Scottsdale/Phoenix, Arizona - Clinical researchers at Arizona Center for Fertility Studies have exciting news showing, that by screening all the chromosomes in an embryo, the number of successful pregnancies could be increased and the number of miscarriages decreased over traditional methods of in-vitro fertilization.
In many ways, human reproduction is an inherently difficult and inefficient process. Statistics show, that any time a sperm meets egg and fertilization occurs, pregnancy rates are only around 30%; 20% resulting in a clinical loss and another 50% lost between ovulation and a women's period. Because many human eggs are "flawed" it can take many sperm, eggs and even embryos to eventually produce one healthy baby. The average woman in this country takes 5.3 months to conceive.
Some of the techniques that help couples overcome infertility involve allowing reproductive medicine physicians (REI- reproductive endocrinologist/infertility specialists) to choose the best of a woman's reproductive tissues to use in order to have a child. In IVF, for example, not all the eggs will fertilize and not all the embryos will develop. Thus, the embryologist has to select which embryos they think will have the highest likelihood of establishing a successful pregnancy. Up to now, morphology, that is, how an embryo looked, has been the main criteria for choosing which embryos to transfer.
The ART-IVF team at Arizona Center for Fertility Studies has found a better way. Using recent breakthrough technology of 23-chromosome microarray, patients at ACFS have a 20+% higher pregnancy rate than those using conventional IVF (see PGS statistics below). Since chromosomal abnormalities (or aneuploidy) accounts for 70-80% of implantation failure (unsuccessful IVF attempt) and/or first trimester pregnancy loss, the team at ACFS strongly recommends chromosome testing for all their patients undergoing IVF.
Using 23-chromosome microarray technology, once each embryo reaches day 5 or the blastocyst stage- link to blastocyst section (about 100+ cells), a biopsy is taken from the outer layer (trophectoderm) using a laser and all 23 of its chromosomes are examined. Than, all the biopsied embryos are frozen. In a subsequently prepared cycle, 1-3 embryos (based on American Society of Reproductive Medicine guidelines for age) that have been found to be chromosomally normal are thawed and transferred into the woman after appropriate uterine preparation (FET- frozen embryo transfer). By comparing a group of patients using 23-chromosome technology with a group of similar patients using traditional methods (IVF without chromosome testing); the team at ACFS found that patients undergoing 23-chromosome microarray testing significantly increased the likelihood of a successful pregnancy and reduced miscarriage rates; especially for patients of advanced maternal age, in whom chromosome problems are more likely.
Above data represents approximately 335 patients, including all ages, over the last 5 years doing IVF with only chromosome testing (PGS). The majority of patients were able to transfer 2 blastocysts. Data represents positive pregnancy test at 9 days post transfer and evidence of a gestational sac on ultrasound at 6-7 weeks. One important change in the last two years is a decrease in miscarriage rates and a subsequent increase in implantation rates in what ACFS feels is directly related to a proactive approach to miscarriage prevention prior to embryo transfer.
If you look at ACFS data, you can not help but notice that the success with transferring two embryos is so much better than with transferring one. A short while ago, our embryologist asked "if a patient had 4 chromosomally normal embryos, would she have the same number of successful pregnancies (babies) if she transferred one at a time as opposed to doing two embryo transfers of two each?" Logically, you would think that the outcome would be the same, unless there was the possibility that by transferring two embryos, one would "help" the other to implant by possibly secreting and/or releasing substances or "signals" that would promote implantation. There has been a big push in the country to transfer only one embryo, mainly to avoid the risks of twins. So, if a patient has four embryos, the recommendation would be to transfer one at a time, until all four embryos would be transferred; as opposed to doing two transfers of two each. ACFS respectfully disagrees with this advice.
As you can see from our data, a two embryo transfer is the way to go to achieve the "best" success rates. This is especially true for women 37 or older. ACFS current data represents the fact that most one embryo transfers are either in younger patients who want a "zero" risk of twins or older patients (37 or older) who only have one chromosome normal embryo to transfer. This suggests, that although chromosome testing (PGS) "goes a long way in eliminating age as a factor", it does not completely wipe out age as a factor. This is evidenced by ACFS data, that shows that the twinning rate at 37 years old or greater is 8% with a two embryo transfer; whereas, less than 37 years old it is 28% with the same number of embryos. Therefore, in order to achieve the "highest success rate possible", ACFS strongly recommends a two embryo transfer. Of course, ACFS will always respect and support a patients choice in how many embryos she wants to transfer.
ACFS has to wonder why clinics "push" a single embryo transfer (SET)? Clearly, one reason is to avoid the risk of twins. Another is maybe the end result of transferring one embryo at a time, eventually results in the same number of successful pregnancies. The third..., should not even be considered as a possibility! But something very important is missing in all this - that although the end result of a single embryo transfer may be the same (ACFS is not 100% sure of this) in the amount of overall successful pregnancies it produces, this thinking fails to consider several very important points:
There is no question in ACFS mind that an elective single embryo transfer (SET) in everyone would produce higher pregnancy rates than our current data of 57.7% which is clearly biased (see above comments); however, there is also no question it would not be close to the success of 83.3% with a two embryo transfer; and thus, statistically would require more transfers. ACFS's goal is not to see how fast we can help you get pregnant (short protocols / fresh transfers), or how many embryos transfers we can do; but to get each and every patient pregnant on their first attempt. A second attempt is for a second pregnancy.
Typically, the average cost of chromosome testing (PGS) is between $6-8000 depending on which clinic you are at. On top of the already high costs of IVF, this generally makes chromosome testing not affordable for most couples. Well, how do you get someone to do something? "You make it worth their while". At ACFS, we believe so strongly in chromosome testing, that we are willing to do it for our cost and charge a total of $2900; which includes day 5 blastocyst biopsy (TE biopsy) and 23-chromosome microarray testing and subsequent freezing (vitrification). Actually, by doing chromosome testing, ACFS loses money (see here for reasons why).
Human reproduction is inherently poor, as evidenced by the high miscarriage rates, suspected to be as high as 70% (20% clinical loss, 50% loss between ovulation and menses) and the average time to achieve pregnancy of 5.3 months. As a women ages reproductively, her ability to make chromosomally normal embryos decreases. As more and more couples are postponing childbirth, the average age of conception at ACFS is now in the mid to late thirties (average @37). As a result, we are seeing not only a decrease in egg production and/or quality but also an increase in chromosomally abnormal embryos. These two factors result in decrease pregnancy rates, increase risk of a first trimester miscarriage and increase risk of having a child born with a chromosome abnormality (Down’s Syndrome).
At ACFS, we have found that the single most important reason for a failed IVF cycle (implantation failure) and/or first trimester loss (miscarriage) is due to the fact that the transferred embryos were chromosomally abnormal (aneuploidy). This is based on the assumption that the ART laboratory operates at a high level of excellence.
ACFS was not able to say this 5-6 years ago, but if your embryos are not able to reach the blastocyst stage (day 5) in ACFS-ART laboratory culture system, than they would not have made it in you if they were transferred. The same is true of frozen embryos, if they do not survive the freeze/thaw process (vitrification)- cryopreservation section at ACFS, than they would not have survived in a fresh transfer. There are clinics that disagree with these conclusions but the overall experience at ACFS is quite the opposite. We have not done a day 3-embryo transfer for the last 4-5 years; and as shown from our data above, we feel very comfortable with our freeze/thaw (or vitrification); which is a very critical part of doing PGS-chromosome testing. Some clinics still will do a day 3 transfer because they are not comfortable with growing embryos out to day 5 (advanced blastocyst culture); and tell their patients "it is better to transfer on day 3". Also, ACFS believes it is more cost effective to see if the embryos make it to day 5; if they do not, ACFS feels that they would not have made it in you either; and at least would not have to pay for a transfer and "anxiously and hopefully" wait for the results of a pregnancy test; not to mention "those" progesterone shots and/or gel.
As a result of our data, ACFS strongly encourages our patients to do chromosome testing or PGS (pregenetic screening) as part of their IVF. Although there are some reports in the literature to suggest that chromosome screening of embryos does not improve success rates, ACFS respectfully strongly disagrees. Our data over the last two years shows quite the contrary, that IVF with chromosome testing significantly improves a couple's IVF success rates; 20+%, over conventional IVF, if two embryos are transferred.
Reasons and Techniques for day 5-6 blastocyst biopsy (TE- trophectoderm biopsy) to test the chromosome makeup of each embryo. Better known as PGS or preimplantation genetic screening.
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