What is the reason that IVF fails?
Implantation failure is defined as the failure of an embryo to implant during an IVF cycle. Because of the desperation of couples attempting to conceive a child and the profound lack of knowledge about this complex area, many snake oil salesmen have emerged and spread their misinformation around the internet, much to the detriment of the couples trying their “magic potions”.
Difficulty arises in studying implantation failure due to the fact that not all scientists agree on a definition. Some doctors will call failure of a single in vitro fertilization cycle implantation failure. Others maintain that it is not implantation failure until a couple has failed to achieve pregnancy despite several in vitro fertilization failures. Still others look at the total number of embryos transferred as opposed to the number of treatment attempts. There are also many exceptions that have to be considered. For example, can a couple be said to have implantation failure if they have a history of a previous successful pregnancy? What about women with a tubal pregnancy? There is much that needs to be learned about human embryo implantation.
Implantation failure can be divided into three areas: Problems with the embryos, problems with the “host uterus” and problems in the interaction between the embryo and uterus. If there is an embryo transfer done, the reason that IVF fails is because of embryo implantation failure. However, that is not very helpful. We know that the embryos were transferred to the uterine cavity - particularly if ultrasound guided embryo transfer is done.
When IVF fails there was implantation failure, but we do not know whether the failure to implant was due to a problem with the embryos or a problem with the uterus. Most fertility specialists believe that in more than 95% of IVF failures it is due to arrest of the embryos. Embryonic arrest is quite often due to chromosomal or other genetic abnormalities in those embryos that made them too "weak" to continue normal development and implantation. Unfortunately, these issues are mostly a "black box" at the present time - we do not have a safe and cost-effective technology currently that would allow us to investigate the chromosomal and/or genetic issues in a manner that does not damage the normal embryos significantly.
PGS or PGD can be used to investigate chromosomal abnormalities in IVF embryos, but has been shown in well-controlled studies to lower chances for pregnancy rather than improving them. Why does IVF fail and what can the fertility specialist clinic do to increase the chance for success on a second IVF? A first IVF cycle is often successful at a high quality program. Unfortunately, many couples will not have successful first cycle IVF results and will need to consider a second cycle of in vitro fertilization. So what should be next after one failed IVF cycle? Let a week or so pass in order to make the difficult adjustment to the devastating news that your cycle did not succeed.
When you feel ready, schedule a consultation with your IVF specialist to go over what might have been learned from the failed IVF attempt. A very important consideration should be whether to change IVF doctors or switch to a different IVF clinic at that point. In vitro fertilization programs are not all equal - some give a much higher chance for success than others. The first thing that should happen is for the IVF specialist physician to review the failed cycle carefully to possibly learn something from the results of the IVF ovarian stimulation process, or from any issues with egg retrieval, egg quality and/or quantity, fertilization results, embryo development, or any problems with the embryo transfer procedure.
Often there will be an issue in one or more of these areas. The ovarian stimulation protocol and results as well as the embryo development issues should be discussed with the couple. Pictures of the embryos and quality scoring issues, including cell stages, fragmentation and regularity of the cells in day 3 transfer cases, or blastocyst grading and expansion scoring for day 5 transfer cases - should also be reviewed and discussed. Then a plan for a second IVF cycle can be formulated.
Inefficiencies in the IVF process will not always be issues that are "fixable" - but they should be studied and discussed with the couple so that they are educated about their situation and their estimated success rates for a second IVF attempt. Many issues seen in a failed first IVF attempt can be addressed in some manner in order to eliminate or reduce the likelihood of the same issue occurring in a second try with in vitro fertilization.
What is the success rate with a second cycle of IVF?
Couples often ask this very reasonable question. However, there is not a good, short answer. Many couples will have a successful second IVF. The chances for that happening depends on many factors, including:
* Age of the female partner
* Egg quality and egg quantity
* Sperm quality
* Quality of the IVF ovarian stimulation - dependent on the skills of the physician controlling this process
* IVF lab quality
* Egg retrieval skills of the physician and overall efficiency of the egg pickup process
* Embryo transfer skills of your IVF doctor and ultrasound equipment and technician
* Number of eggs retrieved
* The cause of your infertility
* Uterine issues
* Embryo developmental rates, embryo quality, and rates of embryonic arrest during development in the lab
* Genetic and chromosomal competence of the embryos
In order to maximize the chances for a successful second IVF try make sure that your doctor has carefully reviewed the issues above. You might also consider changing doctors between IVF cycles. Some reproductive endocrinologists (infertility and IVF specialists) are pulled in many different directions and are not focused on IVF or on having the best possible IVF lab and clinic. Having an outstanding IVF program requires constant diligence and consistent execution. This is not an easy proposition - particularly in very large IVF clinic - where thousands of couples are pushed through annually in a mass production approach. That approach to IVF often works much better for the clinic than it does for the eggs, the embryos, or the infertile couples.
What is the best time to transfer embryos in an IVF cycle?
Many IVF programs still perform embryo transfers three days after the egg retrieval. This is known as a cleavage stage or day three embryo transfer. After only three days in laboratory culture, the embryos have typically divided into six or eight cells. It is difficult, at this point in embryo development, to accurately predict which embryos have the best developmental potential.
To understand this concept, consider a race in which the participants run five laps around a track. If you were to try to predict the winner of the race after the second or third lap, you might guess correctly but often you will not. Occasionally, the early leaders will tire out or some runners who may have started out slowly demonstrate a great “kick” at the end. During IVF, evaluation of embryos works the same way. Some embryos which look great on day three stop developing or develop poorly over the next two days. Alternatively, embryos which didn’t appear to be the best on day three will improve and become very high quality embryos by day five.
Several studies in the past few years have determined that blastocyst transfer is a viable method for improving the chance for IVF implantation. In fact, the combined data from the Centers for Disease Control indicate that at every age group, the chance for IVF implantation is higher with a day five transfer than a day three transfer.
Summary for a second try with IVF:
Get an honest estimate from your IVF doctor on your chances for success rates with a second IVF try. If there were difficulties with the ovarian stimulation or low numbers of eggs - consider modifications to the drug protocol. If there were average or good looking embryos for transfer, but none implanted, try IVF a second time at the same or a different IVF clinic. If there were significant egg and/or embryo quality issues, it is most likely due to an egg problem or an IVF lab quality control problem. Therefore, consider changing the IVF clinic to a program with higher in vitro fertilization success rates to see if these issues were due to egg quality - or a problem with the ovarian stimulation, or a problem in the IVF lab. Donor sperm, donor eggs, or donor embryos could be future considerations, but those are usually further down the road than after one failed IVF cycle. The uterus can be the problem, but that is rare. Implantation failure is almost always because the transferred embryos were too weak to implant and continue normal development. The uterus is almost always receptive for embryo implantation.
Overall, IVF success rates are about the same on the average for second attempts as compared to first IVF tries. Couples with the best egg quality are more likely to get pregnant on their first try, but this is balanced out to some extent by learning from the first failed cycle and making adjustments to maximize success for the second in vitro fertilization attempt.
