What happens when embryos repeatedly fail to implant?

  I. Embryonic factors Embryos with good developmental potential can implant in the fallopian tube, uterine scar, and even in the abdominal environment; therefore, embryo quality is the most critical factor for embryo implantation.  1. Embryo morphology score: The widely used embryo morphology score is convenient and practical, and there is a correlation between the score and embryo implantation rate, but it does not really reflect the quality of embryos and their ability to implant and develop. Patients with multiple transfers of high scoring embryos without pregnancy can consider blastocyst culture to further screen embryos.  2. Embryo chromosomal abnormalities: Embryo chromosomal aneuploidy is one of the reasons for embryo implantation failure. For patients of advanced age, repeated implantation failure, and repeated spontaneous abortions, among them especially those with at least one post-embryonic arrest chorionic villus chromosomal abnormality, pre-implantation genetic screening (PGS) can be considered to screen out chromosomally normal embryos for transfer.  3. Growth rate and timing of embryos: The modern microscopic system for dynamic observation of embryos, the embryo microfilm technique (Time Lapse), can evaluate the growth rate and rhythm of embryos during their development and select the embryos with the most normal developmental timing for transfer. Of course, this is not a foolproof insurance, the technology is still in the process of clinical research.  Uterine factors 1. Uterine cavity abnormalities: Suitable endometrium is needed for embryo implantation to occur, and various uterine cavity pathologies such as endometrial polyps, submucosal fibroids, uterine adhesions, endometritis, and uterine diaphragm may affect embryo implantation. Ultrasound is widely used clinically to measure endometrial thickness, morphology, uterine cavity morphology and blood flow to assess the ability of the endometrium to tolerate embryos. Hysteroscopic surgery may resolve or improve the endometrial environment in some patients and improve the embryo implantation rate.  2. Endometrial vascular thrombosis: Many causes, such as genetic mutations in the coagulation system, elevated autoimmune antibodies, and endothelial damage, may cause thrombosis in the small blood vessels at the placental implantation site, making the endometrial blood supply inadequate and making it difficult for the embryo to survive. These are often referred to as “antiphospholipid syndrome” and “thrombophilia”. However, a series of complicated tests are needed to confirm the diagnosis. Anti-clotting and thrombosis inhibiting drugs such as aspirin, corticosteroids and low molecular heparin can be used for prevention, which has certain clinical effect.  3. Tubal effusion: Tubal effusion contains various inflammatory mixtures that can interfere with the normal embryonic implantation process if it refluxes into the uterine cavity. For those with moderate to severe hydrocele and normal ovarian function, we suggest to deal with the fallopian tubes first and block or remove them to prevent the effect of fluid accumulation on implantation.  4. Endometriosis: There are many reasons for infertility caused by endometriosis, which may reduce the quality of the eggs and change the environment of the endometrium, affecting the embryo’s ability to be bedded. Drugs or laparoscopic surgery will usually be considered to improve the pelvic environment and increase the embryo implantation rate.  Immune factors 1. Immune cell activity in the endometrium: Some studies have found that abnormally elevated activity of natural killer cells throughout the body or locally in the endometrium may have a cytotoxic effect on the embryo and hinder implantation. Immunotherapy can be performed by intravenous infusion of immunoglobulins, but these results are uncertain, the efficacy is still in the clinical observation phase, and the safety of blood products is under concern.  2. Active immune deficiency: These patients are unable to produce active immune antibodies to protect the embryo, and have an immune attack on the embryo, which is often referred to as “closed antibody” deficiency, and can induce their own active immune function through lymphocyte injection by the husband. However, the current flow cytometry detection method does not really reflect the active immune status of the self, so the treatment is somewhat blind.  Other 1.Improve lifestyle: The poor lifestyle (such as obesity, smoking, alcoholism, etc.) and environment of both parties may affect the implantation rate of embryos. Exercise, weight reduction, antioxidant treatment, lifestyle improvement and acupuncture may have some improvement effects.  2. Reduction of ovulation-promoting drug stimulation: For patients with unexplained recurrent implantation failure, we can adopt microstimulation or natural cycle egg preparation protocols to improve egg and embryo quality.  3. Endometrial stimulation or uterine perfusion: It is possible to regulate the local endometrial environment to promote embryo implantation through micro “injury”. However, the efficacy of these methods is uncertain and needs to be further observed.  The causes of repeated embryo implantation failure are complex, and it is a path of exploration for clinicians to analyze the causes and find countermeasures to increase the implantation rate and improve pregnancy outcomes. The causes and countermeasures vary from person to person, and we need to analyze them comprehensively and use countermeasures individually, expecting better pregnancy outcomes for patients with recurrent implantation failure!