Recurrent abortion (Recurrent Spontaneous Abortion, RSA) is a common disease in obstetrics and gynecology, which refers to three or more times of spontaneous abortion in the same woman, which can be characterized by vaginal bleeding and abdominal pain after menopause. Most of RSA are early abortion and a few are late abortion, which are related to genetic and endocrine factors. Due to the development of assisted reproductive technology, endometrial damage has been found to be an important factor leading to recurrent abortion. Intrauterine infusion of drugs or biological agents can directly contact the endometrial gland and act directly on the endometrium to improve and repair the endometrium. The treatment process has the characteristics of less trauma, no pain, simple operation and good patient compliance. This article will review the application of intrauterine infusion of different drugs in patients with recurrent abortion.

Xiaoyuan Xing, Nan Li. Application of Intrauterine Perfusion in Patients with Recurrent Spontaneous. Academic Journal of Medicine & Health Sciences (2024), Vol. 5, Issue 1: 96-102. https://doi.org/10.25236/AJMHS.2024.050115.

[1] Bashiri Asher, Halper Katherine Ida, Orvieto Raoul, et al. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions [J]. Reproductive biology and endocrinology: RB&E, 2018, 16(1):121. 

[2] Nick S. Macklon, Jan J. Brosens. The Human Endometrium as a Sensor of Embryo Quality [J]. Biology of Reproduction, 2014, 91(4):98, 1-8. 

[3] Tarek El-Toukhy, Rudi Campo, Yacoub Khalaf, et al. Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial [J]. The Lancet, 2016, 387(10038):2614-2621. 

[4] Janine G. Smit, Jenneke C. Kasius, Marinus J. C. Eijkemans, et al. Hysteroscopy Before In-Vitro Fertilisation (inSIGHT): A Multicentre, Randomised Controlled Trial [J]. Obstetrical & Gynecological Survey, 2016, 71(10):600-601. 

[5] Madani Tahereh, Ahmadi Firoozeh, Jahangiri Nadia, et al. Does low-dose aspirin improve pregnancy rate in women undergoing frozen-thawed embryo transfer cycle? A pilot double-blind, randomized placebo-controlled trial [J]. The journal of obstetrics and gynaecology research, 2019, 45(1):156-163. 

[6] Ingrid Sketris, Randall Yatscoff, Paul Keown, et al. Optimizing the use of cyclosporine in renal transplantation [J]. Clinical Biochemistry, 1995, 28(3):195-211. 

[7] Tugwell P., Bombardier C., Gent M., et al. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis [J]. The Lancet, 1990, 335(8697):1051-1055. 

[8] Moser G, Windsperger K, Pollheimer J, et al. Human trophoblast invasion: new and unexpected routes and functions [J]. Histochem Cell Biol, 2018, 150(4): 361-370. 

[9] Yan Fengting, Li Dajin, Sun Xiaoxi, et al. Effect of cyclosporin A on the growth of human first trimester cytotrophoblasts in vitro [J]. Chinese Journal of Obstetrics and Gynecology, 2002, (2):13-15+68. 

[10] Yan Fengting, Du Meirong, Li Dajin, et al. Cyclosporin A induces peripheral maternal-fetal immuno-tolerance of the abortion-prone murine model [J]. Chinese Journal of Microbiology and Immunology, 2006, (2):105-109. 

[11] Yan Fengting, Li Dajin, Sun Xiaoxi, et al. Effect of cyclosporine A on pregnancy prognosis of pregnancy failure model in mice [J]. Chinese Journal of Immunology, 2002, (10): 711-713. 

[12] Yan Yuanhua. Cyclosporine A improves the molecular mechanism of mouse embryo implantation [D]. Fudan University, 2014. 

[13] Porter T F, LaCoursiere Y, Scott J R, et al. Immunotherapy for recurrent miscarriage [J]. The Cochrane database of systematic reviews, 2006, (2):CD000112. 

[14] Fu J H. Analysis of the use of cyclosporin A to treat refractory immune recurrent spontaneous abortion [J]. Clinical and experimental obstetrics & gynecology, 2015, 42(6):739-742. 

[15] Qi Lijuan, Bi Shuqin, Fu Jinhua, et al. Efficacy of Intrauterine Perfusion of Cyclosporin A for Intractable Recurrent Spontaneous Abortion Patients With Endometrial Alloimmune Disorders: A Randomized Controlled Trial [J]. Frontiers in Physiology, 2021, 12:737878-737878. 

[16] Zhang Ling, Xu Weihai, Fu Xiaohua, et al. Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis [J]. Archives of gynecology and obstetrics, 2018, 298(5):861-871. 

[17] Ding Guiqin, Wang Jing. Effects of G-CSF on endometrial repair and its related mechanisms [J]. Military Medical Journal of South China, 2018, 32(11): 807-809+817. 

[18] Yanagi K, Makinoda S, Fujii R, et al. Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein [J]. Human reproduction (Oxford, England), 2002, 17(12):3046-3052. 

[19] Salmassi A, Schmutzler A G, Schaefer S, et al. Is granulocyte colony-stimulating factor level predictive for human IVF outcome? [J]. Human reproduction (Oxford, England), 2005, 20(9):2434-2440. 

[20] Jin Sufang, Fang Jinchuan, Li Shi, et al. Effect of intrauterine infusion of rhG-CSF on endometrium receptivity and pregnancy outcome in patients with recurrent abortion [J]. Shaanxi Medical Journal, 2020, 49(5):592-594+F0003. 

[21] Li Suzhen, Shi Yanli. Effects of intrauterine perfusion of recombinant human granulocyte colony-stimulating factor on hormone levels and endometrial receptivity in patients with recurrent abortion [J]. The Journal of Medical Theory and Practice, 2021, 34(22):3957-3959. 

[22] Efficacy of Intrauterine Injection of Granulocyte Colony Stimulating Factor (G-CSF) on Treatment of Unexplained Recurrent Miscarriage: A Pilot RCT Study [J]. Journal of Reproduction & Infertility, 2017, 18(4):379-385. 

[23] Cole Laurence. New discoveries on the biology and detection of human chorionic gonadotropin [J]. Reproductive Biology and Endocrinology, 2009, 7(1):8. 

[24] Licht P, Russu V, Lehmeyer S, et al. Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo [J]. Reproductive biology, 2001, 1(1):10-19. 

[25] Gerolf Zimmermann, Wilfried Ackermann, Henry Alexander, et al. Epithelial Human Chorionic Gonadotropin Is Expressed and Produced in Human Secretory Endometrium during the Normal Menstrual Cycle [J]. Biology of Reproduction, 2009, 80(5):1053-1065. 

[26] S.W. Han, Z.M. Lei, Ch.V. Rao, et al. Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua [J]. Molecular and Cellular Endocrinology, 1999, 147(12):7-16. 

[27] Strug Michael R, Su Renwei, Young James E, et al. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial [J]. Human reproduction (Oxford, England), 2016, 31(7):1552-1561. 

[28] E. Giuliani, M. Olson, M. Strug, et al. Intrauterine hCG infusion affects the distribution of natural killer cells in the endometrium of fertile oocyte donors [J]. Fertility and Sterility, 2015, 104(3):e149-e150. 

[29] Anne eSchumacher, Serban-Dan eCosta, Ana Claudia Zenclussen, et al. Endocrine factors modulating immune responses in pregnancy [J]. Frontiers in Immunology, 2014, 5:196. 

[30] Jun Xing, Jianjun Zhou, Junxia Wang, et al. Effect of intrauterine infusion of hCG on peripheral blood Treg in patients with repeated implantation failure and recurrent abortion [J]. Journal of Nanjing Medical University (Natural Science Edition), 2016, 36(12):1443-1445. 

[31] Shan Wang. Effect of intrauterine infusion of HCG on endometrial pinocytosis and clinical pregnancy rate in patients with recurrent abortion [J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2016, 25(11): 1218-1220. 

[32] Gao MingXia, Jiang XiangYan, Li Bin, et al. Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials [J]. Fertility and Sterility, 2019, 112(1):89-97. 

[33] Tu Zengrong, Wang Liyuan, Duan Ruiyun, et al. Intrauterine perfusion of granulocyte colony-stimulating factor and injection of low molecular weight heparin in patients with thin endometrium following repeated implantation failure: a clinical study [J]. Chinese Remedies & Clinics, 2020, 20(9):1435-1438. 

[34] Mosallaei Meysam, Ehtesham Naeim, Rahimirad Shima, et al. PBMCs: a new source of diagnostic and prognostic biomarkers [J]. Archives of physiology and biochemistry, 2020, 128(4):1-7. 

[35] Benkhalifa Mustapha, Joao Fabien, Duval Cynthia, et al. Endometrium Immunomodulation to Prevent Recurrent Implantation Failure in Assisted Reproductive Technology [J]. International Journal of Molecular Sciences, 2022, 23(21):12787-12787. 

[36] Hiroshi Fujiwara, Atsushi Ideta, Yoshihiko Araki, et al. Immune System Cooperatively Supports Endocrine System-Primed Embryo Implantation [J]. Journal of Mammalian Ova Research, 2009, 26(3):122-128. 

[37] Yu Nan, Yan Wwenjie, et al. HCG-activated human peripheral blood mononuclear cells (PBMC) promote trophoblast cell invasion. PLoS One. 2015; 10(6):e0125589. 

[38] Zhao Ting, Zhang Huakun, Yao Jilong, et al. Study on the mechanism of intrauterine infusion of autologous peripheral blood mononuclear cells in the treatment of unexplained recurrent spontaneous abortion [J]. Journal of Southeast University (Medical Edition), 2019, 38(4):699-703.