Preface: It frustrates me no end that so many couples who have failed to conceive following IVF are often glibly confronted with platitudes such as “It was just bad luck … so just try again,” and in the process are left “spinning their wheels,” feeling abandoned. While “bad luck” could indeed sometimes be a factor, this is not often the case, especially when, in spite of the transfer to the uterus of microscopically “good quality” embryos, the woman fails (often repeatedly) to conceive. The problem is further magnified when it comes to older women for whom time is running out because of an inevitable age-related decline in egg quality (“competency”), and in cases of diminished ovarian reserve (DOR) where the woman’s supply of eggs is rapidly becoming depleted. Most patients who have failed to conceive with IVF intuitively believe that something might have been overlooked in their cases and that, were the issue(s) to be identified, they could be remedied.

Frankly, given all of the good fortune and opportunity afforded me over a 30 year career in the field of IVF , I feel a strong compulsion to put my extensive experience to work where it can do most good and to offer it unconditionally to infertile patients. This is particularly relevant since several major medical advances that I and my colleagues introduced over the years could be applied to the diagnosis and treatment of many such problems, and make a real difference. These include:

a) In-roads made with regard to defining individualized protocols for ovarian stimulation
b) The Introduction of clinical Comparative Genomic Hybridization (CGH) embryo selection
c) The role of Immunologic Implantation Dysfunction (IID) in failed IVF

It is against this background that I have elected (for the foreseeable future) to offer detailed IVF telephone consultations, free of charge to all US and Canadian patients who are interested in my opinion, regardless of where they subsequently choose to be treated. Accordingly, I have designated specific times (daily) in my schedule for this purpose. Please call 800-780-7437 to schedule or submit the request form HERE.

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IVF treatment always exacts a profound emotional and financial toll on patients/couples. Needless to say, the financial burden is often crippling However, ask any woman who has undergone IVF and she will likely tell you that the emotional impact was by far the most devastating….especially when the IVF treatment cycle failed to bring her a baby.

The truth is that even in the simplest of cases (i.e. younger women who have normal ovarian reserve with fertile male partners), and in the most capable of hands, at best 50% will give birth to a baby following the transfer of 1-2 morphologically “normal” embryos. More than 70% will achieve success after two fresh embryo transfers. When this fails to happen, the question will invariably arise as to why the failure occurred.

Currently, in excess of 90% of the IVF patients I treat have at least one prior failed attempt before consulting with me, and more than 80% have failed IVF at least 3 times prior to seeking my services. I could cite many cases where patients have even endured as many as 10 or more prior IVF failures. But there is one case in particular that is permanently embedded in my memory and which highlights the importance of an individualized approach to treating infertility patients, especially when it comes to those with prior IVF failures.

The patient was a 42 year old physician who hailed from Australia. She had endured 23 prior unsuccessful embryo transfers over a period of more than a decade. By the time I got to know her she had developed severely diminished ovarian reserve (her day 3 FSH was 26MIU/ml). After a lengthy telephone consultation with me, I urged her to send a blood sample from Melbourne, Australia to a reputable Reproductive Immunology Reference Laboratory in Southern California for testing, to screen for immunologic implantation dysfunction (IID). It soon became apparent that she had an autoimmune thyroid condition (antithyroid antibodies) plus activation of uterine Natural Killer Cells (NKa+). After putting her on an aggressive agonist/antagonist conversion protocol (A/ACP) with estrogen priming and treating her with selective immunotherapy, I harvested (just) three eggs and subsequently transferred two embryos to her uterus. She conceived on this cycle and gave birth to a very healthy baby boy nine months later.

So then…what are the most common reasons for “unexplained” IVF failure, and what can be done to deal with them?

To adequately address these two all-important questions, we first need to recognize and understand that with the exception of poor technical skill in performing embryo transfer, IVF failure is virtually always due to one of the following two causes, which I will address below:

A. Embryo “Incompetence” (+/- 75% of cases)
B. Dysfunctional/Failed Embryo Implantation (+/- 25% of cases)

A. Embryo Incompetence
What is critical to understand here is that it is the chromosomal integrity (“competence”) of the embryo that is the main determinant of its ability to propagate a normal pregnancy. It is almost always the egg (rather than the sperm) that determines this factor. Only a mature egg (MII) that is numerically chromosomally normal (with 23 chromosomes – also known as a “euploid” egg) at the time of egg retrieval can propagate a “competent” embryo. No manipulation in the IVF laboratory, be it assisted hatching, embryo co-culturing, specialized fancy culture media, or even cytoplasmic transfer from a different (euploid) egg can cause an egg that has an irregular quota of chromosomes (aneuploid) to propagate a competent/euploid embryo (i.e. 46 chromosomes). Patients should be highly skeptical of any suggestion to the contrary. Simply stated, an embryology laboratory can only grow competent embryos from competent eggs.

Thus, egg competency at the time of egg retrieval will ultimately determine the ability to generate competent embryos for embryo transfer. By the time the egg is extracted, the “die has been cast” What this means is that aside from the woman’s age – which influences the percentage of her eggs that will have the potential to develop into euploid mature (MII) eggs following hormonal stimulation – the only manner by which we as IVF physicians can influence egg quality is by applying an individualized approach to ovarian stimulation. Without such an approach, egg development will often be compromised (especially in older women, in those with PCOS, and in women with DOR). Then, the hCG “trigger” would be much more likely to cause disorderly rearrangement of egg chromosomes, leading to a greater likelihood of egg incompetence (aneuploidy) and ultimately to incompetent embryos.

Today, through the use of full embryo chromosomal assessment (i.e. full karyotyping) using CGH, we can identify “competent” embryos for selective transfer. The use of this technique is both diagnostic (in that it allows us to determine whether the cause of IVF failure is embryo incompetence or an implantation issue) and therapeutic (in that we can thereupon selectively transfer only one or two embryos at a time and achieve almost a 70% pregnancy rate while virtually eliminating the chance of high-order multiples (triplets or greater). CGH embryo selection is of special relevance and value in cases of older women or those with DOR for whom “Staggered IVF” with embryo banking is of particular value.

Dysfunctional or Failed Implantation

Endometrial thickness (as measured by ultrasound) is described elsewhere. We previously have published that an ideal endometrium measures at least 9mm in thickness at the time of maximal estrogen stimulation. We have also pointed to the importance of excluding the existence of surface lesions that protrude into the uterine cavity (polyps, fibroid tumors or scarring) as they can, by creating an adverse uterine environment, lead to failed implantation. Only a hysteroscopy or a hysterosonogram (saline ultrasound) can diagnose the latter which needs to be treated surgically before embarking on IVF. A hysterosalpingogram (HSG) is too inaccurate to accomplish this.

Then there is the ever-important and (through either arrogance or ignorance) commonly overlooked issue of immunologic implantation dysfunction (IID) that should always be evaluated and addressed in cases of unexplained or repeated IVF failure. Frankly, since in the absence of Nka+, immunologic problems (regardless of cause) are not likely to cause IID, and given the fact that most of my IVF patients come to see me because of repeated failures in the past, I test almost everyone initially for Nka. If the test result comes back positive, we expand immunologic testing to look for the underlying cause. This having been said, I cannot overemphasize how important it is to always have a high index of suspicion regarding the possibility that failure could be due to IID in any patient who has had an unexplained IVF failure in the past.

To schedule a free telephone consultation with Dr. Sher, please call 800-780-7437, or fill out and submit the form HERE.