Trivector With IUI Training, IVF Training, ICSI Training

8/7/2019 Trivector With IUI Training, IVF Training, ICSI Training

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How likely am I to be successful and how many attempts might it take?

This is one of the most common questions posed by patients undergoing In Vitro

Fertilization. It is also one of the most difficult to answer honestly. All too often a

patient is glibly quoted a percentage as if it would apply to anyone in her age

category. Nothing can be further from the truth, and any patient undergoing IVF

should be cautioned that such a response should immediately raise a red flag

and evoke skepticism.

IVF is a complex process whose success or failure depends upon the

harmonious interaction of a multitude of variables that differ from patient to

patient. In large part, a successful outcome, i.e., the birth of a healthy baby,

requires a successful interplay of factors that are analogous to those involved in

the successful growth of a healthy plant in a garden. In both cases, success

requires that a good quality seed be delicately planted in a receptive soil. In the

case of IVF, the seed is the embryo, the soil is the uterine lining and the

gardeners are the RE and the IVF laboratory. You cannot expect a successful

outcome when a poor ³seed´ is planted in a good soil, when a good ³seed´ is

planted in a poor soil or when the seed is planted in the wrong season or by a

poor gardener. Accordingly, when it comes to IVF outcome, it is the factors that

influence the quality of the embryo, the receptivity of the soil and the competency

of the IVF team that play a deciding role.

Against this background let us analyze how the following factors influence IVF

outcome:



1) Embryo Quality

A) Age of the egg provider: In the absence of severe sperm dysfunction, it is

predominantly the chromosomal integrity of the egg that will determine embryo

competency(the ability to propagate a viable pregnancy). Eggs with an irregular

number of chromosomes (³aneuploid´ eggs), will either fail to fertilize, or will

propagate an ³incompetent´ (aneuploid) embryo, i.e., one that is incapable of

attaching and/or developing into a healthy pregnancy. Since age of the woman is

the main determinant of egg aneuploidy, it follows that as a rule, the older the

woman, the lower will be the yield of competent embryos. When compared with

other mammals, humans have the highest incidence of egg aneuploidy. Since

most infertility and miscarriages (as well as chromosomal birth defects) are due

to egg aneuploidy, it should come as no surprise that we as a species have the

poorest reproductive performance of all mammals. In fact, at age 30-35 about

60% of human eggs are aneuploid, and thus incompetent. This incidence

increases rapidly with age such that by the early to mid 40¶s the incidence of

aneuploidy is higher than 90%. In addition, with advancing age and

encroachment of the menopause comesdiminishing ovarian reserve. This

translates into fewer eggs being available for processing and fertilization. The

combination of declining egg competency and fewer eggs being available

explains why above 35 years of age there is a profound decline in IVF success

rates.



B) Sperm Quality: The advent of Intracytoplasmic Sperm Injection (ICSI) vastly

enhanced the ability to force fertilize eggs. This dramatically improved IVF

pregnancy rates which hitherto had been dismal when IVF was performed in

cases of moderate to severe male infertility. Notwithstanding this, it is a fact that

the poorer the quality of the sperm, the lower the fertilization rate, and the greater

the likelihood of sperm aneuploidy contributing to embryo incompetence.

Therefore, male factor infertility does play a role in IVF outcome in spite of ICSI.

In general, pregnancy rates are lower when the sperm is poorer and miscarriage

rates are higher. There is also an increase in certain developmental disorders in

the resulting children, and in the subsequent incidence of infertility in the male

offspring. The latter is probably due to the fact that a gene that is responsible for

male factor infertility is carried on the Y chromosome (XY = male) and therefore

passed on from father to son. While age can affect sperm function, it is rarely a

significant factor when it comes to IVF outcome.

C) Protocol for Ovarian Stimulation: As outlined in an article on this blog

entitled ³ An Individualized Approach to Ovarian Stimulation for IVF´, patients with

diminished ovarian reserve as well as those who are over the age of 40 years

require a customized and individualized approach to controlled ovarian

stimulation (COS). The ovarian follicles in such women are very sensitive to

overexposure to the male hormones produced by surrounding tissue (theca) in

the ovary. Unfortunately, these are the very women that either overproduce the

hormone LH (which stimulates ovarian male hormone-testosterone production) or

are hypersensitive to it. In addition, certain protocols of ovarian stimulation do not

protect the eggs from overexposure to testosterone in the early stage of COS

(e.g., the use of antagonists such as Ganirelix or Cetrotide starting on day 6-8 of

stimulation). So-called ³flare protocols´ exacerbate the release of LH early inCOS with the same effect. There is compelling evidence to suggest that

overexposure of developing eggs to testosterone and other male hormones can

increase the likelihood of aneuploidy and thereby compromise IVF outcome.



D) Laboratory Expertise: Another vital component in assuring a good quality

embryo is a well seasonedembryology team. It is also true that most IVF labs

have such required expertise. One caveat is that the performance of certain

technical procedures such as ICSI, egg/embryo biopsies (e.g., PGD) and

assisted hatching (AH) require extensive experience. No doubt, the longer the

egg or the embryo is kept outside the incubator in order to perform such

procedures, the poorer the results will be. This perhaps explains why smaller IVF

programs where fewer such procedures are performed will often have lower

success rates when it comes to the treatment of male infertility and the

performance of egg/embryo microsurgical procedures such as PGD or AH.

2) Uterine Receptivity Approximately 30% of female patients at the average IVF program will have a

uterine impediment to embryo implantation. This can be due to a thin or

inadequate uterine lining or the presence of surface lesions (e.g., polyps, scar

tissue, or fibroids) that can interfere with implantation. In addition, about 20% of

women undergoing IVF have an immunologic implantation dysfunction. In my

personal practice where more than 80% of the patients I treat have had 3 or

more prior IVF failures, the incidence of undiagnosed immunologic implantation

dysfunction is probably in the vicinity of 50%. Unfortunately, many IVF

practitioners refuse to accept the concept of immunologic implantation

dysfunction and when their patients fail to conceive in spite of repeated embryo

transfers, they recommend egg donation. The problem is that in the presence of

an intractable implantation dysfunction, egg donation will also be unsuccessful.

Failure to evaluate for and address such issues will inevitably reduce or eliminate

the potential for successful IVF in such patients.



3) IVF Team

Successful IVF demands that a rehearsed relationship exist between all

members of the team (nurses, doctors and laboratory staff). Without such a

relationship outcomes will be poor regardless of individual expertise. The

performance of the embryo transfer is a critical step in IVF and this demands a

lot of experience as well as self confidence on the part of the RE. Unfortunately,

when it comes to this procedure, there is a wide variation in expertise. Poor

technique with regard to embryo transfer is one of the most significant variables

affecting IVF outcome. In my almost 30-year career in the IVF arena, I¶ve had

that opportunity of observing scores of doctors performing embryo transfer and

have witnessed good as well as atrocious technique when it comes to ET and the

results obtained by such practitioners was reflective thereof.

So, when you are glibly quoted an IVF outcome statistic, you should demand of

your doctor that he/she address how the above variables apply to your specific

situation. Do not simply rely on verbal assurance. Worse still, do not rely

on reported statistics by SART/CDC where the results presented are based upon

self generated data presented by the IVF center, and largely published as fact

without any oversight, validation or auditing. It is for this reason that I personally

no longer report data to SART/CDC (other SIRM physicians may feel compelled

to do so because several insurance companies require such reporting as a

condition of reimbursement). To me this has become a matter of principle. I was

a founding member of the forerunner to SART (the ³IVF Special Interest Group´)

and will be more than happy to report to SART/CDC as soon as the required

accountability is in place. Until such time, I regard the situation as ³the fox

guarding the henhouse´ and refuse to participate.



Outcome Based Reporting

At SIRM, we have developed a novel method of reporting IVF statistics known as

the Outcome Based Reporting System (OBRS)which reports IVF statistics under

age categories but sub-categorizes the success rates on the basis of ³categories

of complexity´ which attempt to analyze several other important variables (cited

above) that can influence IVF outcome.

The decision as to how many attempts at IVF a patient/couple should undergo is

a different matter altogether. IVF is expensive, and since insurance

reimbursements are available to less than 20% of those in need in the US, it

follows that the pocketbook will determine access as well as the number of

attempts at IVF that are feasible. From a pure medical standpoint however, the

time to stop trying is when there is no remediable explanation for failure. This

means that patients who fail to conceive need to take the necessary steps to best

identify the reason for failure before deciding on future cycles, even if this

requires getting a 2nd, 3rd or 4th opinion. In general, if IVF does not result in a

baby after numerous embryos have been transferred over 3 attempts, it is

probably time to move on. The good news is that couples/patients who are willing

and able to avail themselves of all IVF-related options including egg

donation and/or gestational surrogacy as well as embryo adoption, will in more

than 90% of cases ultimately be rewarded with a baby. Unfortunately, few can

afford this luxury

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