The correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization (IVF): A meta-analysis

The correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization (IVF): A meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research The correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization (IVF): A meta-analysis Xin-Lei Wang, Zhuo Li, Han Zhang, Ce Shi, Tong Tong, Rui-Zhi Liu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.18753/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Several studies had investigated the role of serum Ca-125 in clinical pregnancy of patients undergoing in vitro fertilization (IVF); however, their conclusions had been inconsistent. This study aimed to evaluate the correlation between serum Ca-125 level and clinical pregnancy in IVF. Methods We systematically review the studies in the databases of Mediline OvidSP, EMBASE OvidSP and Cochrane (CENTRAL Central Register of Controlled Trials). Studies on the correlation between serum Ca-125 level and clinical pregnancy in patients underging IVF with or without Intracytoplasmic sperm injection (ICSI) were considered. The pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) was used in the analysis. Results Seven studies involving 558 patients were included. The meta-analysis showed that there was no significant difference in the serum Ca-125 level before embryo transfer (ET) between clinical pregnant group and nonpregnant group (SMD 0.72; 95% CI [0.01, 1.43], P = 0.05, I 2 = 88%), and the same conclusion was also reached in patients without endometriosis (SMD 0.31; 95% CI [-0.53, 1.16], P = 0.47, I 2 = 89%); However, after embryo transfer, the result showed that the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group (SMD 0.39; 95% CI [0.09, 0.69], P = 0.01, I 2 = 0%). Conclusions Berore ET, there was no significant correlation between serum Ca-125 level and clinical pregnancy in IVF; After ET, the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group, and it might reflect a successful interaction between the embryo and the endometrium in that time period. Endocrinology & Metabolism in vitro fertilization Ca-125 pregnancy outcome embryos transferred Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Prediction of clinical pregnancy is rapidly becoming an important objective in in vitro fertilization (IVF). on the one hand, pregnancy in IVF have a higher risk of obstetric and perinatal complications than spontaneous pregnancies; on the other hand, most IVF patients are successfully fertilized and get embryos transferred (ET), but only a relatively small percentage of transferred embryos actually implant and develop into viable pregnancies. Successful implantation after ET has been shown to depend on two factors: good quality of transferred embryos; and well-prepared endometrium [ 1 ]. At present, endometrial receptivity is judged generally by Ultrasound parameters, such as endometrial thickness and pattern, and Doppler study of uterine arteries and subendometrial flow [ 2 ]. However, morphological assessments of endometrial receptivity have been subjective and disregards embryo interaction [ 1 ]. The idea that some objective parameters could ascertain the endometrial receptivity in a non-invasive and cost efficient way in an Assisted Reproductive Technology cycles is interesting and has important clinical significance. Cancer antigen 125 (Ca-125) is a cell-surface antigenic determinant on a high molecular-weight glycoprotein, as a well-established marker it is mainly used to diagnose endometriosis and epithelial cell ovarian cancer [ 3 , 4 ]. Ca-125 can be measured in the serum. Although the primary source of serum Ca-125 levels is controversial, some studies have found that endometrium may be one of the sources of serum Ca-125: (1) Ng et al. detected Ca-125 in the uterine flushings fluid [ 5 ]; (2) Ca-125 was detected in vitro endometrial tissue culture medium [ 6 ]; (3) The serum Ca-125 level was increased due to endometrial destruction during menstrual period [ 7 ]. If endometrium is the main source of serum Ca-125, then Ca-125 may be used as an indicator of endometrial receptivity in IVF. In addition, several studies had investigated the role of serum CA-125 in clinical pregnancy of patients undergoing IVF; however, their conclusions were inconsistent. Therefore, we conducted a meta-analysis to evaluate the correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization. Methods This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [8]. Exclusion criteria and inclusion criteria Inclusion and exclusion criteria were established prior to literature search. This meta-analysis focused on the correlation between serum Ca-125 level and clinical pregnancy in patients underging IVF with or without Intracytoplasmic sperm injection (ICSI). The inclusion criterias were as follows: (1) Case-control, cohort or cross-sectional studies; (2) All patients were women who underwent IVF treatment with or without ICSI, regardless of the ovarian stimulation protocol employed; (3) Study provided data on serum Ca-125 levels in clinical pregnant and nonpregnant groups, no limit was given for Ca-125 measurement methods; (4) Clinical pregnancy was clarified as a positive heart action or Intrauterine pregnancy sac in transvaginal ultrasound after ET; (5) When multiple studies may contain the same study population, only the most complete study was included; (6) Available full text in English. We excluded: (1) Study contained overlapping or insufficient data; (2) Reviews, editorials, commentaries, animal experiments, and individual case reports. Search Strategy The studies in the databases of Mediline OvidSP, EMBASE OvidSP and Cochrane (CENTRAL Central Register of Controlled Trials) were systematically reviewed until October 25, 2019. The search strategy was shown in Additional file 1. We also manually searched the references of the included studies and reviews for additional studies. Study selection and quality assessment After importing the search results into EndNote X9, duplicated studies were excluded. Two review authors (Li Z and Wang XL) independently screened the studies based on both the titles and abstracts of the selected studies, then retrieved the full text articles for those relevant and determine whether it meets the inclusion criteria. The quality of the included studies were assessed using the Newcastle–Ottawa scale (NOS) for cohort studies, which evaluates studies according to the following three domains: selection of subjects, comparability, and assessment of the results [9]. We rated the studies as ‘high quality’ if they had a score ≧5; otherwise, the studies were rated as ‘low quality’. A discrepancies between Li and Wang was resolved through discussion and consensus with a third reviewer (Zhang Han). Extraction of data Two researchers (Wang XL, Li Z) extracted data independently using a pre-designed data extraction table. A third review author (Zhang Han) resolved any disagreements between the two researchers. We extracted data on study design, number of participants, patients’ age, publication year, included and excluded criteria of patients, ovarian stimulation protocols, and time of blood sample collection, metholds of Ca-125 detected, the mean and standerd deviation (SD) of serum Ca-125 level (In case no means and SD were reported, we used medians, interquartile ranges (IQRs), or ranges to estimate them based on the methods advocated by Wan et al) [10]. Synthesis of results and assessment of heterogeneity All analyses were performed using Review Manager 5.0 software. Statistical heterogeneity was tested with the Q test (chi‐square) and calculated I 2 values. When chi-square test p50%, we thought that there was significant heterogeneity among studies, in which case, we used the randomized effect model, otherwise the fixed effects model was used. We assessed clinical heterogeneity by performing subgroup analyses for different detection methods of Ca-125. We expected the different metholds of Ca-125 detected among studies, so the serum Ca-125 level was shown as standardized mean difference (SMD) with corresponding 95% confidence intervals (95% CIs). The P < 0.05 values could be considered as statistically significant. Sensitivity analysis and assessment of publication bias To evaluate stability and reliability of the meta-analysis, we performed sensitivity analysis whereby: 1. Assessed the influence of each individual study on the pooled SMD by removing each study individually; 2. Different models (fixed effect model or randomized effect model) were used. If enough studies (10 or more) were found, we planned to use a funnel plot to explore the possibility of publication bias. Result Study selection The preliminarily database search retrieved 185 citations. After the initial exclusion of 32 duplicate articles, the remaining 157 articles were screened based on title and abstract. Then we retrieved 32 full-text articles reading, of which we excluded 25. Finally, seven articles were included in our analysis. No articles were included by manual search. The details of study selection was shown in Fig. 1 . Characteristics and quality assessment of the included studies The various baseline characteristics of including studies were shown in Table 1 . A total of 7 studies involving 558 patients were included, and the sample sizes of included studies were ranged from 33 to 182. Three studies directly reported mean and SD [ 11 – 13 ], while data for 4 studies [ 14 – 17 ] that did not were transformated according to the method proposed by Wan et al [ 10 ].Two studies detected serum Ca-125 by enzyme immunoassay method [ 15 , 17 ], while four studies [ 11 , 12 , 14 , 16 ] used Immunoradiometric methods and only one [ 13 ] used Chemiluminescence method. The quality assessment of the included studies was summarised in Table 2 . All studies had a score ≧ 5 and were rated as ‘high quality’. Table 1 The various baseline characteristics of including studies Study auther, year Number of pationts in study Age (years) Causes of infertility Ovarian stimulati-on protocols ART protocol Sample time Metholds of CA-125 detection Clinical pregnant Nonpregnant Urbancsek 2005 182 31 (28–35) Median (25–75 centile range) 32 (30–36) Median (25–75 centile range) NR GnRH-a, HMG, FSH IVF, ICSI post-ET day 11 Immunoradi-ometric Hauzman 2005 112 31.1 ± 3.8 Mean ± SD 30.9 ± 3.5 Mean ± SD male/tubal/ unexplained GnRH-a, HMG, FSH IVF, ICSI on day 1 and on the day of oocyte pickup Immunoradi-ometric Vujisic 2002 33 34 (28–42) Median (range) 35 (31–42) Median (range) Tubal factor/ Unexplained Male factor GnRH-a, HMG IVF on the day of human chorionic gonadotropin (hCG) administration and on the day of ET enzyme immunoassay Baalbergen 2000 44 33.0 (27–40) Median (range) 32.5 (24–41) Median (range) NR GnRH-a, HMG IVF before OPU, 14 days after ET (day ET + 14) and, after the establishment of a clinical pregnancy, on day ET + 21 enzyme immunoassay Tavmergen 2001 75 31.54 ± 0.69 Mean ± SEM 32.6 ± 0.77 Mean ± SEM Male factor, Idiopathic, Tubal, Tubal + male factor GnRH-a, HMG, FSH ICSI on the day before and on the day of HCG administration, and on the day of oocyte retrieval Chemilumine-scence Brandenber-ger 1998 86 34 (26–38) Median (range) 34 (25–41) Median (range) NR GnRH-a, HMG IVF 2 and/or 3 days before OPU (day hCG/hCG-1), on the day of OPU, and on the day of ET Immunoradi-ometric Chryssikop-oulos 1996 26 31.1 ± 4.3 a Means ± SD NR GnRH-a, FSH, HMG IVF on the day of hCG administration, on the day of oocyte retrieval, and on the day of ET Immunoradi-ometric NR = not report; GnRH-a = gonadotrophin-releasing hormone agonist; HMG = human menopausal gonadotrophin; FSH = Follicle-stimulating hormone; IVF = in vitro fertilization; ICSI = Intracytoplasmic sperm injection; ET = embryos transferred. a The data showed the age of the total population. Table 2 The NOS quality assessment of the included studies Studies Score for Selection Score for Comparability Score for Outcome Aggregate score Quality Item 1 Item 2 Item 3 Item 4 Item 1 Item 2 Item 1 Item 2 Item 3 Urbancsek 2005 0 0 1 0 1 1 1 1 1 6 High Hauzman 2005 1 1 1 0 1 1 1 1 1 8 High Vujisic 2002 1 1 1 0 0 1 1 1 1 7 High Tavmergen 2001 0 0 1 0 1 1 1 1 1 6 High Baalbergen 2000 1 1 0 0 0 1 1 1 1 6 High Brandenberger 1998 1 1 1 0 0 1 1 1 0 6 High Chryssikopoulos 1996 1 1 0 0 0 1 1 1 1 6 High NOS: Newcastle-Ottawa scale The correlation between serum Ca-125 level before ET and clinical pregnancy in IVF A total of 349 patients in 6 studies reported the correlation between serum Ca-125 level defore ET and clinical pregnancy in IVF, including 132 clinical pregnant and 217 nonpregnant patients [ 11 – 13 , 15 – 17 ]. When there were multiple blood sample collection times, we considered the values of the closest to the day of ET. The meta-analysis showed that there was no significant difference in the serum Ca-125 level before ET between clinical pregnant group and nonpregnant group (SMD 0.72; 95% CI [0.01, 1.43], P = 0.05, I 2 = 88%; Fig. 2 ). The correlation between serum Ca-125 level after ET and clinical pregnancy in IVF A total of 229 patients in 2 studies reported the correlation between serum Ca-125 level after ET and clinical pregnancy in IVF, including 162 clinical pregnant and 67 nonpregnant patients [ 14 , 17 ]. The result showed that the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group (SMD 0.39; 95% CI [0.09, 0.69], P = 0.01, I 2 = 0%; Fig. 3 ). The correlation between serum Ca-125 level before ET and clinical pregnancy in Patients without endometriosis in IVF Considering that Ca-125 concentrations are known to be elevated in endometriosis [ 18 ], We excluded studies that might include patients with endometriosis [ 11 , 16 ] before ET. The result showed that there was no significant difference in the serum Ca-125 level between clinical pregnant group and nonpregnant group (SMD 0.31; 95% CI [-0.53, 1.16], P = 0.47, I 2 = 89%; Fig. 4 ). Subgroup analysis Before embryo transfer, two studies detected serum Ca-125 level by enzyme immunoassay [15,17], whereas three studies used Immunoradiometric methods [11,12,16], and the remain one used Chemiluminescence [13]. Subgroup analysis showed Ca-125 level was significantly higher in the clinical pregnant group than in the nonpregnant group by Chemiluminescence (SMD 1.49; 95% CI [0.97, 2.01], P <0.001, 1 study) or Immunoradiometric methods (SMD 1.12; 95% CI [0.18, 2.05], P =0.02, 3 study), but not in the enzyme immunoassay subgroup (SMD -0.34; 95% CI [-0.83, 0.14], P =0.16, 2 study) (Fig 5). Sensitivity analysis and publication bias Considering that the number of the included studies on Ca-125 level after ET was small, we didn’t conduct sensitivity analyses about it. We performed a sensitivity analysis for the Ca-125 level before ET, and found that Ca-125 level before ET was significantly higher in the clinical pregnant group compared with the nonpregnant group when the study by Baalbergen et al. [17] or Vujisic et al. [15] was excluded. In addition, the conclusion on Ca-125 level before ET also changed when we used different models. There were insufficient data for any publication bias analysis. Discussion This meta-analysis aimed to assess the correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization. Before ET, our meta-analysis showed that there was no significant correlation between serum Ca-125 level and clinical pregnancy in IVF, and the same conclusion was also reached in patients without endometriosis; After ET, the result revealed that there was a significant correlation between serum Ca-125 level and clinical pregnancy in IVF. Although we included women who underwent IVF treatment with or without ICSI, five studies excluded patients with endometriosis [ 12 – 15 , 17 ]. It is likely that Ca-125 concentrations are known to be elevated in endometriosis [ 18 ]; therefore, evidence related to the correlation between serum Ca-125 level in endometriosis and pregnant outcome is still lacking, which may reduce the overall applicability of the evidence. We found that there was significant heterogeneity among studies on the outcome of correlation between serum Ca-125 level before ET and clinical pregnancy in IVF (I 2 = 88%). The sources of heterogeneity might be explained by the differences in the methods of ca-125 detected, the time of sample collected, the inclusion and exclusion of patiens (eg. Some studies excluded patients with endometriosis), and the ovarian stimulation protocols. However, we found no reduction in heterogeneity when we excluded studies that might include patiens with endimeriosis, and the same as we only included studies which used Immunoradiometric methods. This suggests that patient inclusion criteria or testing methods are not at least the only sources of heterogeneity. The sensitivity analysis found that the conclusion where there was no significant difference in the serum Ca-125 level before ET between clinical pregnant group and nonpregnant group had changed after excluding the study by Baalbergen et al. or Vujisic et al [15,17], which may be attributed to Ca-125 assay used, both of them used enzyme immunoassay. Unfortunately, enzyme immunoassay is a less susceptive detection methods of Ca-125 comparad with Immunoradiometric and Chemiluminescence methods [ 19 ]. In addition, subgroup analyses showed that there was a significant correlation between serum Ca-125 level before ET and clinical pregnancy in IVF by Immunoradiometric or Chemiluminescence methods; which indicated that detecting Ca-125 using more sensitive assays can better predict pregnant outcome in IVF. We should be cautious to assess the impact of conclusion on Ca-125 level before ET, because we used randomized effect model that dealt with the heterogeneity of data by increasing the weight of small sample data and reducing the weight of large sample data [ 20 ], and the direction of effect altered when we used fixed effect model; Therefore, further studies should increase sample sizes to reduce accidental errors. First of all, the concentration of serum Ca-125 fluctuated throughout the menstrual cycle. The different observations reveal that Ca-125 levels were significantly elevated during menstruation [ 21 , 22 ]. The reason may be that the endometrium was destroyed during menstruation, which caused Ca-125 to be released into the blood; So Ca-125 was somehow associated with the integrity of the endometrium. Secondly, immunohistochemistry of Ca-125 showed that the concentration of Ca-125 in endometrium was 20-fold higher than that in ovary and 2-fold higher than those in fallopian tubes; In addition, only in the endometrium Ca-125 content has a significant circulatory change [ 23 ]. This suggests that endometrium might be the main source of serum Ca-125, and therefore, an endocrine or a paracrine function would be possible. However, our meta-analysis showed no correlation between serum Ca-125 level before ET and clinical pregnancy in IVF, the same as patients without endometriosis. The reasons for this phenomenon may be as follows: (1) Although there is some evidence that endometrium is one of the sources of serum Ca-125, other factors (eg. Endometrial thickness, endometrial volume, endometrial pattern, pulsatility index and resistance index of the subendometrial blood flow) play a greater role in the endometrial receptivity [ 24 ]; (2) The achievement of a clinical pregnancy in IVF results from too many factors, such as maternal age and embryo quality, so serum CA-125 level can not directly predict the success of pregnancy in an IVF cycle; (3) Despite the controversy, studies have shown changes of Ca-125 concentration during ovarian stimulation [ 16 , 25 ], hence, changes of the serum Ca-125 level due to ovarian stimulation may mask the changes caused by endometrium. After ET, the meta analysis showed that the serum Ca-125 level had a small but significantly increase in the clinical pregnant group than in the nonpregnant group. In the first trimester of pregnancy, serum Ca-125 level rised in patients with vaginal bleeding and miscarriage [ 26 , 27 ]. Therefore, the increase of Ca-125 concentration might indicate the destruction of decidua. However, these observations were all made over 5 weeks gestation. In our meta analysis, there were 2 studies which reported the correlation between serum Ca-125 level after ET and clinical pregnancy in IVF, one study detected Ca-125 on or closer to post-ET day 11, the another one was on 14 days after ET. Hence, higher Ca-125 levels might reflect a successful interaction between the embryo and the endometrium in that time period. This study has several limitations. Firstly, we conducted a comprehensive search of the corrlation between serum Ca-125 level and clinical pregnancy in IVF. However, It is possible that our findings on serum Ca-125 level before ET cannot be interpreted as truly negative because of the small sample sizes and significant heterogeneity between studies; Secondly, the evidence on Ca-125 level after ET between clinical pregnancy and nonpregnancy is limited, as only two trials were included for our investigation, and needs to be further investigated; Third, publication bias could not be assessed besause of the limited number of studies; Fourth, four studies didn’t directly report mean and its SD, and we employed the method recommended by Wan et al to handle the dates [ 10 ], and it may result certain deviation. Conclusion Our meta-analysis was the first systematic review to confirm the correlation between serum Ca-125 and clinical pregnancy in IVF. This meta-analysis revealed that there was no significant correlation between serum Ca-125 level before ET and clinical pregnancy in IVF, and the same conclusion was also reached in patients without endometriosis; After ET, the Ca-125 level had a small but significantly increase in the clinical pregnant group than in the nonpregnant group, and it might reflect a successful interaction between the embryo and the endometrium in that time period. Declarations Abbreviations: IVF:in vitro fertilization, ET:embryos transferred, Ca-125:Cancer antigen 125, ICSI:Intracytoplasmic sperm injection. Acknowledgements Not applicable. Funding There was no funding source in this study. Availability of data and material All data generated or analysed during this study are included in this published article. Authors’ contributions Took part in the literature search, study characteristics assessment, study quality assessment: WXL, LZ, ZH; took part in the data analysis, interpretation of statistics: SC, TT; conducted the preliminary idea and drafted the paper: XQ; critically reviewed the paper：XQ, LRZ. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Diedrich K, Fauser BC, Devroey P, et al. The role of the endometrium and embryo in human implantation. Hum Reprod Update; 2007;13:365-77. Riad ON, Hak AA. Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination. Gynecol Endocrinol. 2014;30:70-3. Foster W. Diagnosing endometriosis: CA125 rules in, but not out. BJOG. 2016;123:1769. Wang J, Gao J, Yao H, et al. 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CA-125 is present in significant concentrations in periovulatory follicles of in vitro fertilization patients. Fertil Steril. 1992;57:377-80. Fiegler P, Katz M, Kaminski K, et al. Clinical value of a single serum CA-125 level in women with symptoms of imminent abortion during the first trimester of pregnancy. J Reprod Med. 2003;48:982-8. Scarpellini F, Mastrone M, Sbracia M, et al. Serum CA 125 and first trimester abortion. Int J Gynaecol Obstet. 1995;49:259-64. Supplementary Files PRISMAChecklist.doc Additionalfile1.doc Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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University First Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"qi","middleName":"","lastName":"xi","suffix":""}],"badges":[],"createdAt":"2019-12-11 12:20:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.2.18753/v1","doiUrl":"https://doi.org/10.21203/rs.2.18753/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":260301,"identity":"ea73c1e5-8b5c-4fa2-9b26-6e837b2aea0a","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1707448,"visible":true,"origin":"","legend":"The details of study selection","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Fig 1.jpg"},{"id":260303,"identity":"f93300bf-c837-4779-a2f5-4fc6eb005af2","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1988640,"visible":true,"origin":"","legend":"Forest plot of comparison: Clinical pregnant group vs Nonpregnant group, Outcome: serum Ca-125 level before embryos transferred.\nFig 3: Forest plot of comparison: Clinical pregnant group vs Nonpregnant group, Outcome: serum Ca-125 level after embryos transferred.","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Fig 2.jpg"},{"id":260304,"identity":"5e6d024d-5cfd-478e-8517-4e9f29203c42","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1755770,"visible":true,"origin":"","legend":"Forest plot of comparison: Clinical pregnant group vs Nonpregnant group, Outcome: serum Ca-125 level after embryos transferred.","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Fig 3.jpg"},{"id":260305,"identity":"7dddf099-8ede-4b58-982e-40fced9ab333","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1887158,"visible":true,"origin":"","legend":"Forest plot of comparison: Clinical pregnant group vs Nonpregnant group in patients without endometriosis, Outcome: serum Ca-125 level before embryos transferred.","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Fig 4.jpg"},{"id":260306,"identity":"1bac1180-c5b6-4328-8062-a7074d344528","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2454054,"visible":true,"origin":"","legend":"Forest plot of comparison: Clinical pregnant group vs Nonpregnant group, Outcome: Subgroup analysis of different methods of Ca-125 detected before embryos transferred.","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Fig 5.jpg"},{"id":13481868,"identity":"53f72654-6a60-4a7b-b27e-9275e87f44f8","added_by":"auto","created_at":"2021-09-16 21:49:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":624314,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9371/v1/178815d9-5aba-410f-b1a1-01d6762b6a62.pdf"},{"id":260302,"identity":"265fcdcf-580f-46ce-8c05-844ae1e2381a","added_by":"auto","created_at":"2019-12-13 18:22:19","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":59904,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAChecklist.doc","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/PRISMA Checklist.doc"},{"id":260300,"identity":"1b0075bf-eeb7-4b38-9f58-17d1c3598931","added_by":"auto","created_at":"2019-12-13 18:22:18","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":66678,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.doc","url":"https://assets-eu.researchsquare.com/files/e907c0a0-25f2-4572-ad16-caae30850bd1/v1/Additional file 1.doc"}],"financialInterests":"","formattedTitle":"The correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization (IVF): A meta-analysis","fulltext":[{"header":" Background","content":" \u003cp\u003ePrediction of clinical pregnancy is rapidly becoming an important objective in in vitro fertilization (IVF). on the one hand, pregnancy in IVF have a higher risk of obstetric and perinatal complications than spontaneous pregnancies; on the other hand, most IVF patients are successfully fertilized and get embryos transferred (ET), but only a relatively small percentage of transferred embryos actually implant and develop into viable pregnancies.\u003c/p\u003e \u003cp\u003eSuccessful implantation after ET has been shown to depend on two factors: good quality of transferred embryos; and well-prepared endometrium [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. At present, endometrial receptivity is judged generally by Ultrasound parameters, such as endometrial thickness and pattern, and Doppler study of uterine arteries and subendometrial flow [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, morphological assessments of endometrial receptivity have been subjective and disregards embryo interaction [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The idea that some objective parameters could ascertain the endometrial receptivity in a non-invasive and cost efficient way in an Assisted Reproductive Technology cycles is interesting and has important clinical significance.\u003c/p\u003e \u003cp\u003eCancer antigen 125 (Ca-125) is a cell-surface antigenic determinant on a high molecular-weight glycoprotein, as a well-established marker it is mainly used to diagnose endometriosis and epithelial cell ovarian cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Ca-125 can be measured in the serum. Although the primary source of serum Ca-125 levels is controversial, some studies have found that endometrium may be one of the sources of serum Ca-125: (1) Ng et al. detected Ca-125 in the uterine flushings fluid [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]; (2) Ca-125 was detected in vitro endometrial tissue culture medium [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; (3) The serum Ca-125 level was increased due to endometrial destruction during menstrual period [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. If endometrium is the main source of serum Ca-125, then Ca-125 may be used as an indicator of endometrial receptivity in IVF. In addition, several studies had investigated the role of serum CA-125 in clinical pregnancy of patients undergoing IVF; however, their conclusions were inconsistent. Therefore, we conducted a meta-analysis to evaluate the correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eThis study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [8].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion criteria and inclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion and exclusion criteria were established prior to literature search. This meta-analysis focused on the correlation between serum Ca-125 level and clinical pregnancy in patients underging IVF with or without Intracytoplasmic sperm injection (ICSI). The inclusion criterias were as follows: (1) Case-control, cohort or cross-sectional studies; (2) All patients were women who underwent IVF treatment with or without ICSI, regardless of the ovarian stimulation protocol employed; (3) Study provided data on serum Ca-125 levels in clinical pregnant and nonpregnant groups, no limit was given for Ca-125 measurement methods; (4) Clinical pregnancy was clarified as a positive heart action or Intrauterine pregnancy sac in transvaginal ultrasound after ET; (5) When multiple studies may contain the same study population, only the most complete study was included; (6) Available full text in English. We excluded: (1) Study contained overlapping or insufficient data; (2) Reviews, editorials, commentaries, animal experiments, and individual case reports.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch Strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies in the databases of Mediline OvidSP, EMBASE OvidSP and Cochrane (CENTRAL Central Register of Controlled Trials) were systematically reviewed until October 25, 2019. The search strategy was shown in Additional file 1. We also manually searched the references of the included studies and reviews for additional studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy selection and quality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter importing the search results into EndNote X9, duplicated studies were excluded. Two review authors (Li Z and Wang XL) independently screened the studies based on both the titles and abstracts of the selected studies, then retrieved the full text articles for those relevant and determine whether it meets the inclusion criteria. The quality of the included studies were assessed using the Newcastle\u0026ndash;Ottawa scale (NOS) for cohort studies, which evaluates studies according to the following three domains: selection of subjects, comparability, and assessment of the results [9]. We rated the studies as \u0026lsquo;high quality\u0026rsquo; if they had a score ≧5; otherwise, the studies were rated as \u0026lsquo;low quality\u0026rsquo;. A discrepancies between Li and Wang was resolved through discussion and consensus with a third reviewer (Zhang Han).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExtraction of data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo researchers (Wang XL, Li Z) extracted data independently using a pre-designed data extraction table. A third review author (Zhang Han) resolved any disagreements between the two researchers. We extracted data on study design, number of participants, patients\u0026rsquo; age, publication year, included and excluded criteria of patients, ovarian stimulation protocols, and time of blood sample collection, metholds of Ca-125 detected, the mean and standerd deviation (SD) of serum Ca-125 level (In case no means and SD were reported, we used medians, interquartile ranges (IQRs), or ranges to estimate them based on the methods advocated by Wan et al) [10].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSynthesis of results and assessment of heterogeneity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll analyses were performed using Review Manager 5.0 software. Statistical\u0026nbsp;heterogeneity was tested with the Q test (chi‐square) and calculated I\u003csup\u003e2\u003c/sup\u003e values. When chi-square test p\u0026lt;0.1 and the I\u003csup\u003e2\u003c/sup\u003e\u0026gt;50%, we thought that there was significant heterogeneity among studies, in which case, we used the randomized effect model, otherwise the fixed effects model was used. We assessed clinical heterogeneity by performing subgroup analyses for different detection methods of Ca-125.\u0026nbsp;We expected the different metholds of Ca-125 detected among studies, so the serum Ca-125 level was shown as standardized mean difference (SMD) with corresponding 95% confidence intervals (95% CIs). The P \u0026lt; 0.05 values could be considered as statistically significant.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis and assessment of publication bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate stability and reliability of the meta-analysis, we performed sensitivity analysis whereby: 1. Assessed the influence of each individual study on the pooled SMD by removing each study individually; 2. Different models (fixed effect model or randomized effect model) were used. If enough studies (10 or more) were found, we planned to use a funnel plot to explore the possibility of publication bias.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Result","content":" \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eThe preliminarily database search retrieved 185 citations. After the initial exclusion of 32 duplicate articles, the remaining 157 articles were screened based on title and abstract. Then we retrieved 32 full-text articles reading, of which we excluded 25. Finally, seven articles were included in our analysis. No articles were included by manual search. The details of study selection was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCharacteristics and quality assessment of the included studies\u003c/span\u003e \u003c/p\u003e \u003cp\u003eThe various baseline characteristics of including studies were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 7 studies involving 558 patients were included, and the sample sizes of included studies were ranged from 33 to 182. Three studies directly reported mean and SD [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], while data for 4 studies [\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] that did not were transformated according to the method proposed by Wan et al [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].Two studies detected serum Ca-125 by enzyme immunoassay method [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], while four studies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] used Immunoradiometric methods and only one [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] used Chemiluminescence method. The quality assessment of the included studies was summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. All studies had a score\u0026thinsp;≧\u0026thinsp;5 and were rated as \u0026lsquo;high quality\u0026rsquo;.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eThe various baseline characteristics of including studies\u003c/span\u003e\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eStudy auther, year\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of pationts in study\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eAge (years)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCauses of infertility\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eOvarian stimulati-on protocols\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eART protocol\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eSample time\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMetholds of CA-125\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003edetection\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eClinical pregnant\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNonpregnant\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eUrbancsek 2005\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e182\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e31 (28\u0026ndash;35)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (25\u0026ndash;75 centile range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e32 (30\u0026ndash;36)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (25\u0026ndash;75 centile range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eNR\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG, FSH\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF, ICSI\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003epost-ET day 11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eImmunoradi-ometric\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHauzman 2005\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e112\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003emale/tubal/\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eunexplained\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG, FSH\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF, ICSI\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eon day 1 and on the day of oocyte pickup\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eImmunoradi-ometric\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVujisic 2002\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e34 (28\u0026ndash;42)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e35 (31\u0026ndash;42)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eTubal factor/\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eUnexplained Male factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eon the day of human chorionic gonadotropin (hCG) administration and on the day of ET\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eenzyme immunoassay\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBaalbergen 2000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e44\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e33.0 (27\u0026ndash;40)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e32.5 (24\u0026ndash;41)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eNR\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003ebefore OPU, 14 days after ET (day ET\u0026thinsp;+\u0026thinsp;14) and, after the establishment of a clinical pregnancy, on day ET\u0026thinsp;+\u0026thinsp;21\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eenzyme immunoassay\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTavmergen 2001\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e75\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e31.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMean \u0026plusmn; SEM\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e32.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMean \u0026plusmn; SEM\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eMale factor, Idiopathic, Tubal, Tubal\u0026thinsp;+\u0026thinsp;male factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG, FSH\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eICSI\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eon the day before and on the day of HCG administration, and on the day of oocyte retrieval\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eChemilumine-scence\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBrandenber-ger 1998\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e86\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e34 (26\u0026ndash;38)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e34 (25\u0026ndash;41)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eNR\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, HMG\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 and/or 3 days before OPU\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(day hCG/hCG-1), on the day of OPU, and on the day of ET\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eImmunoradi-ometric\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eChryssikop-oulos 1996\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMeans\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eNR\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eGnRH-a, FSH, HMG\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIVF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eon the day of hCG administration, on the day of oocyte retrieval, and on the day of ET\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eImmunoradi-ometric\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNR\u0026thinsp;=\u0026thinsp;not report; GnRH-a\u0026thinsp;=\u0026thinsp;gonadotrophin-releasing hormone agonist; HMG\u0026thinsp;=\u0026thinsp;human menopausal gonadotrophin; FSH\u0026thinsp;=\u0026thinsp;Follicle-stimulating hormone; IVF\u0026thinsp;=\u0026thinsp;in vitro fertilization; ICSI\u0026thinsp;=\u0026thinsp;Intracytoplasmic sperm injection; ET\u0026thinsp;=\u0026thinsp;embryos transferred. \u003csup\u003ea\u003c/sup\u003eThe data showed the age of the total population.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eThe NOS quality assessment of the included studies\u003c/span\u003e\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eStudies\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eScore for Selection\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eScore for Comparability\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eScore for Outcome\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eAggregate score\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eQuality\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 1\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 2\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 3\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 4\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 1\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 2\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 1\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 2\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003eItem 3\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eUrbancsek 2005\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHauzman 2005\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVujisic 2002\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTavmergen 2001\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBaalbergen 2000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBrandenberger 1998\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eChryssikopoulos 1996\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cdiv class=\"SimplePara\"\u003eHigh\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eNOS: Newcastle-Ottawa scale\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eThe correlation between serum Ca-125 level before ET and clinical pregnancy in IVF\u003c/span\u003e \u003c/p\u003e \u003cp\u003eA total of 349 patients in 6 studies reported the correlation between serum Ca-125 level defore ET and clinical pregnancy in IVF, including 132 clinical pregnant and 217 nonpregnant patients [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. When there were multiple blood sample collection times, we considered the values of the closest to the day of ET. The meta-analysis showed that there was no significant difference in the serum Ca-125 level before ET between clinical pregnant group and nonpregnant group (SMD 0.72; 95% CI [0.01, 1.43], P\u0026thinsp;=\u0026thinsp;0.05, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;88%; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eThe correlation between serum Ca-125 level after ET and clinical pregnancy in IVF\u003c/span\u003e \u003c/p\u003e \u003cp\u003eA total of 229 patients in 2 studies reported the correlation between serum Ca-125 level after ET and clinical pregnancy in IVF, including 162 clinical pregnant and 67 nonpregnant patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The result showed that the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group (SMD 0.39; 95% CI [0.09, 0.69], P\u0026thinsp;=\u0026thinsp;0.01, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eThe correlation between serum Ca-125 level before ET and clinical pregnancy in Patients without endometriosis in IVF\u003c/span\u003e \u003c/p\u003e \u003cp\u003eConsidering that Ca-125 concentrations are known to be elevated in endometriosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], We excluded studies that might include patients with endometriosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] before ET. The result showed that there was no significant difference in the serum Ca-125 level between clinical pregnant group and nonpregnant group (SMD 0.31; 95% CI [-0.53, 1.16], P\u0026thinsp;=\u0026thinsp;0.47, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;89%; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore\u0026nbsp;embryo transfer, two studies detected serum Ca-125 level by enzyme immunoassay [15,17], whereas three studies used Immunoradiometric methods [11,12,16], and the remain one used Chemiluminescence [13]. Subgroup analysis showed Ca-125 level was significantly higher in the clinical pregnant group than in the nonpregnant group by Chemiluminescence (SMD 1.49; 95% CI [0.97, 2.01], P \u0026lt;0.001, 1 study) or Immunoradiometric methods (SMD 1.12; 95% CI [0.18, 2.05], P =0.02, 3 study), but not in the enzyme immunoassay subgroup (SMD -0.34; 95% CI [-0.83, 0.14], P =0.16, 2 study) (Fig 5).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis and publication bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsidering that the number of the included studies on Ca-125 level after ET was small, we didn\u0026rsquo;t conduct sensitivity analyses about it. We performed a sensitivity analysis for the Ca-125 level before ET, and found that Ca-125 level before ET was significantly higher in the clinical pregnant group compared with the nonpregnant group when the study by Baalbergen et al. [17] or Vujisic et al. [15] was excluded. In addition, the conclusion on Ca-125 level before ET also changed when we used different models. There were insufficient data for any publication bias analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":" \u003cp\u003eThis meta-analysis aimed to assess the correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization. Before ET, our meta-analysis showed that there was no significant correlation between serum Ca-125 level and clinical pregnancy in IVF, and the same conclusion was also reached in patients without endometriosis; After ET, the result revealed that there was a significant correlation between serum Ca-125 level and clinical pregnancy in IVF.\u003c/p\u003e \u003cp\u003eAlthough we included women who underwent IVF treatment with or without ICSI, five studies excluded patients with endometriosis [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. It is likely that Ca-125 concentrations are known to be elevated in endometriosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]; therefore, evidence related to the correlation between serum Ca-125 level in endometriosis and pregnant outcome is still lacking, which may reduce the overall applicability of the evidence.\u003c/p\u003e \u003cp\u003eWe found that there was significant heterogeneity among studies on the outcome of correlation between serum Ca-125 level before ET and clinical pregnancy in IVF (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;88%). The sources of heterogeneity might be explained by the differences in the methods of ca-125 detected, the time of sample collected, the inclusion and exclusion of patiens (eg. Some studies excluded patients with endometriosis), and the ovarian stimulation protocols. However, we found no reduction in heterogeneity when we excluded studies that might include patiens with endimeriosis, and the same as we only included studies which used Immunoradiometric methods. This suggests that patient inclusion criteria or testing methods are not at least the only sources of heterogeneity. The sensitivity analysis found that the conclusion where there was no significant difference in the serum Ca-125 level before ET between clinical pregnant group and nonpregnant group had changed after excluding the study by Baalbergen et al. or Vujisic et al [15,17], which may be attributed to Ca-125 assay used, both of them used enzyme immunoassay. Unfortunately, enzyme immunoassay is a less susceptive detection methods of Ca-125 comparad with Immunoradiometric and Chemiluminescence methods [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In addition, subgroup analyses showed that there was a significant correlation between serum Ca-125 level before ET and clinical pregnancy in IVF by Immunoradiometric or Chemiluminescence methods; which indicated that detecting Ca-125 using more sensitive assays can better predict pregnant outcome in IVF. We should be cautious to assess the impact of conclusion on Ca-125 level before ET, because we used randomized effect model that dealt with the heterogeneity of data by increasing the weight of small sample data and reducing the weight of large sample data [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and the direction of effect altered when we used fixed effect model; Therefore, further studies should increase sample sizes to reduce accidental errors.\u003c/p\u003e \u003cp\u003eFirst of all, the concentration of serum Ca-125 fluctuated throughout the menstrual cycle. The different observations reveal that Ca-125 levels were significantly elevated during menstruation [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The reason may be that the endometrium was destroyed during menstruation, which caused Ca-125 to be released into the blood; So Ca-125 was somehow associated with the integrity of the endometrium. Secondly, immunohistochemistry of Ca-125 showed that the concentration of Ca-125 in endometrium was 20-fold higher than that in ovary and 2-fold higher than those in fallopian tubes; In addition, only in the endometrium Ca-125 content has a significant circulatory change [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This suggests that endometrium might be the main source of serum Ca-125, and therefore, an endocrine or a paracrine function would be possible. However, our meta-analysis showed no correlation between serum Ca-125 level before ET and clinical pregnancy in IVF, the same as patients without endometriosis. The reasons for this phenomenon may be as follows: (1) Although there is some evidence that endometrium is one of the sources of serum Ca-125, other factors (eg. Endometrial thickness, endometrial volume, endometrial pattern, pulsatility index and resistance index of the subendometrial blood flow) play a greater role in the endometrial receptivity [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]; (2) The achievement of a clinical pregnancy in IVF results from too many factors, such as maternal age and embryo quality, so serum CA-125 level can not directly predict the success of pregnancy in an IVF cycle; (3) Despite the controversy, studies have shown changes of Ca-125 concentration during ovarian stimulation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], hence, changes of the serum Ca-125 level due to ovarian stimulation may mask the changes caused by endometrium.\u003c/p\u003e \u003cp\u003eAfter ET, the meta analysis showed that the serum Ca-125 level had a small but significantly increase in the clinical pregnant group than in the nonpregnant group. In the first trimester of pregnancy, serum Ca-125 level rised in patients with vaginal bleeding and miscarriage [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, the increase of Ca-125 concentration might indicate the destruction of decidua. However, these observations were all made over 5 weeks gestation. In our meta analysis, there were 2 studies which reported the correlation between serum Ca-125 level after ET and clinical pregnancy in IVF, one study detected Ca-125 on or closer to post-ET day 11, the another one was on 14 days after ET. Hence, higher Ca-125 levels might reflect a successful interaction between the embryo and the endometrium in that time period.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Firstly, we conducted a comprehensive search of the corrlation between serum Ca-125 level and clinical pregnancy in IVF. However, It is possible that our findings on serum Ca-125 level before ET cannot be interpreted as truly negative because of the small sample sizes and significant heterogeneity between studies; Secondly, the evidence on Ca-125 level after ET between clinical pregnancy and nonpregnancy is limited, as only two trials were included for our investigation, and needs to be further investigated; Third, publication bias could not be assessed besause of the limited number of studies; Fourth, four studies didn\u0026rsquo;t directly report mean and its SD, and we employed the method recommended by Wan et al to handle the dates [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and it may result certain deviation.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eOur meta-analysis was the first systematic review to confirm the correlation between serum Ca-125 and clinical pregnancy in IVF. This meta-analysis revealed that there was no significant correlation between serum Ca-125 level before ET and clinical pregnancy in IVF, and the same conclusion was also reached in patients without endometriosis; After ET, the Ca-125 level had a small but significantly increase in the clinical pregnant group than in the nonpregnant group, and it might reflect a successful interaction between the embryo and the endometrium in that time period.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e IVF:in vitro fertilization, ET:embryos transferred, Ca-125:Cancer antigen 125, ICSI:Intracytoplasmic sperm injection.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding source in this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTook part in the literature search, study characteristics assessment, study quality assessment: WXL, LZ, ZH; took part in the data analysis, interpretation of statistics: SC, TT; conducted the preliminary idea and drafted the paper: XQ; critically reviewed the paper：XQ, LRZ.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDiedrich K, Fauser BC, Devroey P, et al. The role of the endometrium and embryo in human implantation. Hum Reprod Update; 2007;13:365-77.\u003c/li\u003e\n\u003cli\u003eRiad ON, Hak AA. Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination. Gynecol Endocrinol. 2014;30:70-3.\u003c/li\u003e\n\u003cli\u003eFoster W. Diagnosing endometriosis: CA125 rules in, but not out. BJOG. 2016;123:1769.\u003c/li\u003e\n\u003cli\u003eWang J, Gao J, Yao H, et al. Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis. Tumour Biol. 2014; 35:6127-38.\u003c/li\u003e\n\u003cli\u003eNg EH, Laird SM, Li TC, et al. Concentrations of endometrial protein PP 14 and CA-125 in uterine flushings performed in natural and stimulated cycles. Hum Reprod. 2004;19:905-10.\u003c/li\u003e\n\u003cli\u003eBrumsted JR, McBean JH, Deaton JL, et al. CA-125 secretion by luteal phase endometrium in vitro. Hum Reprod. 1990;5:682-4.\u003c/li\u003e\n\u003cli\u003eMcLemore MR, Aouizerat BE, Lee KA, et al. A comparison of the cyclic variation in serum levels of CA125 across the menstrual cycle using two commercial assays. Biol Res Nurs. 2012; 14:250-6.\u003c/li\u003e\n\u003cli\u003eLiberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.\u003c/li\u003e\n\u003cli\u003eWells GA, Shea B, O\u0026rsquo;Connell D, et al. The Newcastle\u0026ndash; Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. http://www.ohri.ca/programs/clinical_ epidemiology/oxford.asp. Accessed 15 Mar 2015. Biol Res Nurs. 14:250-6.\u003c/li\u003e\n\u003cli\u003eWan X, Wang W, Liu J, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014; 14:135.\u003c/li\u003e\n\u003cli\u003eChryssikopoulos A, Mantzavinos T, Kanakas N, et al. Correlation of serum and follicular fluid concentrations of placental protein 14 and CA-125 in in vitro fertilization-embryo transfer patients. Fertil Steril. 1996;66:599-603.\u003c/li\u003e\n\u003cli\u003eHauzman EE, Lagarde AR, Nagy K, et al. Prognostic value of serum CA-125 measurements on stimulation day 1 and on the day of oocyte pickup in the prediction of IVF treatment outcome. J Assist Reprod Genet. 2005;22:265-8.\u003c/li\u003e\n\u003cli\u003eTavmergen E, Sendag F, Goker ENT, et al. Value of serum CA-125 concentrations as predictors of pregnancy in assisted reproduction cycles. Human Reproduction. 2001;16:1129-34.\u003c/li\u003e\n\u003cli\u003eUrbancsek J, Hauzman EE, Lagarde AR, et al. Serum CA-125 levels in the second week after embryo transfer predict clinical pregnancy. 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Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:202-23.\u003c/li\u003e\n\u003cli\u003eMordel N, Anteby SO, Zajicek G, et al. CA-125 is present in significant concentrations in periovulatory follicles of in vitro fertilization patients. Fertil Steril. 1992;57:377-80.\u003c/li\u003e\n\u003cli\u003eFiegler P, Katz M, Kaminski K, et al. Clinical value of a single serum CA-125 level in women with symptoms of imminent abortion during the first trimester of pregnancy. J Reprod Med. 2003;48:982-8.\u003c/li\u003e\n\u003cli\u003eScarpellini F, Mastrone M, Sbracia M, et al. Serum CA 125 and first trimester abortion. Int J Gynaecol Obstet. 1995;49:259-64.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"in vitro fertilization, Ca-125, pregnancy outcome, embryos transferred","lastPublishedDoi":"10.21203/rs.2.18753/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.18753/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Several studies had investigated the role of serum Ca-125 in clinical pregnancy of patients undergoing in vitro fertilization (IVF); however, their conclusions had been inconsistent. This study aimed to evaluate the correlation between serum Ca-125 level and clinical pregnancy in IVF.\u003c/p\u003e\u003cp\u003eMethods We systematically review the studies in the databases of Mediline OvidSP, EMBASE OvidSP and Cochrane (CENTRAL Central Register of Controlled Trials). Studies on the correlation between serum Ca-125 level and clinical pregnancy in patients underging IVF with or without Intracytoplasmic sperm injection (ICSI) were considered. The pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) was used in the analysis.\u003c/p\u003e\u003cp\u003eResults Seven studies involving 558 patients were included. The meta-analysis showed that there was no significant difference in the serum Ca-125 level before embryo transfer (ET) between clinical pregnant group and nonpregnant group (SMD 0.72; 95% CI [0.01, 1.43], P = 0.05, I 2 = 88%), and the same conclusion was also reached in patients without endometriosis (SMD 0.31; 95% CI [-0.53, 1.16], P = 0.47, I 2 = 89%); However, after embryo transfer, the result showed that the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group (SMD 0.39; 95% CI [0.09, 0.69], P = 0.01, I 2 = 0%).\u003c/p\u003e\u003cp\u003eConclusions Berore ET, there was no significant correlation between serum Ca-125 level and clinical pregnancy in IVF; After ET, the Ca-125 level has a small but significantly increase in the clinical pregnant group than in the nonpregnant group, and it might reflect a successful interaction between the embryo and the endometrium in that time period.\u003c/p\u003e","manuscriptTitle":"The correlation between serum Ca-125 level and clinical pregnancy in in vitro fertilization (IVF): A meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2019-12-13 18:22:17","doi":"10.21203/rs.2.18753/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"df855e0c-e492-4887-bf03-2b7cf7204f68","owner":[],"postedDate":"December 13th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42162,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"","versionOfRecord":[],"versionCreatedAt":"2019-12-13 18:22:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9371","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-9371","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}