November 03, 2006
Embryo Tests More Than Double IVF Pregnancy Rate

Here's a technological advance sure to appeal to women in their 30s and 40s trying to get pregnant from their own eggs or from donor eggs. A new method of testing the viability of embryos produced via in vitro fertilization (IVF) more than doubles the success rate for attempts to start pregnancies.

Currently, only around 34 per cent of IVF cycles in the US result in pregnancy. By selecting embryos on the basis of their metabolic profile, Seli's team increased the pregnancy rate to more than 80 per cent in a pilot study, presented at the annual meeting of the American Society for Reproductive Medicine in New Orleans, Louisiana, last week.

A company stands ready to offer services using these results.

Molecular Biometrics, a privately held metabolomics company, presented results of two clinical studies investigating the use of metabolomic profiling to assess embryo viability, a key step in the treatment of infertility by in vitro fertilization (IVF), at the American Society of Reproductive Medicine's 62nd Annual Meeting in New Orleans, LA.

In a podium presentation (O-270) titled Non-Invasive Metabolomic Profiling of Human Embryo Culture Media Correlates with Pregnancy Outcome, Principle investigator Emre Seli M.D., Ph.D. (et. al.) of the Metabolomic Study Group in ART at Yale University School of Medicine reported results of a retrospective multi-center study. The study was designed to assess embryo viability using a novel technology developed by Molecular Biometrics based on the metabolomic profiling of Oxidative Stress (OS) biomarkers. The goal of the technology is to identify metabolomic differences in viable verses non-viable embryos so only the highest quality embryos can be selected for transfer in IVF. This non-invasive test analyzes OS biomarkers in normally discarded culture media. The biomarkers are quantified using Molecular Biometrics' proprietary spectroscopic analysis and advanced bioinformatics.

The study group concluded that detectable differences exist in the metabolomic profiles found in culture media obtained from embryos that cause pregnancy compared to those that do not. The reported metabolomic parameters were established using two different forms of spectroscopic analysis, Raman and Near Infrared (NIR) spectroscopy, with media samples obtained from three different IVF programs. The metabolomic method achieved high sensitivity and specificity of > 85%.

What I'd like to know: Did some of the women produce only embryos that were unhealthy as measured by these methods? If you want to sell your eggs the ability to show a high rate of viable embryos in one egg sale would let you demand a higher price with later customers. This could be a boon to the egg donation market.

Each of the two spectroscopy methods was highly accurate by itself.

In the study, embryo culture medium from 163 embryos from assisted reproductive technology (ART) cycles using fresh donor and nondonor oocytes were evaluated. Normally discarded media from individually cultured embryos was collected at the time of embryo transfer on day 3, and analyzed using both Raman, and Near Infrared Spectroscopy. Metabolomic profiles of OS biomarker concentrations showed distinct differences between culture media of embryos that resulted in pregnancy compared to those that did not. Using a genetic algorithm with Raman analysis, novel OS molecular species were identified and statistically correlated with pregnancy outcome. The compiled outcomes resulted in a specificity of 82% and sensitivity of 95%. Likewise, analysis by NIR resulted in a specificity of 83% and sensitivity of 73%.

Expect a bigger market for assisted reproductive technology (ART) as a result of this advance. Initially it will decrease the demand for donor eggs by increasing the success rate of women trying to get pregnant from their own eggs. However, in the longer run this advance should increase the market demand for both assisted reproductive technology (ART) in general and donor eggs in particular. Why? Because it lowers the total cost of IVF. Success will happen in fewer attempts. Each attempt costs additional money, emotional pain, physical stress, and also costs time that ages a woman's body and makes her less capable of starting and maintaining a pregnancy.

Lower costs, higher assurances of success, and quicker results will entice more women to use IVF with their own eggs and, for some women, with donor eggs. Also, some egg donors will even be able to more quickly build up track records for producing eggs which result in higher percentages of viable embryos and successful pregnancies.

This result may not just increase IVF pregnancy success rates. It might even reduce the problem of birth defects. Some of the embryos that show up as problematic in these tests might be able to start pregnancies but eventually result in problems after birth. The ability to screen out marginal embryos might therefore reduce the incidence of birth defects. Biotechnological advances seem set to make reproduction with IVF preferred over natural sexual reproduction.

Could IVF-PGD one day become the preferred method of conception?

"It is technically possible," says Simon Fishel, a member of the team responsible for the birth of the first IVF baby in 1978, who now runs the Care Fertility group of clinics in the UK. There are, of course, huge obstacles, not least of which is the cost. "You have to pay per cycle," points out Fishel. "You can attempt to conceive naturally over 12 cycles in a year and it costs you nothing."

The "PGD" mentioned above, Pre-implantation Genetic Diagnosis, is the key to why IVF will probably become the preferred way to start pregnancies. Once genetic testing becomes cheap and the meaning of many human genetic variations becomes known IVF with PGD will provide prospective parents with a way to choose genetic variations for their children. That'll provide a way to avoid many genetic defects and to get children who are better looking, smarter, and with more other desired qualities.

Tests that can sort out high quality embryos will lead to the ability to implant only one embryo to start a pregnancy.

Even singleton IVF babies are around twice as likely to be premature or low birthweight. Again, however, multiple embryos could be to blame, because many IVF pregnancies start out as twin pregnancies. When single embryos are transferred, the differences in health vanish (New Scientist, 25 June 2005, p 14). Many countries limit the number of embryos that can be implanted and single embryo transfer could eventually become the norm.

This latest result reduces the costs of assisted reproduction technologies by reducing the number of cycles needed. It also will probably reduce premature births and birth defects. Once coming technologies make it possible to combine that with sophisticated and cheap genetic testing I predict most prospective parents will choose IVF over natural sexual reproduction.

Share |      Randall Parker, 2006 November 03 05:23 AM  Biotech Reproduction

Bob Badour said at November 3, 2006 9:01 AM:

This test reduces another cost component you did not mention: the cost of multiple births. The way it works now, a couple might end up with triplets, quadruplets or even quints when all of the implanted embryos develop.

The prospect of triplets or quads must make at least some couples hesitate. With an 80% success rate per embryo, a couple could get a 95% chance of successful pregnancy with only a 64% chance of twins and 0% chance of triplets by implanting only two embryos. With only a 34% success rate per embryo, one would have to implant 7 or 8 embryos to get a 95% chance of success. One would have to implant 4 embryos just to get the 80% chance of success from implanting a single screened embryo.

Implanting 4 embryos with a 34% chance of development gives over 1300 quads per 100,000 births compared to less than 0.15 quads per 100,000 births according to Hellin's Law and empirical results. That's almost a 9 thousand fold increase in the chance of quads.

This makes the relative cost of implanting two embryos versus the cost of repeating the whole procedure extremely interesting. If the cost of repeating the procedure with one embryo is sufficiently more expensive than the cost of implanting two embryos, expect a massive increase in the number of twins. The rate of twins from IVF will go from somewhere around 11,500 per 100,000 births to somewhere over 60,000 per 100,000 births.

Hmmmm.... maybe it's time to go short on specialty products for triplets and long on specialty products for twins.

The Superfluous Man said at November 4, 2006 3:34 PM:

Mr. Parker,
If I understand correctly, the technique does not return either a binary "good" or "not good" value, but rather the probability of success (or something similar)? The latter might then entail making tradeoffs (eg, smart pretty baby with 60% chance vs. not so desirably baby with 90% chance).

"most prospective parents will choose IVF over natural sexual reproduction."
Enter the catasrophe scenario predicted by Charles Murray and Richard Herrnstein in the Bell Curve.

Rob said at November 4, 2006 5:30 PM:

The problem with selection is who chooses? We could survey people for what traits they'd select for. Problem is, people lie. Would it be ethical to ask prospective parents at an IVF clinic what traits they would like the child to have, and have them rank them? It is not exactly lying, because the researchers would not say "we're engineering your kid with these traits," but it would almost have to be misleading.

Is there an ethical way to conduct research like that? I'm not up on psych or sociology experimental ethics.

The Superfluous Man said at November 4, 2006 6:42 PM:

"The problem with selection is who chooses?"
I don't quite understand your comment. Are you proposing an experiment to determine people's "designer baby" trait preferences? If so, it's quite simple. The researchers offer free IVF + PGD (and possibly money), and ask the parents what traits they want, and present them with the options, ie. the profiles of all the embryos extracted, and the parents would respond with their preferred embryo. The only problem would be that the people involved in the trial wouldn't be representative of the country generally.

John S Bolton said at November 5, 2006 1:16 AM:

This is a good development, likely to be eugenic ultimately.
In any case everyone should be absolutely loyal to the progress of civilization, which this certainly is an example of.
The pretenses of pseudo-moral posturing and becoming appalled over the ramifications of something eugenic, as if the world ran on envy, are evidence of how egalitarian sentiments
are obstacles to human advancement.

Freddie said at October 30, 2007 7:36 PM:

This is really a very good development because it increases my hope of becoming a real dad. I have been looking for the right lady who will be interested in pregnancy via IVF, someone who also desires a child. This is my only last hope to realize my dream. If you know someone who can be a perfect candidate my personal site is:


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