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

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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.

Tags: Comparative Genomic Hybridization (CGH), embryo competence, Failed IVF, IVF Authority, recurrent miscarriage

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

Lynds says:

May 25, 2011 at 12:40 pm

Hi Dr Sher
I am 36 and have eleveated NK cells (37.7) which decreased to 6 with intralipids. I am heterozygous for MTHFR and have a 4.1 DQ alpha match with my husband. We did CHG and transferred 2 normal blasts and froze 3, only to find that it failed. This is my 4th IVF and I feel as though I am chasing my tail. Is there something more I could have done?
Your thoughts?
Thanks

Reply
Geoffrey Sher, MD says:

May 26, 2011 at 11:44 am

I think I answered this post on the SIRM-Western Region discussion board, yesterday. In that retort I pointed out that the NK cell (CD-56 lymphocytes) concentration in the blood is irrelevant. In fact, the higher the better. It is the NK cell activity (toxicity) as measured by the K-562 target cell test that really matters. Also, it is very difficult to interpret the IL effect in the test tube because that is not how IL work. They regulate tor parent NK cells that journey to the uterus from the bone marrow, every cycle and then only after being exposed to progesterone, thuggery spawn "functional" NK cells. It is the latter, not the former that impacts embryo implantation. In order to down regulate activated NK cells, you need to give IL before progesterone is around so that these down-regulated "parent" NK cells will subsequently spawn "functional", non activated NK cells. This takes about 1 week. thus seeing how IL affect's NK cells in the lab, is erroneous and probably unimportant. If yous want to see how intralipid has down-regulated activated NK cells you need to repeat the K-562 test about 2 weeks after IL infusion.

On the issue of CGH, it is important that if the biopsy was done on day 3, the method of metaphase CGH rather than array CGH was used if you want to be confident that the results are reliable. array CGH should be reserved for blastocyst (trophectoderm) biopsies where you can pool the DNA from several cells for CGH analysis.

Feel free t6o call 800-780-7437 if you would like to discuss this with me.

Geoff Sher

Reply
Manek says:

May 17, 2013 at 7:30 am

Hello Dr. Sher:

I had a cancelled IVF cycle #1 due to poor response. Here’s my history:
33F (Highest FSH 16, AMH <0.3) Regular 28 day cycle with ovulation ranging from day 12-14 with each cycle. No other medical conditions.
Husband is 34 with excellent sperm morphology/motility/counts. No other med. history.

Because of my DOR, I was placed on estrogen priming antagonist protocol for IVF cycle #1.

Estrogen priming antagonist protocol:
- Ovulation = Day 0
- On day 10 post ovulation = started Estrogen patch (one patch every other day; total of three patches)
- On day11 post ovulation = started Ganirelix 250 (one injection for three days)
- On day 14 post ovulation = menses started.
- Day 2 of my cycle blood work and ultrasound: 8 antral follicle count (5=Lf 2=Rt). E2=168 FSH=2.
Started 225U of Follistim and 225U of Menopur on Day of the cycle (and stimmed for total of 10 days at same doses).
- Day 7 (or day 6 of stims) blood work and ultrasound: 5=small follicles on left; on the right one dominant follicle (10mm) and one smaller follicle (3-4mm). E2=100. Uterine lining = 8mm
- Day 9 (or day 8 of stims) blood work and ultrasound. 5=tiny follicles on left (getting smaller); on the right the dominant follicle grown to 14mm and other smaller follicle (5mm). E2=130. Uterine lining = 6mm
- Day 11 (or day 10 of stims) blood work and ultrasound. 5=tiny follicles on left (getting smaller); on the right the dominant follicle grown to 15mm and other smaller follicle (9mm). E2=299. Uterine lining = 9mm. One shot of Ganirelix in the evening along with last round of stimulation medications (Follistim and Menopur).
- Day 12 (no stims) blood work and ultrasound. 5=tiny follicles on left (getting smaller); on the right the dominant follicle grown to 18mm and other smaller follicle (10.5mm). Uterine lining = 9mm. Was prescribed Pregnyl 10, 000IU.
- Day 14-IUI scheduled. IVF cycle cancelled.

Questions:
My antral follicle counts range from 3-5 normally. With this cycle, I was excited that the count was higher (AFC=8). But now the cycle is over, I am confused as to why only one follicle took off? Was this the right protocol for me? Or was the type of stimulation medications used and their dosage appropriate? what would be your recommendation for IVF#2 protocol?

Your expert opinion is much appreciated.

Thank you kindly,
Manek.

Reply
- Geoffrey Sher says:
  
  May 17, 2013 at 8:57 am
  
  Hi Manek,
  
  This is not a protocol I personally would use. See below….n your case I would favor an agonist/antagonist conversion protocol with Staggered IVF and Embryo banking of CGH-normal blastocysts. Please go to the home page of this blog, http://www.IVFauthority.com. When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
  
  2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
  
  3. “Agonist/Antagonist Conversion Protocol”
  
  4. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
  
  5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  6. “Staggered IVF”
  
  7.“Embryo Banking”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply

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