The Failed IVF Cycle
USC Fertility, like nearly every reputable fertility center, no longer performs ZIFT. IVF is the preferred method, making up 98% of assisted reproductive technology.
It happens all too often: The fertility treatment has reached the point where your doctor recommends in vitro fertilization (IVF). The stimulation seems to go well and the egg retrieval procedure yields a reasonable number of good-quality eggs. The eggs are successfully fertilized and on the day of embryo transfer, you are presented with a picture and the option of transferring a certain number of “good-quality” embryos.
There is the usual discussion of the possibility of high-order multiple gestation, so now you know that the doctor is worried about potentially over-shooting, and everything seems to go well during the embryo transfer procedure. Even though you know to keep your expectations low, you cannot help but get excited at the possibility that this will finally be successful. When the pregnancy test is negative, it seems almost impossible. How could it possibly fail? What happened to all those embryos that were put back into the uterus? Where did they go?
Why IVF Fails
The reality is that most embryos do not implant. Depending on the age of the woman providing the eggs, the stage of development of the embryo, and, to a lesser extent, the appearance of the embryo, the chance that any one embryo will implant is quite low. For example, a 40-year-old woman with normal FSH levels and normal-appearing embryos on day 3 can expect that between 5 and about 8% of the embryos will ever reach implantation. That means that 92 to 95% of the transferred embryos will not implant.
Factors that are involved in embryo implantation can be generally grouped into three categories:
– Embryo quality, which means the inherent viability of each embryo,
– Uterine receptivity, meaning whether or not the environment inside the uterus is hospitable for implantation, and
– Transfer efficiency, which is another way of saying that transferring embryos into the uterus with a catheter is not part of the natural process.
In most cases, if the uterine cavity is normal, and the uterine stripe is thick enough (more than 7 mm), the uterus remains receptive to embryo implantation, regardless of the age of the woman. Also, as long as the uterus is normal and the embryo transfer process goes smoothly, the transfer of the efficiency of the transfer process is also good. Therefore, in the majority of instances, IVF fails because of “embryo quality” which is clearly the most important factor in human reproduction.
Embryo quality is mostly dependent on egg quality, and this is the factor that is known to decrease with age. Therefore, the reason that older women are less likely to conceive with the own eggs is because of a decline in egg quality, which leads to lower embryo quality, which leads to lower implantation rates. Embryo quality can also be influenced by other factors, such as problems during ovarian stimulation, problems in the IVF laboratory, which may harm the embryo, etc.
What is ZIFT?
ZIFT stands for zygote intra-fallopian transfer. This is a modification of the standard IVF procedure. ZIFT is identical to IVF throughout ovarian stimulation, egg retrieval, and fertilization. The only difference is when the embryos are replaced, and also where they are placed during the transfer procedure. In standard IVF, embryos are left in the laboratory until day 3 (or until day 5 in certain circumstances). They are then replaced in the uterus, thereby bypassing the fallopian tubes.
That is why IVF was initially developed for women with blocked or irreparably damaged fallopian tubes. But many women have open fallopian tubes and their infertility is caused by other factors than tubal blockage. In these cases, it is possible to take the embryos and to put them back into the body via the fallopian tubes, thereby allowing them to develop (more naturally) in the fallopian tube, and to arrive in the uterus in the way that they normally do in nature.
With ZIFT, the embryos are replaced 24 hours after egg retrieval, just after fertilization has been confirmed in the laboratory. Therefore, they spend less time in the laboratory, and more time in the body prior to implantation.
What Factors Influencing Implantation Are Altered With ZIFT?
When ZIFT is used instead of standard of IVF, uterine receptivity is not affected. After all, the embryos have to implant in the uterus, and it doesn’t matter how they get there. However, transfer efficiency may be improved, especially in those patients who have difficult embryo transfer, or among those who experience a lot of uterine cramping after embryo transfer. It may well be that the more natural “arrival” of the embryos in the uterine cavity may improve the efficiency of the embryo transfer process, especially in those patients who have experienced prior difficulty, or recurrent unexplained failure of embryo implantation.
The fact that the embryo also spends an additional 2 days in the fallopian tube, rather than in the laboratory, also has the potential to improve embryo quality. The IVF laboratory has improved greatly over the past 30 years. However, the field is not yet perfect. It appears that high-quality embryos seem to thrive in the IVF laboratory. However, patients with embryos of a borderline quality, such as those of advanced reproductive age, those who are poor responders to stimulation, or those who have recurrent unexplained implantation failure, may benefit from the more natural environment of the fallopian tube over that of the laboratory.
Is There Any Proof that ZIFT is Better than IVF?
The national statistics generally demonstrate similar pregnancy outcomes for IVF and ZIFT cycles. However, the national statistics do not take into account poor prognosis patients, or those with recurrent previous failure.
In one previous publication, patients with recurrent IVF failure were randomized to another IVF cycle versus ZIFT. The patients in the ZIFT group had significantly higher pregnancy rates that those who were assigned to another IVF cycle. We recently reviewed data from our own institution and found that whereas the pregnancy rate with ZIFT seemed to about the same as those for patients doing standard IVF. However, the ZIFT patients had, on average, at least two more failed cycles prior to undergoing treatment. This suggested to us that the ZIFT procedure may restore normal success rates in patients who have had multiple previous failures.
Since the only way to find out if ZIFT has any advantage over standard IVF is to do a properly designed scientific study, our institution recently embarked on a prospective, randomized trial of ZIFT versus IVF for women of advanced reproductive age with normal open fallopian tubes.
Our goal is to recruit 50 patients who will be randomized to one treatment or the other, with those failing to conceive in their first attempt automatically assigned to the opposite mode of treatment during their subsequent cycle. We are optimistic that our study will help answer the question if ZIFT actually improves pregnancy rates for women with recurrent failure or for those of advanced reproductive age, or if prior positive studies have been influenced by a happy coincidence.