卵泡液中白细胞介素12、18及自然杀伤细胞活化与体外受精-胚胎移植妊娠结局关系探讨

目的探讨卵泡液中白细胞介素12(IL-12)和白细胞介素18(IL-18)与CD56+NK细胞及活化的CD56+NK(CD56+CD69+NK)细胞之间的关系,及其对体外受精-胚胎移植(IVF-ET)妊娠结局的影响。方法 2007年7月至2009年4月对中国医科大学盛京医院首次接受IVF助孕治疗的53例患者,应用流式细胞学技术测定成熟卵泡液NK细胞及活化NK细胞比例,应用酶联免疫方法测定成熟卵泡液中IL-12和IL-18的质量浓度。结果 53例患者移植5周后临床妊娠24例(妊娠组),未妊娠29例(未妊娠组)。未妊娠组中IL-12(1.74±1.81)ng/L、IL-18(134.62±159.71)ng/L明显高于妊娠组(0.67±0.91)ng/L、(78.6±70.18)ng/L,P均<0.05;未妊娠组中CD56+NK细胞数占总淋巴细胞数的百分比(20.06±5.08)%、占CD56+NK细胞的百分比(4.58±2.22)%明显高于妊娠组(14.64±3.20)%、(2.39±1.02)%,P均<0.05;IL-12与CD56+NK细胞比例的相关系数r=0.49,P<0.05,两者存在显著的正相关。IL-18与CD56+NK细胞比例的相关系数r=0.54,P<0.05,两者存在显著的正相关。IL-18与活化的CD56+NK比例的相关系数r=0.57,P<0.05,两者存在显著的正相关。结论卵泡液中IL-12、IL-18和CD56+NK细胞及活化的CD56+NK细胞的比例在接受IVF-ET助孕治疗的非妊娠妇女中明显升高,与妊娠结局呈负相关。     

Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles

The objective of this study was to investigate the role of cytokines in the peri-ovulatory follicular fluid (FF) during IVF cycles. FF from 112 women was obtained during oocyte retrieval for IVF. The concentrations of five cytokines [interleukin (IL)- 1beta, IL-6, IL-12, IL-13, and tumour necrosis factor alpha (TNFalpha )] were measured in FF and their concentrations compared among women who became pregnant and those who did not. Thirty-one endometriosis patients, 15 idiopathic infertility, 21 tubal factor infertility, 15 ovarian factor infertility, and 30 patients with male factor infertility were included. Interleukin-13 and TNFalpha were absent in the peri-ovulatory FF of all patients. Fifty-two patients achieved pregnancy, whereas 60 did not. Both pregnant and non-pregnant groups were comparable for age, parity, ovarian stimulation parameters, fertilization rates, and embryo freezing rates. Concentrations of FF IL-1beta were not significantly different between pregnant and non-pregnant cycles. Concentrations of FF IL-6 were significantly higher in pregnant compared with non-pregnant cycles (P = 0.0005). Concentrations of FF IL-12 were significantly lower in pregnant compared with non-pregnant cycles (P = 0.0002). Higher concentrations of IL-12 and lower concentrations of IL-6 in the peri-ovulatory FF are associated with a negative outcome in IVF treatment. Interleukins-12 and IL-6 are biological markers that appear to affect IVF outcome.     

Role of periovulatory luteinizing hormone concentrations during assisted reproductive technology cycles stimulated exclusively with recombinant follicle-stimulating hormone

OBJECTIVE: To study the effect of endogenous luteinizing hormone (LH) concentration on fertilization, pregnancy, and early pregnancy loss rates. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university center. PATIENT(S): One hundred sixty-six normogonadotropic patients undergoing IVF. INTERVENTION(S): Luteal phase pituitary down-regulation and recombinant FSH (Gonal-F) were used for ovarian stimulation. The mean of 4-5 serum LH concentrations, from stimulation days 5-12, was computed for analysis. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and early pregnancy loss rates according to periovulatory levels of LH. RESULT(S): Data were analyzed by stratifying patients according to a mean periovulatory LH value of 3 mIU/mL. After controlling for confounding variables with logistic regression, results showed that the fertilization rate was significantly lower in patients with a periovulatory LH <3 mIU/mL versus > or = 3 mIU/mL (52% and 58%, respectively; P=.03). Pregnancy rates and spontaneous abortion rates were similar in both groups. There were seven biochemical pregnancies, all in patients with an LH <3 mIU/mL (P=.07). CONCLUSION(S): Low endogenous LH concentrations (<3 mIU/mL) in the late follicular phase of an IVF cycle are associated with significantly lower fertilization rates and a trend toward higher biochemical pregnancy rates. It may be of clinical benefit, when exclusively using r-hFSH in ART cycles, to add LH in the late follicular phase or to further reduce the dose of GnRH agonist.     

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome

OBJECTIVE: To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S): The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES: Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S): The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S): The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.     

High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage

OBJECTIVE: To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage. DESIGN: Prospective observational study. SETTING: National recurrent miscarriage clinic. PATIENT(S): Three hundred forty-four women (median age 32 years; range 18-44) with a history of recurrent first trimester miscarriage (median 4; 3-14; <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners. INTERVENTION(S): Outcome of untreated pregnancies. MAIN OUTCOME MEASURE(S): Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome. RESULT(S): One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome. Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried. CONCLUSION(S): The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome.     

Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome

OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.     

Detection of interleukin-6, interleukin-8, and interleukin-11 in plasma from women with spontaneous abortion

OBJECTIVE: To investigate the role of IL-6, IL-8, and IL-11 in the immune-regulatory mechanisms involved in the spontaneous abortion of the first trimester of pregnancy. STUDY DESIGN: Plasma levels of IL-6, IL-8, and IL-11 were determined in 68 women who had a spontaneous abortion of unknown aetiology during the first trimester of pregnancy. They were compared with the corresponding levels of 73 age-matched pregnant women who had an uneventful pregnancy, and 52 age-matched non-pregnant women. All enrolled women presented without any severe disease, syndrome or recent infection. Cytokine levels were measured by a sensitive sandwich enzyme-linked immunoassay. RESULTS: The women with spontaneous abortion had significantly decreased plasma levels of IL-6, IL-8 and IL-11 compared to those with normal pregnancies (P<0.05). The non-pregnant women had no detectable cytokine levels. CONCLUSIONS: The reduced plasma levels of IL-6, IL-8 and IL-11 in women with spontaneous abortion may be related to the underlying aetiopathogenetic mechanisms, however, there is no sufficient evidence for their use as predictive markers of pregnancy outcome.     

Bromocriptine inhibition of anesthesia-induced hyperprolactinemia: effect on serum and follicular fluid hormones, oocyte fertilization, and embryo cleavage rates during in vitro fertilization

Thirty-two patients undergoing in vitro fertilization (IVF) were given bromocriptine either 1 or 12 hours before anesthesia or received no drug to determine what effect suppression of transient, anesthesia-induced hyperprolactinemia would have on peripheral and follicular fluid hormones, fertilization and cleavage rates, and pregnancy. Thirty minutes after anesthesia, there was a 120-ng/mL rise in serum prolactin (PRL) in control patients versus an insignificant change in women given bromocriptine. Levels of PRL in follicular fluid were significantly less, and estradiol (E2) levels were higher (P less than 0.05) in all bromocriptine-treated patients compared with controls, whereas follicular fluid levels of progesterone (P), inhibin activity, and midluteal serum P were unaffected. Although fertilization and pregnancy rates were similar, a greater proportion of fertilized oocytes from bromocriptine-treated patients advanced to cleaving embryos compared with controls (95% versus 63%, respectively; P less than 0.001). We conclude that bromocriptine, given before anesthesia, can suppress transient, anesthesia-induced hyperprolactinemia and dramatically alter follicular fluid concentrations of PRL and E2. Although these changes in hormonal milieu affected neither oocyte fertilization nor pregnancy rate in our IVF patients, they seemed to have a positive influence on embryonic development after IVF.     

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.     

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.     

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.     

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.     

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.     

颗粒细胞凋亡率联合卵泡液孕激素预测IVF-ET结局

目的:探讨颗粒细胞凋亡率联合卵泡液中孕激素水平检测对体外受精-胚胎移植(IVF-ET)结局的预测价值。方法:选取2011年3月～2012年6月在我院行IVF-ET患者34例,分离收集颗粒细胞及卵泡液,33258荧光染料着色,记录颗粒细胞凋亡率,放射免疫法测定外周血及卵泡液中雌孕激素水平。比较妊娠组与非妊娠组的年龄、基础FSH、Gn用量及持续时间、卵泡数、取卵数、颗粒细胞凋亡率、雌孕激素水平、受精率。对颗粒细胞凋亡率及卵泡液雌孕激素水平进行相关性分析。以丘颗粒细胞凋亡率≤4‰,卵泡液孕激素浓度≤5.0ng/ml为阳性标准,进行联合检测。结果:妊娠组与非妊娠组的年龄、基础FSH、Gn用量及持续时间、卵泡数、取卵数、受精率及雌激素水平均无显著差异(P>0.05),颗粒细胞凋亡率、外周血及卵泡液中孕激素水平差异显著(P<0.05)。相关性分析发现,颗粒细胞凋亡率随孕激素含量升高而升高,但无显著差异(P>0.05)。联合检测阳性组妊娠率为75.8%。结论:颗粒细胞凋亡率、外周血及卵泡液孕激素水平与IVF-ET结局有关。联合检测能较好提高对妊娠结局的预测。     

Homocysteine level in ovarian follicular fluid or serum as a predictor of successful fertilization

OBJECTIVES: There are some data concerning homocysteine influence on fertilization and early embryogenesis, especially in women experiencing recurrent pregnancy loss (RSA). However, limited data support hypothesis that the ovum might be exposed to high homocysteine concentration what may be important in egg-sperm interactions, for example during in vitro-fertilization (IVF) cycle. DESIGN: Therefore, the aim of our study was to determine fasting total homocysteine concentration in follicular fluid or serum of women experiencing reproductive failure after spontaneous or in-vitro fertilization. MATERIALS AND METHODS: Eight nonpregnant RSA women, 8 normal healthy women with previous successful pregnancy outcome and 15 women undergoing IVF (6 with unexplained infertility-UI, 6 with male factor-MF, 3 with tubal obstruction-TO). Total fasting homocysteine level concentrations were established by ELISA method (Axis Homocysteine EIA, Axis-Shield AS) in serum of RSA and normal healthy women or ovarian follicular fluid of women undergoing IVF. RESULTS: Mean fasting total homocysteine concentration in study group were as follows: RSA-18.63 mumol/L +/- 6.67, Normal-13.98 mumol/L +/- 6.62, UI-20.62 mumol/L +/- 8.19, MF-22.60 mumol/L +/- 7.87, TO-36.75 mumol/L +/- 13.26. We found that RSA women have had significantly higher serum homocysteine concentration when compared to normal healthy women (P < 0.05). Among women undergoing IVF, those with following IVF success had not significantly lower homocysteine level when compared to those with IVF failure (22.81 mumol/L +/- 11.27 vs. 24.54 mumol/L +/- 9.50, P > 0.05). CONCLUSIONS: Our preliminary data suggest that high homocysteine level may negatively influence pregnancy outcome following natural or in-vitro fertilization. It cannot be excluded that elevated homocysteine concentrations contribute to defective chorionic villous vascularization during early stages of gestation.     

Serum concentrations of interleukin-2R (IL-2R), IL-6, IL-8, and tumor necrosis factor alpha in patients with ectopic pregnancy

OBJECTIVE: To investigate the diagnostic relevance of serum cytokine concentrations in ectopic pregnancy (EP). DESIGN: Cohort study. SETTING: University hospital. PATIENT(S): Seventeen women with EP, 22 women with miscarriage, and 33 women with normal intrauterine pregnancy, at comparable stages of gestation. INTERVENTION(S): Interleukin (IL)-2 receptor, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) determination by immunoradiometric assay. MAIN OUTCOME MEASURE(S): Serum concentrations of progesterone, beta-hCG, IL-2R, IL-6, IL-8, and TNF-alpha. RESULT(S): Serum levels of IL-6 were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of TNF-alpha were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of IL-8 were higher in women with EP than in those with miscarriage and normal pregnancy. An IL-8 cutoff of >40 pg/mL predicted EP with a sensitivity of 82.4%, a specificity of 81.8%, and positive and negative predictive values of 58.3% and 93.8%. No difference in serum IL-2R levels was found among the groups. CONCLUSION(S): Serum IL-8, IL-6, and TNF-alpha concentrations are higher in women with EP than in those with miscarriage and normal pregnancy. Further studies are needed to determine their diagnostic value.     

Comparison of in vitro fertilization outcome in women with and without sonographic evidence of polycystic ovarian morphology

OBJECTIVE: This study compared the outcome of in vitro fertilization (IVF) treatment in women who had polycystic ovaries (PCO) seen on an ultrasound scan, but who had no clinical symptomatology associated with polycystic ovary syndrome, with that of women who had normal ovarian morphology on ultrasound examination. METHODS: Outcome of IVF 39 women with PCO evidence by ultrasound compared with 102 women, who had normal ovarian morphology by ultrasound. All 141 women had normal early follicular phase serum follicle stimulating hormone (FSH) concentration, were less than 40 years of age and used the long protocol pituitary suppression with gonadotropin-releasing hormone agonist therapy. RESULTS: On average, the women with PCO produced more follicles and oocytes than the women with normal ovaries, but the fertilization cleavage and pregnancy rates were similar. CONCLUSION: Although the response to follicular stimulation in PCO women is better than that for women with normal ovaries, the outcome of pregnancy in vitro fertilization is similar.     

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Purpose

The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF).

Methods

Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women.

Results

Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P?<?0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality.

Conclusion

The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.

     

The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization

OBJECTIVE: To examine the presence of reactive oxygen species (ROS) in the follicular fluid of women undergoing in vitro fertilization (IVF) and identify its role in pregnancy outcome. STUDY DESIGN: In this prospective study, ROS and total antioxidant capacity (TAC) levels were measured by the chemiluminescence method in the follicular fluid of 53 women. Age, number of oocytes recovered, percentage of oocytes fertilized, ROS and TAC levels were compared in women who did and did not become pregnant. RESULTS: Patients who become pregnant had significantly higher log-transformed ROS levels (1.01 +/- 0.14, P = 0.031 than those who did not (0.69 +/- 0.08). Women with endometriosis or male factor infertility who became pregnant had significantly higher ROS levels (1.44 +/- 0.23 and 1.31 +/- 0.19) than those who did not (0.60 +/- 0.17 and 0.67 +/- 0.16; P < .006 and P < .01). CONCLUSION: Follicular fluid ROS, at low concentrations, may be a potential marker for predicting success in IVF patients.