Effects of Management of Heavy Menstrual Bleeding of Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation

Effects of Management of Heavy Menstrual Bleeding of Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effects of Management of Heavy Menstrual Bleeding of Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation Xin Yang, Ruxue Han, Feifeng Zhang, Xiaolin Jiang, Chaohua Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3430942/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 Objective Heavy menstrual bleeding (HMB) was an underestimated bleeding complications of hematopoietic stem cell transplantation (HSCT). The study aims to investigate the benefits of menstrual management in women undergoing HSCT. Methods Patients who had undergone HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included in ten years. The data of hematology and menstruation of all participants had been collected. The management methods of intervention group include GnRHa, COC or low-dose mifepristone. Patients who did not receive management were included in the control group. Results There were 112 patients included in the intervention group and 218 patients included in the control group. There were 90.0% of patients presenting with HMB before HSCT. In the control group, 83.5% of patients experienced uterine bleeding in the LAFR, while only 22.3% did in the intervention group. The rate of recurrent uterine bleeding after HSCT was significantly higher in the control group (50.9% vs. 17.9%, P < 0.001). Patients who did not undergo menstrual management had a higher risk of uterine bleeding than those who did (OR = 18.12, P < 0.001). Conclusion Menstrual management significantly reduces the incidence of uterine bleeding in HSCT patients and acts as a protective factor against uterine bleeding in the LAFR. Health sciences/Risk factors Health sciences/Health care/Disease prevention/Preventive medicine hematological diseases hematopoietic stem cell transplantation heavy menstrual bleeding menstrual management thrombocytopenia Figures Figure 1 Figure 2 1 Introduction Bleeding complications from different systems are important complications of hematopoietic stem cell transplantation (HSCT). High-dose chemotherapy in HSCT conditioning regimens can damage bone marrow cells and blood cells. Before HSCT, patients face varying degrees of overall blood cell reduction. Other post-HSCT complications, such as graft vs. host disease (GVHD), may also exacerbate bleeding and affect patients' clotting function, thereby increasing the risk of post-transplant bleeding. Post-transplant bleeding is associated with decreased patient survival rates [ 1 – 3 ] . Pulmonary bleeding and gastrointestinal bleeding are the most common life-threatening bleeding sites, followed by the central nervous system [ 3 ] . However, most studies focus on overall bleeding after HSCT. Currently, the domestic consensus on the management of bleeding complications after HSCT mainly focuses on skin and mucous membranes, the urinary tract, the digestive tract, intracranial, and alveolar bleeding [ 4 ] . Pre-menopausal females constitute a special group, as they experience periodic menstrual cycles before HSCT. However, there is a very limited number of studies evaluating uterine bleeding during HSCT. Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that affects quality of life. Due to the poor correlation between patient perception and objective menstrual blood volume, as well as the lack of validated diagnostic tools, this is an under-diagnosed and under-treated disease [ 5 ] . National Institute for Health and Care Excellence (NICE) pointed out that HMB should be defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms [ 6 ] . For reproductive-aged women, the symptom of heavy menstrual bleeding is highly prevalent and a major contributor to iron deficiency anemia [ 7 ] . Moreover, the clinical management of abnormal uterine bleeding due to clotting-related disorders (referred to as AUB-C) is challenging. HMB is the most common manifestation of AUB in patients with hematological diseases. For HSCT patients, underlying hematological conditions, chemotherapy regimens, and pre-transplant conditioning can lead to platelet reduction, potentially causing HMB. Among female patients who have not undergone menstrual management before HSCT, the incidence of moderate to HMB can be as high as 40% [ 8 ] , significantly affecting the treatment of underlying diseases and patient safety. Due to the lack of emphasis on menstrual management for pre-menopausal females, there are instances of hematologists using combined oral contraceptives (COC) or hormonal agents inappropriately for gynecologic hemostasis. Menstrual management refers to the use of hormonal medications to decrease the frequency and volume of physiologic menses and, in some cases, achieving amenorrhea [ 9 ] . Uncontrollable HMB in the laminar air-flow room (LAFR) will seriously affect the patient's treatment and life safety. According to the recommendations of existing guidelines [ 8 ] , comprehensive assessments in the field of obstetrics and gynecology should be conducted for HSCT patients before entering the transplant unit. Currently, the focus on female HSCT patients is primarily on preserving fertility and protecting ovarian function. However, there is also a lack of data concerning uterine bleeding during HSCT for pre-menopausal patients, and menstrual management for these patients has not received sufficient attention. Previous studies by our team have shown that GnRHa can effectively reduce the rate of uterine bleeding in LAFR in HSCT patients [ 10 ] . This study aims to investigate the menstrual status in the laminar air-flow room (LAFR) [ 11 ] and associated risks in HSCT patients, providing a reference for the assessment and management of gynecological aspects for hematological disease patients, especially HMB patients, in the future. 2 Method This was a retrospective cohort study. We affirm that: (i) the study was approved by the Ethics Committee of Peking University People's Hospital (No. 2015PHB087-01), including any relevant details; and (ii) all experiments were performed in accordance with relevant guidelines and regulations. All research was performed in accordance with relevant regulations, and appropriate consent was obtained from all participants and/or their legal guardians and signed by the patients or their families. From December 2012 to December 2022, premenopausal female patients who had undergone or were to undergo HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included. Patients with hematological diseases at Peking University People's Hospital routinely undergo gynecological physical examination before HSCT. The inclusion criteria were as follows: (1) women undergoing myeloablative chemotherapy HSCT for hematological diseases; (2) premenopausal patients; and (3) patients underwent HSCT at the Blood Research Institute of Peking University People's Hospital. The exclusion criteria were as follows: (1) Patients who did not use drugs regularly; (2) patients who were unable to survive during HSCT; (3) patients with incomplete clinical data; and (4) patients who received less than 2 courses of GnRHa treatment before myeloablative chemotherapy;(5) Patients who had not yet undergone HSCT. After screening 479 patients, 330 patients were finally included in the study (Fig. 1). The data of hematology and gynecology of all participants had been collected. After informed consent, patients could choose whether to receive menstrual management before HSCT. The patients who recieved menstrual management would be included in the intervention group. The main management methods include gonadotropin-releasing hormone agonist (GnRHa) injection, COC or low-dose mifepristone. Patients who were not counseled on menstrual management before HSCT or did not adopt after counseling were included in the control group. Hematology-related information and gynecology-related information includes would be cellected by gynecological doctors. This study involves the following definitions:(1) Mild anemia: 90g/L ≤ hemoglobin < 120g/L; Moderate anemia: 60g/L ≤ hemoglobin <90g/L; Severe anemia: hemoglobin < 60g/L; (2) Severe thrombocytopenia: platelet count 40U/L or ALT > 40U/L; (4) Abnormal kidney function: Creatinine (Cr) > 104µmol/L. All data were statistically processed using SPSS 22.0 (SPSS Inc., Chicago, IL). Continuous variables are described as mean ± standard deviation and compared using the t-test. For continuous variables that do not follow a normal distribution, descriptions are provided using the median (25th and 75th percentiles), and analysis is conducted using the Mann-Whitney U test. Categorical variables are described using frequencies and proportions, and comparisons of categorical variables are made using the chi-squared test or Fisher's exact test. Logistic regression analysis was performed to identify factors related to uterine bleeding in the LAFR and severe anemia. A significance level of P < 0.05 indicates statistical significance. 3 Result 3.1 Basic hematological disease information for the study population The general conditions of the study population are shown in Table 1 . This study ultimately included a total of 330 patients who underwent HSCT due to hematological diseases. There were 112 patients in the intervention group (112/330, 33.9%) and 218 patients in the control group (218/330, 66.1%). The age of patients at the time of transplantation ranged from 11 to 51 years old. The average age of patients in the intervention group at admission was 25.73 ± 7.37 years, while in the control group, it was 28.23 ± 8.27 years, with no significant difference between the two groups (P = 0.051). The primary hematological diseases were malignant hematological diseases, with ALL, AML, and MDS accounting for 32.7% (108/330), 37.0% (125/330), and 11.5% (38/330) of the total number of patients, respectively. A total of 10.61% (35/330) had non-malignant hematological disease AA, and other hematological diseases for HSCT included chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, among others. There was a statistically significant difference between the two groups in terms of the primary hematological diseases (P = 0.004). Due to different treatment regimens for primary hematological diseases (benign hematological diseases do not undergo chemotherapy), there was a statistically significant difference between the two groups in whether they underwent chemotherapy (85.3% vs. 67.0%, P < 0.001). HLA-haploidentical hematopoietic stem cell transplantation was the primary transplantation method for both groups (80.7% vs. 85.7%, P = 0.260), and there was no significant difference in the incidence of GVHD between the two groups after transplantation (P = 0.664). Table 1 Patient characteristics according to whether got menstrual management Characterics Intervention Group, n = 112(%) Control Group, n = 218(%) P value Age(mean ± SD),yrs 25.73 ± 7.37 28.23 ± 8.27 0.051 Hematologic diseases type 0.004 ALL 35(31.3) 73(33.5) AML 34(30.4) 91(41.7) AA 21(18.8) 14(6.4) MDS 16(14.3) 22(25.1) Other 6(5.4) 18(8.3) HLA-matched situation 0.260 HLA-matched 16(14.3) 42(19.3) HLA-haploidentical 96(85.7) 176(80.7) Cyclic chemotherapy before HSCT <0.001 Yes 75(67.0) 186(85.3) No 37(33.0) 32(14.7) GVHD 0.664 Yes 76(67.9) 153(70.2) No 36(32.1) 65(29.8) P value indicates the differences between the two groups. ALL, Acute lymphocytic leukemia; AML, Acute myelogenous leukemia; AA, Aplastic anemia; MDS, myelodysplastic syndrome; HSCT, hematopoietic stem cell transplantation; GVHD, graft vs host disease. 3.2 Menstrual and general conditions of patients before HSCT Most patients had varying degrees of anemia before HSCT, and only 16.1% of patients were free of anemia. Mild anemia was the most common (54.6%) degree, with 3.9% of patients having hemoglobin levels below 60g/L. Patients in the intervention group had a higher proportion and more severe anemia compared with the control group (Fig. 2). And 35.2% (116/330) of patients who required medication for hemostasis. Totally, there were 90.0% of patients presenting with HMB (accompanied by anemia or required medication for hemostasis). More patients in the intervention group had already required medication for menstrual management before HSCT (43.8% vs. 30.7%, P = 0.019). There were no differences between the two groups in terms of hemoglobin levels, coagulation parameters (PT, APTT, FIB), and liver and kidney function on the day of admission. However, the platelet levels of patients in the intervention group on the day of admission were significantly lower than those in the control group, although their mean values were within the normal range (126.63 ± 93.39 vs. 168.02 ± 83.58, P < 0.001) (Table 2 ). Table 2 Menstrual and general conditions of patients before HSCT Intervention Group, n = 112(%) Control Group, n = 218(%) P value Required medication for uterine bleeding hemostasis Yes 49(43.8) 67(30.7) 0.019 No 63(56.3) 151(69.3) General conditions Hemoglobin levels(g/L) 97.02 ± 22.54 101.68 ± 19.23 0.063 Platelet count(×10 9 /L) 126.63 ± 93.39 168.02 ± 83.58 <0.001 Coagulation parameters PT(s) 11.63 ± 0.90 11.74 ± 0.96 0.35 APTT(s) 31.48 ± 8.69 31.71 ± 9.14 0.985 FIB(mg/dL) 300.54 ± 62.64 278.13 ± 62.68 0.909 Liver and kidney function ALT(U/L) 22.26 ± 15.07 20.12 ± 15.98 0.999 AST(U/L) 21.53 ± 11.40 20.15 ± 9.57 0.217 Cr(µmol/L) 47.75 ± 10.30 46.14 ± 9.93 0.668 P value indicates the differences between the two groups. 3.3 Uterine bleeding and related hematological examinations of patients in LAFR In the control group, 83.5% (182/218) of patients experienced varying degrees of uterine bleeding in the LAFR, while in the intervention group, only 22.3% (25/112) did. This difference is statistically significant (P < 0.001). There were no differences between the two groups in terms of minimum hemoglobin and platelet count in the LAFR. The number of days with severe thrombocytopenia was 11.75 ± 6.37 days in the control group and 10.79 ± 4.97 days in the intervention group (P = 0.247). Among the patients who underwent menstrual management in the intervention group, 65.2% (73/112), and 57.3% (125/218) of the control group could recover to 90g/L within 30 days after reaching the lowest hemoglobin level, but this difference was not statistically significant (P = 0.169). There was no difference in the rate of liver and kidney function abnormalities between the two groups. The Mann-Whitney U test was used to assess whether there were differences in the transfusion volume of red blood cells, plasma, and platelets between the intervention and control groups. The Mann-Whitney U test results showed no statistically significant differences in the transfusion volume of these three blood components between the two groups (P = 0.661, P = 0.848, P = 0.186). Furthermore, we recorded instances of bleeding in other systems within the cabin. Patients in the intervention group had higher rates of bleeding in skin and mucous membranes, as well as major organ systems, compared to the control group, but there were no statistically significant differences between the two groups (P = 0.050). The rate of recurrent uterine bleeding after HSCT was significantly higher in the control group compared to the intervention group (50.9% vs. 17.9%, P < 0.001). In the control group, 83.5% (182/218) of patients experienced new uterine bleeding in the LAFR, while in the intervention group, only 22.3% (25/112) did. The rate of new uterine bleeding in the LAFR in the control group was significantly higher than that in the intervention group (P < 0.001). The degree of uterine bleeding in the LAFR in patients is shown in Table 3 . In both the intervention and control groups, the majority of patients with new bleeding was similar to menstrual flow. Although there was no statistical difference, no cases of bleeding exceeding menstrual flow occurred in the intervention group, while there were 3 cases (3/218, 1.4%) in the control group. (Table 3 ) Table 3 Uterine bleeding and related hematological examinations of patients in the LAFR Intervention Group, n = 112(%) Control Group, n = 218(%) P value Uterine bleeding in LAFR No bleeding 87(77.7) 36(16.5) <0.001 Less than menstrual flow 8(7.1) 15(6.9) 0.929 Similar to menstrual flow 17(15.2) 164(75.2) <0.001 More than menstrual flow 0(0) 3(1.4) 0.212 Minimum hemoglobin (g/L) 68.38 ± 12.34 67.98 ± 10.96 0.168 Minimum platelet count (×10 9 /L) 10.79 ± 4.97 11.75 ± 6.37 0.989 Number of days with severe thrombocytopenia (days) 8.20 ± 4.97 7.58 ± 4.26 0.247 Liver function 0.387 Abnormal 92(94.7) 187(85.8) Normal 20(17.3) 31(14.2) Kidney function 0.396 Abnormal 7(6.3) 9(4.1) Normal 105(93.8) 209(95.9) Blood transfusion Red blood cells (U) 2(0,6) 4(2,6) 0.661 Plasma (ml) 0(0,0) 0(0,0) 0.848 Platelets (U) 5(3,7.75) 5(3,6) 0.186 Systemic bleeding 0.05 No bleeding 72(64.3) 165(75.7) Mucocutaneous hemorrhage 13(11.6) 12(5.5) Major organ system bleeding (eg, hemorrhagic cystitis or gastrointestinal bleeding) 27(24.1) 41(18.8) Uterine bleeding after HSCT <0.001 Yes 20(17.9) 111(50.9) No 92(82.1) 107(49.1) P value indicates the differences between the two groups. LAFR, laminar air-flow room In addition, among patients who had anemia after HSCT, the uterine bleeding rate of patients who chose menstrual management was 21.9%(21/96), while the uterine bleeding rate of patients without intervention was 84.0%(152/181), and the difference was statistically significant(P<0.001). 3.4 Analysis of related factors of uterine bleeding in LAFR in patients with HSCT In order to screen for risk factors of uterine bleeding in the LAFR of HSCT patients, factors with a single-factor analysis P-value < 0.2 were included in the logistic regression analysis. Logistic regression analysis showed that only whether menstrual management was performed before admission was related to uterine bleeding. Patients who did not undergo menstrual management had a significantly higher risk of uterine bleeding than those who did (OR = 18.12, 95% CI 9.638–34.066, P < 0.001). (Table 4 ) Table 4 Risk factors for uterine bleeding in the LAFR. Variables Univariate P value Multivariate HR 95% P value Menstrual management <0.001 18.12 9.638–34.066 <0.001 Hematologic diseases type 0.360 HLA-matched situation 0.679 GVHD 0.069 0.569 0.307–1.055 0.074 Cyclic chemotherapy before HSCT 0.231 Menstrual conditions before HSCT <0.001 1.283 0.694–2.371 0.427 Required medication for uterine bleeding hemostasis 0.169 0.963 0.529–1.753 0.901 Systemic bleeding 0.097 No bleeding 1 1 0.092 Mucocutaneous hemorrhage 1.755 0.596–5.169 0.308 Major organ system bleeding 0.54 0.270–1.078 0.081 Age 0.917 Hemoglobin before HSCT 0.404 Platelet count before HSCT 0.831 PT before HSCT 0.694 APTT before HSCT 0.619 FIB before HSCT 0.577 Minimum platelet count 0.686 Number of days with severe thrombocytopenia 0.043 1.009 0.947–1.075 0.788 P value indicates the differences between the two groups. GVHD, graft vs host disease; HSCT, hematopoietic stem cell transplantation. 3.5 Analysis of related factors of severe anemia in the LAFR of patients undergone HSCT Severe anemia was defined as hemoglobin < 60g/L, and factors related to a decrease in hemoglobin to severe anemia in the LAFR were analyzed. After conducting a single-factor correlation analysis of factors related to intra-LAFR hemoglobin, variables with P < 0.2 and whether menstrual management was chosen were included in the logistic regression analysis. The results suggested that factors related to severe anemia included the occurrence of GVHD, the presence of uterine bleeding, and the hemoglobin level before pretreatment. Patients without uterine bleeding were less likely to develop severe anemia (OR = 0.243, 95% CI 0.097–0.608, P = 0.003). (Table 5 ) Table 5 Risk factors for severe anemia after HSCT. Variables Univariate P value Multivariate HR 95% P value Menstrual management 0.590 0.465 0.194–1.113 0.086 Hematologic diseases type <0.001 ALL 2.397 0.704–8.158 0.162 AML 1.855 0.569–6.040 0.305 MDS 5.243 0.983–27.972 0.052 AA 5.26 0.901–30.720 0.065 HLA-matched situation 0.054 0.407 0.156–1.062 0.066 GVHD 0.035 2.051 1.077–3.906 0.029 Cyclic chemotherapy before HSCT <0.001 0.407 0.156–1.062 0.141 Menstrual conditions before HSCT 0.991 Required medication for uterine bleeding hemostasis HSCT 0.583 Uterine bleeding in LAFR 0.039 0.243 0.097–0.608 0.003 Systemic bleeding 0.329 Age 0.764 Hemoglobin before HSCT <0.001 0.958 0.939–0.979 <0.001 Platelet count before HSCT <0.001 1 0.996–1.005 0.869 PT before HSCT 0.131 1.117 0.813–1.534 0.495 APTT before HSCT 0.719 FIB before HSCT 0.950 Minimum platelet count 0.720 Number of days with severe thrombocytopenia 0.101 1.042 0.973–1.117 0.238 P value indicates the differences between the two groups. ALL, Acute lymphocytic leukemia; AML, Acute myelogenous leukemia; AA, Aplastic anemia; MDS, myelodysplastic syndrome; HSCT, hematopoietic stem cell transplantation; GVHD, graft vs host disease; LAFR, laminar air-flow room. 3.6 Effects of different menstrual management methods on outcomes A total of 112 patients were included in the intervention group of the study, including 85 who chose GnRHa, 19 who chose continuous oral COC, and 8 who chose oral Mifepristone. The LAFR uterine bleeding rates in the GnRHa group, COC group, and Mifepristone group were 12.9% (11/85), 73.7% (14/19), and 0%, respectively, all lower than the control group (182/218, 83.5%). The post-LAFR uterine bleeding rates for the GnRHa and Mifepristone groups were 7.1% (6/85) and 12.5% (1/8), respectively, both lower than the control group (111/218, 50.9%). Furthermore, we observed that the Mifepristone group had lower pre-processing levels of hemoglobin and platelets than the other three groups. (Table 6 ) Table 6 The outcomes of different menstrual management methods GnRHa group, n = 85(%) COC group, n = 19(%) Mifepristone group, n = 8(%) Control group, n = 218(%) Uterine bleeding in LAFR 11(12.9) 14(73.7) 0(0) 182(83.5) Uterine bleeding after HSCT 6(7.1) 13(68.4) 1(12.5) 111(50.9) Hemoglobin before HSCT 99.02 ± 22.35 92.26 ± 22.10 87.00 ± 24.05 101.68 ± 19.23 Platelet count before HSCT 131.02 ± 89.92 124.26 ± 107.00 83.75 ± 97.28 168.02 ± 83.58 Minimum hemoglobin(g/L) 70.20 ± 12.44 62.21 ± 9.22 63.75 ± 13.13 67.98 ± 10.96 Number of days with severe thrombocytopenia 7.56 ± 4.45 10.26 ± 6.04 10.00 ± 6.68 7.58 ± 4.26 LAFR, laminar air-flow room; HSCT, hematopoietic stem cell transplantation. 4 Discussion Patients with benign or malignant hematological diseases may experience abnormal hematological conditions, particularly thrombocytopenia, due to underlying diseases, chemotherapy regimens, HSCT conditioning, and other reasons, making them susceptible to HMB. Current research has found that in patients with normal ovarian function, chemotherapy-induced thrombocytopenia can lead to HMB in 40% of cases [ 12 ] . However, the potent gonadotoxicity of chemotherapy during HSCT conditioning often results in ovarian dysfunction, subsequent hormonal imbalances, further increasing the incidence of HMB, and complicating the patient's condition. Therefore, menstrual management of premenopausal women scheduled for HSCT is crucial in reducing the incidence of uterine bleeding during transplantation and preventing HMB. There is relatively limited research on the feasibility and effectiveness of premenstrual management before HSCT to prevent secondary HMB due to hematological changes in patients after conditioning. Our study aims to investigate the impact of menstrual management before HSCT on uterine bleeding in the LAFR and provide reference for menstrual management of HMB patients. In clinical admissions, there is a high proportion of blood disorder patients complaining of HMB. Due to the poor correlation between patient perception and objective menstrual blood volume, as well as the lack of validated diagnostic tools, HMB is an under-diagnosed and under-treated disease [ 5 ] . NICE pointed out that HMB should be defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms [ 6 ] Anemia can be used as a reference for HMB. Anemia has a wide range of health impacts on female patients, including causing nonspecific symptoms such as fatigue, irritability, hair loss, lack of concentration, palpitations, and dizziness. Severe anemia can lead to arrhythmias, edema, and even heart failure in patients, as well as an increased need for blood transfusions [ 13 , 14 ] . Our study found that 83.9% of patients had varying degrees of anemia before HSCT, suggesting a high likelihood of HMB. Including patients who need medication for hemostasis before HSCT, the proportion of HMB patients in the enrolled population can reach 90% (297/330). At the same time, these patients were a high-risk group for massive uterine bleeding in the LAFR. Menstrual management before HSCT significantly reduced the incidence of uterine bleeding in HSCT patients in the LAFR. The incidence of uterine bleeding in the LAFR was as high as 83.5% in the control group, which in the intervention group was only 22.3%. Compared with the incidence of uterine bleeding in the LAFR reported by Dror et al. [ 15 ] in a retrospective study in 2006 (13/20, 65.0%), the control group in our study had a higher incidence. Regarding the outcomes of patients who had HMB before HSCT (patients with anemia), menstrual management could significantly reduce the risk of uterine bleeding during HSCT for these patients. In both groups, uterine bleeding pattern was mainly equivalent to menstrual bleeding. It is important to note that bleeding that patients describe as "similar to menstrual flow" may amount to HMB. In the intervention group, there was no bleeding greater than menstrual bleeding, which may indicate that menstrual management can effectively prevent significant uterine bleeding in the LAFR. The medical records revealed that among the 25 patients who experienced uterine bleeding in the intervention group, 14 were users of oral COC. The incidence of uterine bleeding in the COC group reached 73.7%. The occurrence of uterine bleeding in COC users may be related to breakthrough bleeding during the low-dose maintenance phase of oral COC [ 16 ] . There was a statistically significant difference between the two groups in post-discharge uterine bleeding. In the control group, 50.9% of patients experienced uterine bleeding ≥ 1 time, while in the intervention group, only 17.9% had bleeding. Patients used GnRHa or Mifepristone had a lower rate of recurrence of uterine bleeding after discontinuation, indicating that GnRHa and medroxyprogesterone acetate may have a better induction effect on amenorrhea, with a lower risk of recurrence of bleeding after discontinuation. The intervention group exhibited a higher proportion of drug-induced AUB hemostasis and lower platelet levels before HSCT, indicating a higher likelihood of previous experience with HMB in these patients. Consequently, they are more vigilant about the risk of HMB and have a stronger awareness of menstrual management. And it was found during retrospective collection of medical records that some patients did not undergo gynecological consultations or seek advice on menstrual management before HSCT. Though the awareness of routine gynecological examinations for HSCT patients before transplantation is gradually increasing, the awareness of menstrual management is lacking. Most patients seek acute hemostasis in gynecology clinics when HMB has already occurred, but this undoubtedly increases the difficulty and risk of hemostasis, and even endangers the patient's life. This suggests the importance of strengthening collaboration between hematology and obstetrics and gynecology departments in the future. Analysis of factors related to uterine bleeding in the LAFR suggested that only menstrual management was associated with it. The risk of uterine bleeding in patients who did not undergo menstrual management was 18.12 times that of patients who underwent that. This indicates that regardless of the patient's primary disease or the menstrua status before HSCT, menstrual management can effectively reduce the risk of uterine bleeding in the LAFR, thereby preventing the occurrence of HMB before platelet engraftment. After analyzing the factors related to severe anemia in the LAFR, although there was no correlation between menstrual management and severe anemia, there was a correlation between uterine bleeding and hemoglobin reaching severe anemia levels. The intervention group's patients were managed with three menstrual management methods: GnRHa, COC, and Mifepristone. The Mifepristone group achieved a 100% rate of amenorrhea in the LAFR, followed by the GnRHa group. The COC group had a uterine bleeding rate of 73.7%. However, regardless of the intervention method, the uterine bleeding rate in the LAFR was lower than that in the control group (83.5%). When comparing the pre-processing conditions before HSCT, we found that the pretreatment hemoglobin and platelet levels of the three menstrual management methods were lower than those in the control group. Especially in the Mifepristone group, the hemoglobin and platelet levels were lower than in the other two intervention groups. Mifepristone was initially used for early pregnancy medical abortion due to its anti-progestin effects, and its indications have expanded to include common gynecological conditions such as uterine fibroids and endometriosis. Mifepristone not only has anti-progestin effects but also affects the hypothalamic-pituitary-ovarian axis. It can act on the hypothalamus to inhibit the secretion of gonadotropin-releasing hormone, affecting FSH and LH secretion, and it can also directly act on the pituitary gland to inhibit FSH and LH release, further lowering serum FSH and LH levels, inducing amenorrhea [ 17 ] . Mifepristone's indications have not yet been included in HMB, but studies in AUB caused by AUB-L and AUB-A have observed that low-dose (2.5-10mg) Mifepristone can achieve amenorrhea rates of 41-98.9% [ 18 – 24 ] , and high-dose (50mg) Mifepristone can achieve a 100% amenorrhea rate [ 25 ] . In our gynecological endocrine clinic, in patients with refractory HMB patients who still have poor hemostasis with ultra-high-dose hormone drugs, adding Mifepristone and gradually reducing the dose of hormone drugs can gradually transition patients to amenorrhea. This may explain why the hemoglobin and platelet levels before pretreatment in the Mifepristone group were lower than those in the other two groups. Mifepristone is often chosen by patients due to low platelet counts and poor effectiveness of hormone drugs. Because the time of using Mifepristone as a menstrual management option is relatively short, this study included only 8 patients using Mifepristone. However, in these 8 patients, the amenorrhea induction effect was satisfactory (8/8, 100%), at a dose of 25mg QD. Nevertheless, further studies with a larger sample size are needed to validate its amenorrhea rate and safety. Each of the three menstrual management methods has its advantages and disadvantages. GnRHa induces amenorrhea by promoting the release of gonadotropins, leading to desensitization of GnRH receptors and inhibiting pulsatile secretion of GnRH, thereby achieving menstrual management in a low gonadotropin state. The advantage of GnRHa is that it does not require daily use. However, the guidelines require patients to receive a GnRHa injection at least 14 days before pre-treatment to prevent heavy uterine bleeding. [ 12 ] . Platelet count < 10×10 9 /L is a contraindication for its use. The effectiveness of GnRHa in reducing uterine bleeding during the period of platelet reduction has been confirmed [ 26 ] . In a 2006 retrospective study, the intra-LAFR amenorrhea rate of GnRHa was 76.9% (30/39) [ 15 ] , and a 2016 retrospective study showed an amenorrhea rate of up to 88% (29/33)in the LAFR [ 27 ] , which is similar to the results of this study (74/85, 87.1%). Both COC and Mifepristone require daily oral maintenance doses of medication, but they do not have specific requirements for the time and platelet levels before HSCT pretreatment and can be started at any time. COC can suppress ovulation and stabilize hormone levels to suppress menstruation. However, COC is associated with increased breakthrough bleeding after missed doses and continuous medication, and it requires some degree of patient compliance. This study also found that even in patients taking medication regularly, there was still a 73.7% intra-LAFR uterine bleeding rate. In addition, COC has relatively more contraindications and a risk of deep vein thrombosis [ 28 ] . This study is the first to describe the impact of pre-transplant menstrual management on uterine bleeding in Chinese HSCT patients and proposes Mifepristone as a menstrual induction medication for high-risk bleeding populations. However, this study still has limitations: a small sample size, various confounding factors, and the selection bias and recall bias associated with a retrospective design. We hope that in the future, large-sample prospective controlled studies can further validate the effectiveness and safety of menstrual management methods in preventing uterine bleeding in HSCT patients. We also hope to work with hematologists to raise awareness of gynecological management before transplantation in patients with hematological diseases to reduce treatment risks and improve patients' quality of life. 5 Conclusion Menstrual management significantly reduces the incidence of uterine bleeding in HSCT patients and it can be used as a method to prevent uterine bleeding within LAFR in patients with HMB. In this study, the rates of uterine bleeding for all three menstrual management methods were lower than in the control group. Mifepristone, as a relatively safe contraceptive hormone, demonstrated a good effect in inducing amenorrhea in this study, but its effectiveness still requires confirmation through large-sample prospective research. Declarations Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions Ruxue Han: Data curation, Formal analysis, Investigation, Writing- Original draft preparation Feifeng Zhang: Data curation, Investigation, Writing- Original draft preparation Xiaolin Jiang: Data curation Chaohua Wang: Methodology, Data curation, Supervision Xin Yang: Methodology, Writing- Reviewing and Editing, Funding acquisition Funding The study was supported by Roche Diagnostics: Dynamic study for the effects of chemotherapy and bone marrow transplantation on ovarian function in pre-adolescent hematological disease survivors (Project no.2018PHB085-01). Data Availability The datasets used and analysed during the current study available from the corresponding author on reasonable request. References Jorge L, Lucia L-A, Estefania P-L, et al. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients [J]. Haematologica, 2013, 98(3): 437-443. Gerber D E, Segal J B, Levy M Y, et al. The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention [J]. Blood, 2008, 112(3): 504-510. Labrador J, López-Corral L, Vazquez L, et al. Incidence and risk factors for life-threatening bleeding after allogeneic stem cell transplant [J]. Br J Haematol, 2015, 169(5): 719-725. Pihusch M. Bleeding complications after hematopoietic stem cell transplantation [J]. Semin Hematol, 2004, 41(1 Suppl 1): 93-100. Perelló J, Rius Tarruella J, Calaf J. Heavy menstrual bleeding and its detection in clinical practice [J]. Med Clin (Barc), 2021, 157(7): 332-338. National Institute for Health and Care Excellence: Clinical Guidelines [M]. Heavy menstrual bleeding: assessment and management. London; National Institute for Health and Care Excellence (NICE) Copyright © NICE 2021. 2021. Munro M G, Mast A E, Powers J M, et al. The relationship between heavy menstrual bleeding, iron deficiency, and iron deficiency anemia [J]. Am J Obstet Gynecol, 2023, 229(1): 1-9. Chang K, Merideth M A, Stratton P. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation [J]. Obstet Gynecol, 2015, 126(4): 779-784. General Approaches to Medical Management of Menstrual Suppression: ACOG Clinical Consensus No. 3 [J]. Obstet Gynecol, 2022, 140(3): 528-541. Han R, Song Z, Li H, et al. Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation [J]. Sci Rep, 2023, 13(1): 14497. Yokoe D, Casper C, Dubberke E, et al. Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated [J]. Bone Marrow Transplant, 2009, 44(8): 495-507. Chang K, Merideth M A, Stratton P. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation [J]. Obstetrics & Gynecology, 2015, 126(4): 779-784. Percy L, Mansour D, Fraser I. Iron deficiency and iron deficiency anaemia in women [J]. Best Pract Res Clin Obstet Gynaecol, 2017, 40: 55-67. Mirza F G, Abdul-Kadir R, Breymann C, et al. Impact and management of iron deficiency and iron deficiency anemia in women's health [J]. Expert Rev Hematol, 2018, 11(9): 727-736. Meirow D, Rabinovici J, Katz D, et al. Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate [J]. Cancer, 2006, 107(7): 1634-1641. Bitzer J. Oral contraceptives in adolescent women [J]. Best Pract Res Clin Endocrinol Metab, 2013, 27(1): 77-89. Cameron S, Reynolds-Wright J. Mifepristone at home [J]. Bmj, 2022, 376: o819. Donnez J, Dolmans M M, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue [J]. Lancet, 2004, 364(9443): 1405-1410. Carbonell J L, Acosta R, Pérez Y, et al. Treatment of Uterine Myoma with 2.5 or 5 mg Mifepristone Daily during 3 Months with 9 Months Posttreatment Followup: Randomized Clinical Trial [J]. ISRN Obstet Gynecol, 2013, 2013: 649030. Carbonell J L, Riverón A M, Leonard Y, et al. Mifepristone 2.5, 5, 10 mg versus placebo in the treatment of endometriosis [J]. Journal of Reproductive Health and Medicine, 2016, 2(1): 17-25. Esteve J L, Acosta R, Pérez Y, et al. Mifepristone versus placebo to treat uterine myoma: a double-blind, randomized clinical trial [J]. Int J Womens Health, 2013, 5: 361-369. Fiscella K, Eisinger S H, Meldrum S, et al. Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial [J]. Obstet Gynecol, 2006, 108(6): 1381-1387. Bagaria M, Suneja A, Vaid N B, et al. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial [J]. Aust N Z J Obstet Gynaecol, 2009, 49(1): 77-83. Esteve J L, Acosta R, Pérez Y, et al. Treatment of uterine myoma with 5 or 10mg mifepristone daily during 6 months, post-treatment evolution over 12 months: double-blind randomised clinical trial [J]. Eur J Obstet Gynecol Reprod Biol, 2012, 161(2): 202-208. Engman M, Granberg S, Williams A R, et al. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial [J]. Hum Reprod, 2009, 24(8): 1870-1879. Bates J S, Buie L W, Woodis C B. Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy [J]. Pharmacotherapy, 2011, 31(11): 1092-1110. Poorvu P D, Barton S E, Duncan C N, et al. Use and Effectiveness of Gonadotropin-Releasing Hormone Agonists for Prophylactic Menstrual Suppression in Postmenarchal Women Who Undergo Hematopoietic Cell Transplantation [J]. J Pediatr Adolesc Gynecol, 2016, 29(3): 265-268. De Bastos M, Stegeman B H, Rosendaal F R, et al. Combined oral contraceptives: venous thrombosis [J]. Cochrane Database Syst Rev, 2014, (3): Cd010813. Additional Declarations The authors have declared there is NO conflict of interest to disclose. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3430942","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":242258484,"identity":"e92c4791-818e-434f-8c99-7e6c68033bd2","order_by":0,"name":"Xin Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYDACZijNz8zY/OADgwQJWiTbm48ZziBKCwwYnDmWIM1DlMrjvMckfu6oZWC4kWNgbPPHIo+/gfnhoxt4tEg286VJ9p45zsA4I8fgcW6bRLHEATZj4xw8WviZecwkeNuOMTBLAG3JbZBIbDjAwyaNTwsbUIvkX6AWNqAWaYs/EonzCWkB2SLN21bDwMMD9D5QY+IGQlokm3mMrWXbDjBIsAMDubdNInHjYQJ+MTh/xvDm27Y6BvvDwKj88acucd7x5oeP8WkBAhZg9B2ub4DzmXErhSv5wMBQR1jZKBgFo2AUjFwAANc2RrDjF422AAAAAElFTkSuQmCC","orcid":"","institution":"Peking University People’s Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Yang","suffix":""},{"id":242258485,"identity":"1d187a7c-816f-4f45-bba5-2ea8a50b86d1","order_by":1,"name":"Ruxue Han","email":"","orcid":"","institution":"Peking University People’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruxue","middleName":"","lastName":"Han","suffix":""},{"id":242258486,"identity":"5c83a36c-7d8b-43d6-a88b-722525603ffa","order_by":2,"name":"Feifeng Zhang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Feifeng","middleName":"","lastName":"Zhang","suffix":""},{"id":242258487,"identity":"72e9d969-b974-4133-b547-9d7a6bb9ce2f","order_by":3,"name":"Xiaolin Jiang","email":"","orcid":"","institution":"Peking University People’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Jiang","suffix":""},{"id":242258488,"identity":"5e0b53a3-47f7-44cd-8a39-d6ac642c089c","order_by":4,"name":"Chaohua Wang","email":"","orcid":"","institution":"Peking University People’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chaohua","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2023-10-11 08:05:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3430942/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3430942/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":45365034,"identity":"c3d406a1-1ba9-4cf8-b559-74a74d6c27b9","added_by":"auto","created_at":"2023-10-28 13:46:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110881,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow sheet explaining patient dropout\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"XXXXXX01.png","url":"https://assets-eu.researchsquare.com/files/rs-3430942/v1/e176e7596c73032598582293.png"},{"id":45365035,"identity":"6fd5b222-a063-4ecb-9f8b-b0d7ebc23a52","added_by":"auto","created_at":"2023-10-28 13:46:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":852028,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAnemia grade of patients before HSCT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. Proportion of anemia degree among all enrolled patients.\u003c/p\u003e\n\u003cp\u003eB. Proportions of degrees of anemia between the intervention group and the control group\u003c/p\u003e\n\u003cp\u003eMild anemia: 90g/L≤hemoglobin \u0026lt;120g/L;\u003c/p\u003e\n\u003cp\u003eModerate anemia: 60g/L≤hemoglobin ＜90g/L;\u003c/p\u003e\n\u003cp\u003eSevere anemia: hemoglobin \u0026lt;60g/L\u003c/p\u003e","description":"","filename":"XXXXXX1.png","url":"https://assets-eu.researchsquare.com/files/rs-3430942/v1/b61e3da496288420562fcc7c.png"},{"id":49471136,"identity":"eceb587d-a416-4dfc-a3ad-3aea390b3e3c","added_by":"auto","created_at":"2024-01-11 11:44:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":705118,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3430942/v1/53cebbe3-3ddc-43c8-afbf-5bd381a36cfc.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Effects of Management of Heavy Menstrual Bleeding of Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eBleeding complications from different systems are important complications of hematopoietic stem cell transplantation (HSCT). High-dose chemotherapy in HSCT conditioning regimens can damage bone marrow cells and blood cells. Before HSCT, patients face varying degrees of overall blood cell reduction. Other post-HSCT complications, such as graft vs. host disease (GVHD), may also exacerbate bleeding and affect patients' clotting function, thereby increasing the risk of post-transplant bleeding. Post-transplant bleeding is associated with decreased patient survival rates\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Pulmonary bleeding and gastrointestinal bleeding are the most common life-threatening bleeding sites, followed by the central nervous system\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. However, most studies focus on overall bleeding after HSCT. Currently, the domestic consensus on the management of bleeding complications after HSCT mainly focuses on skin and mucous membranes, the urinary tract, the digestive tract, intracranial, and alveolar bleeding\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePre-menopausal females constitute a special group, as they experience periodic menstrual cycles before HSCT. However, there is a very limited number of studies evaluating uterine bleeding during HSCT. Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that affects quality of life. Due to the poor correlation between patient perception and objective menstrual blood volume, as well as the lack of validated diagnostic tools, this is an under-diagnosed and under-treated disease\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. National Institute for Health and Care Excellence (NICE) pointed out that HMB should be defined as excessive menstrual blood loss which interferes with the woman\u0026rsquo;s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. For reproductive-aged women, the symptom of heavy menstrual bleeding is highly prevalent and a major contributor to iron deficiency anemia\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, the clinical management of abnormal uterine bleeding due to clotting-related disorders (referred to as AUB-C) is challenging. HMB is the most common manifestation of AUB in patients with hematological diseases. For HSCT patients, underlying hematological conditions, chemotherapy regimens, and pre-transplant conditioning can lead to platelet reduction, potentially causing HMB. Among female patients who have not undergone menstrual management before HSCT, the incidence of moderate to HMB can be as high as 40%\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, significantly affecting the treatment of underlying diseases and patient safety. Due to the lack of emphasis on menstrual management for pre-menopausal females, there are instances of hematologists using combined oral contraceptives (COC) or hormonal agents inappropriately for gynecologic hemostasis. Menstrual management refers to the use of hormonal medications to decrease the frequency and volume of physiologic menses and, in some cases, achieving amenorrhea\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Uncontrollable HMB in the laminar air-flow room (LAFR) will seriously affect the patient's treatment and life safety.\u003c/p\u003e \u003cp\u003eAccording to the recommendations of existing guidelines\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, comprehensive assessments in the field of obstetrics and gynecology should be conducted for HSCT patients before entering the transplant unit. Currently, the focus on female HSCT patients is primarily on preserving fertility and protecting ovarian function. However, there is also a lack of data concerning uterine bleeding during HSCT for pre-menopausal patients, and menstrual management for these patients has not received sufficient attention. Previous studies by our team have shown that GnRHa can effectively reduce the rate of uterine bleeding in LAFR in HSCT patients\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. This study aims to investigate the menstrual status in the laminar air-flow room (LAFR)\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e and associated risks in HSCT patients, providing a reference for the assessment and management of gynecological aspects for hematological disease patients, especially HMB patients, in the future.\u003c/p\u003e"},{"header":"2 Method","content":"\u003cp\u003eThis was a retrospective cohort study. We affirm that: (i) the study was approved by the Ethics Committee of Peking University People's Hospital (No. 2015PHB087-01), including any relevant details; and (ii) all experiments were performed in accordance with relevant guidelines and regulations. All research was performed in accordance with relevant regulations, and appropriate consent was obtained from all participants and/or their legal guardians and signed by the patients or their families.\u003c/p\u003e \u003cp\u003eFrom December 2012 to December 2022, premenopausal female patients who had undergone or were to undergo HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included. Patients with hematological diseases at Peking University People's Hospital routinely undergo gynecological physical examination before HSCT.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows: (1) women undergoing myeloablative chemotherapy HSCT for hematological diseases; (2) premenopausal patients; and (3) patients underwent HSCT at the Blood Research Institute of Peking University People's Hospital. The exclusion criteria were as follows: (1) Patients who did not use drugs regularly; (2) patients who were unable to survive during HSCT; (3) patients with incomplete clinical data; and (4) patients who received less than 2 courses of GnRHa treatment before myeloablative chemotherapy;(5) Patients who had not yet undergone HSCT. After screening 479 patients, 330 patients were finally included in the study (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe data of hematology and gynecology of all participants had been collected. After informed consent, patients could choose whether to receive menstrual management before HSCT. The patients who recieved menstrual management would be included in the intervention group. The main management methods include gonadotropin-releasing hormone agonist (GnRHa) injection, COC or low-dose mifepristone. Patients who were not counseled on menstrual management before HSCT or did not adopt after counseling were included in the control group. Hematology-related information and gynecology-related information includes would be cellected by gynecological doctors.\u003c/p\u003e \u003cp\u003eThis study involves the following definitions:(1) Mild anemia: 90g/L\u0026thinsp;\u0026le;\u0026thinsp;hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;120g/L; Moderate anemia: 60g/L\u0026thinsp;\u0026le;\u0026thinsp;hemoglobin \u0026lt;90g/L; Severe anemia: hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;60g/L; (2) Severe thrombocytopenia: platelet count\u0026thinsp;\u0026lt;\u0026thinsp;25\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L; (3) Abnormal liver function: AST\u0026thinsp;\u0026gt;\u0026thinsp;40U/L or ALT\u0026thinsp;\u0026gt;\u0026thinsp;40U/L; (4) Abnormal kidney function: Creatinine (Cr)\u0026thinsp;\u0026gt;\u0026thinsp;104\u0026micro;mol/L.\u003c/p\u003e \u003cp\u003eAll data were statistically processed using SPSS 22.0 (SPSS Inc., Chicago, IL). Continuous variables are described as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared using the t-test. For continuous variables that do not follow a normal distribution, descriptions are provided using the median (25th and 75th percentiles), and analysis is conducted using the Mann-Whitney U test. Categorical variables are described using frequencies and proportions, and comparisons of categorical variables are made using the chi-squared test or Fisher's exact test. Logistic regression analysis was performed to identify factors related to uterine bleeding in the LAFR and severe anemia. A significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates statistical significance.\u003c/p\u003e"},{"header":"3 Result","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Basic hematological disease information for the study population\u003c/h2\u003e \u003cp\u003eThe general conditions of the study population are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This study ultimately included a total of 330 patients who underwent HSCT due to hematological diseases. There were 112 patients in the intervention group (112/330, 33.9%) and 218 patients in the control group (218/330, 66.1%). The age of patients at the time of transplantation ranged from 11 to 51 years old. The average age of patients in the intervention group at admission was 25.73\u0026thinsp;\u0026plusmn;\u0026thinsp;7.37 years, while in the control group, it was 28.23\u0026thinsp;\u0026plusmn;\u0026thinsp;8.27 years, with no significant difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.051). The primary hematological diseases were malignant hematological diseases, with ALL, AML, and MDS accounting for 32.7% (108/330), 37.0% (125/330), and 11.5% (38/330) of the total number of patients, respectively. A total of 10.61% (35/330) had non-malignant hematological disease AA, and other hematological diseases for HSCT included chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, among others. There was a statistically significant difference between the two groups in terms of the primary hematological diseases (P\u0026thinsp;=\u0026thinsp;0.004). Due to different treatment regimens for primary hematological diseases (benign hematological diseases do not undergo chemotherapy), there was a statistically significant difference between the two groups in whether they underwent chemotherapy (85.3% vs. 67.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). HLA-haploidentical hematopoietic stem cell transplantation was the primary transplantation method for both groups (80.7% vs. 85.7%, P\u0026thinsp;=\u0026thinsp;0.260), and there was no significant difference in the incidence of GVHD between the two groups after transplantation (P\u0026thinsp;=\u0026thinsp;0.664).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics according to whether got menstrual management\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacterics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention Group, n\u0026thinsp;=\u0026thinsp;112(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group, n\u0026thinsp;=\u0026thinsp;218(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD),yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.73\u0026thinsp;\u0026plusmn;\u0026thinsp;7.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.23\u0026thinsp;\u0026plusmn;\u0026thinsp;8.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematologic diseases type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73(33.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(30.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91(41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA-matched situation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA-matched\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA-haploidentical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96(85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176(80.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclic chemotherapy before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75(67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186(85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGVHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76(67.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153(70.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36(32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65(29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eP value indicates the differences between the two groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eALL, Acute lymphocytic leukemia; AML, Acute myelogenous leukemia; AA, Aplastic anemia; MDS, myelodysplastic syndrome; HSCT, hematopoietic stem cell transplantation; GVHD, graft vs host disease.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Menstrual and general conditions of patients before HSCT\u003c/h2\u003e \u003cp\u003eMost patients had varying degrees of anemia before HSCT, and only 16.1% of patients were free of anemia. Mild anemia was the most common (54.6%) degree, with 3.9% of patients having hemoglobin levels below 60g/L. Patients in the intervention group had a higher proportion and more severe anemia compared with the control group (Fig.\u0026nbsp;2). And 35.2% (116/330) of patients who required medication for hemostasis. Totally, there were 90.0% of patients presenting with HMB (accompanied by anemia or required medication for hemostasis).\u003c/p\u003e \u003cp\u003eMore patients in the intervention group had already required medication for menstrual management before HSCT (43.8% vs. 30.7%, P\u0026thinsp;=\u0026thinsp;0.019). There were no differences between the two groups in terms of hemoglobin levels, coagulation parameters (PT, APTT, FIB), and liver and kidney function on the day of admission. However, the platelet levels of patients in the intervention group on the day of admission were significantly lower than those in the control group, although their mean values were within the normal range (126.63\u0026thinsp;\u0026plusmn;\u0026thinsp;93.39 vs. 168.02\u0026thinsp;\u0026plusmn;\u0026thinsp;83.58, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMenstrual and general conditions of patients before HSCT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention Group, n\u0026thinsp;=\u0026thinsp;112(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group, n\u0026thinsp;=\u0026thinsp;218(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eRequired medication for uterine bleeding hemostasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49(43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63(56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151(69.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral conditions\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin levels(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.02\u0026thinsp;\u0026plusmn;\u0026thinsp;22.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101.68\u0026thinsp;\u0026plusmn;\u0026thinsp;19.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count(\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126.63\u0026thinsp;\u0026plusmn;\u0026thinsp;93.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e168.02\u0026thinsp;\u0026plusmn;\u0026thinsp;83.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulation parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.48\u0026thinsp;\u0026plusmn;\u0026thinsp;8.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.71\u0026thinsp;\u0026plusmn;\u0026thinsp;9.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB(mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300.54\u0026thinsp;\u0026plusmn;\u0026thinsp;62.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e278.13\u0026thinsp;\u0026plusmn;\u0026thinsp;62.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.909\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eLiver and kidney function\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.26\u0026thinsp;\u0026plusmn;\u0026thinsp;15.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.12\u0026thinsp;\u0026plusmn;\u0026thinsp;15.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.53\u0026thinsp;\u0026plusmn;\u0026thinsp;11.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.15\u0026thinsp;\u0026plusmn;\u0026thinsp;9.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCr(\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.75\u0026thinsp;\u0026plusmn;\u0026thinsp;10.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.14\u0026thinsp;\u0026plusmn;\u0026thinsp;9.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.668\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eP value indicates the differences between the two groups.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Uterine bleeding and related hematological examinations of patients in LAFR\u003c/h2\u003e \u003cp\u003eIn the control group, 83.5% (182/218) of patients experienced varying degrees of uterine bleeding in the LAFR, while in the intervention group, only 22.3% (25/112) did. This difference is statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no differences between the two groups in terms of minimum hemoglobin and platelet count in the LAFR. The number of days with severe thrombocytopenia was 11.75\u0026thinsp;\u0026plusmn;\u0026thinsp;6.37 days in the control group and 10.79\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97 days in the intervention group (P\u0026thinsp;=\u0026thinsp;0.247). Among the patients who underwent menstrual management in the intervention group, 65.2% (73/112), and 57.3% (125/218) of the control group could recover to 90g/L within 30 days after reaching the lowest hemoglobin level, but this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.169). There was no difference in the rate of liver and kidney function abnormalities between the two groups. The Mann-Whitney U test was used to assess whether there were differences in the transfusion volume of red blood cells, plasma, and platelets between the intervention and control groups. The Mann-Whitney U test results showed no statistically significant differences in the transfusion volume of these three blood components between the two groups (P\u0026thinsp;=\u0026thinsp;0.661, P\u0026thinsp;=\u0026thinsp;0.848, P\u0026thinsp;=\u0026thinsp;0.186). Furthermore, we recorded instances of bleeding in other systems within the cabin. Patients in the intervention group had higher rates of bleeding in skin and mucous membranes, as well as major organ systems, compared to the control group, but there were no statistically significant differences between the two groups (P\u0026thinsp;=\u0026thinsp;0.050). The rate of recurrent uterine bleeding after HSCT was significantly higher in the control group compared to the intervention group (50.9% vs. 17.9%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the control group, 83.5% (182/218) of patients experienced new uterine bleeding in the LAFR, while in the intervention group, only 22.3% (25/112) did. The rate of new uterine bleeding in the LAFR in the control group was significantly higher than that in the intervention group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The degree of uterine bleeding in the LAFR in patients is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In both the intervention and control groups, the majority of patients with new bleeding was similar to menstrual flow. Although there was no statistical difference, no cases of bleeding exceeding menstrual flow occurred in the intervention group, while there were 3 cases (3/218, 1.4%) in the control group. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUterine bleeding and related hematological examinations of patients in the LAFR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention Group, n\u0026thinsp;=\u0026thinsp;112(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group, n\u0026thinsp;=\u0026thinsp;218(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine bleeding in LAFR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87(77.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than menstrual flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimilar to menstrual flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164(75.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than menstrual flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMinimum hemoglobin (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.38\u0026thinsp;\u0026plusmn;\u0026thinsp;12.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.98\u0026thinsp;\u0026plusmn;\u0026thinsp;10.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMinimum platelet count (\u0026times;10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.79\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.75\u0026thinsp;\u0026plusmn;\u0026thinsp;6.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of days with severe thrombocytopenia (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.20\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLiver function\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.387\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(94.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187(85.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKidney function\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105(93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209(95.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood transfusion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cells (U)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(0,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(2,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlasma (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (U)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(3,7.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(3,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic bleeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72(64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165(75.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucocutaneous hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor organ system bleeding (eg, hemorrhagic cystitis or gastrointestinal bleeding)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUterine bleeding after HSCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111(50.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107(49.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eP value indicates the differences between the two groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eLAFR, laminar air-flow room\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, among patients who had anemia after HSCT, the uterine bleeding rate of patients who chose menstrual management was 21.9%(21/96), while the uterine bleeding rate of patients without intervention was 84.0%(152/181), and the difference was statistically significant(P\u0026lt;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Analysis of related factors of uterine bleeding in LAFR in patients with HSCT\u003c/h2\u003e \u003cp\u003eIn order to screen for risk factors of uterine bleeding in the LAFR of HSCT patients, factors with a single-factor analysis P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.2 were included in the logistic regression analysis. Logistic regression analysis showed that only whether menstrual management was performed before admission was related to uterine bleeding. Patients who did not undergo menstrual management had a significantly higher risk of uterine bleeding than those who did (OR\u0026thinsp;=\u0026thinsp;18.12, 95% CI 9.638\u0026ndash;34.066, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors for uterine bleeding in the LAFR.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenstrual management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.638\u0026ndash;34.066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematologic diseases type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA-matched situation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGVHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.307\u0026ndash;1.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclic chemotherapy before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenstrual conditions before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.283\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.694\u0026ndash;2.371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired medication for uterine bleeding hemostasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.963\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.529\u0026ndash;1.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMucocutaneous hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.596\u0026ndash;5.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.308\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMajor organ system bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.270\u0026ndash;1.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum platelet count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.686\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days with severe thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.947\u0026ndash;1.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eP value indicates the differences between the two groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGVHD, graft vs host disease; HSCT, hematopoietic stem cell transplantation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Analysis of related factors of severe anemia in the LAFR of patients undergone HSCT\u003c/h2\u003e \u003cp\u003eSevere anemia was defined as hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;60g/L, and factors related to a decrease in hemoglobin to severe anemia in the LAFR were analyzed. After conducting a single-factor correlation analysis of factors related to intra-LAFR hemoglobin, variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.2 and whether menstrual management was chosen were included in the logistic regression analysis. The results suggested that factors related to severe anemia included the occurrence of GVHD, the presence of uterine bleeding, and the hemoglobin level before pretreatment. Patients without uterine bleeding were less likely to develop severe anemia (OR\u0026thinsp;=\u0026thinsp;0.243, 95% CI 0.097\u0026ndash;0.608, P\u0026thinsp;=\u0026thinsp;0.003). (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors for severe anemia after HSCT.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnivariate P value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenstrual management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.194\u0026ndash;1.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematologic diseases type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.704\u0026ndash;8.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.569\u0026ndash;6.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.983\u0026ndash;27.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.901\u0026ndash;30.720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA-matched situation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.156\u0026ndash;1.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGVHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.077\u0026ndash;3.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclic chemotherapy before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.156\u0026ndash;1.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenstrual conditions before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired medication for uterine bleeding hemostasis HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine bleeding in LAFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.097\u0026ndash;0.608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.764\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.939\u0026ndash;0.979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.996\u0026ndash;1.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.869\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.813\u0026ndash;1.534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.719\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum platelet count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days with severe thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.973\u0026ndash;1.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eP value indicates the differences between the two groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eALL, Acute lymphocytic leukemia; AML, Acute myelogenous leukemia; AA, Aplastic anemia; MDS, myelodysplastic syndrome; HSCT, hematopoietic stem cell transplantation; GVHD, graft vs host disease; LAFR, laminar air-flow room.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Effects of different menstrual management methods on outcomes\u003c/h2\u003e \u003cp\u003eA total of 112 patients were included in the intervention group of the study, including 85 who chose GnRHa, 19 who chose continuous oral COC, and 8 who chose oral Mifepristone. The LAFR uterine bleeding rates in the GnRHa group, COC group, and Mifepristone group were 12.9% (11/85), 73.7% (14/19), and 0%, respectively, all lower than the control group (182/218, 83.5%). The post-LAFR uterine bleeding rates for the GnRHa and Mifepristone groups were 7.1% (6/85) and 12.5% (1/8), respectively, both lower than the control group (111/218, 50.9%). Furthermore, we observed that the Mifepristone group had lower pre-processing levels of hemoglobin and platelets than the other three groups. (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe outcomes of different menstrual management methods\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGnRHa group, n\u0026thinsp;=\u0026thinsp;85(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOC group, n\u0026thinsp;=\u0026thinsp;19(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMifepristone group, n\u0026thinsp;=\u0026thinsp;8(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eControl group, n\u0026thinsp;=\u0026thinsp;218(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine bleeding in LAFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11(12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14(73.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e182(83.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine bleeding after HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6(7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13(68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e111(50.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.02\u0026thinsp;\u0026plusmn;\u0026thinsp;22.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92.26\u0026thinsp;\u0026plusmn;\u0026thinsp;22.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87.00\u0026thinsp;\u0026plusmn;\u0026thinsp;24.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e101.68\u0026thinsp;\u0026plusmn;\u0026thinsp;19.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count before HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131.02\u0026thinsp;\u0026plusmn;\u0026thinsp;89.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e124.26\u0026thinsp;\u0026plusmn;\u0026thinsp;107.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.75\u0026thinsp;\u0026plusmn;\u0026thinsp;97.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e168.02\u0026thinsp;\u0026plusmn;\u0026thinsp;83.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum hemoglobin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70.20\u0026thinsp;\u0026plusmn;\u0026thinsp;12.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62.21\u0026thinsp;\u0026plusmn;\u0026thinsp;9.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.75\u0026thinsp;\u0026plusmn;\u0026thinsp;13.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e67.98\u0026thinsp;\u0026plusmn;\u0026thinsp;10.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days with severe thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.56\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.26\u0026thinsp;\u0026plusmn;\u0026thinsp;6.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eLAFR, laminar air-flow room; HSCT, hematopoietic stem cell transplantation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003ePatients with benign or malignant hematological diseases may experience abnormal hematological conditions, particularly thrombocytopenia, due to underlying diseases, chemotherapy regimens, HSCT conditioning, and other reasons, making them susceptible to HMB. Current research has found that in patients with normal ovarian function, chemotherapy-induced thrombocytopenia can lead to HMB in 40% of cases\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. However, the potent gonadotoxicity of chemotherapy during HSCT conditioning often results in ovarian dysfunction, subsequent hormonal imbalances, further increasing the incidence of HMB, and complicating the patient's condition. Therefore, menstrual management of premenopausal women scheduled for HSCT is crucial in reducing the incidence of uterine bleeding during transplantation and preventing HMB.\u003c/p\u003e \u003cp\u003eThere is relatively limited research on the feasibility and effectiveness of premenstrual management before HSCT to prevent secondary HMB due to hematological changes in patients after conditioning. Our study aims to investigate the impact of menstrual management before HSCT on uterine bleeding in the LAFR and provide reference for menstrual management of HMB patients.\u003c/p\u003e \u003cp\u003eIn clinical admissions, there is a high proportion of blood disorder patients complaining of HMB. Due to the poor correlation between patient perception and objective menstrual blood volume, as well as the lack of validated diagnostic tools, HMB is an under-diagnosed and under-treated disease\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. NICE pointed out that HMB should be defined as excessive menstrual blood loss which interferes with the woman\u0026rsquo;s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e Anemia can be used as a reference for HMB. Anemia has a wide range of health impacts on female patients, including causing nonspecific symptoms such as fatigue, irritability, hair loss, lack of concentration, palpitations, and dizziness. Severe anemia can lead to arrhythmias, edema, and even heart failure in patients, as well as an increased need for blood transfusions\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Our study found that 83.9% of patients had varying degrees of anemia before HSCT, suggesting a high likelihood of HMB. Including patients who need medication for hemostasis before HSCT, the proportion of HMB patients in the enrolled population can reach 90% (297/330). At the same time, these patients were a high-risk group for massive uterine bleeding in the LAFR.\u003c/p\u003e \u003cp\u003eMenstrual management before HSCT significantly reduced the incidence of uterine bleeding in HSCT patients in the LAFR. The incidence of uterine bleeding in the LAFR was as high as 83.5% in the control group, which in the intervention group was only 22.3%. Compared with the incidence of uterine bleeding in the LAFR reported by Dror et al.\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003ein a retrospective study in 2006 (13/20, 65.0%), the control group in our study had a higher incidence. Regarding the outcomes of patients who had HMB before HSCT (patients with anemia), menstrual management could significantly reduce the risk of uterine bleeding during HSCT for these patients. In both groups, uterine bleeding pattern was mainly equivalent to menstrual bleeding. It is important to note that bleeding that patients describe as \"similar to menstrual flow\" may amount to HMB. In the intervention group, there was no bleeding greater than menstrual bleeding, which may indicate that menstrual management can effectively prevent significant uterine bleeding in the LAFR. The medical records revealed that among the 25 patients who experienced uterine bleeding in the intervention group, 14 were users of oral COC. The incidence of uterine bleeding in the COC group reached 73.7%. The occurrence of uterine bleeding in COC users may be related to breakthrough bleeding during the low-dose maintenance phase of oral COC\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. There was a statistically significant difference between the two groups in post-discharge uterine bleeding. In the control group, 50.9% of patients experienced uterine bleeding\u0026thinsp;\u0026ge;\u0026thinsp;1 time, while in the intervention group, only 17.9% had bleeding. Patients used GnRHa or Mifepristone had a lower rate of recurrence of uterine bleeding after discontinuation, indicating that GnRHa and medroxyprogesterone acetate may have a better induction effect on amenorrhea, with a lower risk of recurrence of bleeding after discontinuation.\u003c/p\u003e \u003cp\u003eThe intervention group exhibited a higher proportion of drug-induced AUB hemostasis and lower platelet levels before HSCT, indicating a higher likelihood of previous experience with HMB in these patients. Consequently, they are more vigilant about the risk of HMB and have a stronger awareness of menstrual management. And it was found during retrospective collection of medical records that some patients did not undergo gynecological consultations or seek advice on menstrual management before HSCT. Though the awareness of routine gynecological examinations for HSCT patients before transplantation is gradually increasing, the awareness of menstrual management is lacking. Most patients seek acute hemostasis in gynecology clinics when HMB has already occurred, but this undoubtedly increases the difficulty and risk of hemostasis, and even endangers the patient's life. This suggests the importance of strengthening collaboration between hematology and obstetrics and gynecology departments in the future.\u003c/p\u003e \u003cp\u003eAnalysis of factors related to uterine bleeding in the LAFR suggested that only menstrual management was associated with it. The risk of uterine bleeding in patients who did not undergo menstrual management was 18.12 times that of patients who underwent that. This indicates that regardless of the patient's primary disease or the menstrua status before HSCT, menstrual management can effectively reduce the risk of uterine bleeding in the LAFR, thereby preventing the occurrence of HMB before platelet engraftment. After analyzing the factors related to severe anemia in the LAFR, although there was no correlation between menstrual management and severe anemia, there was a correlation between uterine bleeding and hemoglobin reaching severe anemia levels.\u003c/p\u003e \u003cp\u003eThe intervention group's patients were managed with three menstrual management methods: GnRHa, COC, and Mifepristone. The Mifepristone group achieved a 100% rate of amenorrhea in the LAFR, followed by the GnRHa group. The COC group had a uterine bleeding rate of 73.7%. However, regardless of the intervention method, the uterine bleeding rate in the LAFR was lower than that in the control group (83.5%). When comparing the pre-processing conditions before HSCT, we found that the pretreatment hemoglobin and platelet levels of the three menstrual management methods were lower than those in the control group. Especially in the Mifepristone group, the hemoglobin and platelet levels were lower than in the other two intervention groups. Mifepristone was initially used for early pregnancy medical abortion due to its anti-progestin effects, and its indications have expanded to include common gynecological conditions such as uterine fibroids and endometriosis. Mifepristone not only has anti-progestin effects but also affects the hypothalamic-pituitary-ovarian axis. It can act on the hypothalamus to inhibit the secretion of gonadotropin-releasing hormone, affecting FSH and LH secretion, and it can also directly act on the pituitary gland to inhibit FSH and LH release, further lowering serum FSH and LH levels, inducing amenorrhea\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Mifepristone's indications have not yet been included in HMB, but studies in AUB caused by AUB-L and AUB-A have observed that low-dose (2.5-10mg) Mifepristone can achieve amenorrhea rates of 41-98.9%\u003csup\u003e[\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, and high-dose (50mg) Mifepristone can achieve a 100% amenorrhea rate\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. In our gynecological endocrine clinic, in patients with refractory HMB patients who still have poor hemostasis with ultra-high-dose hormone drugs, adding Mifepristone and gradually reducing the dose of hormone drugs can gradually transition patients to amenorrhea. This may explain why the hemoglobin and platelet levels before pretreatment in the Mifepristone group were lower than those in the other two groups. Mifepristone is often chosen by patients due to low platelet counts and poor effectiveness of hormone drugs. Because the time of using Mifepristone as a menstrual management option is relatively short, this study included only 8 patients using Mifepristone. However, in these 8 patients, the amenorrhea induction effect was satisfactory (8/8, 100%), at a dose of 25mg QD. Nevertheless, further studies with a larger sample size are needed to validate its amenorrhea rate and safety. Each of the three menstrual management methods has its advantages and disadvantages. GnRHa induces amenorrhea by promoting the release of gonadotropins, leading to desensitization of GnRH receptors and inhibiting pulsatile secretion of GnRH, thereby achieving menstrual management in a low gonadotropin state. The advantage of GnRHa is that it does not require daily use. However, the guidelines require patients to receive a GnRHa injection at least 14 days before pre-treatment to prevent heavy uterine bleeding.\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Platelet count\u0026thinsp;\u0026lt;\u0026thinsp;10\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L is a contraindication for its use. The effectiveness of GnRHa in reducing uterine bleeding during the period of platelet reduction has been confirmed\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. In a 2006 retrospective study, the intra-LAFR amenorrhea rate of GnRHa was 76.9% (30/39)\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, and a 2016 retrospective study showed an amenorrhea rate of up to 88% (29/33)in the LAFR\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, which is similar to the results of this study (74/85, 87.1%). Both COC and Mifepristone require daily oral maintenance doses of medication, but they do not have specific requirements for the time and platelet levels before HSCT pretreatment and can be started at any time. COC can suppress ovulation and stabilize hormone levels to suppress menstruation. However, COC is associated with increased breakthrough bleeding after missed doses and continuous medication, and it requires some degree of patient compliance. This study also found that even in patients taking medication regularly, there was still a 73.7% intra-LAFR uterine bleeding rate. In addition, COC has relatively more contraindications and a risk of deep vein thrombosis\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study is the first to describe the impact of pre-transplant menstrual management on uterine bleeding in Chinese HSCT patients and proposes Mifepristone as a menstrual induction medication for high-risk bleeding populations. However, this study still has limitations: a small sample size, various confounding factors, and the selection bias and recall bias associated with a retrospective design. We hope that in the future, large-sample prospective controlled studies can further validate the effectiveness and safety of menstrual management methods in preventing uterine bleeding in HSCT patients. We also hope to work with hematologists to raise awareness of gynecological management before transplantation in patients with hematological diseases to reduce treatment risks and improve patients' quality of life.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eMenstrual management significantly reduces the incidence of uterine bleeding in HSCT patients and it can be used as a method to prevent uterine bleeding within LAFR in patients with HMB. In this study, the rates of uterine bleeding for all three menstrual management methods were lower than in the control group. Mifepristone, as a relatively safe contraceptive hormone, demonstrated a good effect in inducing amenorrhea in this study, but its effectiveness still requires confirmation through large-sample prospective research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eRuxue Han: Data curation, Formal analysis, Investigation, Writing- Original draft preparation\u003c/p\u003e\n\u003cp\u003eFeifeng Zhang: Data curation, Investigation, Writing- Original draft preparation\u003c/p\u003e\n\u003cp\u003eXiaolin Jiang: Data curation\u003c/p\u003e\n\u003cp\u003eChaohua Wang: Methodology, Data curation, Supervision\u003c/p\u003e\n\u003cp\u003eXin Yang: Methodology, Writing- Reviewing and Editing, Funding acquisition\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe study was supported by Roche Diagnostics: Dynamic study for the effects of chemotherapy and bone marrow transplantation on ovarian function in pre-adolescent hematological disease survivors (Project no.2018PHB085-01).\u003c/p\u003e\n\u003cp\u003eData Availability\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJorge L, Lucia L-A, Estefania P-L, et al. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients [J]. Haematologica, 2013, 98(3): 437-443.\u003c/li\u003e\n\u003cli\u003eGerber D E, Segal J B, Levy M Y, et al. The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention [J]. Blood, 2008, 112(3): 504-510.\u003c/li\u003e\n\u003cli\u003eLabrador J, L\u0026oacute;pez-Corral L, Vazquez L, et al. Incidence and risk factors for life-threatening bleeding after allogeneic stem cell transplant [J]. Br J Haematol, 2015, 169(5): 719-725.\u003c/li\u003e\n\u003cli\u003ePihusch M. Bleeding complications after hematopoietic stem cell transplantation [J]. Semin Hematol, 2004, 41(1 Suppl 1): 93-100.\u003c/li\u003e\n\u003cli\u003ePerell\u0026oacute; J, Rius Tarruella J, Calaf J. 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Obstet Gynecol, 2022, 140(3): 528-541.\u003c/li\u003e\n\u003cli\u003eHan R, Song Z, Li H, et al. Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation [J]. Sci Rep, 2023, 13(1): 14497.\u003c/li\u003e\n\u003cli\u003eYokoe D, Casper C, Dubberke E, et al. Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated [J]. Bone Marrow Transplant, 2009, 44(8): 495-507.\u003c/li\u003e\n\u003cli\u003eChang K, Merideth M A, Stratton P. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation [J]. Obstetrics \u0026amp; Gynecology, 2015, 126(4): 779-784.\u003c/li\u003e\n\u003cli\u003ePercy L, Mansour D, Fraser I. Iron deficiency and iron deficiency anaemia in women [J]. Best Pract Res Clin Obstet Gynaecol, 2017, 40: 55-67.\u003c/li\u003e\n\u003cli\u003eMirza F G, Abdul-Kadir R, Breymann C, et al. 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Cochrane Database Syst Rev, 2014, (3): Cd010813.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"hematological diseases, hematopoietic stem cell transplantation, heavy menstrual bleeding, menstrual management, thrombocytopenia","lastPublishedDoi":"10.21203/rs.3.rs-3430942/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3430942/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eHeavy menstrual bleeding (HMB) was an underestimated bleeding complications of hematopoietic stem cell transplantation (HSCT). The study aims to investigate the benefits of menstrual management in women undergoing HSCT.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePatients who had undergone HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included in ten years. The data of hematology and menstruation of all participants had been collected. The management methods of intervention group include GnRHa, COC or low-dose mifepristone. Patients who did not receive management were included in the control group.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere were 112 patients included in the intervention group and 218 patients included in the control group. There were 90.0% of patients presenting with HMB before HSCT. In the control group, 83.5% of patients experienced uterine bleeding in the LAFR, while only 22.3% did in the intervention group. The rate of recurrent uterine bleeding after HSCT was significantly higher in the control group (50.9% vs. 17.9%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients who did not undergo menstrual management had a higher risk of uterine bleeding than those who did (OR\u0026thinsp;=\u0026thinsp;18.12, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMenstrual management significantly reduces the incidence of uterine bleeding in HSCT patients and acts as a protective factor against uterine bleeding in the LAFR.\u003c/p\u003e","manuscriptTitle":"Effects of Management of Heavy Menstrual Bleeding of Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-28 13:46:06","doi":"10.21203/rs.3.rs-3430942/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":"c072d091-638f-4070-863c-28ad8ba76c41","owner":[],"postedDate":"October 28th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":25590659,"name":"Health sciences/Risk factors"},{"id":25590660,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"}],"tags":[],"updatedAt":"2024-03-07T18:20:33+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-28 13:46:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3430942","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3430942","identity":"rs-3430942","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}