Many patients who have undergone multiple IVF-ET/ICSI/FET at our center will experience repeated implantation failure (RIF). Every time they experience RIF, they are worried that they want to continue the transfer in anticipation of a successful pregnancy as soon as possible, but they are also worried that if they continue to transfer blindly, they will be wasting their precious frozen embryos/blastocysts for some unknown reason. Let’s find out what causes repeated failure of implantation. The concept of Repeated Insemination Failure (RIF): At present, there is no uniform definition of the concept of RIF, and one criterion accepted by most of the fertility centers is that at least 3 consecutive IVF cycles with 1~2 good quality embryos transferred in each cycle still fail to achieve clinical pregnancy. It should also be understood that there is a short “implantation window” for embryo implantation, and successful embryo implantation requires proper endometrial tolerance, blastocyst stage embryos, and synchronized development of the embryo and the endometrium during the window. Why is there repeated failure of implantation? What should be done? First, the female factor 1, endometrial polyps Polyps with abnormal vascular epithelial changes may not be conducive to implantation, although sometimes it is only a manifestation of polypoid endometrium or abnormal hyperplastic endometrium. Polyps are also associated with abnormal irregular uterine bleeding and uterine irritability, all of which may jeopardize implantation and placenta formation. Treatment: The American Association of Gynecologic Surgery (AAGL) practice guidelines recommend hysteroscopic polypectomy before assisted conception in infertile patients to improve pregnancy outcomes. The effect of uterine fibroids on pregnancy depends on the location and size of the fibroid. Treatment: subplasma fibroids have no significant effect on pregnancy outcome, surgical resection is suitable for symptomatic; intermural fibroids reduce clinical pregnancy rate, increase the rate of miscarriage, but there is no sufficient evidence to show that myomectomy improves pregnancy outcome; submucous fibroids significantly reduce pregnancy rate, increase the rate of miscarriage, reduce the rate of live births, and surgical resection of leiomyomectomy significantly improves pregnancy outcome. 3, the uterine cavity adhesion is common after abortion or spontaneous abortion scraping, cesarean section and postpartum hemorrhage after scraping. Uterine cavity adhesion affects the pregnancy outcome by affecting the movement of sperm and embryo implantation. MANAGEMENT: The current clinical opinion is that the live birth rate increases after hysteroscopic surgical treatment or 3 to 6 months of high-dose estrogen for mild to moderate adhesions. Routinely for patients with uterine adhesions hysteroscopic adhesion separation surgery, postoperative administration of intrauterine device (IUD) and air bag is beneficial in preventing recurrence of adhesions. 4, endometritis For patients with endometritis, the implantation rate is significantly reduced. Antibiotic and hormone treatment for patients with endometritis can improve the clinical pregnancy rate in natural and assisted reproduction. The fluid in tubal fluid contains many inflammatory mixtures that can affect implantation either by direct action on the endometrium, formation of uterine fluid, or direct action on the embryo. Regardless of the mechanism, surgical management is necessary for patients who have failed to implant due to hydrosalpinx. 6.Endometriosis Endometriosis may interfere with the ovarian response through various pathways, affecting the quality of oocytes and decreasing the quality of embryos, which is detrimental to implantation. Treatment: Clinical use of GnRH-a to improve the rate of implantation of the therapeutic effect has been affirmed to a certain extent. For patients with mild endometriosis, laparoscopic surgery can improve the toxic environment of the pelvis and improve the fertility of patients, and coeliac patients can first do laparoscopic surgery to reduce the risk of infection and improve the conditions for egg retrieval, and then fertilization treatment. Second, sperm factors The male sperm has a close relationship with embryo formation. In patients with RIF, testing for DNA fragmentation analysis of the male semen is necessary. If there is a high incidence of abnormal semen morphology or DNA integrity, intracytoplasmic morphology selection followed by single sperm injection (IMSI) may be used as a method to improve embryo implantation, which has not yet been performed in our center. Embryonic factors 1. Embryonic chromosomal abnormalities Data from preimplantation genetic diagnosis or preimplantation screening (PGD/ PGS) in patients of advanced age, low recurrent pregnancy rate, or multiple IVF failures suggest that abnormalities in the embryo or gamete itself lead to failure of implantation. Treatment: Therefore, in patients with RIF, both chromosomes should be examined and blastocyst culture is recommended for embryo screening, and PGD/PGS is preferably recommended. The role of the zona pellucida after fertilization is to prevent polysemination and to protect the integrity of the embryo in the money at the time of fertilization, which contributes to the transport of the embryo in the fallopian tube. If the zona pellucida hardens abnormally, hatching will be abnormal, which will eventually lead to the occurrence of RIF. Treatment: For embryos with abnormal zona pellucida, it is recommended to carry out blastocyst culture to observe the developmental potential of embryos with abnormal zona pellucida, and then consider assisted hatching if abnormal zona pellucida indeed affects the hatching of embryos. Fourth, immune factors, maternal immune abnormalities are also likely to lead to implantation failure, such as cardiolipin antibody positive, systemic lupus erythematosus, closed antibody negative, the most common is closed antibody negative. For closed antibody-negative recurrent miscarriage patients, line discretionary immunotherapy to increase the IVF fertilization to carry the baby rate. Fifth, other factors such as obesity, smoking, abnormal thyroid function will affect the embryo implantation rate, clinical pregnancy rate and live birth rate. We do not have to worry too much and nervous, the causes of RIF is more diverse and complex, after the emergence of such a situation, experts will analyze the causes and find out countermeasures to help you to increase the rate of implantation and improve the outcome of pregnancy.