Metabolomics-Machine Tests IVF Embryo’s Waste to Achieve Pregnancy

Posted on November 17, 2006 by Steven F. Palter, MD

8-cell human embryo from Gold Coast IVF

Next in my series of updates from my visit to the Annual Meeting of the ASRM (American Society for Reproductive Medicine) is a potentially amazing technology to help identify a healthy embryo in a dish. IVF (in vitro fertilization) has become our most powerful toiol to help infertile couples achieve a pregnancy. More than 100,000 procedures are performed each year in the USA alone. We have come so very far since the birth of Louise Brown 30 years ago (she’s a mon herself now). The technology has progressed to the point where getting eggs and sperm and having them joing to make an embryo is no longer the hurdle it one was. However, picking a healthy embryo from the group growing in the dish remains an inexact science. Today this process is based upon morphology. We have a very crude grading system based esentially on the speed of division of the cells and on how regular the cells appear. This yields a rough system with a grade from 1-5. This would be like your doctor looking at you from across the street and estimating if you were healthy. You’ll get correct information only some of the time. Well the powerful new technique of PGS (preimplantation genetic screening) where we biopsy a growing embryo and test its genetics has shown recently that fully 1/2 of apparently good looking embryos are genetically abnormal and incompatible of leading to a living baby.

Metabolomics is the study of the small-molecule metabolite byproducts left behind from cellular processes. In simple terms it’s like examining poop. The concept is that by measuring the collection of all the byproducts of the cells metabolism you can get a snapshot of the physiology of a cell or embryo and that translates to health.

Molecular Biometrics is looking to turn this new science of metabolomics into a noninvasive test to pick the healthy viable embryo from the dish and increase the chances of pregnancy. I know the Medical Director and the President from my days when I was Clinic Chief of Infertility at Yale University and my former fellow is one of their researchers. I spoke with them at length about ther work.

As they say in their press release:

The study was designed to assess embryo viability using a novel technology developed by Molecular Biometrics based on themetabolomic 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 specificiity >85%.

The bigest advantage in addition to increased pregnancy rates would be that if we can identify a healthy embryo destined to implant, then we can put fewer back into the uterus and lower the risk of multiple pregnancies from IVF treatments. Another study found the system could also identify normal vs abnormal sperm. If it is proven to work this would be a breakthrough technology.

Mini Robot Swims Through Body

Posted on November 13, 2006 by Steven F. Palter, MD

Ok I could not resist. I will posting a series of examinations of my vision for the post-endoscopy future. One of the key developments I forsee are miniaturized self-contained imaging (and then terapeutic) robots. Crazy you say! Well an Israeli compnay has just gone one step further towards realization. As medgadget reported

Israel21c interviewed Dr. Moshe Shoham from Haifa’s Technion, who claims the development of a novel propulsion system for a miniature robot, expected at first to swim through cerebrospinal fluid in the central nervous system, and then, possibly, through other fluid-filled cavities for diagnostic purposes.

The Univesity profiles it here.

I just came back from the AAGL 35th Global congress on Gyn Endoscopy where I gave a general session lecture on just this very concept. Fantastic voyage is coming. oday there are pill-cam capsules you swallow. Tomorrow the MArs rover makes a local stop in your gut. Much much more on this topic to come in the next few days….

First Report- DITM Creator Discovers New Cause of Infertility, Company Producing Device for Bleeding

Posted on November 13, 2006 by Steven F. Palter, MD

This is another exciting first for DITM. I previously posted about my award winning research presented on the development of autofluorescent laparoscopy. Now here is information about my latest research just presented at the AAGL 35th Global International Congress on Gyn Endoscopy.

The study was the first human clinical and primate data supporting the development of a new surgical device to treat abnormal uterine bleeding (AUB) It also describes what would be a new form of uterine infertility that forms the basis for the device development. The study consisted of a human clinical case series of women with a rare form of “Asherman’s Syndrome” or intrauterine scarring and a non-human macaque primate model designed to replicate this disease for the first time.

This study represents an amazing opportunity to help women. We have uncovered a potential new form of uterine infertility that would be missed by traditional diagnostic methods. While I am working to cure this uterine condition, A start-up medical company is working to develop these discoveries into a treatment to help women with excessive bleeding. Their device is in human feasibility clinical trials.

Current surgical treatments are primitive because they destroy the entire uterus to stop bleeding. This would represent the first treatment confined to a tiny portion of the uterus that causes it to simply and reversibly shut its own function off. For the diseae of Asherman’s Syndrome this is an important opportunity to better understand what is happening to help cure women with the disease.

In Asherman’s Syndrome, scar tissue forms inside the uterus causing cessation of menstrual bleeding and infertility. It has been believed that the cessation of bleeding is directly due to the scar tissue damaging the normal endometrial lining tissue. I have a large international referral practice of difficult cases of Asherman’s Syndrome and observed that a subset of women with the disorder has a relatively small amount of scarring confined to the opening of the uterus inside the cervix that reflexively causes menses to stop. What was so interesting is that traditional theories say that when the flow of menses out of the uterus is blocked the uterus will fill up with blood- called a hematometria. We found this is not the case at all in this situation. In fact the opposite occurs. The uterus downregulates its lining which “shuts itself off”. The lining become thin and atrophic. We are conducting further studies to define the mechanism by which this occurs.

The clinical findings support the discovery of a new cause of the cessation of menses. There is potentially a milder form of the disorder that would lead to infertility or miscarriage. Any partial impediment to blood flowing freely out of the uterus could lead to a mild form of the uterus shutting itself off.

Noninvasive ultrasound imaging followed by hysteroscopic examination and correction of scarring demonstrated that the entire upper functional portion of the uterine fundus was normal and that the scar was confined to the lower cervical opening only.

We also presented data from a non-human primate study designed to replicate these findings. Monkeys were treated with hormones (estradiol and progesterone) to induce artificial menstrual cycles. The animals underwent focal surgical attachment of the inner uterine surfaces just above the cervix to partially close the uterus. The uterus was then examined after 5 menstrual cycles. The amount of menstruation was recorded and endometrial thickness under the microscope. Menstrual bleeding reduced 77% with some animals having complete absence of menstruation. Endometrial thickness was also significantly reduced. The findings exactly matched out human cases with the disease!

Why This is Significant:

1) Even women who seem “normal” may suffer from a mild form of this newly-discovered cause of infertility

2) This is the first discovery of a disease where the human reproductive system ”shuts itself off” in response to an injury

3) Abnormal heavy menstrual bleeding is a huge problem for women worldwide leading to D&C’s and hysterectomies. A company is working to make the shut off condition into a reversible treatment. This would be the first nondestructive treatment for heavy uterine bleeding.

Thanks to my coauthors on the study: Jim Coad, MD of the Department of Pathology West Virginia University Medical School and Ov Slayden PhD at the Oregon National Primate Regional Center/Oregon Health Sciences University.

DITM Returns from Conferences- Let the Posts Begin!

Posted on November 13, 2006 by Steven F. Palter, MD

VIRTUAL REALITY SURGERY & MILITARY ROBOTS GO MEDICAL

I’ve been a busy little doc the last two weeks. My research on the development of the autofluorescent laparoscope was awarded a prize paper at the SLS (Society of Laparoendoscopic Surgeons), the American Society for Reproductive Medicine (ASRM), and 2 prizes at the AAGL (“Advancing Minimally Invasive Gynecology Worldwide”). I am truly honored by the recognition of my work.

I will be following with posts on all the new technology I saw at these meetings. Miniaturized endoscopes, stem cell research, preimplantation genetic testing, embryo metabolomics, 3D systems, etc.

I also saw incredible prototypes of new devices, tools, robotics, and visualization – will post as soon as the confidentiality restrictions are freed up. Not ready to go to jail! The best stuff was hidden in hotel rooms at the Paris in Vegas and never made it to the light of the exhbit floor…

I am also honored to have been chosen by the AAGL to have delivered the general session lecture on “Future Vision”. This session layed out my vision for the future on minimaly invasive surgery after endoscopy is obsolete. Looking 10+ years into the future I presented a summary of the current developments in minaturized self-contained robots in the body, virtual endoscopy using high power CT scans linked to 3D reconstructing computers, and virtual reality technology to present and manipulate the data. This was a multimedia view of military, computer, and robotic technologies poised to transform medicine as we know it….

The response to the talk was overwhelming and the society is arranging to stream video of it over the net. I will provide links when they go live. Obgyn.net also did a podcast interview with me on this concept of “Future Vision-Technology Transforming Medicine” (links coming).

All coming soon!