Tag Archives: Embryo selection

Debate Over Genetic Screening of Embryos as New Tests Emerge

As more families opt for pre-implantation genetic diagnosis to screen embryos for inherited diseases, determining the regulatory and ethical guidelines to govern such screenings is “proving difficult,” the Chicago Tribune reports. Although the field of embryonic testing initially focused on identifying genetic defects that are certain to cause suffering or death early in life, it has broadened to include tests for genes linked to breast and ovarian cancer, which are not always fatal, occur later in life and affect 50% to 85% of those who carry the gene, according to the Tribune. The leading U.S. genetic diagnosis clinic, which is the largest in the world, conducted more than 1,800 screenings in 2008 “aimed at weeding out embryos that carried worrisome family conditions, from sickle cell anemia to cystic fibrosis,” the Tribune reports. Different countries vary in their regulation of PGD. In the U.S., doctors are allowed to select embryos for a particular sex, a practice that is not allowed in Great Britain, where each instance of PGD must be registered with the British Human Fertilization and Embryology Authority. BFEA has approved the use of PGD for about 70 genetic defects “after intensive public consultation about what is a serious enough problem to justify trying to eliminate it,” the Tribune reports. It is “significantly easier” to conduct PGD in the U.S. because the government only licenses clinics, not individual procedures, the Tribune reports. Mark Hughes, director of the Detroit-based Genesis Genetics Institute, said his company has tested for 171 genetic defects. In the U.S., “there is no approval mechanism,” Hughes said, adding, “No one is saying you can do this to save a sibling but you can’t do this for BRCA1,” a gene linked to breast cancer. According to a John Hopkins University study, nearly 40% of individuals surveyed believed that embryo screening should be regulated more closely for ethical reasons. An additional 19% said the screening should be banned altogether, for reasons ranging from the belief that discarding an embryo is immoral to concerns that selecting against certain diseases will devalue the lives of people already living with those conditions. Clare Williams, a bioethics specialist at Kings College London, said that during public hearings in Britain, “quite a lot of people felt there could well be treatment (for some conditions) by the time these children grow up, and then (their condition) won’t be an issue.” Some experts say it would be beneficial to place limits on the type of genetic defects doctors are allowed to screen for in the U.S., the Tribune reports. The Hopkins study found that, as of 2006, 65% of about 200 U.S. clinics offering embryo screenings allowed clients to choose the gender of the implanted embryo, regardless of the gender of existing children or whether the child was their first. The Tribune reports that such data and a California-based genetics lab’s recent announcement that it would be able to select eye and hair color have raised public concerns about genetic selection of embryos. The lab’s claims have been “disproved,” and many experts believe that expanded embryo screening “probably is not a slippery slope toward designer babies” because PGD is “costly and difficult,” there are a limited number of embryos to choose from and “finding one that includes a number of desired traits would be very difficult,” the Tribune reports. Hughes said the “things you might want to select for in a child — intelligence, athletic prowess, body stature — involve not single genes but many, many genes.” According to the Tribune, PGD, used in conjunction with in vitro fertilization, costs about $3,500 in the U.S. and twice that in Britain (Goering, Chicago Tribune, 3/25).


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Embryo Grading

One of the trickiest jobs facing a clinical embryologist is the visual assessment of human embryos. Embryo selection prior to embryo transfer clearly has an enormous impact on the success of the treatment and embryo selection for cryopreservation is equally important to the future success of frozen embryo transfers.

 Patients are often awestruck when they see a photo of their embryos for the first time on the morning of their transfer. That morning each embryo is carefully observed under a powerful microscope and the information about the quality of the individual embryos is given to patients prior to their transfer. In general, the way we assess the “quality” of embryos at Rotunda is by determining 3 major components. Cell number, cell regularity (regularity of size), and degree of fragmentation. There are also other things that are also noted about the embryos appearance, such as multinucleation, presence of vacuoles, granularity, thickness of the zona around the embryo, etc. Using this information, decisions are then made about how many embryos to transfer and how many to freeze, and importantly, what to do with embryos that are not developing very well.

When eggs are retrieved from a patient’s ovaries, they are surrounded by thousands of cumulus cells that prevent us from seeing eggs directly or making any comments about quality. For patients having ICSI (Intra-Cytoplasmic Sperm Injection), we strip away the cumulus cells, but even then, very little information on quality can be ascertained. Only when eggs are of particularly poor quality are we able to observe obvious differences from healthy eggs. The vast majority of eggs do not show any characteristics to indicate quality. Therefore, the embryologist will not typically convey any information about egg quality.


Usually, determinations of “quality” are not made until about 48 hours (or later) after the egg retrieval. By 48 hours (“day 2”), we prefer that at least some of the embryos are at least 3 cells –  and preferably 4 cells or more. They must be at least 2 cells by then – or they have basically “arrested”. By 72 hours (“day 3”), we prefer that some of the embryos are at least 6 cells – and preferably at least a few that have 7 cells or more. At Rotunda, we have seen babies that came from an embryo as slow as a 4 cell on day 3, but the chances for pregnancy increase greatly as the cell number increases. 

 Fragmentation is a normal feature in embryos and only about 20% of embryos have no fragments at all. However, the absence of fragments does not guarantee pregnancy as there are many other factors involved in embryo quality. The degree of fragmentation and cell asymmetry is given as a grade, usually A,B,C 0r 1, 2, 3. Grade A  embryos look beautiful and normal in every way. Grade B  embryos will have a small degree of fragmentation and or unevenness, but are still considered high quality. Only if an embryo is in real trouble and has more fragments than cells, will we assign the dreaded Grade C. These embryos very rarely implant after transfer and are not considered viable enough to freeze regardless of how many cells they contain. Patients often ask whether embryos that were given a “low grade” by the embryologist will make “low quality kids”. The children born from low grade embryos are just as cute, intelligent, strong, etc. as those born after transferring high grade embryos. The only difference as far as we know is in the relative chance that the transfer of the embryo(s) will result in a pregnancy and a live birth.

Embryo quality as we see it under the microscope in the IVF lab gives us some reasonable ability to predict the chances for pregnancy from an embryo transfer. However, because there are many other contributing factors involved that we can not measure, these generalizations do not always apply. We see some cycles fail after transferring 3 perfect looking embryos, and we also see beautiful babies born after transferring low grade embryos. The true genetic potential of the embryo to continue development and the quality and receptivity of the uterine lining are really impossible to measure. Hopefully, that will be something for the future. 

Ultimately, the only true test of embryo quality is whether it implants and develops normally and eventually goes home from the hospital with mom. In other words, embryo grading systems are very imperfect, and we always need the pregnancy test to tell us much more about “quality” than the microscope can reveal.

Posted by : Goral Gandhi, MSc,

                   Laboratory Director,

                   Rotunda – Center for Human Reproduction (Pvt) Ltd




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Identification of Viable Embryos in IVF

A group of Australian scientists has used a new genetic analysis technique to assess IVF embryos, to identify those most likely to develop in the womb. The findings were published in the journal Human Reproduction in May 2008.

 Around one per cent of all births in the UK are from IVF treatment and the latest figures show that of 32,600 women who underwent treatment, only 11,000 resulted in births. One in four IVF pregnancies is multiple, compared with one in 80 for a natural conception.

The process of IVF involves extracting many eggs for fertilisation before choosing one, two or sometimes even three embryos for transfer into the uterus. This can lead to multiple pregnancies, which carry extra health risks for mothers and babies. Embryo selection is currently based on observations of morphology (shape and appearance) to predict their potential viability. The problem could be overcome by finding an objective, measurable means of testing embryo viability, rather than a subjective one such as morphology, to definitively pick a single, viable embryo.

 The study, carried out by scientists at the Monash Immunology and Stem Cell Laboratories, Monash University, Australia, and the Centre for Human Reproduction, Genesis Athens Hospital, Athens, Greece, recruited 48 women undergoing IVF treatment. Once their fertilised eggs reached the ‘blastocyst’ stage, an early stage of development around day five, between eight and 20 cells from the surface layer were removed. These samples were then genetically analysed using microarray techniques, which measures gene activity in the cells.

 Of the embryos selected as being viable, one or more were transferred into the 48 women, 25 of whom became pregnant, with 37 babies being born. The scientists took DNA samples from the babies, and used DNA fingerprinting to match which blastocyst grew into which baby. This enabled them to compare the activity levels of key genes, to identify which had been active in the viable, compared to the non-viable early embryos. These genes identified were involved in key processes such as cell adhesion, cell communication, cellular metabolic processes and response to stimuli.

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A new test which helps IVF doctors pick the healthiest embryos for transfer may boost pregnancy rates by up to 15 per cent, was unveiled at a European fertility conference last week. The test, which takes just one minute to carry out and will be used alongside standard IVF methods for embryo selection, is due to start trials later this year and may be available in clinics early next year.
‘We fail to get patients pregnant about two-thirds of the time we transfer an embryo, and one of the reasons is we are not very good at picking the best ones from those available,’ lead researcher Denny Sakkas, professor at Yale University school of medicine, told delegates at the European Society for Human Reproduction and Embryology annual meeting.
Conventional IVF relies on choosing embryos for transfer by examining their size and shape under a microscope. But the researchers found that this method was only accurate at identifying viable embryos – those which would result in a pregnancy – 40 per cent of the time. Their technique – known as ‘ViaTest-E ‘ – involves shining a light through the fluid surrounding the embryo in order to measure it’s metabolic activity – rather like the technique used to tell whether milk is full or half-fat.
Testing the ViaTest-E device on 500 embryos showed accuracy rates of 60-70 per cent, potentially boosting the chance of pregnancy for women under 35 in the UK from 30 percent to 45 per cent. It is anticipated that tests which help doctors select the most viable embryos will be vital in order to support the move towards single embryo transfer, a measure being implemented across Europe and the rest of the world to try and limit multiple births.
Dr Daniel Brison, co-director of the North West Embryonic Stem Cell Centre in Manchester, told the BBC that improvements to IVF success rates were urgently needed. ‘If we can get better at choosing the best embryo to implant then we can increase the efficiency of IVF, move towards single embryo transfers and thus reduce the risk to mothers and babies,’ he said.

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