Why implantation does not occur

Immunological factors have been implicated in the pathogenesis of RIF for a long time and different immunomodulatory agents and approaches have been applied for the treatment of these patients. For these purposes, immunomodulation IVIG intravenous immunoglobulin IgG has been widely used with rather conflicting results reported.

A systematic review of the papers through PubMed made the overall conclusion that immunotherapy with IVIG or intralipids when applied in patients with abnormal immunological risk factors might increase the live birth rates However, a multicenter randomized placebo-controlled trial confirmed the statement that application of IVIG in patients with recurrent miscarriages showed no significant beneficial effects Similarly, in a double blind placebo controlled trial including 51 couples with RIF, no positive effects were recorded on the live birth rates Extensive discussions on the efficacy of application of immunomodulatory agents have not led to one definite conclusion so this immunomodulatory approach is left to the discretion of each clinical setting.

A positive effect of local endometrial injury LEI on the pregnancy and live birth rates was published by Barash et al. The reported results showed that after 4 injuries of the endometrium, the pregnancy rate reached These initial results have been confirmed in a number of studies reported later which demonstrate the posi-tive effect of LEI 67 — The general under-standing is that LEI would induce upregulation of inflammatory cytokines, chemokines and growth factors.

As far as clinical aspects of LEI treatment are concerned, it is still not clear when and how many manipulations should be done in order to achieve the best effects from these treatments.

Later on, some research groups preferred to do the endometrial biopsies twice where the first one was during the proliferative phase day and the second one was during the secretory phase day of the menstrual cycle prior to COH Others reported that a single endo-metrial biopsy done during hysteroscopy on days of the cycle before the embryo transfer cycle leads to a significant increase in clinical pregnancy and live birth rates Effects of LEI are associated with induction of new cascades of inflammation with the participation of various cytokines and growth factors and all these improve the process of decidualization Another advantage of LEI could be a combination of this procedure with the embryo co-culture system with autologous endometrial epithelial cells EEC as a therapeutic approach with proven effectiveness It is quite clear that LEI is a beneficial procedure for patients with RIF, but further well designed studies are needed where a strictly defined procedure is applied in selected patient groups, enlisting a larger number of women.

The most significant endometrial changes occurr during the process of implantation. This review focused on the dysregulation of the endometrial cells at both cellular and molecular levels as a major reason for the lack of implantation when a good quality embryo is transferred into a uterus free of any pathology, in the presence of optimal hormonal levels, i. Tailoring stimulation protocols and individual approaches are some of the steps that could be offered to RIF-patients.

It is our opinion that the concept of the crucial role of the endometrium for embryo implantation and for the repeated failures of implantation deserves a detailed discussion. RIF patients should be enrolled in well designed studies in order to expand our understanding.

J Reprod Infertil. National Center for Biotechnology Information , U. Journal List J Reprod Infertil v. Author information Article notes Copyright and License information Disclaimer. Blagoev str. E-mail: moc. Received Mar 17; Accepted Jul This article has been cited by other articles in PMC. Abstract The success rate of reproductive treatment methods depends on many different factors. Keywords: Decidua, Embryo implantation, Endometrium, In vitro fertilization, Reproductive physiological phenomena.

Introduction Successful embryo implantation is a process which requires both a synchronous development and interaction between hatched blastocyst and endometrium. Open in a separate window. Figure 1. Table 1 Criteria for defining RIF. RIF types In some cases, RIF can be defined as a unique condition due to unidentified abnormalities or damage of the endometrium which would not even allow the initial steps of embryo implantation apposition, attachment.

Figure 2. The endometrium and diagnostic methods Human endometrium is a complex, multicelular tissue that is regulated by steroid hormones estrogens, progesterone, androgens and glucocorticoids and has different characteristics in the various phases of the menstrual cycle. Figure 3. Formation of deciduas The postovulatory rise of progesterone triggers profound changes in the epithelial cells, stromal cells and the matrix and blood vessels of the endo-metrium Therapeutic approaches to improve the functions of the endometrium The treatment offered should be evidence based and aimed to improve endometrial receptivity.

Conclusion The most significant endometrial changes occurr during the process of implantation. Conflict of Interest The authors declare no conflict of interest. References 1. Recurrent implantation failure: definition and management.

Reprod Biomed Online. Racowsky C. High rates of embryonic loss, yet high incidence of multiple births in human ART: is this paradoxical? Time to pregnancy: results of the German prospective study and impact on the management of infertility.

Hum Reprod. Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study. Recurrent implantation failure in assisted reproduction: how to counsel and manage. General considerations and treatment options that may benefit the couple.

Rinehart J. Recurrent implantation failure: definition. J Assist Reprod Genet. Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril. Coulam CB. Implantation failure and immunotherapy. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

Genetic and chromosomal issues causing causing failure of implantation in IVF We know that one of the major factors contributing to in vitro fertilization failure is the high rate of chromosomal abnormalities in human embryos. As women age the incidence of chromosomal abnormalities in mature eggs increases significantly.

Studies have shown that starting in the early 30s, the rate of chromosomal abnormalities in human eggs and therefore in human embryos starts to increase significantly. It is believed that this is mainly due to problems with the spindle apparatus in the egg nucleus. The spindle is involved with properly lining up and segregating the chromosomes as the egg matures at the time of ovulation. This leads to eggs that do not have the proper balance of 23 chromosomes — and will result in a chromosomally abnormal embryo if fertilized.

PGS — preimplantation genetic screening can be done on embryos prior to transfer to evaluate chromosomal competence. Ovarian hyperstimulation syndrome, or OHSS, is a condition with enlarged ovaries and fluid build up.

Ovarian hyperstimulation syndrome, OHSS, is a complication that can occur with in vitro fertilization The. Patient Resource Center. How uterus checks embryo reveals why some do not implant. Written by Catharine Paddock, Ph. Share on Pinterest Discovering how the endometrium chooses an embryo could help improve treatments, like helping embryos in IVF successfully implant.

Exposure to air pollutants may amplify risk for depression in healthy individuals. Costs associated with obesity may account for 3. Related Coverage. Female reproductive organ anatomy. Medically reviewed by Alana Biggers, M. When an older woman uses donor eggs, her chance of achieving IVF success goes up dramatically! This is irrefutable proof that it is embryo quality which plays a major role in implantation and IVF success. The importance of soil quality in agriculture is well known.

Does endometrium play such a crucial role in embryo implantation? What happens when a fertile seed genetically competent embryo is seeded on defective soil non-receptive endometrium? In humans, the receptivity period is between day 20 to day 24 of regular menstrual cycle i. You can calculate the best time for you to get pregnant with this easy-to-use fertility calendar. During frozen embryo transfer , the day of starting progesterone is taken as the first day of ovulation and embryo transfer is done accordingly.

Human embryo implantation is an enigmatic biological phenomenon — after all, in-vivo experiments are impractical and unethical to conduct; and studies with animal models do not translate well to humans. But it is well-known fact that embryo and endometrium talk to each other using molecular signals, and such cross-talk is necessary for successful implantation. However, no reliable molecular markers for endometrial receptivity have been identified.

This makes it difficult to find out whether the endometrium is receptive or not during an IVF cycle. During IVF, endometrial receptivity is assessed crudely with the help of ultrasound images. Endometrial thickness is measured using ultrasound images, and an endometrium of greater than 8mm, which is trilaminar, is believed to be optimum for embryo transfer.

It is a well-known fact that the endometrium becomes receptive only after progesterone exposure. Progesterone brings about necessary changes in endometrium converts the endometrium from proliferative to secretory phase so that it becomes ready to accept the embryo.

Recently, frozen embryo transfers are becoming much more successful than fresh embryo transfers in the field of IVF. It is hypothesized that high estrogen concentration in the body during the fresh IVF cycle compromises endometrial receptivity.

There are also many unproved reasons cited for lack of uterine receptivity, which include immunological theories like the presence of high number of uterine NK cells, excessive HLA matching between partners, and blood clotting issues. The ease with which the uterus can be negotiated for the embryo transfer also plays a pivotal role in achieving successful implantation. If the uterus is hard to access via the cervix for example, in patients with cervical stenosis , then other embryo transfer methods like ZIFT should be used in order to enhance implantation.

Yes, it can be treated, but only if the reason is known. The one and only well-known, scientifically proven reason for implantation failure is genetically incompetent embryos. If you are a woman of advanced maternal age or if you have premature ovarian aging, even if you get some embryos to transfer during an IVF cycle, many a time they can be genetically abnormal and will not implant successfully.

As a result, they believe that surrogacy can help them conceive, which is not true! I have seen so many women of advanced maternal age subjecting themselves to many useless therapies and ultimately finding success when they finally use donor eggs. So if advanced maternal age or poor ovarian reserve is the cause of failed implantation, the only reasonable solution is to use donor eggs.

If your uterine cavity contains adhesions, fibroids or polyps which interfere with implantation, removing them will help in achieving embryo implantation. The role of endometrial thickness in successful implantation is still a question. Many women with thin endometrium do have successful implantation, but the scientific literature shows that an endometrium thickness of more than 8mm is optimum for achieving implantation.

Doctors should resist offering such treatments. They must make sure that the patient understands that the above-mentioned therapies are not evidence-based and may not be a panacea for their problem. When an embryo enters the uterus in the blastocyst stage, it initiates molecular cross-talk with the endometrium.