Low molecular weight heparin increases clinical pregnancy rate in non-thrombophilic women undergoing assisted reproductive technology

Low molecular weight heparin increases clinical pregnancy rate in non-thrombophilic women undergoing assisted reproductive technology | 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 Article Low molecular weight heparin increases clinical pregnancy rate in non-thrombophilic women undergoing assisted reproductive technology Yaxin Guo, Dan Chen, Wenxuan Li, Mengya Zhao, Enqi Yan, Huizi Jin, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4770813/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 Previously, low molecular weight heparin (LMWH) has shown good anti-thrombotic effects and helped improve pregnancy outcomes for women with thrombotic diseases undergoing assisted reproductive technology (ART), prompting its use in women without thrombotic disease. However, there are few standardized medication guidelines for LMWH use in non-thrombotic patients, and it is unclear whether LMWH truly benefits pregnancy outcomes in these patients. There we want to investigate whether LMWH affects pregnancy outcomes of patients without thrombophilia undergoing ART. Methods A total of 3067 infertile women who were undergoing their fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in the Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in 2019 were finally eligible for this retrospective cohort study, with 119 and 2948 administered with LMWH and without LMWH respectively. Clinical pregnancy rate (CPR) and the secondary outcomes include live birth rate (LBR), miscarriage rate (MR), multiple pregnancy rates (MPR), biochemical pregnancy rate (BPR) and ectopic pregnancy rate (EPR) were compared among these two groups. Results Before adjustment for confounders, MPR (8.4% vs. 3.1%, P = 0.001) and MR (15.1% vs. 6.2%, P <0.001) were higher in the LMWH group while CPR (53.8% vs. 46.8%, P = 0.133), LBR (37.8% vs. 40.5%, P = 0.553), BPR (6.7% vs. 6.0%, P = 0.759) and EPR (0.0% vs. 0.7%, P = 1.000) were similar compared to the control group. To investigate the correlation of LMWH administration, confounding variables were adjusted by multivariable logistic regression model and three Propensity score (PS) methods. In multivariable logistic regression, there were significantly higher CPR (AOR = 1.54; 95% CI, 1.05–2.27; P = 0.027) and MR (AOR = 2.93; 95% CI, 1.73–4.97; P < 0.001) among patients with LMWH, without an increase in LBR (AOR = 1.03; 95% CI, 0.70–1.53; P = 0.877), MPR (AOR = 1.29; 95% CI, 0.59–2.81; P = 0.529), BPR (OR = 1.17, 95% CI, 0.56–2.45; P = 0.674), which were consistent in PS Adjustment, and Inverse Probability of Treatment Weighting using propensity score (IPTW), but not in the Propensity score matching (PSM) (1:1) analysis. Subgroup analyses showed that CPR and MR were increased in the LMWH group in the patients with age ≤ 35 years, body mass index (BMI) ≤ 24 and without recurrent pregnancy loss (RPL). Conclusions Low molecular weight heparin may improve clinical pregnancy but not live birth in non-thrombophilic women undergoing ART. Low molecular weight heparin clinical pregnancy assisted reproductive technology non-thrombophilic Figures Figure 1 Figure 2 INTRODUCTION Low-molecular-weight heparins (LMWHs) are derived from unfractionated heparin through controlled enzymatic or chemical depolymerization processes that yield chains with a mean molecular weight of about 5000 [ 1 ]. LMWH is increasingly being administered to women undergoing assisted reproductive technology (ART) due to its possible role in promoting successful embryo implantation in ART [ 2 ]. However, there is little guidance on the use of LMWH in ART. There is also considerable uncertainty regarding which women might benefit from LMWH and when to administer LMWH. There have been some studies focusing on this issue, especially in patients with recurrent implantation failures (RIF) [ 3 – 5 ]. Qublan et al found that LMWH treatment can improve implantation, pregnancy and live birth rates in women with RIF and thrombophilia without significant maternal-fetal complications. However, two other RCTs took different attitudes toward this, in which LMWH did not lead to statistically better pregnancy outcomes in women with unexplained RIF [ 3 , 5 ]. For patients without RIF, relevant studies are relatively sparse. Noci et al enrolled 172 patients without thrombophilia and observed a trend toward improved pregnancy outcomes with LMWH administration but no significant difference [ 6 ]. Lodigiani et al included 247 patients without severe thrombophilia and found no beneficial effects of LMWH [ 7 ]. In contrast to these small sample size studies andtheir controversial results, it's worth noting that LMWH is widely used in China as well as in other countries as an adjuvant on IVF/ICSI pregnancy in non-thrombophilic women [ 8 ]. In this context, in an attempt to elucidate the efficacy of LMWH in general in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) populations, we conducted the present cohort study aiming to gain insights regarding the impact of empirical LMWH administration from the day of embryo transfer on maternal outcomes in patients without thrombophilia. MATERIALS AND METHODS Patients A total of 3440 infertile women who were undergoing their fresh IVF/ICSI cycles in 2019 at the Reproductive Medicine Center of Tongji Hospital were eligible for this study. 3067 of whom were finally included in our study, other 333 were excluded due to the following criterion: abnormal karyotype patients, preimplantation genetic diagnosis (PGD), donor oocytes recipients, not the fresh IVF/ICSI cycle during the enrollment period and/or oocytes retrieved were cryopreserved. Women with chronic disease (liver, renal, thyroid) or hormonal disorder not compensated with a specific therapy and with a immunological disease including autoimmune thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, undifferentiated connective tissue disease and Sjogren Syndrom were excluded. Moreover, women with antiphospholipid syndrome or other severe thrombophilia and patients with previous thrombosis especially during pregnancy and puerperium were excluded. Patients with a positive family history of venous thromboembolism were also excluded, which was defined as when at least one first-degree or second-degree relative had presented with the condition. Relevant uterine malformations interfering with embryo implantation were also noted and ruled out (Supplemental Fig. 1). The baseline and cycle characteristics, as well as clinical outcomes, were extracted from electronic medical records. Information regarding clinical pregnancy, live birth outcomes and LMWH usage was collected separately by special follow-up staff from telephone interviews after delivery. Considering that the main results of this study were clinical pregnancy, we also excluded the patients who used LMWH from the positive hCG test day and other days. Finally only patients who were injected with LMWH starting on the day of embryo transfer and who were not injected with LMWH throughout their pregnancy were left, and thus were divided into two groups. Each patient in the LMWH group received an empirical LMWH injection as ordered by her physician. The study was approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Controlled Ovarian Hyperstimulation (COH) and IVF Conventional IVF or ICSI was performed as previously described [ 9 , 10 ]. The protocol of COH was determined individually according to ovarian reserve testing. Oocytes were retrieved transvaginally 34–36h after hCG injection. The oocyte maturation rate was calculated as the number of metaphase II (MII) oocytes divided by the number of retrieved oocytes. Oocyte fertilization, embryo culture and embryo transfer were conducted according to standard procedures, as described previously [ 11 , 12 ]. To fertilize the oocytes, either standard IVF or ICSI were used. The normal fertilization rate was defined as the number of zygotes with two pronuclei (2PN) divided by the number of retrieved oocytes in IVF, or 2PN divided by the number of MII in ICSI.Embryos were checked on the morning of day 3 after oocyte retrieval. Fresh embryo transfers of single or two embryos were undertaken on Day 3 (cleavage stage) or Day 5 (blastocyst stage). Blastocyst formation rate was the number of blastocysts divided by the number of embryos cultured to the blastocyst stage. Outcome Measures The primary outcome was clinical pregnancy rate (CPR) and the secondary outcomes include live birth rate (LBR), miscarriage rate (MR), multiple pregnancy rates (MPR), biochemical pregnancy rate (BPR) and ectopic pregnancy rate (EPR). Clinical pregnancy was defined as the presence of the intrauterine gestational sac detected by ultrasound. A biochemical pregnancy loss was defined as a positive pregnancy test which did not result in a clinical pregnancy. A miscarriage was defined as a spontaneous loss of an intrauterine pregnancy and live birth was defined as the birth of at least one viable infant, irrespective of the duration of gestation. Sample Size Calculation The sample size of this study was estimated at CPR, which was around 45% in patients underwent IVF/ICSI in our reproductive center [ 13 ]. We postulated that a 15% improvement in CPR after LMWH treatment would be reasonable. In order to capture this difference with 80% power at 5% significance level, 618 patients were required in the control group under the assumption that 100 participants were in the LMWH group. This sample size was sufficiently robust to detect the required difference in the CPR as the primary outcome. Statistical Analysis In descriptive analysis, categorical variables were shown as frequency and percentage while continuous variables were expressed as median (25th percentile, 75th percentile) based on Kolmogorov-Smirnov test. Comparisons between groups were performed with nonparametric Wilcoxon rank sum test, Chi-square test and Fisher exact test, as appropriate. To investigate the correlation between each outcome variable and exposure, two statistical methods were used to control the influence of confouding variables, multivariate logistic regression and propensity score method, respectively. First, univariate logistic regressions between each outcome and all covariates were applied. Covariates with significance level less than 0.2 were selected for the following multivariate logistic regression. Backward selection with significance threshold of 0.1 was used for final model selection. Specifically, exposure and age group were forced to be included into the final model. Meanwhile, multicollinearity was diagnosed using variance of inflation factor (VIF) and tolerance. No. of 2PN and Metaphase II oocytes were removed from all regression models while No. of oocytes retrieved was kept. Hosmer and Lemeshow’s goodness-of-fit test was applied to evaluate the model performance. Odds ratios (ORs) and 95% confidence intervals (CIs) were based on univariate analysis to demonstrate the level of association. The adjusted ORs (AORs) were calculated by multiple logistic regression. Another way to reduce the influence of confounders, propensity score method, was also performed. Due to the unbalanced sample size of two cohorts, three methods were conducted: 1) Propensity score matching (PSM); 2) Propensity score adjustment (PS Adjustment); 3) Inverse Probability of Treatment Weighting using propensity score (IPTW). PSM using the nearest neighbor matching method with a caliper equal to 0.2 and a ratio equal to 1. Matching variables are age, maternal body mass index (BMI), AFC, AMH, Infertility diagnosis, No. of IVF/ICSI attempts, No. of embryos transferred, Spontaneous abortion history, Endometrial thickness and Uterine factors. Uterine factors included uterine adhesions, scarred uterus, uterine fibroids, endometrial polyps, etc. We divided AMH and AFC into classification variables so that more variables can be included for matching. Standardized mean difference (SMD) was used to examine the balance of covariate distribution between two groups. Other than matching, propensity scores itself can be used as a covariate into the multivariate regression models for the adjustment, which is the second method. The last method IPTW is similar to the use of survey sampling weights that are used to weight survey samples so that they are representative of specific populations. The exposure effect will be compared through all four models, which used different technics to control confounding variables. SAS 9.4 and R 3.6 were utilized for data analysis in this study and the significance level was set as 0.05, exclude those specially specified. All reported p values are two sided and were not adjusted for multiple comparisons. Missing value Confounders with missing rate less than 10% were selected into analysis. Missing value was imputed with median due to missing at randomand non-normally distributed. Subgroup analysis Subgroup analysis was conducted on the basis of maternal age, BMI and recurrent pregnancy loss (RPL) history. BMI-based subgroup analysis was performed according to BMI cut-offs by the Working Group on Obesity in China (WGOC) [ 14 , 15 ]. Because there were only 14 (6.8%) cases with BMI 24.0 respectively. Therefore, the patients in our cohorts were assigned into non-overweight group (BMI ≤ 24.0) and overweight group (BMI > 24.0). RPL was defined by two or more pregnancy losses [ 16 ]. Pregnancy losses were defined as clinical miscarriages confirmed by ultrasound and/or histology and biochemical pregnancies and pregnancies of unknown location (PULs) [ 17 ]. RESULTS Baseline and cycle characteristics A total of 3067 patients who fulfilled the inclusion and exclusion criteria were included in this analysis. Of these, 119 and 2948 women were administered with LMWH and without LMWH, respectively (Figure 1). Baseline characteristics were compared between the study groups and are summarized in Table 1, which revealed statistically significant differences ( P <0.05) for age, AMH, AFC, infertility diagnosis, biochemical pregnancy history, spontaneous abortion history and infertility etiology. As for cycle characteristics, the number of retrieved oocytes, MII oocytes, 2PN and Good-quality embryo rate on day 3 were significantly higher in the control group ( P < 0.05). The thickness of endometrium was significantly increased in the control group. And more patients in the control group received single embryo transfer (Table 2). Patients general characteristics between the control group and the LMWH group after PSM are comparable (Supplemental Table 1). Pregnancy outcomes In the absence of adjustment for confounders, MPR and MR were higher in the LMWH group but such differences were not observed for CPR, LBR, BPR and EPR (Table 2). Considering the baseline imbalance, we adopted four methods to control for confounders. Due to the small number of ectopic pregnancies, no statistical value was shown. After adjusted different confounders in terms of different outcomes with significance level less than 0.2 in univariate logistic regression, in multivariable logistic regression models (Figure 2A-E), there were statistically significant associations of CPR (AOR =1.54; 95% CI, 1.05–2.27; P = .027) and MR (AOR =2.59; 95% CI, 1.52–4.43; P < .001) with LMWH adjuvant, but LBR (AOR =1.03; 95% CI, 0.70-1.53; P = 0.877), MPR (AOR =1.29; 95% CI, 0.59-2.81; P=0.529), BPR (OR=1.17, 95% CI, 0.56-2.45; P =0.674) were comparable between groups (Supplemental Table 2). This correlation was maintained after PS adjustment and IPTW, but not in the PSM (1:1) analysis, possibly due to the effect of sample size (Table 3). The absolute standard mean difference diagram showed that the absolute standardized mean difference of each covariate was significantly reduced after matching, and the single variable SD scatter diagram showed that the standard difference after matching was basically concentrated between 0–0.2, indicating that the variables had reached equilibrium and the matching effect was good (Supplemental Figure 1). Subgroup analysis To clarify which populations may benefit from LMWH, subgroup analyses were conducted based on age, BMI and whether or not RPL.CPR and MR were higher in the LMWH group in the subgroup of patients with age ≤35 years, BMI≤24 and without RPL while LBR, MPR and BPR were comparable among patients with and without LMWH in all subgroups (Table 4). DISCUSSION The results of this retrospective cohort study add further evidence to the relationship between LMWH treatment and IVF/ICSI pregnancy outcomes. The study suggests that LMWH administration from embryo transfer day may improve clinical pregnancy rates, especially in young, normal-weight patients with no history of RPL. At the same time, the increase in the miscarriage rate and the similar live birth rate has brought the consideration of the dosage and duration of LMWH administration. Previously, low molecular weight heparin had a good effect in women with thrombotic diseases, prompting the use of this drug in women without thrombotic diseases.Regarding the evaluation of the effect of LMWH on ART, there have been some studies most of which concentrate on patients with RIF or thrombophilia. Sunget al [ 18 ] proposed that anticoagulation treatment significantly increased the IVF success rates and live birth rates in women with RIF or thrombophilia. The same as several other reports a positive trend has been found in which patients with RIF were treated with LMWH [ 5 , 19 , 20 ]. Zhang et al [ 21 ] found that anticoagulant therapy could significantly improve the live birth rate and reduce the miscarriage rate in women with thrombophilia, especially the combination treatment of aspirin and LMWH. However, Siristatidis et al [ 22 ] and Mohammad-Akbari et al [ 23 ] thought that there was no evidence to support the standard addition of LMWH in patients with repeated implantation failures. Importance should be attached to the widespread clinical use of LMWH in the IVF/ICSI general population, which is not proportional to the number of studies on this issue. Only a few papers presented conflicting results. Four studies reported LBR as an outcome. Three studies showed that the LBR results of women treated with LMWH were relatively favorable compared with placebo or untreated control group, but these studies did not show significant differences [ 5 – 7 ]. However, Berker et al found no beneficial effects of LMWH [ 3 ]. The sample size of currently published studies was small, high-quality RCTs are necessary to draw more reliable conclusions. Therefore, we conducted this study and found an association between LMWH and CPR and MR in ART.We have to remark that, in addition to a sufficient sample size, in order to rule out any confounding factor, four different statistical analysis methods were performed in the present study, and the results were relatively stable. Concerning the efficacy of LMWH adjuvant in ART, in particular during peri-implantation, the finding that LMWH may promote an increase in CPR is in accordance with many experimental and clinical papers that underline the role of LMWH in implantation process. Other than prevention of blood clotting during implantation, it has been put forward that there is a potential role of LMWH in modulating the process of decidualization, adhesion of the blastocyst to the endometrial surface [ 24 ], and trophoblastic differentiation and invasion [ 12 , 25 ]. Heparin may improve the uterine environment by preventing cell apoptosis caused by oxidative stress and regulating the decidual process to promote implantation success [ 26 ]. The uterine arteries are the main blood vessels that provide nutrients to the uterus and fetus. Increased resistance to uterine artery flow hinders the development of the endometrium, affects the receptivity of the endometrium, and leads to implantation failure and eventual miscarriage. Studies have shown that both aspirin and low molecular weight heparin attenuate apoptosis in trophoblasts [ 27 ], reduce uterine artery resistance, significantly improve pregnancy outcomes, and have a synergistic effect [ 28 ]. For embryonic attachment and invasion, local immunobiological responses should be coordinated and balanced. The pro-inflammatory environment is critical in the preimplantation phase, and uterine cytokines act as intercellular messengers in this immune remodeling.LMWH has been found to change the secretion of endometrial cytokines, leading to better pregnancy outcomes, and LMWH may be beneficial to patients with three implantation failures and no coagulation dysfunction [ 29 ]. Moreover, LMWH might also promote placental angiogenesis during the first and second trimesters of pregnancywhich helps in adequate perfusion to fetus through placenta, thus improving the perinatal outcome [ 30 , 31 ]. The study is strengthened by the large cohort size and consistent results from four different statistical analysis methods. At the same time, we found a positive correlation between LWMH and CPR and MR in non-thrombophilic women espically patients with age ≤ 35 years, BMI ≤ 24 and without RPL, which shows that the application of LMWH in the IVF/ICSI special population deserves further exploration, and high-quality RCTs are urgently needed to explain its specific role in ART. LMWH represents a large category, and its specific classification, dosage and time of use will bring different clinical effects. Anyway, we cannot exclude a selection bias due to the retrospective design of the study. Although we spared no efforts to eliminate confounding factors by implementing several statistical methods, it is indisputable that there are inevitably some confounding factors that have not been taken into account. In addition, the belief that LMWH can act as a tocolytic agent may also lead to a placebo effect, which can amplify the effect of LMWH in pregnancy. In conclusion, we believe that LMWH may play a role in promoting clinical pregnancy. However, if it is to be extensively used in assisted reproductive populations, or even as a tocolytic agent, as is often done in clinical practice nowadays, it should be emphasized that appropriately powered trials are needed. Declarations Ethics approval and consent to participate The ethics of Committee of Tongji Medical College, Huazhong University of Science and Technology approved the Consent Requirements in the study. (No: TJ-IRB20211282). This study has obtained verbal consent from participants. Consent for Publication Not Applicable. Availability of data and materials The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Competing interests The author declares that they have no conflict of interest. Funding This work was supported by the National Key Research and Development Project of China (No.2021YFC2700603). Authors’ contributions Lei Jin and Rui Nie conceived and designed the study. Dan Chen, Yaxin Guo and Wenxuan Li collected the data. Dan Chen and Yaxin Guo wrote the paper. Yaxin Guo and Xin Sun analyzed the data. Mengya Zhao, Enqi Yan and HuiziJin gave some important suggestions.All authors read and approved the final manuscript. The corresponding authors take the final responsibility for the decision to submit the manuscript for publication. Acknowledgements We thank all the staff of the Reproductive Medicine Center and the obstetric ward for their contributions. References HAO, C, M SUN, H WANG, et al. Low molecular weight heparins and their clinical applications[J]. Prog Mol Biol Transl Sci，2019，163：21-39. AKHTAR, MA, S SUR, N RAINE-FENNING, et al. Heparin for assisted reproduction: summary of a Cochrane review[J]. Fertil Steril，2015，103：33-34. 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Tables Table 1 Patients general characteristics between the control group and the LMWH group. LMWH (N=119) Control (N=2948) P -value Age, years 33.0 (30.0, 35.0) 31.0 (28.0, 33.0) <.001 1 * BMI, kg/m 2 22.0 (20.4, 24.7) 21.7 (20.0, 23.9) 0.070 1 Baseline FSH, mIU/mL 7.3 (6.1, 8.3) 7.4 (6.2, 8.5) 0.405 1 Antral follicle count (AFC) 10.0 (7.0, 14.0) 12.0 (8.0, 18.0) 0.001 1 * AMH level, ng/ml 2.8 (1.4, 5.1) 3.4 (2.0, 6.0) 0.005 1 * Comorbidity Hypertension 0 (0.0%) 11 (0.4%) 1.000 3 Diabetes 4 (3.4%) 47 (1.6%) 0.134 3 Duration of infertility, years 3.0 (1.0, 5.0) 3.0 (2.0, 4.0) 0.848 1 Infertility diagnosis 0.001 2 * Primary infertility, % 62 (52.1%) 2010 (68.2%) Secondary infertility, % 57 (47.9%) 938 (31.8%) Biochemical pregnancy history 11 (9.2%) 151 (5.1%) 0.049 2 * Spontaneous abortion history 34 (28.6%) 390 (13.2%) <.001 2 * Repeated pregnancy loss 20 (16.8%) 104 (3.5%) <.001 2 * Infertility etiology, % Tubal factor 64 (53.8%) 1474 (50.0%) 0.419 2 Male factor 25 (21.0%) 947 (32.1%) 0.011 2 * Anovulatory 7 (5.9%) 283 (9.6%) 0.174 2 Diminished Ovarian Reserve 36 (30.3%) 555 (18.8%) 0.002 2 * Endometriosis 10 (8.4%) 252 (8.5%) 0.956 2 Uterine factors 40 (33.6%) 520 (17.6%) <.001 2 * More than one factor 58 (48.7%) 1254 (42.5%) 0.180 2 BMI, body mass index; FSH, follicle-stimulating hormone; AMH, anti-mullerian hormone; No., Number; IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; COH, controlled ovarian hyperstimulation; GnRH, gonadotropin-releasing hormone; E2, estrogen; hCG, human chorionic gonadotropin; P, progesterone. 1 Kruskal-Wallis p-value; 2 Chi-Square p-value; 3 Fisher Exact P-value; * P< .05. Table 2 Patients cycle characteristics and clinical pregnancy outcomes between the control group and the LMWH group. LMWH (N=119) Control (N=2948) P -value No. of IVF/ICSI attempts 1.0 (1.0, 2.0) 1.0 (1.0, 1.0) <.001 1 * Fertilization method, % 0.420 2 IVF 70 (58.8%) 1885 (63.9%) ICSI 43 (36.1%) 898 (30.5%) Rescue ICSI 6 (5.0%) 165 (5.6%) COH protocols, % 0.213 2 GnRH-a long 12 (10.1%) 314 (10.7%) GnRH antagonist 53 (44.5%) 1038 (35.2%) Depot GnRH agonist 53 (44.5%) 1561 (53.0%) Other protocols 1 (0.8%) 35 (1.2%) E2 on hCG day, pg/mL 1896.0 (1383.0, 2701.0) 1997.0 (1391.5, 2884.5) 0.345 1 P on hCG day, ng/mL 0.7 (0.5, 0.9) 0.7 (0.5, 0.9) 0.375 1 No. of oocytes retrieved 10.0 (7.0, 14.0) 11.0 (7.0, 15.0) 0.037 1 * No. of Metaphase II oocytes 9.0 (5.0, 12.0) 9.0 (6.0, 13.0) 0.042 1 * Oocyte maturation rate 0.9 (0.8, 1.0) 0.9 (0.8, 1.0) 0.969 1 No. of 2PN 5.0 (3.0, 8.0) 6.0 (4.0, 9.0) 0.037 1 * Normal fertilization rate 0.7 (0.5, 0.8) 0.7 (0.5, 0.8) 0.7550 1 Good-quality embryo rate on day 3 2.0 (1.0, 4.0) 3.0 (1.0, 5.0) 0.013 1 * Blastocyst formation rate 0.6 (0.4, 0.8) 0.7 (0.4, 0.9) 0.089 1 No. of > 14 mm follicles 9.0 (6.0, 12.0) 10.0 (7.0, 13.0) 0.050 1 Endometrial thickness, mm 11.0 (9.4, 12.7) 11.4 (9.9, 13.2) 0.027 1 * No. of embryos transferred, % <.001 2 * 1 70 (58.8%) 2529 (85.8%) 2 49 (41.2%) 419 (14.2%) Type of embryos transferred, % 0.100 2 cleavage embryo 112 (94.1%) 2636 (89.4%) blastocyst 7 (5.9%) 312 (10.6%) Clinical Pregnancy, % 64 (53.8%) 1379 (46.8%) 0.133 2 Live Birth, % 45 (37.8%) 1195 (40.5%) 0.553 2 Miscarriage, % 18 (15.1%) 184 (6.2%) <.001 2 * Multiple pregnancy, % 10 (8.4%) 91 (3.1%) 0.001 2 * Biochemical Pregnancy, % 8 (6.7%) 178 (6.0%) 0.759 2 Ectopic pregnancy, % 0 (0.0%) 22 (0.7%) 1.000 3 No., Number; PN, pronuclei. 1 Kruskal-Wallis p-value; 2 Chi-Square p-value; 3 Fisher Exact P -value; * P < .05. Table 3 Odds ratios of pregnancy outcomes based on the multiple logistic regression model ， PSM ， PS Adjustment and IPTW. Multivariate Logistic Regression PSM PS Adjustment IPTW N (119 vs 2948) N (119 vs 119) N (119 vs 2948) N (119 vs 2948) Outcome Odds Ratio P -value Odds Ratio P -value Odds Ratio P -value Odds Ratio P -value Clinical Pregnancy 1.54 (1.05-2.27) 0.027* 1.27 (0.76-2.11) 0.364 1.56 (1.06-2.30) 0.025* 1.50 (1.04-2.16) 0.028* Live Birth 1.03 (0.70-1.53) 0.877 0.93 (0.55-1.57) 0.790 1.05 (0.70-1.56) 0.826 1.00 (0.67-1.51) 0.988 Miscarriage 2.59 (1.52-4.43) <.001* 1.94(0.86-4.41) 0.112 2.63 (1.51-4.61) <.001* 2.57 (1.09-6.08) 0.031* Multiple Pregnancy 1.29 (0.59-2.81) 0.529 1.27 (0.48-3.35) 0.625 1.33 (0.60-2.92) 0.485 1.23 (0.32-4.75) 0.767 Biochemical Pregnancy 1.17 (0.56-2.45) 0.674 1.00 (0.36-2.76) >0.999 1.21 (0.57-2.59) 0.613 1.23 (0.46-3.30) 0.685 PSM, propensity score matching; PS, Propensity score; IPTW, inverse probability of treatment weighting. Clinical pregnancy was adjusted by Group, Age, No. of IVF/ICSI attempts, COH protocols, P on hCG day, Normal fertilization rate, No. of embryos transferred, Endometrial thickness; Live birth was adjusted by Group, Age, Spontaneous abortion history, Tubal factor, No. of IVF/ICSI attempts, COH protocols, Oocyte maturation rate, Normal fertilization rate, No. of embryos transferred, Endometrial thickness; Miscarriage was adjusted by Group, Age, BMI, Spontaneous abortion history, Tubal factor, P on hCG day, Normal fertilization rate, Endometrial thickness; Multiple pregnancy was adjusted by Group, Age, BMI, Repeated pregnancy loss, COH protocols, P on hCG day, No. of oocytes retrieved, Oocyte maturation rate, No. of embryos transferred; Biochemical Pregnancy was adjusted by Group, Age, Biochemical pregnancy history, Anovulatory, cleavage embryo. * P < .05. Table 4 Pregnancy outcomes in subgroup analysis. Clinical pregnancy Live Birth Miscarriage Multiple Pregnany Biochemical Pregnancy Age ≤35 (N =2649) LMWH 57 (59.4%) 40 (41.7%) 16 (16.7%) 8 (8.3%) 8 (8.3%) Control 1256 (49.2%) 1101 (43.1%) 155 (6.1%) 83(3.3%) 164 (6.4%) Adjusted P-value 0.002* 0.410 35 (N=418) LMWH 7 (30.4%) 5 (21.7%) 2 (8.7%) 2 (8.7%) 0 (0.0%) Control 123 (31.1%) 94 (23.8%) 29 (7.3%) 8 (2.0%) 14 (3.5%) Adjusted P-value 0.471 0.340 0.957 0.647 - BMI 24 (N=639) LMWH 20 (52.6%) 12 (31.6%) 7 (18.4%) 1 (2.6%) 2 (5.3%) Control 370 (50.4%) 309 (42.1%) 62 (8.4%) 18 (2.5%) 45 (6.1%) Adjusted P-value 0.305 0.590 0.052 0.668 0.979 RPL No RPL (N =2943) LMWH 54 (54.5%) 36 (36.4%) 17 (17.2%) 6 (6.1%) 8 (8.1%) Control 1341 (47.2%) 1166 (41.0%) 175 (6.2%) 85 (3.0%) 171 (6.0%) Adjusted P-value 0.002* 0.405 <.001* 0.972 0.457 RPL (N =124) LMWHl 10 (50.0%) 9 (45.0%) 1 (5.0%) 4 (20.0%) 0 (0.0%) Control 38 (36.5%) 29 (27.9%) 9 (8.7%) 6 (5.8%) 9 (8.7%) Adjusted P-value 0.372 0.378 0.290 0.311 0.968 LMWH, low-molecular-weight heparins; BMI, body mass index; RPL, recurrent pregnancy loss. * P < .05. 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Technology","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Chen","suffix":""},{"id":330342353,"identity":"42cd9448-3852-4dee-9875-94e6e1e89114","order_by":2,"name":"Wenxuan Li","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Wenxuan","middleName":"","lastName":"Li","suffix":""},{"id":330342355,"identity":"96745420-1a27-44bd-aacd-ef59e138bbf3","order_by":3,"name":"Mengya Zhao","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Mengya","middleName":"","lastName":"Zhao","suffix":""},{"id":330342359,"identity":"d67f227b-45e3-44a8-925d-a86f46af5db0","order_by":4,"name":"Enqi Yan","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Enqi","middleName":"","lastName":"Yan","suffix":""},{"id":330342360,"identity":"4dd39bac-0e0a-40f5-b47c-0dcee919cb44","order_by":5,"name":"Huizi Jin","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Huizi","middleName":"","lastName":"Jin","suffix":""},{"id":330342361,"identity":"bf464874-a8b1-424e-a052-e613bfd9ce50","order_by":6,"name":"Xin Sun","email":"","orcid":"","institution":"Chongqing Nanpeng Artificial Intelligence Technology Research Institute Co., Ltd","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Sun","suffix":""},{"id":330342362,"identity":"0be37e73-73d8-44d7-9be2-070ebe8e0018","order_by":7,"name":"Rui Nie","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Nie","suffix":""},{"id":330342364,"identity":"b0a559ec-b8bd-4752-a4f2-f4f9657afede","order_by":8,"name":"Lei Jin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBACPgbGBoMECDvhMEMFEVrYIFoMoFrOEKUFDMBaGJgZ24jRwt7cUPBwxx85c/4FDw8XzrOWbWA/fHQDXi08BxsMEs8YGFvOeJBweOa2dOMGnrS0G3i1SCQCtbQZJG64cSDhMO+2w4kNEjxm+LXIP0TWMocYLRKMUC3nG4BaGojRwgN2mLGxwQ1gIPMcSzduI+QXfvbjzwx/tsnJGZw/k/yZp8Zatp/98DG8WkAWQSJFIieBgdioYX4Ase/4AbCWBiK0jIJRMApGwcgCAJrlT6jQxJazAAAAAElFTkSuQmCC","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Lei","middleName":"","lastName":"Jin","suffix":""}],"badges":[],"createdAt":"2024-07-20 02:23:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4770813/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4770813/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62819778,"identity":"1f5317f4-709b-45b1-8660-f996aca285cd","added_by":"auto","created_at":"2024-08-19 23:59:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46394,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient enrollment.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4770813/v1/ee7a6e20ce959e1ecc34923d.jpg"},{"id":62819779,"identity":"4e6d53d1-7108-484f-9845-37e6ddeadf5c","added_by":"auto","created_at":"2024-08-19 23:59:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108405,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots of the pregnancy outcomes based on the multiple logistic regression.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4770813/v1/8c5ff1d1c08c534de6600a99.jpg"},{"id":77232913,"identity":"0720d6c2-445a-48b1-a62d-857a76abb139","added_by":"auto","created_at":"2025-02-26 12:39:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1186487,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4770813/v1/05aada26-672f-483f-a57b-b1a430cb66fd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low molecular weight heparin increases clinical pregnancy rate in non-thrombophilic women undergoing assisted reproductive technology","fulltext":[{"header":"INTRODUCTION ","content":"\u003cp\u003eLow-molecular-weight heparins (LMWHs) are derived from unfractionated heparin through controlled enzymatic or chemical depolymerization processes that yield chains with a mean molecular weight of about 5000 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. LMWH is increasingly being administered to women undergoing assisted reproductive technology (ART) due to its possible role in promoting successful embryo implantation in ART [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, there is little guidance on the use of LMWH in ART. There is also considerable uncertainty regarding which women might benefit from LMWH and when to administer LMWH.\u003c/p\u003e \u003cp\u003eThere have been some studies focusing on this issue, especially in patients with recurrent implantation failures (RIF) [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Qublan et al found that LMWH treatment can improve implantation, pregnancy and live birth rates in women with RIF and thrombophilia without significant maternal-fetal complications. However, two other RCTs took different attitudes toward this, in which LMWH did not lead to statistically better pregnancy outcomes in women with unexplained RIF [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. For patients without RIF, relevant studies are relatively sparse. Noci et al enrolled 172 patients without thrombophilia and observed a trend toward improved pregnancy outcomes with LMWH administration but no significant difference [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Lodigiani et al included 247 patients without severe thrombophilia and found no beneficial effects of LMWH [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In contrast to these small sample size studies andtheir controversial results, it's worth noting that LMWH is widely used in China as well as in other countries as an adjuvant on IVF/ICSI pregnancy in non-thrombophilic women [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this context, in an attempt to elucidate the efficacy of LMWH in general in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) populations, we conducted the present cohort study aiming to gain insights regarding the impact of empirical LMWH administration from the day of embryo transfer on maternal outcomes in patients without thrombophilia.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 3440 infertile women who were undergoing their fresh IVF/ICSI cycles in 2019 at the Reproductive Medicine Center of Tongji Hospital were eligible for this study. 3067 of whom were finally included in our study, other 333 were excluded due to the following criterion: abnormal karyotype patients, preimplantation genetic diagnosis (PGD), donor oocytes recipients, not the fresh IVF/ICSI cycle during the enrollment period and/or oocytes retrieved were cryopreserved. Women with chronic disease (liver, renal, thyroid) or hormonal disorder not compensated with a specific therapy and with a immunological disease including autoimmune thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, undifferentiated connective tissue disease and Sjogren Syndrom were excluded. Moreover, women with antiphospholipid syndrome or other severe thrombophilia and patients with previous thrombosis especially during pregnancy and puerperium were excluded. Patients with a positive family history of venous thromboembolism were also excluded, which was defined as when at least one first-degree or second-degree relative had presented with the condition. Relevant uterine malformations interfering with embryo implantation were also noted and ruled out (Supplemental Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe baseline and cycle characteristics, as well as clinical outcomes, were extracted from electronic medical records. Information regarding clinical pregnancy, live birth outcomes and LMWH usage was collected separately by special follow-up staff from telephone interviews after delivery.\u003c/p\u003e \u003cp\u003eConsidering that the main results of this study were clinical pregnancy, we also excluded the patients who used LMWH from the positive hCG test day and other days. Finally only patients who were injected with LMWH starting on the day of embryo transfer and who were not injected with LMWH throughout their pregnancy were left, and thus were divided into two groups. Each patient in the LMWH group received an empirical LMWH injection as ordered by her physician. The study was approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eControlled Ovarian Hyperstimulation (COH) and IVF\u003c/h2\u003e \u003cp\u003eConventional IVF or ICSI was performed as previously described [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The protocol of COH was determined individually according to ovarian reserve testing. Oocytes were retrieved transvaginally 34\u0026ndash;36h after hCG injection. The oocyte maturation rate was calculated as the number of metaphase II (MII) oocytes divided by the number of retrieved oocytes. Oocyte fertilization, embryo culture and embryo transfer were conducted according to standard procedures, as described previously [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. To fertilize the oocytes, either standard IVF or ICSI were used. The normal fertilization rate was defined as the number of zygotes with two pronuclei (2PN) divided by the number of retrieved oocytes in IVF, or 2PN divided by the number of MII in ICSI.Embryos were checked on the morning of day 3 after oocyte retrieval. Fresh embryo transfers of single or two embryos were undertaken on Day 3 (cleavage stage) or Day 5 (blastocyst stage). Blastocyst formation rate was the number of blastocysts divided by the number of embryos cultured to the blastocyst stage. \u003cb\u003eOutcome Measures\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe primary outcome was clinical pregnancy rate (CPR) and the secondary outcomes include live birth rate (LBR), miscarriage rate (MR), multiple pregnancy rates (MPR), biochemical pregnancy rate (BPR) and ectopic pregnancy rate (EPR). Clinical pregnancy was defined as the presence of the intrauterine gestational sac detected by ultrasound. A biochemical pregnancy loss was defined as a positive pregnancy test which did not result in a clinical pregnancy. A miscarriage was defined as a spontaneous loss of an intrauterine pregnancy and live birth was defined as the birth of at least one viable infant, irrespective of the duration of gestation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSample Size Calculation\u003c/h2\u003e \u003cp\u003eThe sample size of this study was estimated at CPR, which was around 45% in patients underwent IVF/ICSI in our reproductive center [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We postulated that a 15% improvement in CPR after LMWH treatment would be reasonable. In order to capture this difference with 80% power at 5% significance level, 618 patients were required in the control group under the assumption that 100 participants were in the LMWH group. This sample size was sufficiently robust to detect the required difference in the CPR as the primary outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eIn descriptive analysis, categorical variables were shown as frequency and percentage while continuous variables were expressed as median (25th percentile, 75th percentile) based on Kolmogorov-Smirnov test. Comparisons between groups were performed with nonparametric Wilcoxon rank sum test, Chi-square test and Fisher exact test, as appropriate. To investigate the correlation between each outcome variable and exposure, two statistical methods were used to control the influence of confouding variables, multivariate logistic regression and propensity score method, respectively.\u003c/p\u003e \u003cp\u003eFirst, univariate logistic regressions between each outcome and all covariates were applied. Covariates with significance level less than 0.2 were selected for the following multivariate logistic regression. Backward selection with significance threshold of 0.1 was used for final model selection. Specifically, exposure and age group were forced to be included into the final model. Meanwhile, multicollinearity was diagnosed using variance of inflation factor (VIF) and tolerance. No. of 2PN and Metaphase II oocytes were removed from all regression models while No. of oocytes retrieved was kept. Hosmer and Lemeshow\u0026rsquo;s goodness-of-fit test was applied to evaluate the model performance. Odds ratios (ORs) and 95% confidence intervals (CIs) were based on univariate analysis to demonstrate the level of association. The adjusted ORs (AORs) were calculated by multiple logistic regression.\u003c/p\u003e \u003cp\u003eAnother way to reduce the influence of confounders, propensity score method, was also performed. Due to the unbalanced sample size of two cohorts, three methods were conducted:\u003c/p\u003e \u003cp\u003e1) Propensity score matching (PSM);\u003c/p\u003e \u003cp\u003e2) Propensity score adjustment (PS Adjustment);\u003c/p\u003e \u003cp\u003e3) Inverse Probability of Treatment Weighting using propensity score (IPTW).\u003c/p\u003e \u003cp\u003ePSM using the nearest neighbor matching method with a caliper equal to 0.2 and a ratio equal to 1. Matching variables are age, maternal body mass index (BMI), AFC, AMH, Infertility diagnosis, No. of IVF/ICSI attempts, No. of embryos transferred, Spontaneous abortion history, Endometrial thickness and Uterine factors. Uterine factors included uterine adhesions, scarred uterus, uterine fibroids, endometrial polyps, etc. We divided AMH and AFC into classification variables so that more variables can be included for matching. Standardized mean difference (SMD) was used to examine the balance of covariate distribution between two groups. Other than matching, propensity scores itself can be used as a covariate into the multivariate regression models for the adjustment, which is the second method. The last method IPTW is similar to the use of survey sampling weights that are used to weight survey samples so that they are representative of specific populations.\u003c/p\u003e \u003cp\u003eThe exposure effect will be compared through all four models, which used different technics to control confounding variables. SAS 9.4 and R 3.6 were utilized for data analysis in this study and the significance level was set as 0.05, exclude those specially specified. All reported p values are two sided and were not adjusted for multiple comparisons.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eMissing value\u003c/h2\u003e \u003cp\u003eConfounders with missing rate less than 10% were selected into analysis. Missing value was imputed with median due to missing at randomand non-normally distributed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis\u003c/h2\u003e \u003cp\u003eSubgroup analysis was conducted on the basis of maternal age, BMI and recurrent pregnancy loss (RPL) history. BMI-based subgroup analysis was performed according to BMI cut-offs by the Working Group on Obesity in China (WGOC) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Because there were only 14 (6.8%) cases with BMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5, 8 (3.9%) cases with BMI\u0026thinsp;\u0026ge;\u0026thinsp;28.0 in the cohorts, we incorporated them into the group of BMI\u0026thinsp;\u0026le;\u0026thinsp;24.0 and \u0026gt;\u0026thinsp;24.0 respectively. Therefore, the patients in our cohorts were assigned into non-overweight group (BMI\u0026thinsp;\u0026le;\u0026thinsp;24.0) and overweight group (BMI\u0026thinsp;\u0026gt;\u0026thinsp;24.0). RPL was defined by two or more pregnancy losses [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Pregnancy losses were defined as clinical miscarriages confirmed by ultrasound and/or histology and biochemical pregnancies and pregnancies of unknown location (PULs) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eBaseline and cycle characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 3067 patients who fulfilled the inclusion and exclusion criteria were included in this analysis. Of these, 119 and 2948 women were administered with LMWH and without LMWH, respectively (Figure 1).\u0026nbsp;Baseline characteristics were compared between the study groups and are summarized in Table 1, which revealed statistically significant differences (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05) for age, AMH, AFC, infertility diagnosis, biochemical pregnancy history, spontaneous abortion history and infertility etiology. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs for cycle characteristics, the number of retrieved oocytes, MII oocytes, 2PN and Good-quality embryo rate on day 3 were significantly higher in the control group (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05). The thickness of endometrium was significantly increased in the control group. And more patients in the control group received single embryo transfer (Table 2). Patients general characteristics between the control group and the LMWH group after PSM are comparable (Supplemental Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePregnancy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the absence of adjustment for confounders, MPR and MR were higher in the LMWH group but such differences were not observed for CPR, LBR, BPR and EPR (Table 2). Considering the baseline imbalance, we adopted four methods to control for confounders. Due to the small number of ectopic pregnancies, no statistical value was shown.\u003c/p\u003e\n\u003cp\u003eAfter adjusted different confounders in terms of different outcomes with significance level less than 0.2 in univariate logistic regression, in multivariable logistic regression models (Figure 2A-E), there were statistically significant associations of CPR\u0026nbsp;(AOR =1.54; 95% CI, 1.05–2.27; \u003cem\u003eP\u003c/em\u003e= .027) and MR (AOR =2.59; 95% CI, 1.52–4.43; \u003cem\u003eP\u003c/em\u003e\u0026lt; .001) with LMWH adjuvant, but LBR (AOR =1.03; 95% CI, 0.70-1.53; \u003cem\u003eP\u003c/em\u003e = 0.877), MPR (AOR =1.29; 95% CI, 0.59-2.81; P=0.529), BPR (OR=1.17, 95% CI, 0.56-2.45; \u003cem\u003eP\u003c/em\u003e=0.674) were comparable between groups (Supplemental Table 2). This correlation was maintained after PS adjustment and IPTW, but not in the PSM (1:1) analysis, possibly due to the effect of sample size (Table 3). The absolute standard mean difference diagram showed that the absolute standardized mean difference of each covariate was significantly reduced after matching, and the single variable SD scatter diagram showed that the standard difference after matching was basically concentrated between 0–0.2, indicating that the variables had reached equilibrium and the matching effect was good (Supplemental Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo clarify which populations may benefit from LMWH, subgroup analyses were conducted based on age, BMI and whether or not RPL.CPR and MR were higher in the LMWH group in the subgroup of patients with age ≤35 years, BMI≤24 and without RPL while LBR, MPR and BPR were comparable among patients with and without LMWH in all subgroups (Table 4).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe results of this retrospective cohort study add further evidence to the relationship between LMWH treatment and IVF/ICSI pregnancy outcomes. The study suggests that LMWH administration from embryo transfer day may improve clinical pregnancy rates, especially in young, normal-weight patients with no history of RPL. At the same time, the increase in the miscarriage rate and the similar live birth rate has brought the consideration of the dosage and duration of LMWH administration.\u003c/p\u003e \u003cp\u003ePreviously, low molecular weight heparin had a good effect in women with thrombotic diseases, prompting the use of this drug in women without thrombotic diseases.Regarding the evaluation of the effect of LMWH on ART, there have been some studies most of which concentrate on patients with RIF or thrombophilia. Sunget al [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] proposed that anticoagulation treatment significantly increased the IVF success rates and live birth rates in women with RIF or thrombophilia. The same as several other reports a positive trend has been found in which patients with RIF were treated with LMWH [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Zhang et al [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] found that anticoagulant therapy could significantly improve the live birth rate and reduce the miscarriage rate in women with thrombophilia, especially the combination treatment of aspirin and LMWH. However, Siristatidis et al [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and Mohammad-Akbari et al [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] thought that there was no evidence to support the standard addition of LMWH in patients with repeated implantation failures.\u003c/p\u003e \u003cp\u003eImportance should be attached to the widespread clinical use of LMWH in the IVF/ICSI general population, which is not proportional to the number of studies on this issue. Only a few papers presented conflicting results. Four studies reported LBR as an outcome. Three studies showed that the LBR results of women treated with LMWH were relatively favorable compared with placebo or untreated control group, but these studies did not show significant differences [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, Berker et al found no beneficial effects of LMWH [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The sample size of currently published studies was small, high-quality RCTs are necessary to draw more reliable conclusions. Therefore, we conducted this study and found an association between LMWH and CPR and MR in ART.We have to remark that, in addition to a sufficient sample size, in order to rule out any confounding factor, four different statistical analysis methods were performed in the present study, and the results were relatively stable.\u003c/p\u003e \u003cp\u003eConcerning the efficacy of LMWH adjuvant in ART, in particular during peri-implantation, the finding that LMWH may promote an increase in CPR is in accordance with many experimental and clinical papers that underline the role of LMWH in implantation process. Other than prevention of blood clotting during implantation, it has been put forward that there is a potential role of LMWH in modulating the process of decidualization, adhesion of the blastocyst to the endometrial surface [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and trophoblastic differentiation and invasion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Heparin may improve the uterine environment by preventing cell apoptosis caused by oxidative stress and regulating the decidual process to promote implantation success [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The uterine arteries are the main blood vessels that provide nutrients to the uterus and fetus. Increased resistance to uterine artery flow hinders the development of the endometrium, affects the receptivity of the endometrium, and leads to implantation failure and eventual miscarriage. Studies have shown that both aspirin and low molecular weight heparin attenuate apoptosis in trophoblasts [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], reduce uterine artery resistance, significantly improve pregnancy outcomes, and have a synergistic effect [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. For embryonic attachment and invasion, local immunobiological responses should be coordinated and balanced. The pro-inflammatory environment is critical in the preimplantation phase, and uterine cytokines act as intercellular messengers in this immune remodeling.LMWH has been found to change the secretion of endometrial cytokines, leading to better pregnancy outcomes, and LMWH may be beneficial to patients with three implantation failures and no coagulation dysfunction [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Moreover, LMWH might also promote placental angiogenesis during the first and second trimesters of pregnancywhich helps in adequate perfusion to fetus through placenta, thus improving the perinatal outcome [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe study is strengthened by the large cohort size and consistent results from four different statistical analysis methods. At the same time, we found a positive correlation between LWMH and CPR and MR in non-thrombophilic women espically patients with age\u0026thinsp;\u0026le;\u0026thinsp;35 years, BMI\u0026thinsp;\u0026le;\u0026thinsp;24 and without RPL, which shows that the application of LMWH in the IVF/ICSI special population deserves further exploration, and high-quality RCTs are urgently needed to explain its specific role in ART. LMWH represents a large category, and its specific classification, dosage and time of use will bring different clinical effects. Anyway, we cannot exclude a selection bias due to the retrospective design of the study. Although we spared no efforts to eliminate confounding factors by implementing several statistical methods, it is indisputable that there are inevitably some confounding factors that have not been taken into account. In addition, the belief that LMWH can act as a tocolytic agent may also lead to a placebo effect, which can amplify the effect of LMWH in pregnancy.\u003c/p\u003e \u003cp\u003eIn conclusion, we believe that LMWH may play a role in promoting clinical pregnancy. However, if it is to be extensively used in assisted reproductive populations, or even as a tocolytic agent, as is often done in clinical practice nowadays, it should be emphasized that appropriately powered trials are needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethics of Committee of Tongji Medical College, Huazhong University of Science and Technology approved the Consent Requirements in the study. (No: TJ-IRB20211282). This study has obtained verbal consent from participants.\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\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Key Research and Development Project of China (No.2021YFC2700603).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLei Jin and Rui Nie conceived and designed the study. Dan Chen, Yaxin Guo and Wenxuan Li collected the data. Dan Chen and Yaxin Guo wrote the paper. Yaxin Guo and Xin Sun analyzed the data. Mengya Zhao, Enqi Yan and HuiziJin gave some important suggestions.All authors read and approved the final manuscript. The corresponding authors take the final responsibility for the decision to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the staff of the Reproductive Medicine Center and the obstetric ward for their contributions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHAO, C, M SUN, H WANG, et al. Low molecular weight heparins and their clinical applications[J]. Prog Mol Biol Transl Sci，2019，163：21-39.\u003c/li\u003e\n\u003cli\u003eAKHTAR, MA, S SUR, N RAINE-FENNING, et al. Heparin for assisted reproduction: summary of a Cochrane review[J]. Fertil Steril，2015，103：33-34.\u003c/li\u003e\n\u003cli\u003eBERKER, B, S TAŞKIN, K KAHRAMAN, et al. The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study[J]. Fertil Steril，2011，95：2499-2502.\u003c/li\u003e\n\u003cli\u003eQUBLAN, H, Z AMARIN, M DABBAS, et al. Low-molecular-weight heparin in the treatment of recurrent IVF-ET failure and thrombophilia: a prospective randomized placebo-controlled trial[J]. Hum Fertil (Camb)，2008，11：246-253.\u003c/li\u003e\n\u003cli\u003eURMAN, B, B ATA, K YAKIN, et al. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial[J]. Hum Reprod，2009，24：1640-1647.\u003c/li\u003e\n\u003cli\u003eNOCI, I, MN MILANINI, M RUGGIERO, et al. Effect of dalteparin sodium administration on IVF outcome in non-thrombophilic young women: a pilot study[J]. Reprod Biomed Online，2011，22：615-620.\u003c/li\u003e\n\u003cli\u003eLODIGIANI, C, F DENTALI, E BANFI, et al. The effect of parnaparin sodium on in vitro fertilization outcome: A prospective randomized controlled trial[J]. Thromb Res，2017，159：116-121.\u003c/li\u003e\n\u003cli\u003ePAPADAKIS, E, A POULIAKIS, \u0026Alpha; AKTYPI, et al. Low molecular weight heparins use in pregnancy: a practice survey from Greece and a review of the literature[J]. Thromb J，2019，17：23.\u003c/li\u003e\n\u003cli\u003eHU, S, B XU，L JIN. Perinatal outcome in young patients with diminished ovarian reserve undergoing assisted reproductive technology[J]. Fertil Steril，2020，114：118-124.e111.\u003c/li\u003e\n\u003cli\u003eGUO, Y, H JIANG, S HU, et al. Efficacy of three COS protocols and predictability of AMH and AFC in women with discordant ovarian reserve markers: a retrospective study on 19,239 patients[J]. J Ovarian Res，2021，14：111.\u003c/li\u003e\n\u003cli\u003eXU, B, D GEERTS, S HU, et al. The depot GnRH agonist protocol improves the live birth rate per fresh embryo transfer cycle, but not the cumulative live birth rate in normal responders: a randomized controlled trial and molecular mechanism study[J]. Hum Reprod，2020，35：1306-1318.\u003c/li\u003e\n\u003cli\u003eZHU, L, Q XI, H ZHANG, et al. Blastocyst culture and cryopreservation to optimize clinical outcomes of warming cycles[J]. Reprod Biomed Online，2013，27：154-160.\u003c/li\u003e\n\u003cli\u003eHUANG, B, K QIAN, Z LI, et al. Neonatal outcomes after early rescue intracytoplasmic sperm injection: an analysis of a 5-year period[J]. Fertil Steril，2015，103：1432-1437.e1431.\u003c/li\u003e\n\u003cli\u003e[Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents][J]. Zhonghua Liu Xing Bing Xue Za Zhi，2004，25：97-102.\u003c/li\u003e\n\u003cli\u003eQIAN, K, L TAN, S LI, et al. Comparison of different BMI cut-offs to screen for child and adolescent obesity in urban China[J]. 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J Obstet Gynaecol Res，2023，49：803-811.\u003c/li\u003e\n\u003cli\u003eNIU, Z, M ZHOU, L XIA, et al. Uterine cytokine profiles after low-molecular-weight heparin administration are associated with pregnancy outcomes of patients with repeated implantation failure[J]. Front Endocrinol (Lausanne)，2022，13：1008923.\u003c/li\u003e\n\u003cli\u003eRODGER, MA, JC GRIS, JIP DE VRIES, et al. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials[J]. Lancet，2016，388：2629-2641.\u003c/li\u003e\n\u003cli\u003eSOBEL, ML, J KINGDOM，S DREWLO. Angiogenic response of placental villi to heparin[J]. Obstet Gynecol，2011，117：1375-1383.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 Patients general characteristics between the control group and the LMWH group.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003eLMWH\u003cbr\u003e\u0026nbsp;(N=119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003cbr\u003e\u0026nbsp;(N=2948)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eAge,\u0026nbsp;years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e33.0 (30.0, 35.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e31.0 (28.0, 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e22.0 (20.4, 24.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e21.7 (20.0, 23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.070\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline FSH, mIU/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e7.3 (6.1, 8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e7.4 (6.2, 8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.405\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eAntral follicle count (AFC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e10.0 (7.0, 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e12.0 (8.0, 18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eAMH level, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e2.8 (1.4, 5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e3.4 (2.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.005\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e11 (0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e4 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e47 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.134\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eDuration of infertility, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e3.0 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e3.0 (2.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.848\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eInfertility diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary infertility, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e62 (52.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e2010 (68.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eSecondary infertility, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e57 (47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e938 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eBiochemical pregnancy history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e11 (9.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e151 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.049\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eSpontaneous abortion history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e34 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e390 (13.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eRepeated pregnancy loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e20 (16.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e104 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eInfertility etiology, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eTubal factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e64 (53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e1474 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.419\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eMale factor\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e25 (21.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e947 (32.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.011\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eAnovulatory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e7 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e283 (9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.174\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eDiminished\u0026nbsp;Ovarian\u0026nbsp;Reserve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e36 (30.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e555 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e10 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e252 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.956\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eUterine factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e40 (33.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e520 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.72477064220183%\" valign=\"top\"\u003e\n \u003cp\u003eMore than one factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73394495412844%\" valign=\"top\"\u003e\n \u003cp\u003e58 (48.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.08256880733945%\" valign=\"top\"\u003e\n \u003cp\u003e1254 (42.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.458715596330276%\" valign=\"top\"\u003e\n \u003cp\u003e0.180\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eBMI, body mass index; FSH, follicle-stimulating hormone; AMH, anti-mullerian hormone;\u0026nbsp;No., Number; IVF, in vitro fertilization;\u0026nbsp;ICSI,\u0026nbsp;intracytoplasmic sperm injection;\u0026nbsp;COH, controlled ovarian hyperstimulation; GnRH, gonadotropin-releasing hormone; E2, estrogen; hCG, human chorionic gonadotropin; P, progesterone.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eKruskal-Wallis p-value; \u003csup\u003e2\u003c/sup\u003eChi-Square p-value; \u003csup\u003e3\u003c/sup\u003eFisher Exact P-value; \u003csup\u003e*\u003c/sup\u003e P\u0026lt; .05.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Patients cycle characteristics and clinical pregnancy outcomes between the control group and the LMWH group.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003eLMWH\u003cbr\u003e\u0026nbsp;(N=119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003cbr\u003e\u0026nbsp;(N=2948)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of IVF/ICSI attempts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e1.0 (1.0, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1.0 (1.0, 1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eFertilization method, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.420\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e70 (58.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1885 (63.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e43 (36.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e898 (30.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eRescue ICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e6 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e165 (5.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eCOH protocols, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.213\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eGnRH-a long\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e12 (10.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e314 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eGnRH antagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e53 (44.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1038 (35.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eDepot GnRH agonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e53 (44.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1561 (53.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eOther protocols\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e35 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eE2 on hCG day, pg/mL\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e1896.0 (1383.0, 2701.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1997.0 (1391.5, 2884.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.345\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eP on hCG day, ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 (0.5, 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 (0.5, 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.375\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of oocytes retrieved\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e10.0 (7.0, 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e11.0 (7.0, 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.037\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of Metaphase II oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e9.0 (5.0, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e9.0 (6.0, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.042\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eOocyte maturation rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e0.9 (0.8, 1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e0.9 (0.8, 1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.969\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of 2PN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e5.0 (3.0, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.037\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNormal fertilization rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 (0.5, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 (0.5, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.7550\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eGood-quality embryo rate on day 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e2.0 (1.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e3.0 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.013\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eBlastocyst formation rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e0.6 (0.4, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 (0.4, 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.089\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of \u0026gt; 14 mm follicles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e9.0 (6.0, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e10.0 (7.0, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.050\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eEndometrial thickness, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e11.0 (9.4, 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e11.4 (9.9, 13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.027\u003csup\u003e1\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of embryos transferred, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e70 (58.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e2529 (85.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e49 (41.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e419 (14.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eType of embryos transferred, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.100\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003ecleavage embryo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e112 (94.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e2636 (89.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eblastocyst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e7 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e312 (10.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eClinical Pregnancy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e64 (53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1379 (46.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.133\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eLive Birth, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e45 (37.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e1195 (40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.553\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eMiscarriage, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e18 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e184 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eMultiple pregnancy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e10 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e91 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003e2\u003c/sup\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eBiochemical Pregnancy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e8 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e178 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e0.759\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.33457249070632%\" valign=\"top\"\u003e\n \u003cp\u003eEctopic pregnancy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.00371747211896%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.86245353159851%\" valign=\"top\"\u003e\n \u003cp\u003e22 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.799256505576208%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eNo., Number; PN, pronuclei.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eKruskal-Wallis p-value; \u003csup\u003e2\u003c/sup\u003eChi-Square\u0026nbsp;p-value;\u003csup\u003e\u0026nbsp;3\u003c/sup\u003eFisher Exact \u003cem\u003eP\u003c/em\u003e-value; * \u003cem\u003eP\u003c/em\u003e\u0026lt; .05.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Odds ratios of pregnancy outcomes based on the multiple logistic regression model\u003c/strong\u003e\u003cstrong\u003e，\u003c/strong\u003e\u003cstrong\u003ePSM\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e，\u003c/strong\u003e\u003cstrong\u003ePS Adjustment and IPTW.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"558\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.025089605734767%\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.32616487455197%\" colspan=\"2\"\u003e\n \u003cp\u003eMultivariate Logistic Regression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.967741935483872%\" colspan=\"2\"\u003e\n \u003cp\u003ePSM\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.71326164874552%\" colspan=\"2\"\u003e\n \u003cp\u003ePS Adjustment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.967741935483872%\" colspan=\"2\"\u003e\n \u003cp\u003eIPTW\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.025089605734767%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.32616487455197%\" colspan=\"2\"\u003e\n \u003cp\u003eN (119 vs 2948)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.967741935483872%\" colspan=\"2\"\u003e\n \u003cp\u003eN (119 vs 119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.71326164874552%\" colspan=\"2\"\u003e\n \u003cp\u003eN (119 vs 2948)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.967741935483872%\" colspan=\"2\"\u003e\n \u003cp\u003eN (119 vs 2948)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eClinical Pregnancy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003e1.54 (1.05-2.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.027*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.27 (0.76-2.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.56 (1.06-2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e0.025*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003e1.50 (1.04-2.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e0.028*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eLive Birth\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003e1.03 (0.70-1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e0.93 (0.55-1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.790\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.05 (0.70-1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e0.826\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003e1.00 (0.67-1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eMiscarriage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003e2.59 (1.52-4.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e\u0026lt;.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.94(0.86-4.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.112\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e2.63 (1.51-4.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e\u0026lt;.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003e2.57 (1.09-6.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e0.031*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eMultiple Pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003e1.29 (0.59-2.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.27 (0.48-3.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.33 (0.60-2.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e0.485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003e1.23 (0.32-4.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.086330935251798%\"\u003e\n \u003cp\u003eBiochemical Pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.532374100719425%\"\u003e\n \u003cp\u003e1.17 (0.56-2.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.00 (0.36-2.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.870503597122303%\"\u003e\n \u003cp\u003e\u0026gt;0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.992805755395683%\"\u003e\n \u003cp\u003e1.21 (0.57-2.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.79136690647482%\"\u003e\n \u003cp\u003e0.613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.633093525179856%\"\u003e\n \u003cp\u003e1.23 (0.46-3.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.23021582733813%\"\u003e\n \u003cp\u003e0.685\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"9\"\u003e\n \u003cp\u003ePSM, propensity score matching; PS, Propensity score; IPTW, inverse probability of treatment weighting.\u003c/p\u003e\n \u003cp\u003eClinical pregnancy was adjusted by Group, Age, No. of IVF/ICSI attempts, COH protocols, P on hCG day, Normal fertilization rate, No. of embryos transferred, Endometrial thickness; Live birth was adjusted by Group, Age, Spontaneous abortion history, Tubal factor, No. of IVF/ICSI attempts, COH protocols, Oocyte maturation rate, Normal fertilization rate, No. of embryos transferred, Endometrial thickness; Miscarriage was adjusted by Group, Age, BMI, Spontaneous abortion history, Tubal factor, P on hCG day, Normal fertilization rate, Endometrial thickness; Multiple pregnancy was adjusted by Group, Age, BMI, Repeated pregnancy loss, COH protocols, P on hCG day, No. of oocytes retrieved, Oocyte maturation rate, No. of embryos transferred; Biochemical Pregnancy was adjusted by Group, Age, Biochemical pregnancy history, Anovulatory, cleavage embryo.\u003c/p\u003e\n \u003cp\u003e* \u003cem\u003eP\u003c/em\u003e\u0026lt; .05.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Pregnancy outcomes in subgroup analysis.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"102%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.547169811320755%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.864493996569468%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006861063464838%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.036020583190394%\"\u003e\n \u003cp\u003eClinical pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.977701543739279%\"\u003e\n \u003cp\u003eLive Birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.922813036020584%\"\u003e\n \u003cp\u003eMiscarriage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.379073756432247%\"\u003e\n \u003cp\u003eMultiple Pregnany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.265866209262436%\"\u003e\n \u003cp\u003eBiochemical Pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.547169811320755%\" rowspan=\"6\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.864493996569468%\" rowspan=\"3\"\u003e\n \u003cp\u003e\u0026le;35\u003c/p\u003e\n \u003cp\u003e(N =2649)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006861063464838%\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.036020583190394%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003cp\u003e(59.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.977701543739279%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003cp\u003e(41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.922813036020584%\"\u003e\n \u003cp\u003e16 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.379073756432247%\"\u003e\n \u003cp\u003e8 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.265866209262436%\"\u003e\n \u003cp\u003e8 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e1256\u003c/p\u003e\n \u003cp\u003e(49.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e1101 (43.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e155 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e83(3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e164 (6.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eAdjusted P-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e0.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e0.798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.91465677179963%\" rowspan=\"3\"\u003e\n \u003cp\u003e\u0026gt;35\u003c/p\u003e\n \u003cp\u003e(N=418)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.987012987012987%\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.100185528756958%\"\u003e\n \u003cp\u003e7\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.873840445269016%\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(21.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.14100185528757%\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.471243042671615%\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.512059369202227%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003cp\u003e(31.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003cp\u003e(23.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e29 (7.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e8 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e14 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eAdjusted P-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e0.340\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.547169811320755%\" rowspan=\"6\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.864493996569468%\" rowspan=\"3\"\u003e\n \u003cp\u003e\u0026lt;=24\u003c/p\u003e\n \u003cp\u003e(N=1928）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006861063464838%\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.036020583190394%\"\u003e\n \u003cp\u003e44 (54.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.977701543739279%\"\u003e\n \u003cp\u003e33 (40.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.922813036020584%\"\u003e\n \u003cp\u003e11 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.379073756432247%\"\u003e\n \u003cp\u003e9(11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.265866209262436%\"\u003e\n \u003cp\u003e6 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e1009 (45.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e886 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e122 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e73(3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e133 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eAdjusted P-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.91465677179963%\" rowspan=\"3\"\u003e\n \u003cp\u003e\u0026gt;24 (N=639)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.987012987012987%\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.100185528756958%\"\u003e\n \u003cp\u003e20 (52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.873840445269016%\"\u003e\n \u003cp\u003e12 (31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.14100185528757%\"\u003e\n \u003cp\u003e7 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.471243042671615%\"\u003e\n \u003cp\u003e1 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.512059369202227%\"\u003e\n \u003cp\u003e2 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e370 (50.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e309 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e62 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e18 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e45 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eAdjusted P-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e0.305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e0.979\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.547169811320755%\" rowspan=\"6\"\u003e\n \u003cp\u003eRPL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.864493996569468%\" rowspan=\"3\"\u003e\n \u003cp\u003eNo RPL\u003c/p\u003e\n \u003cp\u003e(N =2943)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006861063464838%\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.036020583190394%\"\u003e\n \u003cp\u003e54 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.977701543739279%\"\u003e\n \u003cp\u003e36 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.922813036020584%\"\u003e\n \u003cp\u003e17 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.379073756432247%\"\u003e\n \u003cp\u003e6 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.265866209262436%\"\u003e\n \u003cp\u003e8 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e1341 (47.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e1166 (41.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e175 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e85 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n 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width=\"14.100185528756958%\"\u003e\n \u003cp\u003e10 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.873840445269016%\"\u003e\n \u003cp\u003e9 (45.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.14100185528757%\"\u003e\n \u003cp\u003e1 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.471243042671615%\"\u003e\n \u003cp\u003e4 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.512059369202227%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e38 (36.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e29 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e9 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e6 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e9 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.086206896551724%\"\u003e\n \u003cp\u003eAdjusted P-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\"\u003e\n \u003cp\u003e0.372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.793103448275861%\"\u003e\n \u003cp\u003e0.378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.810344827586206%\"\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.18103448275862%\"\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLMWH, low-molecular-weight heparins; BMI, body mass index; RPL, recurrent pregnancy loss.\u003c/p\u003e\n\u003cp\u003e* \u003cem\u003eP\u003c/em\u003e\u0026lt; .05.\u003c/p\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":"Low molecular weight heparin, clinical pregnancy, assisted reproductive technology, non-thrombophilic","lastPublishedDoi":"10.21203/rs.3.rs-4770813/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4770813/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePreviously, low molecular weight heparin (LMWH) has shown good anti-thrombotic effects and helped improve pregnancy outcomes for women with thrombotic diseases undergoing assisted reproductive technology (ART), prompting its use in women without thrombotic disease. However, there are few standardized medication guidelines for LMWH use in non-thrombotic patients, and it is unclear whether LMWH truly benefits pregnancy outcomes in these patients. There we want to investigate whether LMWH affects pregnancy outcomes of patients without thrombophilia undergoing ART.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 3067 infertile women who were undergoing their fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in the Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in 2019 were finally eligible for this retrospective cohort study, with 119 and 2948 administered with LMWH and without LMWH respectively. Clinical pregnancy rate (CPR) and the secondary outcomes include live birth rate (LBR), miscarriage rate (MR), multiple pregnancy rates (MPR), biochemical pregnancy rate (BPR) and ectopic pregnancy rate (EPR) were compared among these two groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBefore adjustment for confounders, MPR (8.4% vs. 3.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and MR (15.1% vs. 6.2%, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) were higher in the LMWH group while CPR (53.8% vs. 46.8%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.133), LBR (37.8% vs. 40.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.553), BPR (6.7% vs. 6.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.759) and EPR (0.0% vs. 0.7%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000) were similar compared to the control group. To investigate the correlation of LMWH administration, confounding variables were adjusted by multivariable logistic regression model and three Propensity score (PS) methods. In multivariable logistic regression, there were significantly higher CPR (AOR\u0026thinsp;=\u0026thinsp;1.54; 95% CI, 1.05\u0026ndash;2.27; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027) and MR (AOR\u0026thinsp;=\u0026thinsp;2.93; 95% CI, 1.73\u0026ndash;4.97; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) among patients with LMWH, without an increase in LBR (AOR\u0026thinsp;=\u0026thinsp;1.03; 95% CI, 0.70\u0026ndash;1.53; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.877), MPR (AOR\u0026thinsp;=\u0026thinsp;1.29; 95% CI, 0.59\u0026ndash;2.81; P\u0026thinsp;=\u0026thinsp;0.529), BPR (OR\u0026thinsp;=\u0026thinsp;1.17, 95% CI, 0.56\u0026ndash;2.45; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.674), which were consistent in PS Adjustment, and Inverse Probability of Treatment Weighting using propensity score (IPTW), but not in the Propensity score matching (PSM) (1:1) analysis. Subgroup analyses showed that CPR and MR were increased in the LMWH group in the patients with age\u0026thinsp;\u0026le;\u0026thinsp;35 years, body mass index (BMI)\u0026thinsp;\u0026le;\u0026thinsp;24 and without recurrent pregnancy loss (RPL).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLow molecular weight heparin may improve clinical pregnancy but not live birth in non-thrombophilic women undergoing ART.\u003c/p\u003e","manuscriptTitle":"Low molecular weight heparin increases clinical pregnancy rate in non-thrombophilic women undergoing assisted reproductive technology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-19 23:59:33","doi":"10.21203/rs.3.rs-4770813/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":"5a255557-cbd3-4fa3-95cf-a3a6c064ad1d","owner":[],"postedDate":"August 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-26T12:38:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-19 23:59:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4770813","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4770813","identity":"rs-4770813","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}