Vascular endothelial growth factor and its soluble receptor in patients with polycystic ovary syndrome undergoing IVF

We aimed to examine the behaviour of the angiogenetic factor vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in polycystic ovary patients undergoing In vitro fertilisation (IVF) compared with respect to normally ovulating controls. Levels of VEGF and sVEGFR-1 were compared in follicular fluid and serum, both on the day of human choriogonadotropin (hCG) administration and on the day of oocyte retrieval (OR), in controls and polycystic ovarian syndrome (PCOS) patients undergoing IVF cycles. The bioactivity of VEGF (VEGF/sVEGFR-1 ratio) in the two groups was calculated.

Thirty PCOS patients and 20 controls referring to the IVF Centre of the University of Pisa (Italy) were enrolled. In each patient, blood samples were collected on the day of hCG and on the day of OR administration, and follicular fluid samples. VEGF and sVEGFR-1 were measured by Enzyme Linked Immuno Sorbant Assay (ELISA).

Serum VEGF bioactivity markedly increased in both groups after hCG administration. Serum and follicular fluid VEGF bioactivity was greater in PCOS patients than in controls on the day of OR. The increase in VEGF bioactivity in PCOS patients undergoing IVF was not only because of increasing levels of VEGF but also to decreasing levels of its soluble receptor. We believe that additional studies will clarify their role in the pathogenesis of ovarian hyperstimulation syndrome, which most often occurs in patients with PCOS.     

Vascular endothelial growth factor, interleukin-6 and interleukin-2 in serum and follicular fluid of patients with ovarian hyperstimulation syndrome

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.     

Lack of insulin-like growth factor binding protein-3 variation after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization.

OBJECTIVE: To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Naples. PATIENT(S): Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF. INTERVENTION(S): The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay. RESULT(S): The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation. CONCLUSION(S): The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.     

The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1beta, interleukin-6, and vascular endothelial growth factor

OBJECTIVE: To evaluate systemic and ovarian changes in levels of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG administration to determine which may be the potential initiator of vascular effects and to identify the main source of the substance; to evaluate serum and follicular fluid levels of these cytokines as markers of ovarian hyperstimulation syndrome (OHSS), and to compare levels of these cytokines under basal conditions in women with normal ovulation and those with polycystic ovary syndrome (PCOS). DESIGN: Prospective controlled study. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): Women undergoing IVF, in whom the first two study objectives were analyzed, and women with normal ovulation and patients with PCOS undergoing retrieval of immature oocytes in natural cycles or cycles stimulated for IUI but cancelled during induction of ovulation, in whom the third study objective was analyzed. INTERVENTION(S): Serum was collected before and after hCG administration, and follicular fluid was collected at ovum pick-up. MAIN OUTCOME MEASURE(S): Serum and follicular fluid levels of IL-1beta, IL-6, and VEGF. RESULT(S): There was a significant increase in serum VEGF levels after hCG administration in patients who were at risk for OHSS compared with those who were not at risk for OHSS. Significantly lower VEGF levels were found in the follicular fluid of patients who were at risk; this decrease was the only useful marker to discriminate between the two groups. Moreover, both groups had similar cytokine production under basal conditions. An increase in serum E2 occurred coincident with a decrease in IL-1beta, IL-6, and VEGF in patients with PCOS. CONCLUSION(S): Vascular endothelial growth factor seems to be the mediator of hCG on the vascular tree. There was an early systemic increase in VEGF that may have significance in the development of OHSS. A decrease in the follicular fluid VEGF concentration is a valid marker to identify women in whom OHSS will develop. The pattern of cytokine release in patients with PCOS under basal conditions was not different from that in women with normal ovulation.     

Concentration of vascular endothelial growth factor released by cultured human luteinized granulosa cells is higher in women with polycystic ovaries than in women with normal ovaries

To test the hypothesis that increased serum levels of vascular endothelial growth factor (VEGF) in women with polycystic ovaries or the polycystic ovary syndrome (PCOS) result from excess release by ovarian granulosa cells.Prospective study.Academic research setting.Twenty women undergoing IVF treatment, of whom 10 had normal ovaries and 10 had polycystic ovaries.Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval. Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin. Serum and follicular fluid concentrations of VEGF were measured.Release of VEGF from granulosa lutein cells and serum levels of VEGF.Incubation with human hCG, and luteinizing hormone increased release of VEGF into the culture medium. Insulin alone did not increase release of VEGF, but addition of insulin increased hCG-stimulated release of VEGF. Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome.The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin. The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell.     

Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles

OBJECTIVE: To investigate the serum and intrafollicular tumor necrosis factor-alpha and interleukin-6 concentrations in infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS: Thirty-one patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating women matched for age and body mass index and undergoing IVF for male infertility were the control group. Serum tumor necrosis factor-alpha, interleukin-6, and estradiol levels were assayed before recombinant follicle-stimulating hormone stimulation under gonadotropin-releasing hormone analogue suppression and 34-36 hours after human chorionic gonadotropin (hCG) administration at the time of the oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in the follicular fluids obtained at the time of oocyte retrieval. RESULTS: The patients with PCOS had higher serum and follicular fluid tumor necrosis factor-alpha and interleukin-6 concentrations (P <.001) and lower follicular fluid estradiol levels (P <.05) than control women. In both groups, the serum tumor necrosis factor-alpha, interleukin-6, and estradiol values increased significantly after hCG stimulation. In both groups, the follicular fluid cytokine concentrations were higher than those found in the serum. In the PCOS women the follicular fluid tumor necrosis factor-alpha values were significantly and inversely correlated to the follicular fluid estradiol values (rho = -0.79; P <.001); this correlation was not found in the control subjects. CONCLUSION: In infertile women with PCOS, 1). serum and follicular fluid interleukin-6 and tumor necrosis factor-alpha values were higher than those found in control women, 2). the cytokine concentrations were higher in the follicular fluid than in the serum, and 3). the intrafollicular tumor necrosis factor-alpha concentrations were significantly and inversely correlated to the estradiol levels. These results suggest an involvement of the immune system in PCOS.     

Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle

OBJECTIVE: To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG. DESIGN: In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval. SETTING: This study was carried out in a university-affiliated IVF program. PATIENT(S): Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration. INTERVENTION(S): S.c. or i.m. injection of hCG. MAIN OUTCOME MEASURE(S): Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval. RESULT(S): There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L). CONCLUSION(S): After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.     

血管内皮生长因子水平变化与IVF-ET关系的研究

目的 :探讨体外受精 胚胎移植 (IVF ET)治疗周期的不孕症患者在不同阶段血清及卵泡液内血管内皮生长因子 (VEGF)的浓度变化以及它与卵泡生长发育、卵母细胞成熟、受精、卵裂及胚胎质量的关系。方法 :IVF治疗周期妇女 6 0例 ,在应用促性腺激素前、注射绒毛膜促性腺激素日、取卵日分别抽取外周血 ,穿刺取卵时留取卵泡液 ,应用酶联免疫法 (ELISA)检测血清及卵泡液中VEGF的浓度变化 ,并记录相应卵子的成熟度、受精、卵裂情况与胚胎质量。结果 :(1)控制超排卵过程中 ,随着卵泡的生长发育 ,VEGF浓度逐步升高 ,在取卵日达到较高水平 ;(2 )在控制超排卵过程中 ,卵巢反应类型不同 ,其VEGF水平亦不同 ,卵巢高反应组在取卵日血清中VEGF水平差异有显著性 (P <0 .0 5 )。患者卵泡液中VEGF浓度均明显高于外周血浓度 (P <0 .0 0 1) ;(3)成熟卵的卵泡液中VEGF浓度明显高于未成熟卵 ;(4)受精卵卵泡液中VEGF水平高于未受精卵 ,VEGF浓度高的卵母细胞受精后优质胚胎形成率高 (P <0 .0 5 )。结论 :VEGF调节卵母细胞的成熟、受精、卵裂过程 ,并可能影响早期胚胎的质量。     

Vascular endothelial growth factor in the plasma, follicular fluid and granulosa cells of women with endometriosis submitted to in vitro fertilization--a pilot study.

Vascular endothelial growth factor (VEGF), a potent angiogenic factor that is altered in endometriosis, supports the immunological mechanism involved in this disease. The aim of the present study was to assess VEGF concentration in the plasma, follicular fluid (FF) and culture medium (CM) of granulosa cells from patients with endometriosis submitted to in vitro fertilization (IVF). A case-control study was conducted on 14 patients with endometriosis and 14 women without endometriosis submitted to IVF. Peripheral blood samples were collected before and after administration of human chorionic gonadotropin (hCG), in addition to FF and CM samples. Plasma VEGF levels increased after hCG administration in women with endometriosis and in controls, but were significant only in controls. VEGF levels were lower in FF but were significantly increased in the CM of patients with endometriosis. There was no correlation between VEGF and age, response to ovarian stimulation, oocyte or embryo quality, and pregnancy result. The increase of VEGF levels after hCG in both groups demonstrated a positive effect of this hormone on VEGF. VEGF in the FF and CM presented opposite results in endometriosis, suggesting that granulosa cells may show a different behavior in vivo and in vitro.     

Follicular blood flow is a better predictor of the outcome of in vitro fertilization-embryo transfer than follicular fluid vascular endothelial growth factor and nitric oxide concentrations

OBJECTIVE: To investigate the relationship between follicular blood flow and the follicular fluid vascular endothelial growth factor (VEGF) and nitric oxide (NO) concentrations and to determine which factor might be a better predictor of the outcome of IVF-ET. DESIGN: Prospective study. SETTING: Academic research laboratory. PATIENT(S): Forty-seven cycles of IVF (tubal factor, 25 cycles; male factor, 22 cycles) at the infertility clinic of Pusan National University Hospital from February 2002 to June 2002. INTERVENTION(S): Follicular blood flow was estimated on the day of hCG administration. Each follicular fluid sample was collected at oocyte retrieval, and follicular fluid VEGF and NO concentrations were assessed. MAIN OUTCOME MEASURE(S): Follicular blood flow and follicular fluid VEGF and NO concentrations according to the age of patients, the cause of infertility, and pregnancy rate. RESULT(S): Of 47 cycles, 18 (38.3%) cycles resulted in a pregnancy. Follicular blood flow was significantly higher in the pregnant group compared with the nonpregnant group, but there was no statistically significant difference in age and infertility cause. Follicular fluid concentrations of VEGF and NO did not show statistically significant differences in age, infertility cause, or pregnancy outcome. As the follicle size increases, the follicular blood flow and follicular fluid VEGF concentrations increased significantly but the follicular fluid NO concentrations decreased. There was no correlation between VEGF and NO concentrations in the follicular fluid by linear regression analysis. CONCLUSION(S): Our study showed that follicular blood flow was positively associated with the outcome of pregnancy. This is the first study to investigate the direct association of the follicular blood flow with pregnancy outcome after IVF-ET. These results suggest that follicular blood flow might be a more effective prognostic marker of the pregnancy outcome of IVF than follicular fluid VEGF or NO concentrations.     

Serum vascular endothelial growth factor levels before starting gonadotropin treatment in women who have developed moderate forms of ovarian hyperstimulation syndrome.

The study aims to evaluate whether serum vascular endothelial growth factor (VEGF) levels, before treatment with gonadotropins, may be considered a predictive marker of moderate ovarian hyperstimulation syndrome (OHSS). At the University of Pisa hospital infertility unit we have retrospectively selected 10 patients who developed moderate forms of OHSS and 30 control patients who presented a normal response to ovarian stimulation among 400 women undergoing in vitro fertilization (IVF). Serum samples were collected before starting pFSH administration (150-300 IU/day). VEGF levels in serum were measured. No statistically significant difference was found between the serum VEGF levels of patients who developed moderate forms of OHSS and women without any symptoms of the syndrome. Further, serum VEGF concentrations were not significantly correlated with the age of the patients, the number of international units of FSH administered during the cycle of stimulation, the follicle and oocyte numbers counted on the day of the egg retrieval or estradiol levels detected on the same day. This study demonstrates that serum VEGF levels, before starting gonadotropin treatment, are not predictive of the subsequent development of moderate forms of ovarian hyperstimulation syndrome.     

卵巢过度刺激综合征患者血管内皮生长因子的变化

目的:探讨卵巢过度刺激综合征(OHSS)发病过程中血管内皮生长因子(VEGF)的作用机理。方法:ELISA法测定hCG注射日、胚胎移植日血清及取卵日卵泡液VEGF浓度;半定量RT-PCR技术检测取卵日颗粒细胞VEGF mRNA的表达。结果:OHSS组与非OHSS组血清VEGF浓度相比,hCG注射日未见显著性差异(102.5±40.8比90.23±34.62 pg/mL,P>0.05),胚胎移植日则差异显著(150.93±59.91,104.18±20.76 pg/mL,P<0.01);两组卵泡液相比有显著性差异(782.86±136.87比362.5±231.85 pg/ml,p<0.05)。OHSS组hCG注射日与胚胎移植日血清VEGF浓度有显著性差异,而对照组则未见差异。半定量RT-PCR结果显示,两组VEGF/β-actin之比有显著差异(0.54±0.24比0.27±0.12,P<0.01),OHSS组VEGF mRNA表达明显增强。结论:VEGF在OHSS发病机理中起一定作用。卵泡液及胚胎移植日血清VEGF浓度与OHSS的发生有着密切的关系。     

Influence of severe endometriosis on gene expression of vascular endothelial growth factor and interleukin-6 in granulosa cells from patients undergoing controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer

OBJECTIVE: To evaluate how endometriosis affects expression of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in granulosa cells. DESIGN: Prospective study. SETTING: IVF-ET program at Osaka Medical College. PATIENT(S): Seventeen patients with revised American Fertility Society stage IV endometriosis and 17 patients with tubal infertility and no endometriosis. INTERVENTION(S): Granulosa cells obtained at oocyte retrieval were examined for VEGF and IL-6 gene expression. MAIN OUTCOME MEASURE(S): Serum E(2) and P levels at hCG administration, number of oocytes, fertilization rate, high-quality embryo rate, and pregnancy rate, and expression of VEGF and IL-6 genes. RESULT(S): Total hMG and FSH levels were statistically significantly higher in patients with endometriosis; however, the number of retrieved oocytes and the fertilization rate were lower compared with patients with tubal infertility. Serum E(2) levels and expression of VEGF in patients with tubal infertility were statistically significantly higher than those in patients with endometriosis. Interleukin-6 gene expression did not differ between the groups. CONCLUSION(S): In severe endometriosis, lower VEGF gene expression in granulosa cells may adversely affect oocyte development and maturation.     

Follicular fluid concentrations of vascular endothelial growth factor, inhibin A and inhibin B in IVF cycles: are they markers for ovarian response and pregnancy outcome?

OBJECTIVE(S): The aim of this study was to measure concentrations of vascular endothelial growth factor (VEGF), inhibin A and inhibin B in follicular fluid (FF) of women undergoing to in vitro fertilization (IVF) cycles and to determine their relationship with ovarian response and pregnancy. STUDY DESIGN: Follicular fluid was collected from 58 patients undergoing oocyte retrieval for IVF. Ovulation was induced with GnRH analogues and gonadotropins. Follicular fluids of mature follicles (>17 mm) were aspirated and pooled for each patient. Follicular fluid steroid hormone levels (E2, P) and VEGF, inhibin A, inhibin B concentrations were studied. The serum levels of E2, P and VEGF were also assessed on the day of the oocyte retrieval. These parameters and characteristics of the cycles were compared between the pregnant (group 1) and non pregnant (group 2) patients. RESULTS: The serum and FF VEGF levels were found to be significantly lower in the group in whom the pregnancy was achieved (P < 0.001). The FF inhibin A and FF inhibin B were found to be significantly higher in pregnant group (P < 0.001). However, age, day 3 FSH, dosage of gonadotropin administered, fertilization rate, sperm count, motile and morphologically normal sperm percentage were not significantly different in the two groups. There was an negative correlation between VEGF and number of follicles, number of oocytes, FF inhibin A, FF inhibin B. The number of oocytes retrieved, the fertilization rate were positively correlated with FF inhibin B and FF inhibin A. CONCLUSION: This study demonstrated that decreased FF VEGF, serum VEGF and elevated FF inhibin A and B are associated with better ovarian response and high pregnancy rate.     

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: Observations in unstimulated in vitro fertilization cycles

Objective: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. Study Design: We compared cycles with elevated day 3 FSH levels (>20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. Patients: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. Results: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E₂) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. Conclusions: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.     

Influence of body mass index and self-administration of hCG on the outcome of IVF cycles: a prospective cohort study

Final maturation of the oocyte in in vitro fertilization (IVF) cycles is achieved through the administration of a timed injection of human chorionic gonadotrophin (hCG). The success of mature oocyte retrieval is dependent on serum concentrations of the hormone reaching values capable of initiating meiosis and triggering the release of the cumulus-oocyte complex into the follicular fluid. The objective of this prospective cohort study was to examine the effect of adiposity, as measured by body mass index (BMI), on serum concentrations of hCG and gonadotrophins and to relate this to IVF outcome. A comparison was also made between professionally and non-professionally administered hCG to assess any possible effect on cycle parameters. A total of 50 patients with a high BMI (> or = 26 kg m(-2)) who underwent IVF treatment at the Assisted Conception Unit, St James's University Hospital, Leeds, was recruited prospectively into the study. They were matched with 50 patients with a normal BMI (18-25 kg m(-2)) who acted as a control group. The two groups were matched for age (mean of 32 years and range of 22-42 years) and cause of infertility. Serum gonadotrophins, oestradiol and hCG concentrations, measured at the time of oocyte retrieval, and the clinical outcome of the two groups were compared. Patients with a high BMI had a significantly lower mean serum hCG concentration compared with controls (63.9 versus 99.6 iu l(-1), P < 0.0003). They also required a higher dosage of gonadotrophin (3660 versus 3007 iu) to achieve follicular maturation than the controls. Similarly, the high BMI group of patients had higher serum concentrations of follicle-stimulating hormone (FSH) (12.3 versus 11.2 iu l(-1)) and lower oestradiol (3499 versus 3506 pmol l(-1)) compared with controls. Patients with a high BMI had significantly fewer oocytes aspirated, resulting in a significant decrease in the oocyte:follicle ratio compared with controls (33.9 versus 41.7, P < 0.05). The fertilization rate (46.2 versus 61.3%, P < 0.05) and clinical pregnancy rate per cycle (26.6 versus 37.1%, P < 0.05) were also lower in the patients with high BMI compared with those with normal BMI. The administration of hCG by the patient or her partner did not have a significant effect on clinical outcome. The mean serum hCG at the time of oocyte recovery was equivalent in both groups (87.1 versus 89.7 iu l(-1)). Furthermore, the oocyte:follicle ratio (0.73 versus 0.72), fertilization rate (46.2 versus 54.2%) and clinical pregnancy rate (38.9 versus 36.5%) were similar. These findings indicate that high BMI is detrimental to the success of IVF treatment and has an important influence on the distribution and metabolism of hCG. The results also indicate that non-professional administration of hCG does not compromise cycle outcome.     

血管内皮生长因子在卵巢过度刺激综合征发病机理中作用的初步研究

目的通过对卵巢过度刺激综合征(OHSS)患者血管内皮生长因子(VEGF)水平和表达的测定,初步探讨VEGF在OHSS发病机理中的作用.方法采用酶联免疫吸附试验方法对14例中、重度OHSS患者(OHSS组)和同期13例非OHSS患者(对照组)取卵日卵泡液、人绒毛膜促性腺激素(hCG)注射日、胚胎移植(ET)日血清VEGF水平进行测定;采用免疫组织化学方法和逆转录聚合酶链反应技术检测取卵日卵巢黄素化颗粒细胞VEGF及其mRNA的表达.结果 OHSS组和对照组的卵泡液、hCG注射日血清VEGF水平分别为(1 257.2±648.0)与(1 745.1±802.4) ng/L,(250.1±109.5)与(196.7±81.7) ng/L,两组比较,差异无显著性(P>0.05);OHSS组ET日血清VEGF水平及注射hCG后血清VEGF水平变化程度,显著高于对照组[分别为(342.9±158.5)与(222.2±84.6) ng/L,(92.8±106.7)与(25.9±21.8) ng/L,P<0.05].OHSS组取卵日卵巢黄素化颗粒细胞VEGF mRNA的表达,显著高于对照组,VEGF/β肌动蛋白比值分别为1.50±0.60、0.96±0.56(P<0.05).两组取卵日卵巢黄素化颗粒细胞有较活跃的VEGF表达.结论 VEGF在OHSS的发病机理中可能起一定的作用.     

A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization

OBJECTIVE: To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day. DESIGN: Prospective, randomized, multicenter study. SETTING: Private practice and university centers. PATIENT(S): Eighty patients undergoing IVF who met the appropriate inclusion criteria. INTERVENTION(S): Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered. MAIN OUTCOME MEASURE(S): The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate. RESULT(S): Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups. CONCLUSION(S): The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.     

The effect of serum and follicular fluid amyloid-associated protein levels on in vitro fertilization outcome in patients with polycystic ovary syndrome

Purpose

In this study, we aimed to investigate serum and follicular fluid amyloid A protein levels in non-obese non-hyperandrogenic patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) and IVF outcome.

Methods

A total of 81 patients undergoing IVF treatment, 41 patients diagnosed as PCOS according to the Rotterdam criteria (group I) and 40 patients with the etiology of male factor infertility (group II), were included in the study. On the day of oocyte pickup, serum and follicular fluid samples were collected from all patients.

Results

Serum E2 level on the day of hCG (2849.93 ± 541.54 vs. 2494.28 ± 712.98) and total number of retrieved oocytes (13.73 ± 3.57 vs. 10.53 ± 4.07) were significantly higher in group I when compared to group II (p < 0.05). However, number of mature oocytes, fertilization rate, and clinical pregnancy rate did not differ (p > 0.05). No significant difference was found between two groups regarding the serum and follicular fluid amyloid A protein levels on the day of oocyte retrieval (p > 0.05).     

Vascular endothelial growth factor in the plasma,follicular fluid and granulosa cells of women with endometriosis submitted to in vitro fertilization – a pilot study

Vascular endothelial growth factor (VEGF), a potent angiogenic factor that is altered in endometriosis, supports the immunological mechanism involved in this disease. The aim of the present study was to assess VEGF concentration in the plasma, follicular fluid (FF) and culture medium (CM) of granulosa cells from patients with endometriosis submitted to in vitro fertilization (IVF). A case–control study was conducted on 14 patients with endometriosis and 14 women without endometriosis submitted to IVF. Peripheral blood samples were collected before and after administration of human chorionic gonadotropin (hCG), in addition to FF and CM samples. Plasma VEGF levels increased after hCG administration in women with endometriosis and in controls, but were significant only in controls. VEGF levels were lower in FF but were significantly increased in the CM of patients with endometriosis. There was no correlation between VEGF and age, response to ovarian stimulation, oocyte or embryo quality, and pregnancy result. The increase of VEGF levels after hCG in both groups demonstrated a positive effect of this hormone on VEGF. VEGF in the FF and CM presented opposite results in endometriosis, suggesting that granulosa cells may show a different behavior in vivo and in vitro.