My IVF Cycle Failed – What Went Wrong? Question #4: Was the IVF Medication Protocol Right For My Specific Needs?

03 May
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This is the fourth in a series of responses to common questions about Failed IVF Treatment.

Question #4: Was the IVF Medication Protocol Right For My Specific Needs?

IVF treatment is an emotional, physical and financial roller coaster ride.Even those that succeed in having a baby after a single attempt rarely will come out unscathed. The fact is that at best, only 40-50% of those that embark upon the journey will, after a single attempt, end up having a baby.For the rest, the question of why this happened inevitably comes up.The responsibility falls on the treating physician to explain and then address the possible reasons.

There are 3 basic reasons why IVF fails.The first is that embryo(s) transferred to the uterus were “incompetent” (abnormal and thus unable to propagate a viable pregnancy).In most cases, this is due to an irregular number of chromosomes in the embryo (aneuploidy).In the remainder, it is due to genetic or molecular embryo abnormalities.

The second reason is an underlying implantation dysfunction that prevents the embryo from properly attaching to the uterine lining.The commonest causes for this include:

a) A thin endometrium (measuring less than 9 mm) at the peak of estradiol stimulation. (i.e., at the time of the hCG trigger or the initiation of progesterone administration)

b) Surface lesions that protrude into the uterine cavity (scarring, polyps and uterine fibroids) that create a local adverse environment that prevents implantation.

c) Immunologic dysfunction that results in implantation failure.

The third reason relates to technical difficulty in the performance of embryo transfer, which is a rate limiting factor.It is an undeniable fact that not all RE’s are equally skilled at the performance of this important step of the IVF process.

All of the above have been addressed in some detail elsewhere on this site.In several of my more recent blog posts I alluded to the imperative that the above mentioned factors be carefully re-evaluated before embarking on a subsequent IVF attempt.

If I were to single out the most common of all of the above factors, I would have no hesitation in saying that the first factor, i.e., embryo “incompetence” (chromosomal abnormalities in the embryo) tops the list of reasons for IVF failure.Embryo competence declines with advancing age. This is attributable to an inevitable age-related increase in egg aneuploidy (missing or extra chromosomes in the egg).

Unfortunately, there is nothing that anyone can do about this.But it is also true that the ovarian environment created in the process of controlled ovarian stimulation (COS) can profoundly influence egg development and thus ultimately the likelihood of egg/embryo aneuploidy.

Accordingly, it is imperative that a very individualized and strategic approach to COS be taken.This is highly relevant in older women who, in the best of circumstances, will produce progressively fewer eggs that upon hCG induced maturation will have the potential to be euploid (chromosomally normal).It is also very important to recognize that the eggs of women with conditions such as PCOS and those with diminished ovarian reserve are usually much more vulnerable to the hormonal environment created by COS.

The recent introduction of genetic embryo selection through Comparative Genomic Hybridization (CGH) allows us for the first time to identify those embryos that are chromosomally intact and thus are most likely to be “competent”.But CGH does not improve the likelihood that the embryo will indeed be competent.All it does is identify those that are.In other words, it serves as an efficiency tool that improves the likelihood of a CGH selected embryo being able to propagate a viable pregnancy, reduces the risk of miscarriages (which are most commonly due to embryo aneuploidy) and thereby minimizes the risk of chromosomal birth defects such as Down Syndrome.CGH embryo analysis has special benefits in cases of:

a) unexplained IVF failure

b) recurrent miscarriages

c) women who wish to avert multiple births or chromosomal miscarriages and/or birth defects

d) of woman who produce a large number of embryos and do not wish to preserve those that are “incompetent”

e) embryo banking

In about 20% of cases of “unexplained” IVF failure, the cause relates to immunologic implantation dysfunction.This is very often overlooked, largely because of misinformation, controversy and the hitherto exorbitant cost associated with immunotherapy using IVIg.Recently it was demonstrated that a product called Intralipid is just as effective as IVIg in down-regulating activated NK cells, is much safer, virtually free of risk or side effects, and costs about 20 times less.It has been interesting to observe the steady increase in acceptance of the role of immunologic factors as a cause of IVF failure since the introduction of Intralipid a few years ago.In my opinion, failure to embrace this concept can compromise the likelihood of success in patients who would have otherwise been able to conceive and start/build their family.

When Steptoe and Edwards first introduced human IVF, we all believed that a successful outcome was simply dependent upon fertilizing eggs outside the body and then transferring the embryos to the uterus.We understood very little about the factors that affected embryo competency or uterine receptivity.With the emergence of scientific knowledge we can now address the variables involved in this intricate “seed-soil” relationship and address them strategically.But there remain many large voids in our knowledge.As more and more becomes known, we will hopefully become progressively better equipped to address the reasons for IVF failure and better help our patient go from infertility to family.


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