When IVF does not work, implantation problems may be the reason
At times very excellent appearing embryos are transferred back into a patient and pregnancy does not occur. It is important to try to consider possible reasons that pregnancy did not occur prior to doing another IVF cycle.
Most commonly we suspect that the embryos were not chromosomally normal in spite of their very normal appearance. Two other potential reasons that are less well understood are cytoplasmic competence and implantation defects. Cytoplasmic competence involves the ability of the embryo to divide its cellular materials and produce the chemicals required for development (such an adequate energy) prior to implantation. Implantation defects are abnormalities of the environment in which the embryo finds itself as it tries to attach to the mother.
Generally we rely on a woman’s uterus to respond robustly and correctly to the hormone estrogen and grow a normal appearing thickened uterine lining that responds to the hormone progesterone in a time specific way (the implantation window) to produce those chemicals/molecules required for implantation.
Endometriosis is associated with implantation defects on several levels. Endometriosis may inhibit the full expression of the effect of progesterone on the cells lining the uterus (progesterone resistance). Even if endometriosis has been treated surgically, implantation issues may need to be treated before the start of the cycle. The majority of patients with a history of endometriosis will have polypoid tissue in their uterus making the lining structurally abnormal. A hysterosalpingogram (HSG) is inadequate to evaluate the lining for minor structural abnormalities (hysteroscopy or saline infusion ultrasound is required). If IVF is planned, medical pre-treatment may be a better choice than a laparoscopy to diagnose endometriosis. Generally we prefer to work around endometriosis rather than ablate the surface of the ovary which can destroy eggs.
One approach to implantation issues is to try to enhance implantation rather than correct deficiencies. One of the first IVF papers on this was an observational study out of Stanford which looked at the interval from a D&C/ hysteroscopy to an IVF cycle and found a higher success rate when these interventions were closer together. Since then, there have been three small studies in which endometrial biopsies were done just before or during the IVF cycle which demonstrated a higher pregnancy rate after biopsy. It has also been shown that an endometrial biopsy increased important molecules for implantation and that these important factors remain elevated for at least a cycle after the biopsy.
The uterus is an important factor in achieving pregnancy. If a woman fails to get pregnant with IVF, implantation issues should be one of the focuses as part of the next preparation for future IVF cycles.