovaries (PCO). MAIN OUTCOME MEASURE: The amount of gonadotropin used, development of follicles greater than or equal to 14 mm, number of oocytes collected, fertilized, cleaved and replaced, serum and follicular fluid (FF) insulin-like growth factor I (IGF-I) concentrations. RESULTS: Cotreatment with GH was associated with a significant reduction in gonadotropins requirement (P less than 0.05). In patients with US-diagnosed PCO more follicles developed (P less than 0.05), more oocytes were collected (P less than 0.03), fertilized (P less than 0.004), and cleaved (P less than 0.02). A significantly higher FF IGF-I concentrations were found in patients receiving cotreatment with GH compared with those who received placebo (P less than 0.04). CONCLUSION: We believe that there may be a place for GH treatment in selected IVF cycles after pituitary suppression but what the role of IGF-I should further be investigated.     

Leptin,VEGF, IGF-1, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization

We studied the influence of recombinant follicle-stimulating hormone (rFSH) stimulation on the concentration of leptin, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum and follicular fluid (FF) in women undergoing assisted reproduction. To test the hypothesis that these hormones could predict successful implantation and that the levels correlate with pregnancy rate. Sequential serum samples were drawn at the beginning of stimulation and on the day of embryo transfer (ET) from 84 women undergoing IVF. The follicular fluid (FF) obtained during oocyte retrieval was collected and the concentration of leptin, VEGF, IGF-1 and IGFBP-3 were measured in all samples. The hormones were measured by commercially available IRMA, RIA or EIA. Patients' characteristics and results of the assisted reproductive cycles were registered. Serum concentrations of VEGF, IGF-1 and IGFBP-3 significantly decreased during rFSH treatment. In contrast, serum leptin significantly increased after rFSH treatment. A strong correlation was found between the FF - levels of IGF-1, IGFBP-3, leptin and respective serum levels. With regard to IVF outcome, higher serum concentrations of IGF-1, IGFBP-3 and VEGF on the day of oocyte retrieval were observed in conception cycles vs. non-conception cycles. No such difference, however, was apparent at the beginning of the stimulation cycle. There was no association between FF levels of any of these hormones and IVF outcome. Our results demonstrate that VEGF, IGF-1, IGFBP-3 and leptin levels are affected by rFSH during controlled ovarian hyperstimulation and that there is a direct association between serum and FF levels, albeit without clinical implications     

多囊卵巢综合征胰岛素抵抗与卵巢局部IGF-I系统的相关性研究

目的探讨卵巢局部胰岛素样生长因子-I(IGF-I)系统在PCOS胰岛素抵抗发病机制中的作用。方法选择30例PCOS胰岛素抵抗患者为研究组,30例输卵管性不孕患者为对照组。测定并比较两组的血清、小卵泡液中IGF-I、胰岛素样生长因子结合球蛋白-1(IGFBP-1)及各项性激素、糖代谢及卵巢超声指标,分析其与各项指标之间的相关性。结果研究组小卵泡液IGF-I高于对照组和其血清水平(P0.01),血清和小卵泡液的IGFBP-1低于对照组(P0.05,P0.01),小卵泡液IGFBP-1水平低于血清(P0.05)。研究组小卵泡液IGF-I与总睾酮(T0)、雌二醇(E2)及卵巢体积(OV)、卵巢总面积(TA)、卵泡数(FN)、空腹胰岛素(FI)和口服葡萄糖后2h胰岛素(2h胰岛素)呈正相关(r分别为0.94、0.51、0.52、0.49、0.65、0.76和0.58,P值均0.05);血清IGF-I与胰岛素敏感指数(ISI)、体重指数(BMI)和腰臀比(WHR)呈正相关(r分别为0.47、0.61和0.58,P0.05),与定量胰岛素敏感指数(QUICKI)呈负相关(r=-0.34,P0.05);研究组小卵泡液及血清IGFBP-1与FINS、2h胰岛素呈负相关(r=-0.48,P0.001;r=-0.39,P0.05;r=0.54,P0.05;r=-0.52,P0.05)。结论 PCOS患者的外周胰岛素抵抗可能通过影响卵巢局部IGF-I系统,刺激卵巢组织产生大量雄激素,导致排卵障碍。     

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.     

Anti-FSH antibodies associate with poor outcome of ovarian stimulation in IVF

FSH is required for spontaneous folliculogenesis and is widely used in ovarian stimulation in IVF. Previously, increased concentrations of antibodies against FSH (anti-FSH) have been demonstrated in infertile women. This study aimed to: (i) assess the possible association of anti-FSH with an adverse outcome of IVF with regard to clinical parameters characterizing the ovarian reserve; and (ii) compare serum and follicular fluid (FF) anti-FSH concentrations in relation to follicle size and endocrine markers. IVF patients (n = 182) subjected to gonadotrophin-releasing hormone-antagonist protocol were assessed for anti-FSH using enzyme-linked immunosorbent assay. Increased concentrations of serum anti-FSH immunoglobulin (Ig)G and IgA were associated with impaired ovarian stimulation outcome, with cut-off values <1.0 arbitrary units predicting poor ovarian response (相似文献   

Insulin-like growth factor I (IGF-I) levels in follicular fluid from human preovulatory follicles: correlation with serum IGF-I levels

Insulin-like growth factor I (IGF-I) levels were measured in both serum and fluid of preovulatory follicles (n = 156) in 43 women undergoing in vitro fertilization (IVF). The mean IGF-I level in follicular fluid (FF) was significantly lower than in serum (0.52 +/- 0.02 IU/L versus 0.66 +/- 0.23 IU/L), and FF levels were significantly correlated with individual serum IGF-I levels as well as with follicular size and FF volume but not with oocyte maturity, granulosa cell appearance, or IVF. This suggests that FF IGF-I levels cannot serve as a clinical indicator for the degree of oocyte/granulosa cell differentiation or a predictor for IVF. Serum IGF-I levels were inversely correlated with the number of human menopausal gonadotropin ampules administered during treatment, suggesting that IGF-I might enhance ovarian gonadotropic stimulation.     

Interest of growth hormone-releasing hormone administration for improvement of ovarian responsiveness to gonadotropins in poor responder women.

OBJECTIVE: We have investigated the beneficial effect of a somatotroph axis stimulation on ovarian response to gonadotropin. DESIGN: Growth hormone-releasing hormone (GH-RH) was administered in a prospective study in women undergoing an in vitro fertilization protocol. PATIENTS: Twelve patients were selected for their poor ovarian response to previous stimulations using gonadotropin-releasing hormone analog (GnRH-a) and human menopausal gonadotropins (hMG). INTERVENTIONS: Five hundred micrograms of GH-RH1-29 were administered two times daily concomitantly with GnRH-a and hMG from day 2 of the cycle to the time of ovulation. MAIN OUTCOME MEASURES: Stimulation of somatotroph axis was appreciated by measuring over-night urinary growth hormone (GH) output, plasma GH, and insulin-like growth factor I (IGF-I) and follicular fluid (FF) IGF-I. The effects of GH-RH administration on ovarian function were determined by plasma estradiol levels and follicular data. RESULTS: Administration of GH-RH was associated with a significant improvement of urinary (P less than 0.025) and plasma (P less than 0.001) GH concentrations and of the hormonal response to hMG (P less than 0.01). Levels of IGF-I followed a biphasic plasma variation, and a slight increase in recruited follicles, retrieved oocytes, and FF IGF-I content was also observed. CONCLUSIONS: Activation of the somatotroph axis by GH-RH enhances the hormonal ovarian response to hMG and may be an adjunctive therapy to improve follicular maturation.     

In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17,20-desmolase deficiency

OBJECTIVE: To present a case with 17,20-desmolase activity deficiency in which in vitro fertilization (IVF) served not only as a therapeutic approach but also as a diagnostic tool for the specificity of the enzymatic deficiency. DESIGN: IVF in the patient under study compared with a control group. All women treated with pure follicle-stimulating hormone (FSH). SETTING: IVF program at the Instituto Valenciano de Infertilidad. PATIENTS, PARTICIPANTS: A patient with primary amenorrhea, who was the subject under study, and seven normally cycling control patients undergoing IVF in the same series. INTERVENTIONS: IVF, steroidogenesis in vitro of granulosa-luteal cell obtained at ovum pick-up. MAIN OUTCOME MEASURE(S): Oocyte fertilization and embryo cleavage. Serum and follicular fluid (FF) levels of estradiol (E2), progesterone (P), testosterone (T), androstendione (A), 17 alpha-hydroxyprogesterone (17-OHP). In vitro accumulation of E2 and P. RESULTS: Ovulation induction with FSH was successful in achieving follicular development despite low circulating E2. Fertilization and cleavage rates were similar to the control subjects. The patient developed ovarian hyperstimulation. The lack of 17,20-desmolase activity was detected by normal P levels in serum and FF, high 17-OHP, and low T, A, and E2 levels in serum and FF. Granulosaluteal cell cultures in the presence of T restored normal E2 and P production in response to gonadotropins. CONCLUSIONS: In patients with 17,20-desmolase deficiency, follicular development, oocyte maturation, and fertilization can take place in a low estrogenic environment.     

Sex ratio and birth weights of infants born as a result of blastocyst transfers compared with early cleavage stage embryo transfers

OBJECTIVE: To investigate relations between dose of GnRH antagonist and follicular phase characteristics. DESIGN: Randomized controlled multicenter trial. SETTING: Tertiary referral fertility centers. PATIENT(S): Three hundred and twenty-nine IVF patients. INTERVENTION(S): Ovarian stimulation for IVF with recombinant FSH starting on cycle day 2. From cycle day 7 onwards, cotreatment was provided with 0.0625, 0.125, 0.25, 0.5, 1.0, or 2.0 mg/d GnRH antagonist. MAIN OUTCOME MEASURE(S): Number of follicles, total follicular surface area, gonadotropin, and serum steroid concentrations. RESULT(S): In 311 patients, similar follicular growth was observed in all treatment groups. FSH levels increased during the follicular phase. Late follicular phase LH, androstenedione (AD), and E(2) levels showed a GnRH antagonist dose-related decrease (P<0.05). Late follicular phase E(2) levels correlated with total follicular surface area, AD, LH, and FSH (all P<0.001). Increasing GnRH antagonist doses exhibited additional suppressive action on E(2) levels. CONCLUSION(S): Follicular growth was unaffected by the dose of GnRH antagonist. A rise in follicular phase FSH serum concentrations during the follicular phase, largely related to exogenous FSH, enabled ongoing follicular growth in all treatment groups. The effect of GnRH antagonist on late follicular phase E(2) levels could not be exclusively attributed to suppression of LH.     

Detection of immunoreactive interleukin-11 in human follicular fluid: correlations with ovarian steroid, insulin-like growth factor I levels, and follicular maturity

Objective: To prove the presence of interleukin-11 (IL-11) in the follicular fluid (FF), to determine its source and the correlation between IL-11 and fertilization outcome, follicular size, number of follicles per patient, steroids, and insulin-like growth factor-1 (IGF-I) levels.

Design: Interleukin-11 levels were measured in FFs, aspirated during oocyte pickup for IVF.

Setting: Academic hospital and research environment.

Patient(s): Follicular fluid and serum were obtained with informed consent from 44 patients undergoing IVF-ET. Granulosa cells were isolated from 17 patients.

Main Outcome Measure(s): We hypothesized that IL-11 might play a role in follicular development, as do other related cytokines present in FF. Interleukin-11 was measured with ELISA.

Result(s): Interleukin-11 was absent in the serum but present in FF and in conditioned medium from granulosa cells. Atretic follicles had higher concentrations of IL-11. No correlation was found between IL-11 and fertilization outcome, follicular size, steroid, IGF-I, and total protein concentrations.

Conclusion(s): We conclude that IL-11 is present in FF. The role of IL-11 in follicular development should be the object of further investigations.     

Gonadotropin-releasing hormone antagonists increase follicular fluid insulin-like growth factor-I and vascular endothelial growth factor during ovarian stimulation cycles.

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E2) levels (p < 0.001 and p < 0.05, respectively), FF E2 and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E2 levels.     

Concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-3 in the follicular fluid of women undergoing ovarian hyperstimulation with different gonadotropin preparations.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have an important regulatory role in follicular development and oocyte maturation. The aim of this prospective, randomized, double-blind study was to measure the concentrations of IGF-I and IGFBP-3 in follicular fluids collected from infertile women undergoing ovarian hyperstimulation using three different gonadotropin preparations. Twenty infertile women (mean age 33 years, range 28-40) undergoing in vitro fertilization (IVF) programs were recruited. After a written informed consent, each woman randomly underwent a long-protocol for ovarian hyperstimulation using gonadotropin-releasing hormone (GnRH)-analog and one of the following recombinant- and urinary-gonadotropins--alpha-follitropin, beta-follitropin or urofollitropin. Serum 17 beta-estradiol (E2) levels and follicle growth were assessed during the follicular phase. The concentrations of IGF-I and IGFBP-3 in the follicular fluid of aspirated dominant follicles were measured directly. Women treated with alpha-follitropin needed significantly lower doses of follicle-stimulating hormone (FSH) compared to those receiving beta-follitropin (p < 0.05). No other statistically significant differences were detected between groups. Serum E2 levels increased in the three groups from early to late follicular phase. Follicular fluid IGF-I and IGFBP-3 concentrations did not differ significantly in the three groups of women. A statistically significant relationship was observed between follicular fluid IGF-I and IGFBP-3 levels (r = 0.41, p = 0.001). Oocyte maturation correlated in a positive manner with IGF-I (r = 0.34, p = 0.01) and IGFBP-3 (r = 0.29, p = 0.03). These findings show that both recombinant- and urinary-gonadotropin preparations were equally effective in releasing IGF-I and IGFBP-3 in the follicular fluid of dominant follicles, and confirmed the role of these compounds on oocyte maturation.     

Effect of growth hormone administration on human ovarian function and steroidogenic gene expression in granulosa-luteal cells.

OBJECTIVE: To study the effect of growth hormone (GH) in combination with an ultrashort-term gonadotropin-releasing hormone analogue/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) regimen in ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized placebo-controlled study. SETTING: University-based IVF program. PATIENTS: Fifty-four normally cycling women (27 control and 27 GH-treated) participated in this study. INTERVENTIONS: Human recombinant GH (24 IU)/placebo was given intramuscularly on alternate days starting on cycle day 4 until the day of last hMG injection. RESULTS: Serum estradiol (E2) and progesterone (P) concentrations were slightly lower in the GH group than in the placebo group on the day of hCG injection and 1 day thereafter (P < 0.01 to 0.001). Serum luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone (T), and sex hormone-binding globulin did not differ between the groups. The follicular fluid (FF) concentration of T was higher in the GH group than in the placebo group (15.9 +/- 6.0 nmol/L versus 10.2 +/- 4.9 nmol/L, P < 0.005), and no differences were observed in the FF concentrations of E2, P, and insulin-like growth factor I between the groups. In granulosa cells isolated from patients who received GH treatment, the levels of 3 beta-hydroxysteroid dehydrogenase and aromatase messenger ribonucleic acid were significantly higher than in the patients receiving placebo. The number of hMG ampules needed for follicular development and the number of follicles and oocytes recovered were similar in both groups. CONCLUSIONS: These results indicate that GH administration modifies ovarian steroidogenic response to gonadotropins in IVF patients, suggesting a role for GH in the regulation of human ovarian function.     

Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization

OBJECTIVE: To determine whether alterations in preovulatory follicular fluid (FF) levels of LH, FSH, and steroids are associated with the probability of fertilization. DESIGN: Retrospective analysis of prospective study results. SETTING: Reproductive medicine clinic of a university teaching hospital. PATIENT(S): Infertile women, with unstimulated, apparently regular cycles in an IVF research program. INTERVENTION(S): Measurement of preovulatory FF levels of LH, FSH, E2, and P and serum LH levels by fluoroimmunometry. MAIN OUTCOME MEASURE: Oocyte fertilization. RESULT(S): There were 84 transferable embryos (rate of normal fertilization and cleavage, 67%), and 41 oocytes (33%) failed to fertilize. Analysis of the matched FF showed that the median concentration of FF LH was significantly higher for cleaving embryos than for unfertilized oocytes (14.6 vs. 10.4 IU/L). Serum LH concentrations were similarly higher in cycles with cleaving embryos. There were no statistically significant differences in FF concentrations of FSH, E2, or P in the two groups. CONCLUSION: Reduced preovulatory FF LH levels are associated with impaired fertilization of oocytes in vitro, despite normal FF FSH and steroid levels.     

Pregnancy-induced changes in insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) in patients with growth hormone (GH) deficiency and excess

BACKGROUND: Under most circumstances with altered growth hormone (GH) secretion, the changes of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) are in parallel. The aim of the present study was to compare the effects of pregnancy in a hypopituitary patient with those of pregnancy in an acromegalic patient on IGF-I, IGFBP-3, and ALS. METHODS AND RESULTS: IGF-I and ALS were low before pregnancy in the hypopituitary patient under glucocorticoid and thyroxine treatment. Gonadotropin treatment allowed her to become pregnant; IGF-I and ALS levels rose in the second half of pregnancy and fell again after delivery. IGF-I concentrations were elevated in the patient with persistent acromegaly before and dropped into the normal range during the first half of pregnancy. In the second half of pregnancy and following delivery, IGF-I levels increased again. IGFBP-3 levels (as assessed by immunoblot analysis as well as by 125I-IGF II ligand blotting) decreased markedly during pregnancy in both patients, suggesting that the placenta rather than pituitary GH regulates IGFBP-3 proteolysis in human pregnancy. The increase of IGF-I (and ALS) during the second half of pregnancy in the individual with pituitary GH deficiency may be attributed to placental GH. The fall of IGF-I (and ALS) into the normal range in the acromegalic patient during the first trimester of pregnancy may be related to decreased production or decreased half-life of these proteins. CONCLUSION: Our data suggest that measures to continuously replace GH or to suppress GH secretion during pregnancy in patients with GH deficiency or excess, respectively, may not be warranted.     

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures

OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups. RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups. CONCLUSION(S): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.     

Raised serum levels of matrix metalloproteinase-9 in women with polycystic ovary syndrome and its association with insulin-like growth factor binding protein-1

Background.?It has been suggested in recent studies that matrix metalloproteinases (MMPs) may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS) through regulating ovarian tissue remodeling. In addition to degrading the extracellular matrix, MMPs exhibit the ability to cleave insulin-like growth factor binding protein-1 (IGFBP-1), the major regulator of insulin-like growth factor-I (IGF-I) in serum. The present study aimed to investigate the possible role of MMPs in the pathophysiology of PCOS.

Methods.?Serum levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), IGF-I and IGFBP-1 were measured in 42 patients with PCOS and 30 healthy women with regular menstruation, matched for age and body mass index. Correlation between IGFBP-1 and other parameters in the PCOS group was analyzed by Pearson's linear correlations.

Results.?Serum MMP-9 concentrations and MMP-9/TIMP-1 ratios were significantly higher in PCOS women than in controls. Serum levels of IGFBP-1 were markedly lower in the PCOS group. There was a negative correlation between serum IGFBP-1 and MMP-9 in women with PCOS.

Conclusion.?Our results raise the possibility that MMPs may be implicated in the pathophysiology of PCOS either by regulating ovarian tissue remodeling or indirectly by facilitating IGF-I bioavailability through proteolysis of IGFBP-1.     

胰岛素、雄激素、胰岛素样生长因子、血管内皮生长因子对多囊卵巢综合征患者卵泡发育的影响

多囊卵巢综合征(polycyctic ovary syndrome,PCOS)是一种极为复杂的代谢异常病理状态,它与多基因相关。胰岛素对PCOS患者卵泡的影响很复杂,可能主要与糖代谢和卵泡对FSH的敏感性有关。高雄激素血症在PCOS患者中非常常见,高雄激素会抑制优势卵泡形成,造成闭锁。PCOS的卵巢间质血管内皮生长因子(VEGF)呈高表达,VEGF可能增加卵巢血管化,使更多因子渗透,引起多囊卵巢。胰岛素样生长因子(IGF)系统与PCOS患者亦有很密切的关系,IGF-I具有促进有丝分裂、参与新陈代谢等胰岛素样生物学效应。当IGF-I受体下调时,糖吸收障碍,会导致卵泡发育障碍。影响卵泡发育的因素众多,这些因素之间也存在相互影响的关系,高胰岛素和FSH联合作用会促进卵泡膜细胞产生大量雄激素,高胰岛素又增高IGF-I,胰岛素与LH联合还会增加VEGF的表达,这一切都将影响卵泡生长。