How come IVF failed?
IVF fails in approximately 50% of transfers – pregnancy does not occur in most cases because the embryo(s) transferred were not genetically correct. Other causes of failure include compromise of the uterine environment, a traumatic transfer or possible immune factors. Progesterone levels following embryo transfer are for the most part normal without supplementation, most programs however routinely supplement. Support can be provided with either intramuscular or vaginal progesterone (equally effective). Women are born with a certain number of eggs and never make anymore eggs their whole life, eggs accumulate genetic errors as a function of time, therefore, the older the female partner is the greater the likelihood of a genetically abnormal egg resulting in a genetically abnormal embryo. Men constantly make new sperm all their lives, therefore, the great majority of sperm even in men into their 60s and older are genetically normal.
What can we do to improve the chances for a successful next IVF cycle?
At the Florida Institute for Reproductive Medicine we analyze all failed IVF cycles looking for ways to improve outcome. Specifically we review stimulation protocols, day of transfer, three or day five, was the transfer easy or not. Sometimes more aggressive stimulation protocols are indicated. Sometimes stimulation protocols are decreased to avoid an increased risk of ovarian hyperstimulation syndrome a potentially serious condition that is more likely if transfer, i.e., a pregnancy occurs. If a difficult transfer was encountered prior cervical dilatation or hysteroscopy is often recommended. In patients with repeated failures we have seen encouraging results with the addition of growth hormone to stimulation cycles. We provide a highly discounted multiple cycle IVF package specifically for individuals with a poorer prognosis to allow for possible repeated transfers. The cost of this program rivals the cost of a single IVF cycle at many programs. If a patient is a high response patient, i.e, getting large numbers of eggs/embryos, preembryo genetic screening (PGS) may be a offered. Preembryo genetic screening is a technology, whereby cells can be removed from a day five embryo and assessed for normality. The most up-to-date data regarding PGS has not shown any decrease in implantation rates or increased incidence of fetal anomalies. If a patient is found to have very low ovarian reserve, i.e., stimulated very poorly – donor egg or embryo will be discussed. At the Florida Institute for Reproductive Medicine we do not push patients into the use of third party options, rather we try to give our patients as much information as possible so that they can make the decision that is right for them. We have very large, active donor egg, donor embryo as well as donor egg bank IVF programs.
Factors known to cause IVF failure.
Factors that have strong evidence for impaired implantation include blocked tubes filled with fluid (hydrosalpinx) – fluid is believed to flow retrograde into the endometrial cavity impeding implantation. It is recommended that a hydrosalpinx be removed prior to embryo transfer. There is strong evidence that uterine polyps and fibroids representing foreign bodies in the endometrium also impede implantation or increase the risk of miscarriage. At the Florida Institute for Reproductive Medicine we routinely perform what is known as a sono-HSG to evaluate the uterine cavity prior to proceeding with embryo transfer. If there is evidence of a filling defect hysteroscopy is performed.
Unexplained IVF failure.
One of the most frustrating situation for patients and clinicians is the repeated failure of high quality perhaps even PGS or donor embryos. As physicians and scientists we understand very little about the implantation process, it is extremely difficult to study. What we do know, primarily from the use of donor embryos, is that implantation is largely determined by the embryo itself. If an embryo is genetically normal it has a very high tendency to implant, if it is not it will either not implant or will result in an early miscarriage. Patients that have repeated failures using donor embryos or PGS/euploid embryos raise the question of an endometrial or possible immune factor. There have been studies pointing to the importance of certain proteins in the endometrium known as integrins – low integrins being associated with poor implantation. Unfortunately integrin testing and treatment have been inconsistent, treatment disappointing. Likewise various immune problems have been correlated with problems of implantation and recurrent pregnancy loss. Again, most of these immune studies are poorly defined, treatments expensive and disappointing. If an individual is felt to have a high likelihood of immune problem referral to a tertiary academic center performing bonafide controlled studies should be considered. Costs to participate in such studies should be minimal if anything.