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Xadzkgm. Journal List Biomed Res Int PMC5745683 Biomed Res Int. 2017; 2017 3512784. Rosalie Cabry-Goubet, 1 , 2 Florence Scheffler, 1 , 2 Naima Belhadri-Mansouri, 1 Stephanie Belloc, 3 Emmanuelle Lourdel, 1 Aviva Devaux, 1 , 2 Hickmat Chahine, 4 Jacques De Mouzon, 4 Henri Copin, 1 and Moncef Benkhalifa 1 , 2 AbstractObjective To evaluate the IUI success factors relative to controlled ovarian stimulation COS and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. Results We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples' parameters, including the female age, the IUI attempt rank, and the sperm quality. Conclusion Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count 1 × 106. The exclusion criteria were TMS ≤ 1 × 106; sperm donation; seropositivity for human immunodeficiency virus HIV for any couple member; inseminations performed in a natural cycle or with clomiphene citrate CC. IUI ProtocolAll couples had undergone a standard infertility evaluation, which included medical history, physical examination, and assessment of tubal patency by either hysterosalpingography or laparoscopy and hormonal analysis on cycle day 3. A transvaginal ultrasound scan was performed on the second day of the cycle. On the same day, ovarian stimulation was carried out with recombinant FSH follitropin α; rFSH; Gonal-F, Merck Serono, France, or follitropin β; Puregon, MSD, France, urinary FSH urofollitropin, Fostimon, France, or hMG menotropin, Menopur, France at a starting dose of 75 IU/day from the second day of the response and endometrial thickness were monitored by transvaginal ultrasonography starting on day 6 of stimulation and then on alternate days; the gonadotropin dose was adjusted according to the ovarian response and the patient's characteristics. When at least one mature follicle reached a diameter >17 mm and E2 level > 150 pmol/mL, the recombinant human chorionic gonadotropin hCG, Ovitrelle, Merck Serono, France was administered, and endometrial thickness was single IUI was performed 36 h after hCG injection using a soft catheter classic Frydman catheter; Laboratoire CCD, Paris, France or a hard catheter SET TDT, International Laboratory CDD. The semen samples used for insemination were processed within 1 hour of ejaculation by density gradient centrifugation, followed by washing with a culture medium after determining the TMS and semen analysis according to the WHO criteria [26]. Outcome VariableThe main clinical outcome measures were clinical pregnancy and live-birth rates per cycle. Clinical pregnancy was defined as the evidence of pregnancy by ultrasound examination of the gestational sac at weeks 5– Statistical AnalysisThe stimulation protocols were divided into 4 categories according to the gonadotropin used for COS rFSH/Gonal-F, rFSH/Puregon, uFSH/Fostimon, and hMG/ type was considered in seven categories cervical factor, dysovulation, endometriosis, tubal factor, male factor, and unexplained infertility. After statistical analysis of the results, it was necessary to determine the parameter cut-offs to give infertile couples more chances through IUI before carrying out other ART techniquesGroups were compared for all main couples' characteristics and cycle outcomes. Data are presented as mean ± standard deviation SD or percentage of the total. Data were analysed with Student's t-test for means comparisons or with the chi-squared test for comparison of percentages using Statistical Package, version SAS; Institute Inc., Cary, NC, USA; p 15 Sperm motility ≥40 % versus ≤39 TMS ≥5 × 106 versus <5 s power calculation showed a power of 80% to demonstrate a difference across the COS groups in delivery rates of 10% between groups 1 and 4 and 2 and 4, of 11% between groups 3 and 4, of 8% between groups 2 and 3, of 8% between groups 2 and 4, of 7% between groups 1 and 2, 6% between recombinant FSH and urinary products, and of 9% between FSH and HMG4. DiscussionAs a first step in ART, IUI keeps a central place in the management of infertile couples for its simplicity, but it still offers weak effectiveness. Indeed, IUI success is still a subject of controversy, with a clinical pregnancy rate between 8% and 25% [16, 18, 27–31]. Furthermore, based on a recent prospective study in seven French ART centres, the overall live-birth rate was 11% per cycle, varying from 8% to 18% between centres [9]. Similarly, we attained 13% for clinical pregnancy and 11% for live-birth for the 1251 couples who underwent homologous IUI with gonadotropins for COS Table 1.Indeed, gonadotropin use had proved its superiority to improve clinical outcomes of IUI compared to other COS protocols, such as CC and letrozole [32–38]. Erdem et al. [36] showed that, for IUI success, rFSH Gonal-F was more effective than using CC to reach 28% for clinical pregnancy and 24% of live-birth. Nevertheless, it is still not clear which of the currently available medications is preferable for COS [15, 23, 39–43]. However, several studies compared different types of gonadotropin efficiency rFSH, uFSH, or hMG [15, 25, 44–47]. Indeed, in the first part of this work, we compared four gonadotropins for COS in IUI rFSH/Gonal-F; rFSH/Puregon; uFSH/Fostimon and hMG/Menopur while rFSH was the most used in 72% of couples Table 1.This preference was noticed in other studies [9, 15, 25, 36] without finding any significant improvement on clinical outcomes. Indeed, as demonstrated in our study, there was no significant difference between different protocols used for COS rFSH/Gonal-F; rFSH/Puregon; uFSH/Fostimon; and hMG/Menopur; Table 2, although, in contrast, some authors pointed to the greater potency of rFSH [22, 48]. However, other studies have reported higher pregnancy rates for hMG [33, 49–53]. Even if our study had 80% power to demonstrate differences in PR of 6% to 11% between 2 groups, according to their size, it is clear that the differences we observed were very low, in favour of a low impact of the 4 used COS regimen on the results. This was less clear for infertility origin because of the very low numbers of some groups. However, the results of the multivariate logistic model confirmed the results observed at the first step analysis, reinforcing their valueGenerally, rFSH is commonly used to minimize the possibility of developing ovarian cysts associated with LH contamination and to improve the probability of a more consistent, effective, and efficient ovarian response [22, 48].Although there was no significant difference between the efficiency of gonadotropins for COS, other COS protocol factors could be involved to improve the clinical outcomes, especially regarding the starting dose and the total doses of treatment as proved by several studies [15, 23–25, 54].To explain the absence of a significant difference between the four COS groups, we analysed other factors relative to COS protocol female age, IUI attempt rank, and sperm quality. As expected, our studied population showed its heterogeneity involving multiple factors, which was the reason not to have a real consensus about the efficiency of COS, and this made it harder to really evaluate its impact. The sperm motility significantly affected the live-birth in rFSH groups Table 3. Furthermore, the IUI attempt rank had a significant negative correlation with clinical outcomes with unequal values between groups Table 3. Indeed, it is not legitimate to consider the COS as a strong predictive factor of clinical outcomes in IUI, while other factors could not all be controlledInfertility type has been discussed throughout several studies as a nonnegligible indicator of IUI clinical outcomes [15, 30, 38, 50, 55–59], while the latest National Institute for Health and Care Excellence NICE guideline on fertility [59] recommends that IUI should not be routinely offered to people with unexplained infertility, mild endometriosis, or mild male factor infertility who are having regular unprotected sexual this reason, in the second part of this study, we were more focused on evaluating the infertility type effect on IUI success. As a result, there was no significant difference between clinical outcomes of the different groups based on the infertility type Table 4. Although unexplained infertility was most couples' indication for IUI 36% Table 1, as noticed in the recent report of Monraisin et al. [9] with a value of 39%, the lack of significant difference in clinical outcomes with other IUI indications was not unexpected, while its aetiology kept the multifactorial profile [57] shared with other infertilities. Our results are confirmed by the recent study of [38]. However, some teams report the best pregnancy rates in cervical indications [30, 55] and in anovulation infertilities [15, 50, 56]. Indeed, the pregnancy rate per cycle for patients with anovulation due to PCOS was 13%, which was probably corrected by Controlled Ovarian Hyperstimulation COH [15]. On the other hand, endometriosis was considered a bad prognostic factor for IUI success with lower pregnancy between 6% and 9% than other IUI indications [20, 50, 60]. Indeed, endometriosis, which is among the most difficult disorders to treat [21], decreased the IUI success rate for mild compared to severe cases 6% of success rate. This fact can argue the limitation of IUI to a maximum of two to three cycles [15, 19, 50, 60, 61]. This fact could explain our weak population size in the endometriosis group with just 35 couples, while the majority of couples were directed to undergo predictors of success have been widely studied on the COS effect and the infertility type effect. The most discussed effect was the age of the women, with a large debate on its impact on IUI success. Age has been accepted by many authors as a major predictive factor for pregnancy after IUI [29, 30, 60].The female age was a predictive variable for the live-birth rate but not for clinical pregnancy due to the increased miscarriage rate with age dependence, as can be observed in predictive unadjusted models [9, 57, 62]. The female age became a significant variable predictive for clinical pregnancy and live-birth rate with an adjusted model designed by Van Voorhis et al. [63] and, subsequently, Hansen et al. [57].In contrast with the aforementioned authors, our results did not show a significant correlation between the women's age and the clinical pregnancy rate Table 1, which was confirmed by several studies [11, 15, 16, 28, 64, 65]. This is due both to the intervention of other factors used in patients' selection including ovarian reserve and to the low numbers of women aged 40 or the female age impacted the success of IUI. A recent study by Bakas et al. [66] demonstrated a significant negative correlation between the age of the women and the clinical outcome of IUI r = − Indeed, with the female age cut-off of 40 years, clinical pregnancy was significantly affected Table 6 as shown throughout several studies, while the pregnancy rate decreased from 13–38% to 4–12% when the women were older than 40 years [30, 60, 67].The female age impact on IUI success could be masked in our study, because only were over 35 years and over 40 years. There may be a too low power to show a significant impact of age 40 and more in the multilogistic model, even if OR for this age category was very low Moreover, a multilogistic model including age as a continuous variable showed a significant negative impact on the delivery chance. On the other hand, age may also be linked to other factors, especially the IUI attempt rank. It is logical that, with more IUI attempts, the age advances. For this reason, Aydin et al. [68] could find no significant effect of female age on the clinical pregnancy rate in the first IUI cycle. Indeed, the rank attempt is determinant for IUI success. In our study, pregnancy rates and live births decreased significantly with the rank of insemination p = and p < resp. from rank 4 for both parameters p = see Table 6. Hendin et al. [67] and Merviel et al. [30] obtained 97% and 80%, respectively, of clinical pregnancies in their first three attempts. Plosker et al. [69] advocated a passage in IVF after three failed cycles of IUI. However, Soria et al. [15] demonstrated that from the fourth IUI cycle clinical pregnancy is negatively affected, which confirms our Blasco et al. [62] proved that the number of previous IUI cycles of the patient did not show a positive association with the cycle outcome in any of the developing steps of the models. In our study, IUI attempt rank did not have a clear correlation with clinical outcomes in different COS groups, but it did show a negative correlation with live-birth rates for patients with PCOS, unexplained infertility and male factor Tables 3 and 5. This could be explained by the evidence of severity of infertility type throughout time with an accumulation of IUI attempt failures, while IUI as a simple technique is less efficient than other ART techniques in achieving a clinical pregnancy. Particularly for infertile couples with male factor, the sperm quality becomes the determinant for IUI success [11, 70, 71], which was shown in our findings with a positive correlation of sperm concentration Table 5. It would be difficult to determine a universal threshold for sperm concentration, and each centre should define a threshold for its population and laboratory [72]. Nevertheless, Belaisch-Allart et al. [73] and Sakhel et al. [74] determined a sperm concentration cut-off at 10 × 106/mL and 5 × 106/mL, respectively. Indeed, the impact of semen quality was weak in our study, except for concentrations <5 × 106/mL, which remains nonsignificant due to small numbers of patients 8% of included population Table 6Sperm motility also appeared as a key factor in the study of Merviel et al. [30], where the pregnancy rate declined from 41% to 19% when the sperm motility was less than 70%. In our multivariable analysis with a sperm motility cut-off at 40%, we did not find any significant correlation with IUI clinical outcomes even with a large population size. This observation is reported also by Stone et al. [75].However, the TMS cut-off at 1 × 106, which was present in 21% of the included infertile patients, was a significant predictor of IUI clinical pregnancy Table 6. This finding was confirmed by two studies [9, 10] while others determined a higher threshold of TMS at 2 × 106 [68]; 3 × 106 [62, 76]; 5 × 106 [11, 77]; 10 × 106 [63, 78]. Indeed, the IUI clinical outcomes were improved with higher TMS, from × 106 to 12 × 106 [38]. Furthermore, regarding the sperm parameters, TMS was found to be an independent factor for clinical pregnancy after IUI in accordance with many authors [28, 63, 74, 77, 79–81]. However, Ozkan et al. [82] found just a minimal influence of TMS on the IUI success after TMS is a key factor for choosing IUI treatment or IVF, although a TMS threshold value of 5 × 106 to 10 × 106 has been reported as the criterion for undergoing IVF. Nevertheless, other sperm parameters could be better predictors of sperm morphology [58]. Although the predictive weakness of conventional sperm parameters for ART clinical outcomes has been demonstrated, sperm genome decay tests [83] could become a strong diagnostic tool to achieve clinical pregnancy for infertile couples undergoing homologous predictive factors for success have been found in some studies, such as duration of infertility, body mass index [15, 60, 82, 84, 85], and smoking [37], which were not regularly noted in our records and, therefore, could not be ConclusionThis study, is in concordance with our preliminary work [86] and demonstrate that there is no significant difference in clinical outcomes between different COS protocols rFSH, uFSH, or hMG and infertility types, even after taking into account the usual prognostic factors, including the female's age, the IUI attempt rank, and the sperm quality. However, unexplained infertility had a significant impact on IUI success, which revealed the need to look for more efficient ART strategies. Furthermore, since the fourth IUI attempt or with the female aged over 40 years, clinical pregnancy declined in IUI. Regarding the sperm quality, TMS with a threshold of 5 × 106 seemed a good predictor for IUI success. Indeed, over the obtained cut-off of the chosen indicators, other ART techniques might be more favourable for IVF live-birth infertile patients with male factor, sperm concentration was a determinant to achieve pregnancy, which necessitated some additional tests, such as sperm genome decay tests, before undergoing IUI and reviewing the couple's etiological factors for antioxidant prescriptions. Finally, every decision must be individualized to each couple's profile taking into account factors involved in the success of authors acknowledge the help of the embryology team of the IVF Centre of Amiens Hospital and the andrology team of Eylau Laboratory, Paris. 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球员名单 球队简介 名称:广东 主教练:杜锋 助理教练:伊戈尔 领队:马永忠 创建时间:1993 最好成绩:2003-04,04-05,05-06,07-08,08-09,09-10,10-11赛季总冠军 给球队打分 平均得分 参与人数 30326 球队微集体 一键关注 CBA联赛21-22 场均总计 号码 球员 场次 出场时间 2分球 3分球 罚球 进攻篮板 防守篮板 助攻 抢断 灌篮 盖帽 失误 犯规 得分 9 易建联 37 53% 39% 81% 11 周鹏 38 50% 44% 67% 12 苏伟 36 57% 0% 61% 20 任骏飞 34 56% 31% 74% 10 赵睿 26 54% 34% 75% 5 王薪凯 29 48% 33% 94% 22 曾繁日 41 55% 0% 56% 3 胡明轩 45 52% 34% 80% 13 威姆斯 27 53% 40% 82% 2 徐杰 43 53% 39% 90% 18 杜润旺 33 75% 45% 67% 32 里卡多-雷多 18 49% 37% 85% 0 刘权标 9 61% 33% 67% 25 张皓嘉 14 60% 41% 92% 30 汤杰 12 29% 25% 90% 17 赵锦洋 18 65% 42% 60% 21 张昊 12 53% 25% 58% 1 马力克 7 33% 0% 22% 27 张明池 12 58% 50% 75% 19 徐昕 6 58% 0% 71% CBA联赛近期赛程赛果 时间 对手 2分球 3分球 罚球 进攻篮板 防守篮板 助攻 抢断 灌篮 盖帽 失误 犯规 得分 2021-10-16 主场 10683 深圳 30-61 49% 11-29 38% 13-18 72% 14 31 31 10 0 5 16 25 106 2021-10-18 客场 10390 青岛 20-47 43% 17-33 52% 12-14 86% 13 31 29 6 0 5 16 19 103 2021-10-21 主场 11094 浙江 30-57 53% 11-28 39% 17-24 71% 16 30 29 13 1 9 13 31 110 2021-10-24 客场 11297 上海 33-58 57% 9-21 43% 19-27 70% 10 36 31 8 0 4 16 24 112 2021-10-26 主场 111108 四川 29-60 48% 12-32 38% 17-24 71% 19 36 18 5 1 5 8 13 111 2021-10-28 客场 10690 深圳 28-52 54% 8-24 33% 26-31 84% 12 32 23 5 1 6 17 22 106 2021-10-30 客场 101124 浙江 29-58 50% 5-26 19% 28-38 74% 12 27 11 8 0 9 15 31 101 2021-11-01 主场 9891 福建 36-57 63% 3-15 20% 17-26 65% 14 30 30 5 0 4 17 20 98 2021-11-04 客场 9784 江苏 26-40 65% 8-19 42% 21-32 66% 8 35 30 9 2 8 21 18 97 2021-11-06 主场 6791 北京 20-46 43% 4-20 20% 15-22 68% 6 28 15 8 1 2 13 16 67 2021-11-09 客场 11098 天津 28-46 61% 10-22 45% 24-31 77% 7 43 30 6 2 8 31 23 110 2021-11-12 主场 10873 江苏 23-48 48% 9-22 41% 35-46 76% 17 27 34 16 1 3 22 23 108 2021-11-14 客场 9280 北京 26-39 67% 8-20 40% 16-22 73% 2 20 24 14 3 3 19 30 92 2021-12-26 客场 8698 广厦 20-41 49% 9-40 23% 19-23 83% 12 21 25 11 0 1 20 32 86 2021-12-28 主场 99125 山西 20-45 44% 11-23 48% 26-30 87% 5 29 22 3 0 5 23 18 99 2021-12-30 客场 11699 吉林 32-48 67% 13-26 50% 13-15 87% 10 32 33 4 1 5 17 18 116 2022-01-01 主场 95115 辽宁 22-43 51% 11-32 34% 18-21 86% 12 25 29 6 3 7 16 19 95 2022-01-03 客场 10186 同曦 32-55 58% 6-11 55% 19-21 90% 9 31 28 8 7 8 24 21 101 2022-01-06 客场 11196 山西 32-56 57% 8-21 38% 23-31 74% 12 37 33 7 2 4 15 22 111 2022-01-08 主场 9995 吉林 31-52 60% 3-9 33% 28-33 85% 13 35 24 6 5 6 25 22 99 2022-01-10 主场 10187 同曦 28-54 52% 4-11 36% 33-42 79% 7 34 26 5 1 5 20 25 101 2022-01-13 客场 90102 辽宁 20-44 45% 10-28 36% 20-24 83% 9 34 26 6 4 6 23 29 90 2022-01-15 主场 94114 广厦 18-39 46% 15-30 50% 13-20 65% 7 22 19 4 3 5 14 12 94 2022-01-18 客场 108104 福建 29-50 58% 11-26 42% 17-23 74% 14 30 34 9 2 1 16 20 108 2022-01-21 主场 11891 天津 32-42 76% 14-38 37% 12-15 80% 11 34 34 7 3 3 13 24 118 2022-01-23 主场 9891 青岛 14-34 41% 13-35 37% 31-37 84% 9 31 23 9 1 3 21 20 98 2022-01-26 客场 11076 四川 28-43 65% 11-32 34% 21-29 72% 6 42 27 8 1 3 10 14 110 2022-01-28 主场 101108 上海 30-58 52% 9-26 35% 14-21 67% 10 24 25 8 2 5 13 13 101 2022-03-01 主场 127101 山东 36-57 63% 11-25 44% 22-25 88% 8 36 34 11 4 4 14 27 127 2022-03-03 客场 107109 新疆 35-64 55% 7-19 37% 16-23 70% 13 28 29 7 4 3 21 31 107 2022-03-05 主场 9889 广州 22-46 48% 12-31 39% 18-22 82% 10 33 23 6 1 1 15 21 98 2022-03-09 客场 93106 北控 29-55 53% 5-30 17% 20-28 71% 8 32 17 8 1 5 21 26 93 2022-03-11 主场 11188 宁波 33-60 55% 7-19 37% 24-33 73% 14 33 25 9 4 2 18 23 111 2022-03-13 客场 101120 广州 25-51 49% 7-28 25% 30-36 83% 12 27 24 6 1 2 12 26 101 2022-03-15 主场 10980 北控 28-55 51% 11-27 41% 20-27 74% 20 37 29 10 1 2 18 25 109 2022-03-18 客场 10680 宁波 25-43 58% 11-30 37% 23-34 68% 4 35 30 10 2 1 11 18 106 2022-03-20 主场 11899 新疆 36-63 57% 12-26 46% 10-13 77% 11 25 30 15 2 2 16 20 118 2022-03-22 客场 110111 山东 23-52 44% 16-35 46% 16-27 59% 11 34 32 9 0 1 20 27 110 2022-04-01 主场 124101 天津 27-43 63% 17-30 57% 19-25 76% 7 33 31 9 2 0 19 20 124 2022-04-03 客场 122104 天津 42-57 74% 7-25 28% 17-19 89% 8 36 30 6 5 2 14 22 122 2022-04-07 客场 9998 浙江 21-54 39% 13-26 50% 18-21 86% 14 26 21 10 2 5 12 24 99 2022-04-09 主场 9782 浙江 23-56 41% 7-19 37% 30-35 86% 15 33 17 6 4 6 16 24 97 2022-04-12 客场 7992 辽宁 13-34 38% 11-30 37% 20-33 61% 9 30 19 5 0 4 21 24 79 2022-04-14 客场 8396 辽宁 18-41 44% 11-33 33% 14-19 74% 4 24 16 11 0 4 9 22 83 2022-04-16 主场 116117 辽宁 24-50 48% 15-38 39% 23-27 85% 13 29 29 12 1 3 17 28 116
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Color Harmonies Scheme Complementary The complementary color of 56,33,86 is 63,86,33. When combined, they cancel each other out this means that they produce a grayscale color. When placed next to each other, they create the strongest contrast. Triad A triadic color scheme use three colors that are evenly spaced around the color wheel. Triadic color harmonies tend to be quite vibrant, even if you use pale or unsaturated versions of your hues. To use a triadic harmony successfully, the colors should be carefully balanced - let one color dominate 56,33,86 and use the two others for accent 86,56,33, 33,86,56. Square The square color scheme has four colors spaced evenly around the color circle. This creates a balance between warm 86,33,37, 63,86,33 and cool 56,33,86, 33,86,82 colors in your design. The square color scheme works best if you let one color be dominant. Adjacent / Analogous / Analogic Dominance Harmony Analogous color schemes use colors that are next to each other on the color wheel. They usually match well and create serene and comfortable designs. The nearest colors, with enough contrast, of 56,33,86 are 82,33,86 and 33,37,86. Choose one color to dominate and a second to support. The third color is used along with black, white or gray as an accent. Split ComplementaryCompound Harmony The split-complementary color scheme is a variation of the complementary color scheme. In addition to the base color 56,33,86, it uses the two colors adjacent to its complement 86,82,33 and 37,86,33. This color scheme has the same strong visual contrast as the complementary color scheme, but has less tension. The split-complimentary color scheme is often a good choice for beginners, because it is difficult to mess up. Rectangle Tetradic The rectangle or tetradic color scheme uses four colors arranged into two complementary pairs 56,33,86 and his complementary 63,86,33 with 86,33,63 33,86,56 or 86,56,33 33,63,86. This rich color scheme offers plenty of possibilities for variation. The tetradic color scheme works best if you let one color be dominant. You should also pay attention to the balance between warm and cool colors in your design. Tints, Shades, and Tones Tints Adding white to the color same hue and saturation of 56,33,86, but brighter. Shades Adding black to the color same hue and saturation of 56,33,86, but darker. Tones Adding gray to the color same hue and luminosity of 56,33,86, but less saturation. SIMILAR COLORS Colors with similar hue of 56,33,86.
33 1 86 56 03 16