There is no question the IVF is the most powerful treatment option available to infertile couples. Because most patients are well aware of this fact, when IVF fails, it is particularly burdensome to the infertile couple. There is great concern on the part of the couple that they will never be successful because the “best” treatment has failed. Presenting the couple with statistical information is important in this context so that they have a realistic expectation of success based upon data provided by their clinic for patients of similar age and circumstances. However, when repeated failure occurs in defiance of the statistical expectations of success for a given couple, it is incumbent upon the IVF team to carefully review all aspects of the couples care and to ask the important question “Are we missing something?” The reproductive team must ask and attempt to answer the following questions:
1) Have we ruled out anatomical problems which may very well be reducing prospects for success? For example, it is well known that the presence of hydrosalpinges (fluid filled damaged fallopian tubes) leads to a substantial reduction in IVF success if they are not removed or cauterized surgically. The patients’ tubal evaluation should be reviewed to be certain that hydrosalpinges were not overlooked.
2) Did the controlled ovarian hyperstimulation go well? Was there an adequate number of mature follicles at the time the decision for the HCG trigger was made? Was the estradiol level appropriate for the number and size of follicles?
3) Does there appear to be consistency in the follicular progression through the stimulation phase of treatment? Lack of consistency with respect to vaginal sonography can be problematic due to inter-observer variability. This issue becomes especially important when treating egg donors who may be having several of their ultrasound studies at an off-site center.
4) Did the physician performing the egg retrieval obtain the expected number of eggs given the ultrasound and endocrine parameters? If not, was it due to equipment problems, technical problems related to the patient’s body habitus, or some other correctable factor?
5) What comments does the embryologist have with respect to the appearance and behavior of the gametes in culture as well as under the microscope? Experienced embryologists are quite adept at identifying occult egg quality issues and their input is invaluable in these situations.
6) In programs where patients are batched, have there been an unexpectedly large number of failures in one group of patients? This would lead to a suspicion of quality control issues in the laboratory relating to air quality or incubator conditions.
7) Was there difficulty at the time of embryo transfer? It is well established that difficult or lengthy embryo transfers result in reduced success. The embryologists description of the embryo transfer catheter after the procedure may offer some clues, especially if the catheter harbors excessive mucous or blood.
8) Did the patient follow all post transfer medication instruction? This should be reviewed to be sure that progesterone support was taken properly.
9) Has the patient’s ovarian reserve been carefully and recently evaluated? We have all seen patients whose ovarian reserve was normal a few months prior to her procedure only to find diminished ovarian reserve on retesting.
10) Has the patient had a hysteroscopy? Several studies have suggested that hysteroscopy provides a more thorough evaluation on the uterine cavity than does x-ray or sonographic evaluation of the uterine cavity.
While the above list is certainly not exhaustive, it does highlight a number of potential explanations for repeated IVF failure. It is incumbent upon the IVF team to do the hard work required to investigate repeated IVF failure and most importantly to have a thorough and frank discussion with the couple as to the specifics of your investigation, findings, and plans for future evaluation and treatment. It has been my experience that patients understand and accept our failures. However, we owe them the time and energy required to perform a thorough review of their situation and an honest appraisal of their prospects for success based upon our experience.