{"id":11648,"date":"2018-10-02T18:56:52","date_gmt":"2018-10-02T18:56:52","guid":{"rendered":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/?p=11648"},"modified":"2020-05-28T19:15:20","modified_gmt":"2020-05-28T19:15:20","slug":"driving-toward-100-success-rate-in-preimplantation-genetic-screening-in-malaysia","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/driving-toward-100-success-rate-in-preimplantation-genetic-screening-in-malaysia\/","title":{"rendered":"Driving Toward 100% Success Rate in Preimplantation Genetic Screening in Malaysia"},"content":{"rendered":"

Dr. Colin Lee Soon Soo is a gynecologist and fertility\u00a0specialist at the Alpha Fertility Centre<\/a> in Selangor, Malaysia. Dr. Lee\u2019s interest in preimplantation genetic screening\u00a0(PGS) and fertility has led to more than 100 scientific\u00a0publications over the years. The discussion below touches\u00a0on current challenges for in vitro fertilization (IVF) research\u00a0and how Dr. Lee\u2019s team addresses them.<\/p>\n

Today\u2019s challenges in PGS<\/h3>\n

Thermo Fisher Scientific:<\/strong> As a leader of preimplantation genetic screening research\u00a0in Malaysia, can you share how you view PGS, and what\u00a0challenges exist today?<\/p>\n

Lee:<\/strong> At the Alpha Fertility Centre, we are working to be at\u00a0the forefront of preimplantation genetic screening research. We are not a large centre,\u00a0with about 1,100 fresh cycles run last year. What we are\u00a0noticing is that many of the people we see choose to have\u00a0PGS after they receive full counseling regarding the pros\u00a0and cons of such testing; when people are made aware of\u00a0what PGS offers, a majority of them choose it. For example,\u00a0in the last four months, 70% of our participants undergoing\u00a0egg pickup have opted for PGS. That\u2019s very encouraging.<\/p>\n

However, increasing interest comes with several\u00a0challenges. First, there is a lack of awareness around\u00a0the need for preimplantation genetic screening, not just among patients, but among\u00a0many doctors as well. For instance, if I told you that\u00a0among certain age groups, as many as 90% of the eggs\u00a0are chromosomally abnormal, you may not believe me.\u00a0It is difficult for anyone to accept that, including doctors.\u00a0That is a big hurdle to overcome in terms of awareness\u00a0and education.<\/p>\n

A second challenge is ensuring the reliability of results: that\u00a0when we say the embryo is abnormal, it really is abnormal.\u00a0We as clinical researchers are developing a better\u00a0understanding that an abnormal embryo will have a certain\u00a0degree of mosaicism. We now realize that many of these\u00a0embryos actually \u201cself-correct\u201d, resulting in a normal baby.\u00a0While the sensitivity and specificity of PGS technology is\u00a0improving, more work is still being done to help ensure\u00a0healthy outcomes.<\/p>\n

The third challenge I would raise is about cost. As it stands,\u00a0the technology is still fairly expensive. It is not just the\u00a0screening process itself that costs money. In my view, preimplantation genetic screening\u00a0is best implemented in an elective, frozen embryo transfer\u00a0protocol. That too costs additional money and time for the\u00a0patient. So awareness and education, refinements in the\u00a0technology, and cost are three big hurdles that the field still\u00a0needs to address.<\/p>\n

Moving to next-generation sequencing (NGS)<\/h3>\n

Thermo Fisher:<\/strong> You mentioned the sensitivity and\u00a0specificity of PGS technology as a challenge. What are the\u00a0technologies you have used for PGS?<\/p>\n

Lee:<\/strong> We started preimplantation genetic screening\u00a0in 2004, and that time was the era\u00a0of fluorescence in situ hybridization (FISH) and also the era\u00a0where most people did their biopsy on day 3 embryos. Of\u00a0course, we now know the limitations of those two things.\u00a0We then moved on to microarray comparative genomic\u00a0hybridization (CGH). In fact, we were the first in Asia and\u00a0Australia to use microarray CGH with fresh transfer in\u00a02009. We started doing all that when the microarray CGH\u00a0technology became available, which was also in 2009.\u00a0Then, three years ago we moved on to next-generation\u00a0sequencing (NGS) using the Ion Torrent\u2122 system<\/a>.<\/p>\n

Thermo Fisher:<\/strong> What impact has NGS had on your work?<\/p>\n

Lee:<\/strong> Before we switched to NGS, we were using\u00a0microarray CGH, which basically detects aneuploidy\u00a0copy number variation. Many people who require PGS\u00a0present with thalassemia. As such, those cases would\u00a0need another PCR method, typically Sanger sequencing<\/a>.\u00a0Another challenge was that initially they would require two\u00a0biopsies, and we know that has negative effects on the\u00a0viability of the embryo or blastocyst.<\/p>\n

As our understanding grew, we saw the need for increased\u00a0use of preimplantation genetic diagnosis (PGD). That is\u00a0one of the main reasons we chose the Ion Torrent system;<\/a>\u00a0we can do PGS and PGD using a single biopsy sample on\u00a0a single platform. We spare the embryo or the blastocyst a\u00a0double biopsy. It also saves time since these two things are\u00a0done simultaneously. Further, the entire workflow process\u00a0is optimized. In fact, we are now starting to do human\u00a0leukocyte antigen (HLA) typing in addition to PGD and\u00a0PGS\u2014all on the same biopsy sample.<\/p>\n

Thermo Fisher:<\/strong> How did you go about selecting an NGS\u00a0system? What criteria were important to you?<\/p>\n

Lee:<\/strong> First and foremost, I think the reliability of the system\u00a0is critical. So, we looked at the sensitivity and specificity\u00a0to be sure that results obtained are accurate. Another key\u00a0consideration is the cost of setting up the system and not\u00a0just that, the cost to run a sample. We have to align that to\u00a0the number of samples that we expect to run.<\/p>\n

The complexity of using the system, the complexity of the\u00a0machine, the complexity of the labor, and the amount of\u00a0labor that is needed are considerations. Another important\u00a0benchmark that I looked at before we made a decision\u00a0is the flexibility of what this system can do: the capability\u00a0of extending beyond just screening to diagnosis, and as I\u00a0mentioned earlier, the ability to do HLA typing as well.<\/p>\n

One more point is that in addition to copy number\u00a0variations, we also want a system that can tell us about\u00a0chromosomal aberration. Evidence is coming out that\u00a0chromosomal aberrations can also contribute to a failure of\u00a0either implantation or causing early miscarriages. So, when\u00a0I consider buying a system, one of the things to consider\u00a0is whether the system is able to help us in reporting\u00a0chromosomal aberrations because it is something that\u00a0we are gaining a better understanding of now, and will\u00a0continue to research in the years to come.<\/p>\n

Thermo Fisher:<\/strong> What do you like about Ion Torrent NGS?<\/p>\n

Lee:<\/strong> We have been using Ion Torrent NGS<\/a> now for about\u00a0three years. The result are clear. We don\u2019t have many\u00a0ambiguous or questionable results. That is something\u00a0we like. The scalability of the system is good, and as\u00a0our experience with the system increases, so does\u00a0our confidence in the results we obtain. I\u2019m sure that\u00a0confidence is evident when we discuss results. So, the\u00a0volume that we expected to run before we bought the\u00a0Ion Torrent system<\/a> has been far exceeded.<\/p>\n

Flexibility and scalability are important to our lab. Using Ion\u00a0Torrent NGS<\/a>, we\u2019re able to add PGD onto PGS. Recently,\u00a0we\u2019ve been very excited about being able to add HLA\u00a0typing onto the platform as well, so we can get results for\u00a0three things at once.<\/p>\n

Thermo Fisher:<\/strong> How did you implement NGS?<\/p>\n

Lee:<\/strong> We were using microarray CGH and we obviously\u00a0did not stop doing microarray CGH to switch to NGS\u00a0completely. What we did was a sensible thing. We actually\u00a0ran the two systems at the same time, and as we gained\u00a0confidence in the new system, we slowly phased out\u00a0the old one. So today, we have completely phased out\u00a0microarray CGH and we are using NGS exclusively.<\/p>\n

Thermo Fisher:<\/strong> What advantages does the\u00a0Ion ReproSeq\u2122\u00a0PGS Kit<\/a> give you over other methods\u00a0you\u2019ve tried?<\/p>\n

Lee:<\/strong> We compared two methods in the past. For FISH, of\u00a0course, we were using only five probes and occasionally\u00a0more. I don\u2019t think there is really a comparison. And, if you\u00a0look at the microarray CGH, we were very happy with it.\u00a0I think it served our purpose at that time. But as we now\u00a0are experiencing higher volume, NGS in fact is a little bit\u00a0cheaper per sample compared to microarray CGH. And,\u00a0we have made a very important move in the last two\u00a0years; NGS helps us optimize cost per sample in the area\u00a0of elective frozen embryo transfer. Of course, the other\u00a0main advantage is that we were doing PGS, and now we\u00a0are doing both PGS and PGD. As our confidence in the\u00a0technology increases, so too does the number of PGD\u00a0cases we see. Now that we are on more confident footing,\u00a0we can tell people if they have this problem, we may be\u00a0able to help.<\/p>\n

The future of PGS<\/h3>\n

Thermo Fisher:<\/strong> What do you think still needs to be\u00a0done to move our understanding in this field even\u00a0further forward?<\/p>\n

Lee:<\/strong> At this stage, we are able to determine whether an\u00a0embryo is chromosomally, even genetically normal. Yet,\u00a0when we transfer that embryo to the womb, we are not\u00a0able to achieve a 100% pregnancy rate. We are above 80%\u00a0implantation rate with excellent blastocysts in frozen cycles.\u00a0That gap needs to be filled with evolving technologies,\u00a0methodologies, and techniques in the clinic, in the\u00a0laboratory, and in the transfer room. We hope to narrow\u00a0that gap as much as it is possible. I suppose we will never\u00a0reach 100%, but we would certainly want to get very close\u00a0to that.<\/p>\n

Thermo Fisher:<\/strong> What about this work drives you and gives\u00a0you the greatest satisfaction?<\/p>\n

Lee:<\/strong> The bottom line is that we want to see a couple\u00a0having a positive result, which is the delivery of a healthy\u00a0child. And in that process, we want to provide a new\u00a0hope using a new technology, a new form of treatment\u00a0that can give patients success where previously that\u00a0wasn\u2019t achievable.<\/p>\n

Thermo Fisher:<\/strong> How do you think your research will\u00a0impact future generations?<\/p>\n

Lee:<\/strong> One of the things we are doing now is demonstrating\u00a0the potential use of apronuclear (0PN)- and unipronuclear\u00a0(1PN)-derived embryos. Based on our findings, we noticed,\u00a0if the 0PN and 1PN develop into morphologically normal-looking\u00a0embryos or blastocysts (as defined by decent\u00a0quality or morphological assessment using an embryo-grading\u00a0system), these embryos will share similar euploid\u00a0rates as those derived from 2PN embryos. We have already\u00a0published data proving it and will continue to demonstrate\u00a0this with more data. This continuing research will impact\u00a0the basic practice of IVF around the world as 0PN and 1PN\u00a0will no longer be thrown away. This will help to expand the\u00a0opportunities for quite a few people.<\/p>\n

For Research Use Only. Not for use in diagnostic procedures.\u00a0<\/em><\/span><\/p>\n

 <\/p>\n

<\/p>\n

<\/p>\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Dr. Colin Lee Soon Soo is a gynecologist and fertility\u00a0specialist at the Alpha Fertility Centre in Selangor, Malaysia. Dr. Lee\u2019s interest in preimplantation genetic screening\u00a0(PGS) and fertility has led to more than 100 scientific\u00a0publications over the years. The discussion below touches\u00a0on current challenges for in vitro fertilization (IVF) research\u00a0and how Dr. Lee\u2019s team addresses them.<\/p>\n","protected":false},"author":120,"featured_media":11647,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[182],"tags":[23,6,43,74],"division":[],"class_list":{"0":"post-11648","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-reproductive-genomics","8":"tag-ion-reproseq-kit","9":"tag-next-generation-sequencing","10":"tag-pcr","11":"tag-sequencing","12":"entry"},"_selected_authors":"","_selected_reviewers":"","acf":[],"yoast_head":"\nDriving Toward 100% Success Rate in Preimplantation Genetic Screening in Malaysia - Behind the Bench<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.thermofisher.com\/blog\/behindthebench\/driving-toward-100-success-rate-in-preimplantation-genetic-screening-in-malaysia\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Driving Toward 100% Success Rate in Preimplantation Genetic Screening in Malaysia\" \/>\n<meta property=\"og:description\" content=\"Dr. Colin Lee Soon Soo is a gynecologist and fertility\u00a0specialist at the Alpha Fertility Centre in Selangor, Malaysia. 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