Treatment For Repeated Failures of IVF

An embryo may not implant either because there is something wrong with the embryo itself that it can’t implant, or there is something in the uterine environment that doesn’t allow a normal embryo to implant.

Problems with the embryo
The most common abnormality found in pre-implantation embryos is an abnormal chromosome complement. Data from preimplantation genetic diagnosis suggest that 30% to 90% of in vitro fertilized eggs depending on maternal age are chromosomally abnormal. Furthermore, it has been estimated that 75% of karyotypically normal pre-implantation embryos fail to implant. Other than chromosomal abnormalities, problems with the pregnancies can include abnormal genes or abnormal DNA contributing to their losses. While mutations in HLA G genes have been associated with post-implantation recurrent pregnancy loss, secretion of soluble HLA G protein by pre-implantation embryos has been used to predict implantation potential of in vitro fertilized eggs before embryo transfer into the uterus. Fragmented DNA from the sperm has also been associated with poor embryo quality and implantation failure.

Problems within the uterus
Problems within the uterine environment that inhibits the embryo from implanting have been classified as anatomic, hormonal and immunologic.
a. Anatomic abnormalities are lesions inside the uterus that mechanically inhibit implantation. These anatomic abnormalities act like an intrauterine device to prevent implantation of the embryo and include:

Endometrial polyps-- benign outgrowths of the uterine lining that protrude into the uterine cavity)
Submucous fibroids – benign tumors of the uterine wall that protrude into the uterine cavity
Uterine synechia - scarring or adhesions inside the uterine cavity
b. Hormonal responses of the lining of the uterus to both estrogen and progesterone are necessary for the uterus to be receptive to the embryo. Mutations in some of the genes encoding for the progesterone receptor have been associated with recurrent implantation failure.
c. Immunologic mechanisms involved in implantation are being identified. The uterus as well as the embryo has to be made amenable (receptive) to implantation. Uterine receptivity requires continuous interactions between the embryo and the mother. These interactions are communicated through proteins known as cytokines. Cytokines are secreted by the cells within the uterine lining including the immune cells. During the pre-implantation period preparation of the uterine lining for implantation involves stimulation expression of adhesion systems that hold the embryo to the uterus. If the immune cells don’t send proper signals through secretion of appropriate cytokines to the embryo or if these cells don’t respond to signals from the embryo, then adhesion and thus subsequent implantation will not occur.