Combination therapy of dydrogesterone and progesterone together with folic acid in the treatment of recurrent abortion on the outcome of Re-pregnancy

Combination therapy of dydrogesterone and progesterone together with folic acid in the treatment of recurrent abortion on the outcome of Re-pregnancy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Combination therapy of dydrogesterone and progesterone together with folic acid in the treatment of recurrent abortion on the outcome of Re-pregnancy Xia wang, Wen Yuan, Juan Yang, Sparkle Star This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4706080/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 This study aimed to assess the impact of combining dydrogesterone and progesterone with folic acid in the treatment of recurrent abortion on re-pregnancy outcomes. A retrospective analysis was conducted on 94 women with recurrent abortion admitted between June 2020 and July 2022. Participants were randomly assigned to a control group (treated with progesterone and folic acid) and a research group (treated with dydrogesterone, progesterone, and folic acid). Clinical effectiveness, adverse effects, serum cytokine levels, T lymphocyte subsets, endometrial parameters, and uterine artery perfusion indices were evaluated, along with pregnancy outcomes. The research group exhibited a significantly higher overall effective rate (89.36%) compared to the control group (70.21%). Both groups showed a reduction in interferon (IFN) and interleukin-6 (IL-6) levels and an increase in IL-10 levels post-treatment (P < 0.05). The research group showed higher Treg/CD4 + levels, better endometrial thickness, and fewer adverse reactions (8.51% vs. 23.40%) compared to the control group. The success rate of fetal preservation was higher in the research group (82.98%) compared to the control group (59.57%). The combination of dydrogesterone and progesterone with folic acid effectively improves the success rate of fetal preservation, modulates T lymphocyte levels, reduces inflammatory factors, and enhances endometrial receptivity, positively influencing pregnancy outcomes in cases of recurrent abortion. recurrent abortion dydrogesterone progesterone folic acid pregnancy outcomes Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Recurrent abortion is one of the common pregnancy complications whose incidence tends to increase year by year 1 . At present, it has been found that chromosomal abnormalities, endocrine disorders, infections, immune tolerance disorders, genital tract anatomy abnormalities and other factors can be regarded as risk factors for recurrent abortion. However, it is still difficult to determine the pathogenesis factors in 50% of patients 2–4 . Clinically, patients with recurrent abortion are mainly treated through drugs, including traditional Chinese medicine and hormone treatment, which can ameliorate the clinical condition of the patient to in some degree, but their long-term curative effects are not ideal. In addition, the long-term massive use of glucocorticoids can lead to many adverse reactions, which places a severe threat on the sufferers' sense of quality of living and mental and emotional health, and there is no unified treatment specification and standard 5–7 . Therefore, it is particularly important to further reveal the etiology and mechanism of recurrent abortion, and seek effective ways to prevent and treat the disease to protect reproductive health of women of childbearing age and improve pregnancy outcomes 8 . As a natural progestogen drug, dydrogesterone can significantly promote endometrial receptive response, which is beneficial to improve proliferation ability of lymphocyte and restore immune regulation function, and has an important value in reducing the incidence of abortion 9–10 . Progesterone is a necessary for maintaining pregnancy, which can inhibit the maternal rejection for fetus and trophoblasts to promote embryo implantation and improve the development of placental villus, which promotes fetal growth and development 11–12 . Folic acid has been proved that it has an important role in the treatment of recurrent abortion, which can play a role by reducing the serum homocysteine levels of patients 13 . Despite the known benefits of dydrogesterone, progesterone, and folic acid individually, there are few studies on their combined effects on pregnancy outcomes in recurrent miscarriage cases. This study aims to evaluate the effectiveness of combining dydrogesterone and progesterone with folic acid in improving pregnancy outcomes for women with recurrent abortion. By examining clinical effectiveness, inflammatory markers, T lymphocyte subsets, endometrial parameters, uterine artery perfusion, and pregnancy outcomes, we aim to provide insights into optimizing treatment protocols for recurrent abortion. Methods and materials Data and methodsGeneral data Ninety-four recurrent miscarriage procedures dealt with in our institution during June 2020 to July 2022 were analysed as a retrospective basis. The patients indicate here are women with recurrent abortion. Inclusion criteria: ( 1 ) The patients women with recurrent abortion and the men were normal by chromosome examination; ( 2 ) The number of consecutive spontaneous abortions was more than 3 times; ( 3 ) Patients with normal communication and without mental illness; ( 4 ) Written informed consent executed by the patient or family; ( 5 ) Permission from the hospital ethics board (approval number: KY20203225-1). Exclusion criterion. ( 1 ) Patients with hypersensitivity to study-related drugs; ( 2 ) Patients suffering from thyroid dysfunction; ( 3 ) Patients with serious infection; ( 4 ) Patients with abortion caused by the males; ( 5 ) Patients with diabetes mellitus and chronic liver and kidney dysfunction; ( 6 ) Patients who dropped out from the study halfway. 94 patients with recurrent abortion were separated into the controlling group and the research group, with 47 cases in each group, using the randomized number table approach. In the controlling group, the average age was (28.59 ± 3.99), the average number of pregnancies was (3.93 ± 0.98) times, and the number of abortions was (3.34 ± 0.93) times; In the study group, the average age was (29.40 ± 3.48), the average number of pregnancies was (4.02 ± 0.97) times, and the number of abortions was (3.30 ± 0.91) times; The general data of the two groups did not diffuse in a significant way (P < 0.05), as illustrated in Table 1 . Table 1 General data profiling of the two groups(‾ x ± s ) grouping n Age (years) Number of pregnancies (Times) Number of abortions (Times) Study group 47 29.03 ± 3.63 4.02 ± 0.97 3.53 ± 0.78 control group 47 28.59 ± 3.99 3.93 ± 0.98 3.34 ± 0.93 T 0.877 0.642 0.924 P 0.383 0.522 0.457 Methods Therapy The controlling group was operated with progesterone combined with folic acid, in which progesterone injection (SFDA approval number H33020828, provided by Zhejiang Xianju Pharmaceutical Co., Ltd.) was injected intramuscularly, 40mg each time, once a day, and folic acid (SFDA approval number H10970079, provided by Beijing Silian Pharmaceutical Co., Ltd.) was taken orally at 0.4 ~ 0.8 mg once a day in accordance with the patient's own situation. On the basis of the controlling group, the study group was orally controlled with drospirenone tablets (SFDA approval number H20170221, provided by Abbott biologicals B.V., the Netherlands), 10 mg once, twice daily. Both groups were continuously cured until 12 weeks after pregnancy. Blood sample collection Fasting elbow venous blood was collected from both groups pre- and post-treatment and after anticoagulation treatment, it was centrifuged in a table top high-speed low-temperature centrifuge (provided by Thermo Fisher Scientific) for 10min at a speed of 1500r/min, and the supernatant was stored in a -80 ℃ ultra-low temperature refrigerator (provided by Haier, China) for detection. Observation indexes ( 1 ) Clinical efficacy: It is divided into three aspects: cure, becoming better and invalid. Overall efficiency (%) = ( the number of cured cases + the number of cases that turned out to be better)/total observed cases × 100%. ( 2 ) Inflammatory factors: The levels of serum interferonsγ(IFN), nterleukin-10 (IL-10) and IL-6 in these two groups was measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment. ( 3 ) T lymphocyte subsets: The levels of CD4 + regulatory T cell, Treg (Treg/CD4+), CD4 + helper T cell Th17 (Th17/CD4+) and helper T cell / regulatory T cell (Treg/Th17) in the two groups were detected by flow cytometry before and after treatment. ( 4 ) Endometrial receptivity: The endometrial thickness, uterine artery blood perfusion resistance index (RI) and pulsatility index (PI) in the two groups were detected by vaginal B-ultrasound pre- and post-treatment. ( 5 ) Occurrence of undesirable reactions in both groups should be closely monitored during the treatment process, and then the total incidence was calculated. ( 6 ) Pregnancy outcomes: The pregnancy outcomes were recorded and analyzed, including premature delivery, full-term delivery and abortion, and the success rate of fetal protection was calculated. The formula was (number of premature births + number of full-term births) / total number of observed cases × 100%. Statistical methods SPSS21.0 software was utilized for the data analysis. The counting information was presented as n (%). The measurement data were written in the form of(‾ x ± s ), and x 2 was applied to assess the pairwise comparison. By using t, the pairwise comparison was assessed. The difference was deemed to be significant at P < 0.05. Results Analysis of clinical efficacy of the two groups While in the control group, 15 instances were healed, 18 instances improved, and the overall effective rate was 70.21% (33/47), in the study group, 31 instances were cured, 11 instances improved, and the overall effective rate was 89.36% (42/47). According to Table 2 and Fig. 1 , there was a statistically meaningful difference in the total effective rate between the two groups (P < 0.05). Table 2 Comparing the effective rates for both groups n (%) grouping n cure Becoming better invalid Total effective Study Group 47 31 (65.96) 11 (23.40) 5 (10.64) 42 (89.36) control group 47 15 (31.91) 18 (38.30) 14 (29.79) 33 (70.21) x 2 5.342 P 0.021 Contrast of the two groups' serum inflammatory factors The levels of serum IFN- γ and IL-6 in both groups were substantially reduced after treatment as compared to those before treatment, whereas the levels of IL-10 were massively increased after treatment as compared to those before therapies (P < 0.05); additionally, the levels of serum IFN- γ and IL-6 in the study group were greatly reduced after treatment as compared to those in the controlling group (P < 0.05), as illustrated in Table 3 and Fig. 2 . Table 3 The comparison of serum IFN-γ, IL-10 and IL-6 levels in both groups(‾ x ± s ) grouping n time IFN- γ (pg/ml) IL-10 (pg/ml) IL-6 (pg/ml) Study Group 47 Before treatment 20.73 ± 5.24 7.94 ± 2.61 29.25 ± 11.36 After treatment 6.95 ± 2.38 *# 14.93 ± 3.12 *# 17.78 ± 6.25 *# control group 47 Before treatment 21.12 ± 4.96 7.98 ± 2.40 28.87 ± 11.50 After treatment 10.28 ± 2.34 * 10.34 ± 3.16 * 22.90 ± 8.34 * Note: * represents P < 0.05 as compared to pre-treatment; # represents P < 0.05 as compared to post-treatment control. Analysis of T lymphocyte subsets levels in the two groups Treg / CD4 + levels in both groups rose sharply post-treatment as compared to pre-treatment, whereas Th17 / CD4 + and Treg / Th17 levels were substantially lower after treatment as compared to before treatment (P < 0.05); additionally, after treatment, Treg / CD4 + levels in the study concentrations showed significantly higher, whereas Th17 / CD4 + and Treg / Th17 levels were lower than those in the controlling group (P < 0.05), as illustrated in Table 4 and Fig. 3 . Table 4 T-lymphocyte subpopulation comparing between both groups (‾ x ± s ) grouping n time Treg/CD4+ (%) Th17/CD4+ (%) Treg/Th17 (%) Study Group 47 Before treatment 4.23 ± 0.50 4.86 ± 0.40 1.82 ± 0.24 After treatment 6.83 ± 1.13 *# 1.78 ± 0.29 *# 0.60 ± 0.21 *# control group 47 Before treatment 4.19 ± 0.52 4.92 ± 0.42 1.81 ± 0.25 After treatment 5.42 ± 1.09 * 2.75 ± 0.33 * 0.84 ± 0.11 * Note: * indicates that P < 0.05 compared with that before treatment; Compared with the control group after treatment, # indicates that P < 0.05 Analysis of endometrial receptivity in the two groups Treg / CD4 + levels in both groups rose sharply post-treatment as compared to pre-treatment, whereas Th17 / CD4 + and Treg / Th17 levels were substantially lower after treatment as compared to before treatment (P < 0.05); additionally, after treatment, Treg / CD4 + levels in the study concentrations showed significantly higher, whereas Th17 / CD4 + and Treg / Th17 levels were lower than those in the controlling group (P < 0.05), as illustrated in Table 5 and Fig. 4 . Table 5 Comparison of endometrial thickness, RI and PI between the two groups (‾ x ± s ) grouping n time Endometrial thickness (mm) RI (m/s) PI (m/s) Study Group 47 Before treatment 0.77 ± 0.20 0.96 ± 0.30 2.37 ± 0.41 After treatment 0.98 ± 0.29 *# 0.69 ± 0.13 *# 1.86 ± 0.19 *# control group 47 Before treatment 0.78 ± 0.20 0.97 ± 0.31 2.35 ± 0.39 After treatment 0.87 ± 0.26 * 0.80 ± 0.17 * 2.01 ± 0.21 * Note: * indicates that P < 0.05 compared with that before treatment; Compared with the control group after treatment, # indicates that P < 0.05 Analysing the negative reactions in both groups As for the study group, there were 1 skin rash, 2 instances of breast swelling and 1 instance of mild gastric distension, with a total incidence of 8.51%. In the controlling group, there were 5 instances of subcutaneous collapse, 2 instances of percutaneous infection, 1 instance of rash, 2 instances of breast swelling, and 1 instance of mild gastric distension, with a total incidence of adverse reactions of 23.40%. The difference of statistical significance is observed between the two groups (P < 0.05), as summarized in Table 6 . Table 6 The comparison of the incidence of negative reactions among the two groups n (%) grouping Subcutaneous induration Pericutaneous infection rash Breast swelling Mild gastric distention Total occurrence Study group (n = 47) 0 (0.00) 0 (0.00) 1 (2.13) 2 (4.26) 1 (2.13) 4 (8.51) Control group (n = 47) 5 (10.64) 2 (4.26) 1 (2.13) 2 (4.26) 1 (2.13) 11 (23.40) T 3.887 P 0.049 Analysis of pregnancy outcomes in the two groups There were 8 cases of premature delivery and 31 cases of full-term delivery in the study group, and the success rate of fetal protection was 82.98%. There were 13 cases of premature delivery and 15 cases of full-term delivery in the control group, and the success rate of fetal protection was 59.57%. The discrepancy of the two groups was found to be statistical significant (P < 0.05), as illustrated in Table 7 and Fig. 5 . Table 7 Comparison of pregnancy outcomes of the two groups n (%) grouping n premature delivery Full-term delivery abortion Successful fetal protection Study Group 47 8 (17.02) 31 (65.96) 8 (17.02) 39 (82.98) control group 47 13 (27.66) 15 (31.91) 19 (40.43) 28 (59.57) T 18.008 P 0.000 Discussion Dydrogesterone is a natural progestogen with high bioavailability after oral administration, which has been confirmed that its role in endometrial receptor affinity reaction mechanism is better than progesterone and can promote lymphocyte proliferation in a dose-dependent manner and form blocking factors induced by progesterone. In addition, dydrogesterone also has the role of coordinating immune function 14–15 . Dydrogesterone can promote the large release of Th2 type immune response related factors by inducing lymphocytes. At the same time, it can also inhibit these factors, and promote the normal development of embryos by regulating the maternal fetal immune balance 16 . The study group had a higher aggregate effectiveness rate than the controlling group, while the aggregate incidence of adverse reactions was 8.51%, which was clearly lower than that of the controlling group. These findings suggest that the use of progesterone, estrogen and folic acid in the treatment of patients with recurrent miscarriage can successfully improve the success rate of fetal preservation, reduce the incidence of adverse reactions and prevent pregnancy. The three drugs can play their respective functions to make up for their limitations for complement each other, playing important roles in the treatment of patients with recurrent abortion 17–18 . Zhu [19 and other studies have shown that there is a link between pregnancy outcome and Th1 and Th2 immune responses in patients with recurrent abortion. Another report has shown that the immune rejection and tolerance of Th1/Th2 in patients with recurrent spontaneous abortion were out of balance, and tumor necrosis factor α (TNF- α) and IFN- γ both belong to Th1 type immune response related factors, which play important roles in embryonic growth and development and trophoblast activity 20–21 . IL-10 and IL-6 belong to Th2 type immune response related factors, and the former can induce B cells to produce effects on maternal immunity, and the latter can participate in the regulation of maternal fetal immune compatibility by controlling the expression of Th1 cytokines 22–23 . Reports have shown that the imbalance of Th17/Treg is associated with pregnancy outcome and immune tolerance 24 . After therapy, the serum IFN - γ, IL-6, Th17 / CD4 +, and Treg / Th17 levels were clearly down-regulated in both groups as compared to pre-treatment, while the levels of IL-10 and Treg / CD4 + were clearly up-regulated as compared to pre-treatment (P < 0. 05); while in the study group, the levels of serum IFN- γ, IL-6, Th17 / CD4 +, and Treg / Th17 were clearly down-regulated as compared to the controlling group after therapy. while the levels of IL-10 and Treg / CD4 + were clearly upregulated (P < 0.05), suggesting that the treatment of dydrogesterone and progesterone combined with folic acid can regulate the body immunity of patients with recurrent abortion. The reason is that dydrogesterone can induce lymphocyte proliferation by improving endometrial receptivity in patients with recurrent abortion, which is conducive to the regulation of cellular immunity to maintain the function of normal growth and the development of embryos, and ultimately reduce the risk of miscarriage 25–26 . Endometrial receptivity plays a key role in the process of fertilized egg implantation. Endometrial thickness can reflect endometrial receptivity, and RI and PI values can reflect uterine blood perfusion 27–28 . The findings of this study demonstrated that the endometrial thickness increased significantly in both groups after therapy as compared to pre-treatment, while RI and PI values decreased obviously as compared to pre-treatment (P < 0.05); after therapy, the endometrial thickness increased clearly in the study group, while RI and PI values decreased significantly as compared to the controlling group (P < 0.05), suggesting that the treatment of dydrogesterone and progesterone combined with folic acid may provide for improvement of endometrial receptivity in patients with recurrent miscarriage, which is due to the fact that dydrogesterone can supplement progestational hormone and induce uterine angiogenesis, which is conducive to improving uterine blood circulation and ultimately improving endometrial receptivity. Meanwhile, it was found in this study that the fertility preservation success rate was clearly superior in the study group than in the controlling group, indicating that the combination of didrogestrel and progesterone with folic acid was effective in treating patients with recurrent miscarriage, which has a positive significance for pregnancy outcome. This is because dydrogesterone is a kind of reversal progesterone, which can reduce prostaglandin secretion and inhibit uterine contraction, which is conducive to promoting embryo implantation. In addition, the drug can also improve placental blood flow and reduce the secretion of peanut tetraacetic acid, which plays an obvious role in improving the effect of fetal protection 29–30 . Dydrogesterone and progesterone combined with folic acid to cure recurrent miscarriage can effectively enhance the success rate of fetal preservation by regulating the levels of T lymphocytes and inflammatory factors, improve endometrial receptivity, and have a positive significance in improving pregnancy outcomes. Combined Therapy with Dydrogesterone, Progesterone, and Folic Acid Enhances Pregnancy Outcomes through Modulation of T Lymphocytes, Reduction of Inflammatory Factors, and Improved Endometrial Receptivity in Women with Recurrent Abortion Limitations and Future Directions Despite the positive findings, this study has limitations. The retrospective design may introduce bias, and the sample size, while adequate, limits the generalizability of the results. Future studies should include larger, multicenter trials with diverse populations to validate these findings. Additionally, exploring the molecular mechanisms underlying dydrogesterone's effects on immune modulation and endometrial receptivity would provide deeper insights into its therapeutic potential. Clinical Implications Clinically, the results advocate for incorporating dydrogesterone into the treatment regimen for recurrent abortion. This combination therapy not only improves pregnancy outcomes but also offers a safer profile with fewer adverse reactions. These findings should inform clinical guidelines and encourage further research into optimizing hormone therapies for recurrent miscarriage. Conclusion In conclusion, the combination of dydrogesterone, progesterone, and folic acid offers a promising approach to treating recurrent abortion. By enhancing endometrial receptivity, modulating immune responses, and reducing inflammatory markers, this therapy significantly improves pregnancy outcomes. Future research should focus on large-scale, prospective studies to confirm these benefits and explore the underlying mechanisms further. References Zhu X, Liu H, Zhang Z, Wei R, Zhou X, Wang Z, Zhao L, Guo Q, Zhang Y, Chu C, Wang L, Li X (2020) miR-103 protections from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization. Int j Biol Sci 16(12):2248–2264 Jiang X, Zhao S, Pan X, Qiu X, Niu X, Li M, Xie X, Liu S (2019) Detection of chromosomal abnormalities in approximate problems derived from patients with recurrent complications using Bob technique. Zhonghua Yi Xue Yi Chuan Xue ZA zhi 36(5):502–504 Chen B, Shi QQ, Liang KL, Xu YY, Fang YY, Chen SH, Lyu GY (2018 may) Effect and mechanism of Yungang oral liquid in regulating endocrine system and VEGF signaling pathway and reducing abort rate in recurrent abort mice. Zhongguo Zhong Yao ZA Zhi 43(9):1894–1900 Jin M, Li D, Ji R, Liu W, Xu X (2020) andFeng X. Changes in gut microstructure in patients with positive immune antibody associated recurrent antibody. Biomed Res int. ; 2020:4673250 Shi Y, Tan D, Hao B, Zhang x, Geng W, Wang Y, Sun J, Zhao Y (2022) Efficiency of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: a systematic review and meta-analysis. Am J Reprod Immunol 88(5):e13615 Zhao L, Bi S, Fu J, Qi l, Li L, Fu Y (2021) Retrospective analysis of fondaparinux and low molecular weight heparin in the treatment of women with recurrent spontaneous abortion. Front Endocrinol (Lausanne) 12:717630 Saccone G, Schoen C, Franasiak JM, Scott RT Jr, Berghella V (2017) Supply with precursors in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril 107(2):430–438e3 Zeng L, Yang K, Liu L, Zhang T, Liu H, Tan Z, Lei L (2020) Systemic biological and proteomics strategies to explore the regulation mechanism of Shoutai Wan on recurrent spontaneous abortion's biological network. J Ethnoharmacol 263:113156 Lee HJ, park TC, Kim JH, Norwitz Ea, Lee B (2017) The influence of oral dydrogesterone and vaginal progesterone on threatened abortion: a systematic review and meta-analysis. Biomed Res Int. ; 2017:3616875 Griesinger G, Blockeel C, Kahler E, Pexman Fieth C, Olofsson Ji, Driessen S, Tournaye H (2020) Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: a systematic review and individual participant data meta-analysis. PLoS ONE 15(11):e0241044 Grossman D, White K, Harris L, Reeves M, Blumenthal PD, Winikoff B, Grimes DA (2015) Continuing prognosis after mifepristone and reverse of first-trimester medical abortion: a systematic review Concept. ; 92 (3): 206 – 11 Ali MK, Ahmed SE, Sayed GH, Badran EY, Abbas (2020) AM Effect of adaptive vaginal progenone after McDonald complaint on the rate of second trimester above in singleton pregnancy: a randomized controlled trial. Int J Gynaecol Obstet 149(3):370–376 Mao YY, Yang L, Li m, Liu J, Zhu QX, He Y, Zhou, Wj (2020) Periconceptional folic acid supply and the risk of spontaneous abortion among women who prepared to conform: impact of supply initiation timing. Nutrients 12(8):2264 Iwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, mizuuchi M, Moriwaka O, Kamiya H (2021) new treatment strategy for epidemiology using promising prime ovarian stimulation with diet: a prospective cohort study, comparison of diet versus dysdrogesterone. Reprod Biol 21(1):100470 Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E (2018) Pexman Fieth C andTournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in ivf: a randomized clinical trial. Hum Reprod 33(12):2212–2221 Tournaye H, sukhikh GT, Kahler E, Griesinger G (2017) A phase III randomized controlled trial comparing the efficiency, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in vitro utilization. Hum Reprod 32(5):1019–1027 Bi SJ, Huang YX, Feng LM, Yue SJ, Chen YY, Fu RJ, Xu DQ, Tang Yp (2022) Network pharmacology based study on immunological mechanism of Danggui Yimucao herb pair for the treatment of RU486 induced abortion. J Ethnoharmacol 282:114609 Mao YY, Yang L, Li M, Liu J, Zhu QX, He Y, Zhou, Wj (2020) Periconceptional folic acid supply and the risk of spontaneous abortion among women who prepared to conform: impact of supply initiation timing. Nutrients 12(8):2264 Zhu L, Chen h, Liu m, Wang Yy, Chen Z, Wei Y, Su J F and, Zhang J (2017) Treg/th17 cell imbalance and IL-6 profile in patients with unexplained recurrent spontaneous abortion. Reprod Sci 24(6):882–890 Arefieva A, Nikolaeva M, Stepanova E, Krechetova L, Golubeva E, Teturashvili N, Sukhikh G (2021) Association of CD200 expression in regional lymphocytes with female th1/th2 balance and wealth establishment at immunology of recurrent spontaneous abortion. Am J Reprod Immunol 85(3):e13355 Gu H, Li L, Du M, Xu H, Gao M, Liu X, Wei X, Zhong X (2021) Key gene and functional pathways identified in unexplained recurrent spontaneous abortion using targeted RNA sequencing and clinical analysis. Front Immunol 12:717832 Wang P, Jiang G, Ju W, Cai Y, Wang J, Wu F (2021) Influence of Bushen Tiaochong cycle therapy on th1/th2 deviation, sex hormone level, and prestige outcome of alloimmune recurrent spontaneous abortion Evid Based Complement Alternate Med. SEP 21; 2021:8624414 Alkhuriji AF, Al Omar SY, babay ZA, El khadragy MF, Mansour La, Alharbi WG, Khalil MI (2020) Association of IL-1 β, IL-6, TNF- α, And TGF β 1 gene polymers with recurrent spontaneous antibody in polycystic ovary syndrome. Dis Markers. ; 2020:6076274 Wu L, Luo LH, Zhang YX, Li Q, Xu B, Zhou GX (2014) Luan Hb and Liu Ys. Alternation of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol 12:74 Pei L, Wu J, Li J, MI X, Zhang X, Li Z, Zhang Y (2019) Hum Reprod 34(8):1587–1594 Lee HJ, Park TC, Kim JH, Norwitz E, Lee B (2017) The influence of oral dydrogesterone and vaginal progesterone on threatened abortion: a systematic review and meta-analysis Biomed Res int. ; 2017:3616875 Dieamant F, Vagnini LD, Petersen CG, Mauri Al, Renzi A, Petersen B, Mattila MC, Nicoletti A, Oliveira JBA, Baruffi R, Franco JG Jr (2019) New therapeutic protocol for improvement of environmental responsiveness (primer) for patients with recurrent implantation failure (RIF) - A pilot study. Jbra Assist Reprod 23(3):250–254 Saxtorph MH, hallager T, Persson G, Petersen KB, Eriksen Jo, Larsen LG, Hvid TV, Macklon N (2020) Assessing endogenous reception after recurrent intervention failure: a prospective controlled cohort study Reprod BioMed online. ; 41 (6): 998–1006 Tournaye H, Sukhikh GT, Kahler E, Griesinger G (2017) A phase III randomized controlled trial comparing the efficiency, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in vitro utilization. Hum Reprod 32(5):1019–1027 Ott J, egarter C, Aguilera A (2022) Dydrogesterone after 60 years: a grace at the safety profile Gynecol Endocrinol. 38(4):279–287 Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-4706080","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":324216672,"identity":"1792df7e-53be-41b5-be5f-ab2cc77d7316","order_by":0,"name":"Xia wang","email":"","orcid":"","institution":"Department of Gynecology and Obstetrics, Jian Tong First People's Hospital, Jiangsu 213200, Changzhou Province, China","correspondingAuthor":false,"prefix":"","firstName":"Xia","middleName":"","lastName":"wang","suffix":""},{"id":324216673,"identity":"dec65801-ad39-4a68-9c7a-a180617858d8","order_by":1,"name":"Wen Yuan","email":"","orcid":"","institution":"Department of Gynecology and Obstetrics, Jian Tong First People's Hospital, Jiangsu 213200, Changzhou Province, China","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Yuan","suffix":""},{"id":324216677,"identity":"82de0808-9fea-44d5-a820-4bff5f9dd5bd","order_by":2,"name":"Juan Yang","email":"","orcid":"","institution":"Department of Gynecology and Obstetrics, Jian Tong First People's Hospital, Jiangsu 213200, Changzhou Province, China","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Yang","suffix":""},{"id":324216681,"identity":"4e46f379-031e-4875-a1aa-18c5bf4ebe2b","order_by":3,"name":"Sparkle Star","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIie3PvQrCMBDA8QuBTME6pkv1EQKBTn0Tl4RCJ3VxcehQEeroqm8h+AKRgF0CXTv2Eeqkk1+bWzI65L8d3O/gAEKhvyy6P+Q6SyKML72v4WywhYh3JOfeJD7WRvGWpmO//U5KQQmWwkAKUGYzN7Fa55SSZWqg6OFaLConaTaVoYyuPqThqDIexGC0pZyp8xbVzI80NUYHydUJY+JHYmsJDFoKZgjm0ueXUTcnoJ6vJNq3t34oMzeZ6t9Juta/TZxHQ6FQKPQGYAk/3BTtBxMAAAAASUVORK5CYII=","orcid":"","institution":"Department of Gynecology and Obstetrics, Jian Tong First People's Hospital, Jiangsu 213200, Changzhou Province, China","correspondingAuthor":true,"prefix":"","firstName":"Sparkle","middleName":"","lastName":"Star","suffix":""}],"badges":[],"createdAt":"2024-07-08 13:56:55","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4706080/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4706080/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60023327,"identity":"ef1b92b2-1eb0-4961-b5b9-805690fa2c56","added_by":"auto","created_at":"2024-07-10 16:40:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":88824,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution chart analysis of the two clinical efficacy groups\u003c/p\u003e\n\u003cp\u003eNote: Figure A: The distribution diagram of clinical efficacy in the study group; Figure B: The distribution diagram of clinical efficacy in the control group\u003c/p\u003e\n\u003cp\u003eContrast of the two groups' serum inflammatory factors\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/53f6e6c250caf684a268bef6.png"},{"id":60023991,"identity":"cadae927-d78b-4bca-9cb6-4ba316755073","added_by":"auto","created_at":"2024-07-10 16:47:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28902,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the levels of serum IFN- γ, IL-10 and IL-6 of the two groups\u003c/p\u003e\n\u003cp\u003eNote: Figure A: Difference in serum IFN- γ levels of the two groups; Figure B. Difference in serum IL-10 levels of the two groups; Figure C: Difference in serum IL-6 levels of the two groups. Compared with the treated control group, *** represents P \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/235d9d63995717e2179ee6f6.png"},{"id":60023326,"identity":"08830c73-5796-4aea-a956-a6d19089eb21","added_by":"auto","created_at":"2024-07-10 16:40:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":22654,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of T lymphocyte subsets between the two groups\u003c/p\u003e\n\u003cp\u003eNote: Figure A: Comparison of Treg/CD4+ levels between the two groups; Figure B: Comparison of Th17/CD4+ levels between the two groups; Figure C: Comparison of Treg/Th17 between the two groups. Compared with the control group after treatment, *** indicates that P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/2a333e676f1e588da7daff6f.png"},{"id":60023992,"identity":"bdc52be6-0e2b-4f32-a6eb-556579a51303","added_by":"auto","created_at":"2024-07-10 16:48:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28853,"visible":true,"origin":"","legend":"\u003cp\u003eEndometrial thickness, RI and PI values were compared in both groups\u003c/p\u003e\n\u003cp\u003eNote: Figure A compares the thickness of the endometrium in the two groups; Figure B compares the RI values as in two groups; and Figure C compares the PI values with in two groups. *** denotes that P ＜ 0.05 following treatment when compared to the controlling group.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/6eefa9faab4a084897634618.png"},{"id":60023323,"identity":"f8652b13-9f88-49bf-a015-e7f369c48f5a","added_by":"auto","created_at":"2024-07-10 16:40:00","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":50849,"visible":true,"origin":"","legend":"\u003cp\u003eThe distribution diagram analysis of pregnancy outcomes in the two groups\u003c/p\u003e\n\u003cp\u003eNote: Figure A: The distribution diagram of pregnancy outcomes in the study group; Figure B: The distribution diagram of pregnancy outcomes in the control group\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/849e16d112efee3c2728ba97.png"},{"id":60024395,"identity":"94b6f8ff-6d04-4721-9f8a-0e2abfe5a8ca","added_by":"auto","created_at":"2024-07-10 16:56:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":825231,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4706080/v1/53162eaf-6d7e-439f-b497-067f1081c857.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eCombination therapy of dydrogesterone and progesterone together with folic acid in the treatment of recurrent abortion on the outcome of Re-pregnancy\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRecurrent abortion is one of the common pregnancy complications whose incidence tends to increase year by year\u003csup\u003e1\u003c/sup\u003e. At present, it has been found that chromosomal abnormalities, endocrine disorders, infections, immune tolerance disorders, genital tract anatomy abnormalities and other factors can be regarded as risk factors for recurrent abortion. However, it is still difficult to determine the pathogenesis factors in 50% of patients\u003csup\u003e2\u0026ndash;4\u003c/sup\u003e. Clinically, patients with recurrent abortion are mainly treated through drugs, including traditional Chinese medicine and hormone treatment, which can ameliorate the clinical condition of the patient to in some degree, but their long-term curative effects are not ideal. In addition, the long-term massive use of glucocorticoids can lead to many adverse reactions, which places a severe threat on the sufferers' sense of quality of living and mental and emotional health, and there is no unified treatment specification and standard\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e. Therefore, it is particularly important to further reveal the etiology and mechanism of recurrent abortion, and seek effective ways to prevent and treat the disease to protect reproductive health of women of childbearing age and improve pregnancy outcomes\u003csup\u003e8\u003c/sup\u003e. As a natural progestogen drug, dydrogesterone can significantly promote endometrial receptive response, which is beneficial to improve proliferation ability of lymphocyte and restore immune regulation function, and has an important value in reducing the incidence of abortion\u003csup\u003e9\u0026ndash;10\u003c/sup\u003e. Progesterone is a necessary for maintaining pregnancy, which can inhibit the maternal rejection for fetus and trophoblasts to promote embryo implantation and improve the development of placental villus, which promotes fetal growth and development\u003csup\u003e11\u0026ndash;12\u003c/sup\u003e. Folic acid has been proved that it has an important role in the treatment of recurrent abortion, which can play a role by reducing the serum homocysteine levels of patients\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite the known benefits of dydrogesterone, progesterone, and folic acid individually, there are few studies on their combined effects on pregnancy outcomes in recurrent miscarriage cases.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the effectiveness of combining dydrogesterone and progesterone with folic acid in improving pregnancy outcomes for women with recurrent abortion. By examining clinical effectiveness, inflammatory markers, T lymphocyte subsets, endometrial parameters, uterine artery perfusion, and pregnancy outcomes, we aim to provide insights into optimizing treatment protocols for recurrent abortion.\u003c/p\u003e "},{"header":"Methods and materials","content":"\u003cp\u003eData and methodsGeneral data\u003c/p\u003e \u003cp\u003eNinety-four recurrent miscarriage procedures dealt with in our institution during June 2020 to July 2022 were analysed as a retrospective basis. The patients indicate here are women with recurrent abortion. Inclusion criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The patients women with recurrent abortion and the men were normal by chromosome examination; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The number of consecutive spontaneous abortions was more than 3 times; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Patients with normal communication and without mental illness; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Written informed consent executed by the patient or family; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Permission from the hospital ethics board (approval number: KY20203225-1). Exclusion criterion. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Patients with hypersensitivity to study-related drugs; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Patients suffering from thyroid dysfunction; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Patients with serious infection; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Patients with abortion caused by the males; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Patients with diabetes mellitus and chronic liver and kidney dysfunction; (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Patients who dropped out from the study halfway. 94 patients with recurrent abortion were separated into the controlling group and the research group, with 47 cases in each group, using the randomized number table approach. In the controlling group, the average age was (28.59\u0026thinsp;\u0026plusmn;\u0026thinsp;3.99), the average number of pregnancies was (3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98) times, and the number of abortions was (3.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93) times; In the study group, the average age was (29.40\u0026thinsp;\u0026plusmn;\u0026thinsp;3.48), the average number of pregnancies was (4.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97) times, and the number of abortions was (3.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91) times; The general data of the two groups did not diffuse in a significant way (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eGeneral data profiling of the two groups(\u0026oline;\u003cem\u003ex\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003es\u003c/em\u003e)\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=\"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\"\u003e \u003cp\u003egrouping\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of pregnancies (Times)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNumber of abortions (Times)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.59\u0026thinsp;\u0026plusmn;\u0026thinsp;3.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.877\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.383\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMethods\u003c/p\u003e \u003cp\u003eTherapy The controlling group was operated with progesterone combined with folic acid, in which progesterone injection (SFDA approval number H33020828, provided by Zhejiang Xianju Pharmaceutical Co., Ltd.) was injected intramuscularly, 40mg each time, once a day, and folic acid (SFDA approval number H10970079, provided by Beijing Silian Pharmaceutical Co., Ltd.) was taken orally at 0.4\u0026thinsp;~\u0026thinsp;0.8 mg once a day in accordance with the patient's own situation. On the basis of the controlling group, the study group was orally controlled with drospirenone tablets (SFDA approval number H20170221, provided by Abbott biologicals B.V., the Netherlands), 10 mg once, twice daily. Both groups were continuously cured until 12 weeks after pregnancy.\u003c/p\u003e \u003cp\u003eBlood sample collection Fasting elbow venous blood was collected from both groups pre- and post-treatment and after anticoagulation treatment, it was centrifuged in a table top high-speed low-temperature centrifuge (provided by Thermo Fisher Scientific) for 10min at a speed of 1500r/min, and the supernatant was stored in a -80 ℃ ultra-low temperature refrigerator (provided by Haier, China) for detection.\u003c/p\u003e \u003cp\u003eObservation indexes\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Clinical efficacy: It is divided into three aspects: cure, becoming better and invalid. Overall efficiency (%) = ( the number of cured cases\u0026thinsp;+\u0026thinsp;the number of cases that turned out to be better)/total observed cases \u0026times; 100%. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Inflammatory factors: The levels of serum interferonsγ(IFN), nterleukin-10 (IL-10) and IL-6 in these two groups was measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) T lymphocyte subsets: The levels of CD4\u0026thinsp;+\u0026thinsp;regulatory T cell, Treg (Treg/CD4+), CD4\u0026thinsp;+\u0026thinsp;helper T cell Th17 (Th17/CD4+) and helper T cell / regulatory T cell (Treg/Th17) in the two groups were detected by flow cytometry before and after treatment. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Endometrial receptivity: The endometrial thickness, uterine artery blood perfusion resistance index (RI) and pulsatility index (PI) in the two groups were detected by vaginal B-ultrasound pre- and post-treatment. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Occurrence of undesirable reactions in both groups should be closely monitored during the treatment process, and then the total incidence was calculated. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Pregnancy outcomes: The pregnancy outcomes were recorded and analyzed, including premature delivery, full-term delivery and abortion, and the success rate of fetal protection was calculated. The formula was (number of premature births\u0026thinsp;+\u0026thinsp;number of full-term births) / total number of observed cases \u0026times; 100%.\u003c/p\u003e \u003cp\u003eStatistical methods\u003c/p\u003e \u003cp\u003eSPSS21.0 software was utilized for the data analysis. The counting information was presented as n (%). The measurement data were written in the form of(\u0026oline;\u003cem\u003ex\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003es\u003c/em\u003e), and x\u003csup\u003e2\u003c/sup\u003e was applied to assess the pairwise comparison. By using t, the pairwise comparison was assessed. The difference was deemed to be significant at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAnalysis of clinical efficacy of the two groups\u003c/p\u003e\n\u003cp\u003eWhile in the control group, 15 instances were healed, 18 instances improved, and the overall effective rate was 70.21% (33/47), in the study group, 31 instances were cured, 11 instances improved, and the overall effective rate was 89.36% (42/47). According to Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, there was a statistically meaningful difference in the total effective rate between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparing the effective rates for both groups n (%)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ecure\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBecoming better\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003einvalid\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal effective\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudy Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31 (65.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (23.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (10.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (89.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econtrol group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (31.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (38.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (29.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (70.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ex\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eContrast of the two groups\u0026apos; serum inflammatory factors\u003c/p\u003e\n\u003cp\u003eThe levels of serum IFN- \u0026gamma; and IL-6 in both groups were substantially reduced after treatment as compared to those before treatment, whereas the levels of IL-10 were massively increased after treatment as compared to those before therapies (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); additionally, the levels of serum IFN- \u0026gamma; and IL-6 in the study group were greatly reduced after treatment as compared to those in the controlling group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe comparison of serum IFN-\u0026gamma;, IL-10 and IL-6 levels in both groups(\u0026oline;\u003cem\u003ex\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003es\u003c/em\u003e)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003etime\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIFN- \u0026gamma; (pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-10\u003c/p\u003e\n \u003cp\u003e(pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003cp\u003e(pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eStudy Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.73\u0026thinsp;\u0026plusmn;\u0026thinsp;5.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.25\u0026thinsp;\u0026plusmn;\u0026thinsp;11.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.95\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.12\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.25\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003econtrol group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.12\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.98\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.87\u0026thinsp;\u0026plusmn;\u0026thinsp;11.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.28\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.90\u0026thinsp;\u0026plusmn;\u0026thinsp;8.34\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eNote: * represents P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as compared to pre-treatment; # represents P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as compared to post-treatment control.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAnalysis of T lymphocyte subsets levels in the two groups\u003c/p\u003e\n\u003cp\u003eTreg / CD4\u0026thinsp;+\u0026thinsp;levels in both groups rose sharply post-treatment as compared to pre-treatment, whereas Th17 / CD4\u0026thinsp;+\u0026thinsp;and Treg / Th17 levels were substantially lower after treatment as compared to before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); additionally, after treatment, Treg / CD4\u0026thinsp;+\u0026thinsp;levels in the study concentrations showed significantly higher, whereas Th17 / CD4\u0026thinsp;+\u0026thinsp;and Treg / Th17 levels were lower than those in the controlling group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eT-lymphocyte subpopulation comparing between both groups (\u0026oline;\u003cem\u003ex\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003es\u003c/em\u003e)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003etime\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreg/CD4+ (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTh17/CD4+ (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreg/Th17 (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eStudy Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003econtrol group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eNote: * indicates that P \u0026lt; 0.05 compared with that before treatment; Compared with the control group after treatment, # indicates that P \u0026lt; 0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAnalysis of endometrial receptivity in the two groups\u003c/p\u003e\n\u003cp\u003eTreg / CD4\u0026thinsp;+\u0026thinsp;levels in both groups rose sharply post-treatment as compared to pre-treatment, whereas Th17 / CD4\u0026thinsp;+\u0026thinsp;and Treg / Th17 levels were substantially lower after treatment as compared to before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); additionally, after treatment, Treg / CD4\u0026thinsp;+\u0026thinsp;levels in the study concentrations showed significantly higher, whereas Th17 / CD4\u0026thinsp;+\u0026thinsp;and Treg / Th17 levels were lower than those in the controlling group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of endometrial thickness, RI and PI between the two groups (\u0026oline;\u003cem\u003ex\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003es\u003c/em\u003e)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003etime\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEndometrial thickness\u003c/p\u003e\n \u003cp\u003e(mm)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRI\u003c/p\u003e\n \u003cp\u003e(m/s)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePI\u003c/p\u003e\n \u003cp\u003e(m/s)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eStudy Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003csup\u003e*#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003econtrol group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eNote: * indicates that P \u0026lt; 0.05 compared with that before treatment; Compared with the control group after treatment, # indicates that P \u0026lt; 0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAnalysing the negative reactions in both groups\u003c/p\u003e\n\u003cp\u003eAs for the study group, there were 1 skin rash, 2 instances of breast swelling and 1 instance of mild gastric distension, with a total incidence of 8.51%. In the controlling group, there were 5 instances of subcutaneous collapse, 2 instances of percutaneous infection, 1 instance of rash, 2 instances of breast swelling, and 1 instance of mild gastric distension, with a total incidence of adverse reactions of 23.40%. The difference of statistical significance is observed between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe comparison of the incidence of negative reactions among the two groups n (%)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSubcutaneous induration\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePericutaneous infection\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003erash\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBreast swelling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMild gastric distention\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal occurrence\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudy group (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (8.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (10.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (23.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.887\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAnalysis of pregnancy outcomes in the two groups\u003c/p\u003e\n\u003cp\u003eThere were 8 cases of premature delivery and 31 cases of full-term delivery in the study group, and the success rate of fetal protection was 82.98%. There were 13 cases of premature delivery and 15 cases of full-term delivery in the control group, and the success rate of fetal protection was 59.57%. The discrepancy of the two groups was found to be statistical significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of pregnancy outcomes of the two groups n (%)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egrouping\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003epremature delivery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFull-term delivery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eabortion\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSuccessful fetal protection\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudy Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (17.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31 (65.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (17.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39 (82.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econtrol group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (27.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (31.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (40.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (59.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDydrogesterone is a natural progestogen with high bioavailability after oral administration, which has been confirmed that its role in endometrial receptor affinity reaction mechanism is better than progesterone and can promote lymphocyte proliferation in a dose-dependent manner and form blocking factors induced by progesterone. In addition, dydrogesterone also has the role of coordinating immune function\u003csup\u003e14\u0026ndash;15\u003c/sup\u003e. Dydrogesterone can promote the large release of Th2 type immune response related factors by inducing lymphocytes. At the same time, it can also inhibit these factors, and promote the normal development of embryos by regulating the maternal fetal immune balance\u003csup\u003e16\u003c/sup\u003e. The study group had a higher aggregate effectiveness rate than the controlling group, while the aggregate incidence of adverse reactions was 8.51%, which was clearly lower than that of the controlling group. These findings suggest that the use of progesterone, estrogen and folic acid in the treatment of patients with recurrent miscarriage can successfully improve the success rate of fetal preservation, reduce the incidence of adverse reactions and prevent pregnancy. The three drugs can play their respective functions to make up for their limitations for complement each other, playing important roles in the treatment of patients with recurrent abortion\u003csup\u003e17\u0026ndash;18\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eZhu\u003csup\u003e[19\u003c/sup\u003e and other studies have shown that there is a link between pregnancy outcome and Th1 and Th2 immune responses in patients with recurrent abortion. Another report has shown that the immune rejection and tolerance of Th1/Th2 in patients with recurrent spontaneous abortion were out of balance, and tumor necrosis factor α (TNF- α) and IFN- γ both belong to Th1 type immune response related factors, which play important roles in embryonic growth and development and trophoblast activity\u003csup\u003e20\u0026ndash;21\u003c/sup\u003e. IL-10 and IL-6 belong to Th2 type immune response related factors, and the former can induce B cells to produce effects on maternal immunity, and the latter can participate in the regulation of maternal fetal immune compatibility by controlling the expression of Th1 cytokines\u003csup\u003e22\u0026ndash;23\u003c/sup\u003e. Reports have shown that the imbalance of Th17/Treg is associated with pregnancy outcome and immune tolerance\u003csup\u003e24\u003c/sup\u003e. After therapy, the serum IFN - γ, IL-6, Th17 / CD4 +, and Treg / Th17 levels were clearly down-regulated in both groups as compared to pre-treatment, while the levels of IL-10 and Treg / CD4\u0026thinsp;+\u0026thinsp;were clearly up-regulated as compared to pre-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0. 05); while in the study group, the levels of serum IFN- γ, IL-6, Th17 / CD4 +, and Treg / Th17 were clearly down-regulated as compared to the controlling group after therapy. while the levels of IL-10 and Treg / CD4\u0026thinsp;+\u0026thinsp;were clearly upregulated (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that the treatment of dydrogesterone and progesterone combined with folic acid can regulate the body immunity of patients with recurrent abortion. The reason is that dydrogesterone can induce lymphocyte proliferation by improving endometrial receptivity in patients with recurrent abortion, which is conducive to the regulation of cellular immunity to maintain the function of normal growth and the development of embryos, and ultimately reduce the risk of miscarriage\u003csup\u003e25\u0026ndash;26\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEndometrial receptivity plays a key role in the process of fertilized egg implantation. Endometrial thickness can reflect endometrial receptivity, and RI and PI values can reflect uterine blood perfusion\u003csup\u003e27\u0026ndash;28\u003c/sup\u003e. The findings of this study demonstrated that the endometrial thickness increased significantly in both groups after therapy as compared to pre-treatment, while RI and PI values decreased obviously as compared to pre-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); after therapy, the endometrial thickness increased clearly in the study group, while RI and PI values decreased significantly as compared to the controlling group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that the treatment of dydrogesterone and progesterone combined with folic acid may provide for improvement of endometrial receptivity in patients with recurrent miscarriage, which is due to the fact that dydrogesterone can supplement progestational hormone and induce uterine angiogenesis, which is conducive to improving uterine blood circulation and ultimately improving endometrial receptivity. Meanwhile, it was found in this study that the fertility preservation success rate was clearly superior in the study group than in the controlling group, indicating that the combination of didrogestrel and progesterone with folic acid was effective in treating patients with recurrent miscarriage, which has a positive significance for pregnancy outcome. This is because dydrogesterone is a kind of reversal progesterone, which can reduce prostaglandin secretion and inhibit uterine contraction, which is conducive to promoting embryo implantation. In addition, the drug can also improve placental blood flow and reduce the secretion of peanut tetraacetic acid, which plays an obvious role in improving the effect of fetal protection\u003csup\u003e29\u0026ndash;30\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDydrogesterone and progesterone combined with folic acid to cure recurrent miscarriage can effectively enhance the success rate of fetal preservation by regulating the levels of T lymphocytes and inflammatory factors, improve endometrial receptivity, and have a positive significance in improving pregnancy outcomes. Combined Therapy with Dydrogesterone, Progesterone, and Folic Acid Enhances Pregnancy Outcomes through Modulation of T Lymphocytes, Reduction of Inflammatory Factors, and Improved Endometrial Receptivity in Women with Recurrent Abortion\u003c/p\u003e\n\u003ch3\u003eLimitations and Future Directions\u003c/h3\u003e\n\u003cp\u003eDespite the positive findings, this study has limitations. The retrospective design may introduce bias, and the sample size, while adequate, limits the generalizability of the results. Future studies should include larger, multicenter trials with diverse populations to validate these findings. Additionally, exploring the molecular mechanisms underlying dydrogesterone's effects on immune modulation and endometrial receptivity would provide deeper insights into its therapeutic potential.\u003c/p\u003e\n\u003ch3\u003eClinical Implications\u003c/h3\u003e\n\u003cp\u003eClinically, the results advocate for incorporating dydrogesterone into the treatment regimen for recurrent abortion. This combination therapy not only improves pregnancy outcomes but also offers a safer profile with fewer adverse reactions. These findings should inform clinical guidelines and encourage further research into optimizing hormone therapies for recurrent miscarriage.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the combination of dydrogesterone, progesterone, and folic acid offers a promising approach to treating recurrent abortion. By enhancing endometrial receptivity, modulating immune responses, and reducing inflammatory markers, this therapy significantly improves pregnancy outcomes. Future research should focus on large-scale, prospective studies to confirm these benefits and explore the underlying mechanisms further.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhu X, Liu H, Zhang Z, Wei R, Zhou X, Wang Z, Zhao L, Guo Q, Zhang Y, Chu C, Wang L, Li X (2020) miR-103 protections from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization. Int j Biol Sci 16(12):2248\u0026ndash;2264\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang X, Zhao S, Pan X, Qiu X, Niu X, Li M, Xie X, Liu S (2019) Detection of chromosomal abnormalities in approximate problems derived from patients with recurrent complications using Bob technique. Zhonghua Yi Xue Yi Chuan Xue ZA zhi 36(5):502\u0026ndash;504\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen B, Shi QQ, Liang KL, Xu YY, Fang YY, Chen SH, Lyu GY (2018 may) Effect and mechanism of Yungang oral liquid in regulating endocrine system and VEGF signaling pathway and reducing abort rate in recurrent abort mice. Zhongguo Zhong Yao ZA Zhi 43(9):1894\u0026ndash;1900\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJin M, Li D, Ji R, Liu W, Xu X (2020) andFeng X. Changes in gut microstructure in patients with positive immune antibody associated recurrent antibody. Biomed Res int. ; 2020:4673250\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Tan D, Hao B, Zhang x, Geng W, Wang Y, Sun J, Zhao Y (2022) Efficiency of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: a systematic review and meta-analysis. Am J Reprod Immunol 88(5):e13615\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao L, Bi S, Fu J, Qi l, Li L, Fu Y (2021) Retrospective analysis of fondaparinux and low molecular weight heparin in the treatment of women with recurrent spontaneous abortion. Front Endocrinol (Lausanne) 12:717630\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaccone G, Schoen C, Franasiak JM, Scott RT Jr, Berghella V (2017) Supply with precursors in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril 107(2):430\u0026ndash;438e3\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng L, Yang K, Liu L, Zhang T, Liu H, Tan Z, Lei L (2020) Systemic biological and proteomics strategies to explore the regulation mechanism of Shoutai Wan on recurrent spontaneous abortion's biological network. J Ethnoharmacol 263:113156\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee HJ, park TC, Kim JH, Norwitz Ea, Lee B (2017) The influence of oral dydrogesterone and vaginal progesterone on threatened abortion: a systematic review and meta-analysis. Biomed Res Int. ; 2017:3616875\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGriesinger G, Blockeel C, Kahler E, Pexman Fieth C, Olofsson Ji, Driessen S, Tournaye H (2020) Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: a systematic review and individual participant data meta-analysis. PLoS ONE 15(11):e0241044\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrossman D, White K, Harris L, Reeves M, Blumenthal PD, Winikoff B, Grimes DA (2015) Continuing prognosis after mifepristone and reverse of first-trimester medical abortion: a systematic review Concept. ; 92 (3): 206\u0026thinsp;\u0026ndash;\u0026thinsp;11\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli MK, Ahmed SE, Sayed GH, Badran EY, Abbas (2020) AM Effect of adaptive vaginal progenone after McDonald complaint on the rate of second trimester above in singleton pregnancy: a randomized controlled trial. Int J Gynaecol Obstet 149(3):370\u0026ndash;376\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao YY, Yang L, Li m, Liu J, Zhu QX, He Y, Zhou, Wj (2020) Periconceptional folic acid supply and the risk of spontaneous abortion among women who prepared to conform: impact of supply initiation timing. Nutrients 12(8):2264\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, mizuuchi M, Moriwaka O, Kamiya H (2021) new treatment strategy for epidemiology using promising prime ovarian stimulation with diet: a prospective cohort study, comparison of diet versus dysdrogesterone. Reprod Biol 21(1):100470\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGriesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E (2018) Pexman Fieth C andTournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in ivf: a randomized clinical trial. Hum Reprod 33(12):2212\u0026ndash;2221\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTournaye H, sukhikh GT, Kahler E, Griesinger G (2017) A phase III randomized controlled trial comparing the efficiency, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in vitro utilization. Hum Reprod 32(5):1019\u0026ndash;1027\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBi SJ, Huang YX, Feng LM, Yue SJ, Chen YY, Fu RJ, Xu DQ, Tang Yp (2022) Network pharmacology based study on immunological mechanism of Danggui Yimucao herb pair for the treatment of RU486 induced abortion. J Ethnoharmacol 282:114609\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao YY, Yang L, Li M, Liu J, Zhu QX, He Y, Zhou, Wj (2020) Periconceptional folic acid supply and the risk of spontaneous abortion among women who prepared to conform: impact of supply initiation timing. Nutrients 12(8):2264\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu L, Chen h, Liu m, Wang Yy, Chen Z, Wei Y, Su J F and, Zhang J (2017) Treg/th17 cell imbalance and IL-6 profile in patients with unexplained recurrent spontaneous abortion. Reprod Sci 24(6):882\u0026ndash;890\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArefieva A, Nikolaeva M, Stepanova E, Krechetova L, Golubeva E, Teturashvili N, Sukhikh G (2021) Association of CD200 expression in regional lymphocytes with female th1/th2 balance and wealth establishment at immunology of recurrent spontaneous abortion. Am J Reprod Immunol 85(3):e13355\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu H, Li L, Du M, Xu H, Gao M, Liu X, Wei X, Zhong X (2021) Key gene and functional pathways identified in unexplained recurrent spontaneous abortion using targeted RNA sequencing and clinical analysis. Front Immunol 12:717832\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang P, Jiang G, Ju W, Cai Y, Wang J, Wu F (2021) Influence of Bushen Tiaochong cycle therapy on th1/th2 deviation, sex hormone level, and prestige outcome of alloimmune recurrent spontaneous abortion Evid Based Complement Alternate Med. SEP 21; 2021:8624414\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlkhuriji AF, Al Omar SY, babay ZA, El khadragy MF, Mansour La, Alharbi WG, Khalil MI (2020) Association of IL-1 β, IL-6, TNF- α, And TGF β 1 gene polymers with recurrent spontaneous antibody in polycystic ovary syndrome. Dis Markers. ; 2020:6076274\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu L, Luo LH, Zhang YX, Li Q, Xu B, Zhou GX (2014) Luan Hb and Liu Ys. Alternation of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol 12:74\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePei L, Wu J, Li J, MI X, Zhang X, Li Z, Zhang Y (2019) Hum Reprod 34(8):1587\u0026ndash;1594\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee HJ, Park TC, Kim JH, Norwitz E, Lee B (2017) The influence of oral dydrogesterone and vaginal progesterone on threatened abortion: a systematic review and meta-analysis Biomed Res int. ; 2017:3616875\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDieamant F, Vagnini LD, Petersen CG, Mauri Al, Renzi A, Petersen B, Mattila MC, Nicoletti A, Oliveira JBA, Baruffi R, Franco JG Jr (2019) New therapeutic protocol for improvement of environmental responsiveness (primer) for patients with recurrent implantation failure (RIF) - A pilot study. Jbra Assist Reprod 23(3):250\u0026ndash;254\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaxtorph MH, hallager T, Persson G, Petersen KB, Eriksen Jo, Larsen LG, Hvid TV, Macklon N (2020) Assessing endogenous reception after recurrent intervention failure: a prospective controlled cohort study Reprod BioMed online. ; 41 (6): 998\u0026ndash;1006\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTournaye H, Sukhikh GT, Kahler E, Griesinger G (2017) A phase III randomized controlled trial comparing the efficiency, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in vitro utilization. Hum Reprod 32(5):1019\u0026ndash;1027\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtt J, egarter C, Aguilera A (2022) Dydrogesterone after 60 years: a grace at the safety profile Gynecol Endocrinol. 38(4):279\u0026ndash;287\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Department of Gynecology and Obstetrics, Jian Tong First People's Hospital, Jiangsu 213200, Changzhou Province, China","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":"recurrent abortion, dydrogesterone, progesterone, folic acid, pregnancy outcomes","lastPublishedDoi":"10.21203/rs.3.rs-4706080/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4706080/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to assess the impact of combining dydrogesterone and progesterone with folic acid in the treatment of recurrent abortion on re-pregnancy outcomes. A retrospective analysis was conducted on 94 women with recurrent abortion admitted between June 2020 and July 2022. Participants were randomly assigned to a control group (treated with progesterone and folic acid) and a research group (treated with dydrogesterone, progesterone, and folic acid). Clinical effectiveness, adverse effects, serum cytokine levels, T lymphocyte subsets, endometrial parameters, and uterine artery perfusion indices were evaluated, along with pregnancy outcomes.\u003c/p\u003e \u003cp\u003eThe research group exhibited a significantly higher overall effective rate (89.36%) compared to the control group (70.21%). Both groups showed a reduction in interferon (IFN) and interleukin-6 (IL-6) levels and an increase in IL-10 levels post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The research group showed higher Treg/CD4\u0026thinsp;+\u0026thinsp;levels, better endometrial thickness, and fewer adverse reactions (8.51% vs. 23.40%) compared to the control group. The success rate of fetal preservation was higher in the research group (82.98%) compared to the control group (59.57%).\u003c/p\u003e \u003cp\u003eThe combination of dydrogesterone and progesterone with folic acid effectively improves the success rate of fetal preservation, modulates T lymphocyte levels, reduces inflammatory factors, and enhances endometrial receptivity, positively influencing pregnancy outcomes in cases of recurrent abortion.\u003c/p\u003e","manuscriptTitle":"Combination therapy of dydrogesterone and progesterone together with folic acid in the treatment of recurrent abortion on the outcome of Re-pregnancy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-10 16:39:55","doi":"10.21203/rs.3.rs-4706080/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":"d3781312-7978-4713-8444-aa4a686858d6","owner":[],"postedDate":"July 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-10T16:39:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-10 16:39:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4706080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4706080","identity":"rs-4706080","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}