2019 VOL. 1
SYNGAMY NEWSLETTER BROUGHT BY ISAR SIG EMBRYOLOGY
WHAT'S INSIDE? HISTORY OF IVF IN INDIA BENCHMARKING FOR INDIA: SURVEY STATS COVER STORY EMBRYOLOGY CONSENSUS CANDID QUESTIONS MY TAKE : GENE EDITING HEALTH OF THE EMBRYOLOGISTS
THE EDITOR'S SEAT EMBRYOLOGY @ INDIA
Its time to consolidate practices..
SPECIAL FEATURE
The Indian Embryology scenario is advancing at a rapid pace, with as many as 50-70 post graduates in clinical embryology entering india every year, it is a great sign for the times to come. This Year ISAR
HEALTH OF
realises the need to focus on embryology, and is doing various events
EMBRYOLOGISTS
centered around embryological practices in the country. With so many IVF centers opening up it becomes important for us embryologists to self regulate our practices. The importance of Documentation and Witnessing is profound in this time. Safeguarding ourselves from litigation is also equally important. The only way forward is practicing ethically and not
SPECIAL FEATURE
overburdening ourselves with work. It is also important for us to keep ourselves updated with the new tech thats coming in our field. One more important topic is Embryologist Burnoutwith long working hours in a constant
SAFEGUARDING
position our health is something that we neglect often, and that can
AGAINST
be catastrophic. Our health directly correlate to our performance in the lab and its something that we should start focussing on.
LITIGATION
The tilte of this newsletter is Syngamy, we constantly aim to achieve the the best outcomes in the laboratory and with this newsletter the aim is to stimulate minds in order to motivate each one to work together in unison, for a more standardised, updated, ethical practice and also to inculcate a sense of self love, so that we stay healthy while we work towards spreading smiles across the country Happy Reading...
Dr. Keshav Malhotra Director Rainbow IVF dr.keshavmalhotra@gmail.com
ABOUT THE SIG This Year the Indian Society of Assisted Reproduction has started 9 Special interest groups in order to create a more focussed environment for discussion and give a platform to showcase standardised pracitces from the country and portay it at the level of the society as well as internationally. The Embryology SIG is chaired by Sudesh Kamat and Co chaired by Vijay kumar chelur and has 9 members in the group - Preeti Trivedi, Prabhakar Singh, Akansha Mishra, Hima Shah, Shilpa bolding, Priya Kannan, Jignasha Chauhan, Sapna Srinivas and Keshav Malhotra.
TOWARDS BETTER PRACTICES, BETTER OUTCOMES BY JAIDEEP MALHOTRA Hello friends, greetings from the president, throughout my years of infertility practice i have come across numerous scenarios where the need for standardisation was evident. The embryologists are the crux of any successful IVF program, but in the current scenario with the lack of embryologists in the country our dependence on batch ivf is quite high. This makes us vulnerable to certain risks in the laboratories which need to be addressed by all of you. The need to document. each and every procedure and get it witnessed is very important, we also have to stay away from external pressures and continue our ethical practices.
SYNGAMY BULLETIN
The main aim of this SIG is to promote standardised practices in the country, we also aim to provide information regarding new technology, evidence based practices, protocols, tips and tricks also we plan to host ssome surveys regarding current practices and those will also be shared with the readers on a timely basis. the group will also design workshops and certificate courses which can be availed by ISAR members and we aim to provide you with our first monogragh on selecting the right embryo by this year.
This years theme for ISAR is towards better practices, better outcomes. With this in mind ISAR has launched a variety of programs for standardising. practices. The most important of them being the Skill certification program scheduled for 2329th September. Here 3 international assessors will certify embryologists on their skill of micro manipulation, virtification and biopsy and this certification will be an important document helping embryologists to procure better jobs in the country.
THE ONLY WAY FORWARD, IF WE ARE GOING TO IMPROVE THE QUALITY OF THE PROFESSION, IS TO GET EVERYBODY INVOLVED. A newsletter is just a step towards reaching out to the masses and motivating them towards one goal, towards better practices in our country which will ultimately lead to better outcomes for our patients. I'm very happy to release this on world embryology day, A day which marks the contribution of embryologists in this field, and i wish everyone working in this field great success, may you be happy, healthy and spread even more happiness throught the country.
COVER STORY ISAR EMBRYOLOGY CONSENSUS PAGE 2
THE UNTOLD HISTORY By Sudesh Kamat, Embryology Chair
The history of IVF in India is debatably as old as the history of IVF itself. Its origin was contested and its subsequent development no less so. dr Mukherjee laid the foundation for assisted conception treatment in India and created the ground on which contests for the legitimate ownership of the first ‘test-tube baby miracle’ were fought.
SUBHASH MUKHOPADHYAY, a Bengali physician from Hazaribagh, Bihar (now
This eminent scientist once mentioned in a journal
in Jharkhand), India, who created the world's second and
on ‘A critique of Mukherjee 's technique, 'The brief
India's first child using in-vitro fertilisation- Durga
description given by Mukherjee in his letter dated 19
(Kanupriya Agarwal), who was born in 1978, just 67 days
October 1978 to the Director of Health Services,
after the first IVF baby in United Kingdom. Unfortunately,
Government of West Bengal, the reports he gave
Dr. Subhash Mukhopadhyay was harassed by the state
over the television interviews and reported in the lay
government and Indian Government and not allowed to
press describe how Mukherjee carried out the
share his achievements with the international scientific
procedure of in vitro fertilisation. On T.C. Anand
community.
Kumar’s initiative, Mukhopahdhyay was mentioned
Facing
social
ostracisation, bureaucratic negligence,
as the architect of the first Indian test tube baby in a
reprimand and insult instead of recognition from the West
document
Bengal government, and refusal of the Government of
intercourse in ICMR. India’s first test tube baby
India to allow him to attend international conferences, he
"Durga", whose parental name is Kanupriya Agarwal,
committed suicide in his Calcutta residence on 19 June
works in a Multinational Company as a Marketing
1981. An insulting silence carried on with every passing
Executive in Delhi. On her 25th birthday she first
day. According to scientific records, Harsha vardhan reddy buri (born 16 August 1986) become the first human test tube baby of India. The credit for this achievement went to T. C. Anand Kumar, Director of IRR (ICMR). In 1997, he went to Kolkata to participate in a Science Congress. It was
there
that
Mukhopadhyay
all
were
the
research
handed
over
documents to
him.
of
After
meticulously scrutinising and having discussions with Durga's parents, he became certain that Mukhopadhyay was the architect of first human test tube baby in India.
related
to
the
subject
of
artificial
exposed her identity in a ceremony organised in the memory of Mukhopahdhyay. She spoke about her creator in front of the media and proved once again that
her
creator's
claim
was
not
bogus.
The
'Dictionary of Medical Biography,’ published by World Foundation, enlists names of 1100 Medical Scientists from 100 countries around the world for their path breaking contributions to the medical science. Dr. Mukhopadhyay's name is one of those names.
SYNGAMY ISAR SIG BULLETIN August 2019 | Vol. 1
BENCHMARKING FOR INDIA
DR. PRABAHKAR SINGH, NIMAAYA, SURAT
QUALITY OR ACCESSABILITY India is a challenging country as far as benchmarking for IVF is concerned. There is a huge sea of difference between the infrastructure and clinical experience among IVF centres in India. Insurance model not prevalent , burden of cost on the patient exists and in trying to reduce costs some amount of compromise on quality does exist. KPIs is a type of performance measurement. Any process ( bio-medical or non bio medical ) can be subject to inherent deviations from the optimum or established units. These deviation may lead to defective end products or in medical field, defective patient care. Published Studies are almost non existent. Information is usually obtained through classes on QC or opinions of authors in text books. KPIs are qualitative and or quantitative assessments that are result of a comparison between an actual value and a target value over specific time periods. The Vienna consensus produced 19 Performance indicators including 12 KPIs and 5 PIs and 2 Reference Indicators in the chart above, which have been accepted generally for most laboratories. We also conducted a survey regarding the same the results of which has been shared. Its important to note that there is a voluntary registry (NARI) which exists for india but very few clinics actually provide their data for this. If we want to improve our practices, we really need to start submitting our data so that we can have a better understanding of which area needs more attention.
SURVEY RESULTS This Survey gave us a lot of insight into infertility practices in the country, and how an indian embryologist thinks regarding Key performance indicators in the laboratory. We were happy to see that not everyone is practicing 100% ICSI, the problem area here is batch IVF, where generally 100% ICSI is the norm. Everyone who participated were keeping a note of polyspery in their lab and thought that <5% was acceptable which is in lieu with the international standards. The ICSI damage rate also being less than 5 % was something which was similar to the Vienna consensus, again happy to note that these were being monitored. The fertilisation rates was where things started to vary, even cleavage and blastocyst development were variable and we did get some over enthusiastic responses. A point to take forward from here was to do monthly audits for at least fertilisation, cleavage, blastulation and implantation rates, and then discuss these with the team, this can be a good team building exercise and can also help in imporving outcomes and mitigating risks.
COVER STORY ISAR EMBRYOLOGY CONSENSUS WRITTEN BY KESHAV MALHOTRA
WHY NOW ??
Over the last few decades Infertility practices in india have regularised, we now have more embryologists in the country who are academically strong and technically sound. The scenario has leaped from one of indifference to a more evidence based approach, which is exactly why now was the best time to consolidate practices and create a consensus amongst key opinion leaders which could be translated amongst the masses. Its also high time we start setting standards for ourselves rather than follow the western world.
MODERATORS
SUDESH KAMAT PANKAJ TALWAR PRIYA KANNAN GAURAV MAJUMDAR KESHAV MALHOTRA RITU HARI
FIRST TIME IN INDIA IVF is a globally adopted technique supporting an extremely lucrative medical industry which has revolutionised human reproduction by offering hope of a family where none existed before. Patients routinely pay large sums of money for treatment and many are willing to try anything that might help them improve their chances of having a baby.The vast majority of IVF clinics want to help their patients achieve this objective as much as possible, which may involve undertaking unproven procedures and tests supported by anecdotal, low quality or unpublished evidence. Most of the evidence which exists, exists for a western pool of population and cannot be applied to the indian scenario. Through this consensus we aimed to combine indian data and come up with practice guidelines and policies to ensure a safer and efficient use of technology in the ART laboratory. This consensus involved a large working group of 40 key opinion leaders, masters in the field of IVF, to discuss on three major areas, Safe and ethical practices in the Laboratory, Add-ons in Embryology and Preimplantation Genetic testing. ISAR curated a team of experts to moderate this consensus with the aim of coming up with a publication for each topic relevant to the indian subcontinent.
"YOU DON’T LEAD BY POINTING AND TELLING PEOPLE SOME PLACE TO GO. YOU
SAFE AND ETHICAL
LEAD BY GOING TO THAT PLACE AND MAKING A CASE."
PRACTICES
This group, the lab falcons as they like to call themselves , have done a fantastic job at making crisp recommendations for establising and standardising laboratories. They also discussed on handling biological material, discarding embryos all the different checklists and consents needed Pankaj sir and priya were superb in moderating the lab falcons and making a great practice document to follow.
PREIMPLANTATION
GENETIC TESTING
PGT is becoming a necessity more than an option now a days, with so many patients falling in the unclear zone of when to opt for an embryo biopsy, we still don’t have a clear cut understanding of which genetic diseases are prevalent or which patients can really benefit from PGT. This group was no less than an Arnab goswami show, with debates arising over each point and kudos to both gaurav and ritu for managing the show so well.
ADD ONS IN IVF
It becomes a very difficult situation for us when we have so many advances and we have hardly any clue of when to use what. Most of us try different modalities which are available which say they can improve outcomes and I’m sure many of us have fallen prey to a few gimmicks as well. The problem is that we don’t have Data, Sudesh sir and me tried to steer this group to a consensus on when to use what, mostly focussing of indications and implications. Our main goal was long term safety of IVF offsprings and that reflects in the document throughout.
CANDID QUESTIONS SWAMINATHAN DAKSHINAMOORTHY, SHRIKANT YATNALE, SUJATA RAMAKRISHNAN, PRIYA KANNAN, SANKET DHUMAL, ATITA SHINDE, PARAG NANDI, NISHAD CHIMOTE
Will they be smarter than a 5th grader. Sometimes in the monotony of our profession we forget that we have a life too, and the balance between profession and personal life is something we all need to create. So here are 8 embryologist in various stages of their career, 16 questions ranging from politics to significant others and the answers will have you in splits.
Asked to choose between date with your partner or your celebrity crush Atita : Akshay Kumar Nishad : Shrikant : Pitna hai kya Priya : i'd rather go out with my girlfriendsSanket : Parag : Shreya Ghoshal Sujata : My partner Swami : Shopping :P
If you were the prime minister If you had the opportunity to leave india and work abroad would you take it ?
Swami : Regulate ART in INDIA Shrikant : ill go for an official world tour Priya : Abolish peeing on the road Sujata : Scrap reservation Atita : Discontinue Reservation (lose the election :P), start merit
Swami : INDIA always Shrikant : yes, Europe Priya: Abroad Sujata : yes, somewhere colder
based priority for higher
Atita : India meri jaan Nishad :yes, only to direct a big chain Sanket : no, i'd like to give back. Parag :India always
education Nishad : subsidize IVF Sanket : women safety Parag : Bill on food Adulteration
A song that describes your love life ? Swami : Tera chehra kitna suhana lagta hai. Shrikant : Tu, tu hai wahi.. Priya: so many !!! Sujata : hehe.. blushes !! Atita : Bavara mann dekhane chala ek Sapna Nishad : Somewhere over the rainbow Sanket : Undiporaadhey from Husharu. Parag : Kora kagaz tha yeh man mera
Do you sing in the shower or dance in the shower
On a scale of 1-10 how important are conference Lectures Swami : 7 Shrikant : 3
Swami : SING
Priya : 10/10
Shrikant : Sing
Sujata : 7
priya : I don't
Atita : 9
Sujata : sing
Nishad : 3
sometimes
Sanket : 7
Atita : Indian idol
Parag : 8/10
Biggest Fear
Nishad : sing Sanket : sing and dance Parag : Sing
likh diya naam uspe tera
If you were to spend one month salary on something ? Atita : roaming the world Swami : Shopping :P Nishad : Travel 100% Shrikant : World tour :p Sanket : go on a vacation Priya : EMI on that last Parag : online shopping, new shopping binge SLR or a mirror less camera Sujata : shop or travel
Swami : Height Shrikant : That i might actually become the PM Priya : being out of work Sujata : Heights Atita : Cockroach Nishad : lab malfunctions Sanket : None Parag : Nuclear war
If you were to be in some other profession what would it be ? Swami : agriculture
Favourite excuse to get out of a tricky situation?
Shrikant : Politics Priya : Intensivist Sujata : im happy
Swami : no excuses, only solutions
Favourite passtime
How much time do you spend on your phone?
Swami : Ghazals
Swami : 13 hrs
Shrikant : Biking
Shrikant : 70%
Priya : Movies
Priya : 2-4 hrs
Sujata : Movies
Sujata : mostly
Atita : Music,
Atita : hardly
cooking
Nishad : 4 hrs on
Nishad : Cooking
baby makers group
Shrikant : ICSI karni hai Priya : im working Sujata : Work is the best excuse for us Atita : bahut traffic hai yaar Nishad : Cases hai yaar Sanket : Girlfriend said no :P Parag : Don't like excuses
Atita : Army/Airforce Nishad : Masterchef Sanket : Something to do with space Parag : Pilot
Sanket : nature treks Sanket : 5 hours Parag : Movies
Have you ever broken a bone ?
Parag : haha next question !!
Swami : No, presidents don't break bones
Dream vacation
Shrikant : Almost Priya : Self yes, others no Sujata : best friends Atita : mine no, other yes Nishad : Nope Sanket :a few hehe !!
Swami : Kashmir
Parag : yes 5th meta tarsal of left foot
Shrikant : Bali Priya :anyplace cold
Movie title to describe your relation with your boss ? Swami : Bade miyan chote miyan Shrikant : Tu anari main Khiladi Priya : The devil wears Prada Sujata : Frozen
Atita : Tom and Jerry Nishad : Whiplash Sanket : Nagarahavu Parag : Yaarana
chennai is too hot Sujata : Machu Pichu Atita : World tour 3 months Nishad : Havana, Cuba Sanket : Madagascar or venice Parag : Switzerland
SYNGAMY ISAR SIG BULLETIN
MY TAKE
GENE EDITING: an insight into the Crispr-cas9 technology.
THE WORRY OF “POSITIVE EUGENICS” OF “DESIRED TRAITS” Classical
textbooks
of
genetics
genetic
diseases
cannot
be
teach
us
treated
that and
management is the only option. However, advances in
genome
research
and
technologies
have
provided us with the options of editing the DNA and provide means to cure genetic diseases. This commentary
is
aimed
to
provide
a
basic
understanding of this technology and the current status of its use in assisted reproduction. Finally, the article will summarize the way forward on the use of genome editing in reproductive medicine. What is genome editing ?
Like in a conventional text editor, one would need tools to identify the errors, cut at the right places and either delete or replace the inappropriate texts in the genome. The molecular tools that are used in genome editor are CRISPR and Cas9. CRISPR stands for
Clustered
Regularly
Interspaced
Short
Palindromic Repeats. The first requirement is a RNA strand that contains the genome alphabets that we may want to edit. This RNA sequence has to be incorporated in a protein called Cas9.
DR. DEEPAK MODI
The RNA
sequence guides the Cas9 and takes it to the specific
locations
where
Cas9
(the
molecular
SCIENTIST E AND HEAD
scissors) cuts at the DNA. As a result, it will either
MOLECULAR AND CELLULAR BIOLOGY
delete the target sequences or allow insertion and
LABORATORY
replacement of the genome alphabets. See
ICMR-NATIONAL INSTITUTE FOR RESEARCH
video
IN REPRODUCTIVE HEALTH
(https://www.broadinstitute.org/research-highlights-
INDIAN COUNCIL OF MEDICAL RESEARCH
crispr) for an animated version of how CRISPR
PAREL, MUMBAI 12
works.
the here
AUGUST 2019, VOL. 1
Applications of genome editing in reproductive medicine Since its original discovery CRISPR, the technology has undergone several modifications with each newer version better over another. The present day CRISPR technology is very precise, robust and highly reproducible. It is now adaptable in most laboratories with relative ease and researchers have used this tool to inactivate genes, edit different parts of genomes and even repair faulty genes to correct genetic diseases in cells gown in lab dishes, worms, flies and even mice. In assisted reproduction, Preimplantation Genetic Testing (PGT) was traditionally introduced to screen out genetically defective embryos which are discarded and normal embryos are offered for transfer. However, it it not more logical and perhaps ethical, to “fix” the abnormal gene rather than allowing an affected embryo to be generated only to be discarded later ? . For this we need to move from Preimplantation Genetic Testing (PGT) to Preimplantation Genetic Correction (PGC). In the last five years researchers have successfully applied CRISPR technology and demonstrated precise genome editing in human embryos (REFS). By injecting the CRISPR, it has been possible to achieve correction of the beta thalassemia mutations, a mutation causing cardiomyopathy and also delete the gene causing HIV entry in to the cells (REFS). Two live births have also been reported of babies who have had their CCR5 gene deleted in the embonic stages and are now supposedly free from any possibility of HIV infection. These are unprecedented feats and we have witnessed a history in making. All these novel studies aimed to have largely address if CRISPR technique can “Repair” every single cell (preventing “mosaicism”) and avoid gene editing at other sites in the genome (rates of “off target effects”) in human embryos. While the technology is evolving and methods being optimized, the results of four major studies published in scientific journals have been quite assuring.
FOLLOWING POINTS NEED TO BE BORNE IN MIND 1) Human embryonic genomes could be successfully edited with minimal to almost no offtarget effects. 2) We yet don’t understand the precise mechanism by which the editing has been achieved inside the embryonic nuclei. 3) The technology is successful (and reliable) only when applied in oocytes just prior to fertilization; trying to edit after fusion of the 2PN is unreliable and leads to mosaic embryos. 4) Before editing, one needs to diagnose which embryos are carrying the mutation.
AUGUST 2019, VOL. 1
Despite these limitations, I see the glass as half full. We have overcome many hurdles and progressed with the the technical dos and don’ts. It’s a matter of time that they will be optimized and the powerful tools of genome edited embryos will be made available in the clinics across the world. Soon we may have clinics that may not just make embryos, but diagnose them and even correct them before initiating the pregnancy. Definitely the realms of an ART clinic will expand beyond fertility treatment. However, concerns have been raised regarding the abuse of CRISPR technology. Should editing of mutations for treatable conditions allowed?
Should we offer gene editing to families that carry
mutations of late onset disease or those that increase the cancer risk but not always cause it (e.g., BRCA1 and breast cancer). The worry of “positive eugenics” of “desired traits” (e.g intelligence, physical appearance) and “social genetics” (HLA matched embryos) is growing amongst the circles of social scientists and bioethicists. Not surprisingly, with the announcement of the Chinese scientists reporting birth of Lulu and Nana (the CCR5 gene edited babies), a section of the scientific and the bioethics fraternity have displayed a knee jerk reaction and called for a total ban on human embryo editing (REFS). In India too, ICMR has imposed a ban on embryonic genome editing until proven safe (REF), however the system is open to discussion when needed. However, the “slippery slope” and “designer baby” concerns that have resurfaced are not unfamiliar to the ART fraternity. These dilemmas and knee jerk reactions have already encountered by us when IVF was first demonstrated and PGT was first applied clinically. As this is a matter of concern. The horrifying stories of Bob Edward and Siddharth Mukherjee are the witness to the hostility the system. Instead of reinventing the wheel each time, lets learn from these examples and not let history
repeat
itself.
Let
us
accept
that
germ
line/embryonic genome editing is a reality and beneficial to the society at large. Banning and pushing it under the carpet with the hope it will die or improve by itself is being immature and definitely not scientific. It will only lead to its further abuse and cause more harm than good. Let’s not the ethics lag the scientific progress. Instead, it’s time to work together and set up the guidelines to define steps that will be required to appropriately use CRISPR technology for clinical use in assisted reproduction. It should be the responsibility of the medical and scientific fraternity to take the appropriate steps and establish progressive guidelines to make sure that the human embryo genome editing is placed in morally responsible hands. Let us not leave it only to the policy makers and a social scientist to make the regulatory guidelines for us and our patients. We are and should be the torch bearers to develop the guidelines and make a positive impact of the genome editing technology for the benefit of mankind. Note: The views expressed in the article are of the author and not necessary of those of ICMR or NIRRH or ISAR.
ARTIFICIAL INTELLIGENCE THE FUTURE OF ART DR.SAYALI KANDARI, DR SANKET DHUMAL
The birth of the first In-vitro Fertilization (IVF) baby in 1978 was a remarkable milestone in the field of human reproductive biology. In the last 40 years, the clinical practice & embryology laboratory has advanced from bell jars to AI driven time-lapse incubators. The Progress of A.R.T: Improved culture media and culture systems, the expanding horizons of IVF including new advances in ICSI, vitrification, morpho-kinetics and lab QA/QC have increased the number of measurable parameters from single digits to thousands of data points with more than 300 key performance indicators and counting (Alpha, ESHRE Good practice guidelines). So the question arises- Is human intervention enough? What is A.I? Artificial intelligence can be classified into three different types of systems: analytical, human-inspired, and humanized artificial intelligence. We deal only with Analytical AI in the field of Reproductive medicine. The prime goal is to allow data collation & real-time analysis of millions of data points. The components of Artificial Intelligence application are: Risk Stratification &amp; Threshold modelling, Machine Learning, Training Phase, Algorithm development, Prediction Analysis, Gold Standard Validation, Next version RS and TM (Point 1) The most recent example is the use of Artificial Intelligence to evaluate risk in Recurrent Miscarriage at ESHRE Annual Meeting 2019, Vienna. Can A.I advance A.R.T? Reproductive experts can determine the best treatment for the individual infertility of patients by incorporating AI and machine learning models (Siristatidis et al. 2016). Infertility patients can be provided with the most appropriate therapy, increasing the successful pregnancy rates and reducing the financial burden. At the social level, unnecessary use of medical resources can be avoided leading to a reduction of health care costs (Senders et al., 2018).
Few AI solutions available are 1. Eeva test, which uses time-lapse imaging microscopy to collect data over the length of the embryoâ&#x20AC;&#x2122;s culture period, and an algorithm to predict which embryo has the best chance of progressing. 2. IVY - in Australia, Aengus Tran and his colleagues have developed an AI that 93% of the time correctly predicts particular embryo progress to the fetal heartbeat. The fully automated system analyzes timelapse video sequences and requires no human input, and thus is not subject to embryologist variability 3. STORK developed by Weill Cornell. USA is not commercially available moreover, current data used INCEPTION IV platform for AI development again, using Time Lapse images. 4. FUTURE FERTILITY is working on developing AI for oocyte quality monitoring, focusing on static and time-lapse 2D imaging. They have plans to integrate Ultrasound imaging and embryo scoring in their algorithm.
Up to two-thirds of patients experience failed cycles- but the hope is now that Artificial Intelligence (AI) systems might be able to flag the most viable embryos. A very recent study from Australia concluded that the agreement between embryologists selecting a single day five embryo for transfer was generally good, Although not optimal, even among experienced embryologists (Storr A et al. Inter-Observer and Intraobserver agreement between embryologists during the selection of a single Day 5 embryo for transfer: a multicenter study(Hum Reprod 2016; 32: 307- 314). Sixteen AI and machine learning (ML) approaches were reported at 2018 annual congresses of the American Society for Reproductive Biology (ASRM) and European Society for Human Reproduction and Embryology (ESHRE). Nearly every aspect of patient care was investigated, including sperm morphology, sperm identification, identification of empty or oocyte-containing follicles, predicting embryo cell stages, predicting blastocyst formation from oocytes, assessing human blastocyst quality, predicting live birth from blastocysts, improving embryo selection, and for developing optimal IVF stimulation protocols. Currently, there are three major categories of AI methods widely used in medical applications: machine learning (ML), natural language processing (NLP), and robotic surgery. The ML method attempts to cluster the features of patients and predict the outcome of diseases by analysing structured data such as medical imaging and genetic data (Darcy et al. 2016).A true AI system uses “deep learning” to refine itself on the fly based on new information. The “learning” in deep learning is achieved through training: hundreds or thousands of data points are fed into the model so that future outcomes can be predicted—and then the predictions are compared against actual outcomes.AI systems for IVF are still in the experimental phase, but the results so far have been promising. Overall, the artificial intelligence system will be having a high percentage of accuracy, catching small details that signalled poor quality embryos human evaluators could not see. AI can be a useful pre-screening tool that would allow us to identify and genetically test only those embryos which are viable, with a low likelihood of genetic defects. This can result in significant cost savings for patients, and also has the potential to improve pregnancy success. A true “end-to-end” AI for infertility care will have to integrate complex (and diverse) datasets that are currently managed in multiple, incompatible systems—patient demographics and medical histories; drug-treatment regimens, pre-implantation genetic screening; and clinical pregnancy outcome data. It would help embryologists and fertility doctors to choose among several treatment options that have the highest success rates, and accept new information based on the patient’s responses to treatments.In clinical embryology, we do not yet know the feature or set of features that are most predictive of IVF success. It is possible that the most important variable for a successful IVF cycle could still be unknown to science but that could in principle be uncovered by an AI system. AI technologies have tremendous potential to help the field of infertility medicine to transcend its current narrow focus on individual embryos and uncover new patterns hidden in the patient data for the treatment of stubborn infertility.
References: 1.Dimitriadis, I. et al. Artificial intelligence-enabled system for embryo classification and selection based on image analysis. Fertil. Steril. 111, e21 (2019). 2.Hardy, T., Feng, J., Lawrence, D., Fullston, T. &amp; Scott, H. Application of Artificial Intelligence To Analysis of The Embryonic Genome For Preimplantation Genetic Diagnosis. Pathology 51, S65 (2019). 3. Rocha, J. C. et al. A Method Based on Artificial Intelligence To Fully Automatize The Evaluation of Bovine Blastocyst Images. Sci. Rep. 7, 1–10 (2017). 4.Siristatidis, C., Pouliakis, A., Chrelias, C. &amp; Kassanos, D. Artificial intelligence in IVF: A need. Syst. Biol. Reprod. Med. 57, 179–185 (2011). 5. Tran, a., Cooke, S., Illingworth, P. J. &amp; Gardner, D. K. Artificial intelligence as a novel approach for embryo selection. Fertil. Steril. 110, e430 (2018). 6. Wang, R. et al. Artificial intelligence in reproductive medicine. Reproduction 1–54 (2019). doi:10.1530/rep-18-0523
Syngamy ISAR SIG BULLETIN August 2019
THE AGE OF AUTOMATION SHOULD I BE HAPPY OR WARY ?
Dr. Krishna Chaitanya Lab Director Oasis Fertiltiy.
It has been a remarkable four decades journey of Assisted Reproduction since the birth of Louis in 1978. The science of ART has emerged from basic science of IVF to gene editing, the success rates have improved from 6% to 60%, however failure is a still a major concern and prediction of successful outcome has been an enigma. Primary goal of ART has been birth of a healthy child, nevertheless the focus also has been to encourage minimal deviation from normal physiology, have minimal side effects from the treatments offered, minimise errors and offer shortest time to pregnancy and last but not the least make the treatments affordable and accessible to all. Automation in IVF lab seems to be one among the efficient ways of minimising the errors and maximising the success rates. There has been tremendous effort in automating the process and this newsletter is a brief overview of the various aspects of automation in human IVF lab.
Syngamy ISAR SIG BULLETIN August 2019
Human errors in ART is a problem !!
Time-lapse monitoring of embryos for their developmental
Automation would only streamline the IVF lab.
with time-lapse technology and also will ensure optimal
dynamics and enhancing embryo selection to optimise the reproductive outcomes has been the latest developments with incubators and embryo selection. Lab on Chip is the concept that scientists have been working hard
which
enables
an
un-disturbed
culture
condition,
continuous supply of nutrients as per the developmental needs of the embryos. Lab on chip also would provide images micro-environment of embryo development. Automation of IVF lab is the way ahead, which would
Equipments are an integral and the most
eliminate
important segment of IVF labs. There has
conditions, optimise gamete and embryo selection to have
been a constant endeavour to automate the
maximum success rates and this in turn would help us
total quality management of these equipments.
accomplish our goal of elective single embryo transfer and
Multiple softwareâ&#x20AC;&#x2122;s are now readily available
birth of healthy live singleton baby.
in
the
market
that
monitor
the
human
error,
offer
un-disturbed
culture
the
microenvironment in the lab and offer a constant watch on the essential elements of IVF
lab.
Semen
analysis,
though
an
important step in starting the fertility journey has the least predictive value to predict the outcomes of ART. Computer Assisted Semen Analysis (CASA), is one of the advancement in semen analysis and helped address the human error and improve the predictive power of
semen
analysis.
Optimising
the
sperm
selection criteria is another important step in optimising the success of ART cycles and there has been a significant improvement in this aspect. MACS, microfluidics, Hyaluronan sperm
biniding
and
IMSI
have
been
the
commonly practiced ones. Invent of polscope
Its human nature to be wary of new things, specially when it
has
of
feels like their integrity would be threatened, but automation
identifying the spindle apparatus during ICSI
has. so many pros that eventually it will be the only way to
and also helped optimise the outcomes of IVM
do IVF. History speaks for itself, we all were sceptics
oocytes
warmed
about cryopreservation, look where we are now, same was
oocytes.Incubators are an essential element in
with PGT and its gaining a lot of acceptance, Automation is
culture systems and there has been a marked
in the same boat, and it can never replace an embryologist.
advancement with the incubators. Continuous
The only thing automation would do is to make IVF safer,
monitoring
now
hopefully. But till its standardised we still have to be vary of
possible with the new generation incubators
it, read : Robot killed patient when it knocked doctor's
which makes troubleshooting more easier.
hand during heart surgery.
helped
automating
and
of
the
process
Vitrified
micro-environment
is
My experience as an young ambassador was very enriching as this made me get completely immersed in scientific sessions. Those three days make you feel responsible because not only you are learning from whatever you listen but its important that you interpret all your learning in an appropriate way and put it in the right manner in front of the entire world. All that you tweet as a young ambassador is posted on the official ESHRE 5 tweeter account and is also retweeted by ESHRE. This puts you on a world platform where even researchers who are delivering the talks in ESHRE, later on, go onto the ESHRE 5 twitter handle and follow you if you are right in tweeting about their talk and may also troll you if you go wrong about tweeting what they said. The programme offers you an opportunity to make friends from all around the globe and brings you in limelight. One of another ambassador alongside me was a senior research scientist working on the application of artificial intelligence in the field of assisted reproduction. Never before this programme had I thought of how artificial intelligence has become an integral part of Human Reproduction and Embryology. Learning something new like this opens up a completely new door to your imagination and brings you closer to the people who are actually working on automation which you might be using in your day to day lab activities. One of the major topic discussed in this ESHRE was how artificial intelligence is
THE ESHRE 5 MY EXPERIENCE
changing our field. Time-Lapse imaging has played a major
NAVAL SHAH
more productive to make the outcome of cycle fruitful. Did
role in our understanding of embryology and with every passing day new software and automation is making it anyone imagine a few years back that an embryologist can sit at home and grade embryos? Now we are one step
As an Embryologist, one always dreams of going
ahead of where we were and even grading will be given by
to a conference like ESHRE which presents the
various algorithms fed in software and Embryologist just
new frontiers of science in front of you every
has to validate those gradings. Topics like, “Is IVF affecting
year
and
Human Evolution?” was also discussed and attended by
symposium
hundreds emphasizing how important was to know the
participants
reality of such Sci-fi perceptions. How many of us had
from over 100 hundred countries every year. As
given major thought on a topic like this! Right from how PN
our ancestors have said that “patience yields
scoring, morula formation time and trophectoderm grading
sweet fruits” my dream came true I didn't only
can predict the potential outcome of IVF cycle to CRISPR
get a chance to visit Vienna in Austria for ESHRE
technology to fresh vs frozen embryo transfer to how poor
2019 but I was also selected as one of the 5
was our world in old days while implementing luteal phase
young ambassadors of ESHRE for 2019. ESHRE
support for better outcome of IVF cycle to different types
selects 5 young ambassadors every year through
of stimulation protocols to PGT to mosaicism to basic
its selection criteria to cover all the scientific
research which still remains core of all the science we are
sessions of the conference.
implementing in our labs everything was discussed in these
in
field
Embryology. attracts
of This
Human
reproduction
awe-inspiring
approximately
10K-12K
three days colossal summit.
DO we need regulation in IVF ? is self regulation enough ? by Rizwan Abid The widespread use of this technology throughout India has prompted a desire by the public, governmental bodies, and professional organisations to create mechanisms that evaluate the utilisation of ART. There is urgent need to embark on a massive nationwide sensitisation and advocacy campaign for proper law that specific focus on the importance of ART service to reinforce the view started by law commission of india. “ART service an asset not a burden”. Why do we need regulation? We all know india is one of the fastest growing market in terms of infertility industry, so to protect patients and their children, to allay public concerns, to protect scientific freedom and to protect IVF practitioners from claims of unethical behaviour we NEED regulation. The regulation should not be limited to paper it should be implemented in real terms by the law bodies. “ONE NATION ONE LAW FOR ART CENTRES”
Regulation if not followed strictly would be of no use. Every state should have one regulatory body to maintain ethics for ART centres. Each state should be cross verified by other national authorities. A voluntary national registry could be a start. We all know the consent form we sign and keep in individual ART centres, All consent form could be filled online (Digital India) easing the pathway to a national registry. Consents should have, Identification number, mobile number, and the Address. After every live birth, centres should update online, Improved laws for mishandling of gametes is required. Surrogacy should not be banned in india, few couples really need and don’t have other option. Rather the selection of patient it should be transparent and should be monitored by state authorities, and a registry for surrogates and donors could also solve this problem. Upper age limit should be fixed for embryo transfer. If couple is in age where they cannot take care of baby, it should not be entertained. we've seen india's image being spoiled by reports of ivf pregnancies in 70 year olds and that is absolutely unethical. Centralised data system for donors like i mentioned should be there, so that professional donors should cannot cheat the ART centres, and vice versa. Doctors and centres should be safeguarded from patient. If patient threat the doctors, strict action should be taken from regulation. Self regulation is not enough because every individual will follow according to his/her convenience which other may not be aware. Surely law and regulation guide for the betterment of society and organisation. It is our responsibility to make law and regulation to follow and make worth of it.
"Science is a beautiful gift to humanity; we should not distort it” – A.P.J. Abdul Kalam
AUGUST 22, 2019
SYNGAMY ISAR SIG BULLETIN AUGUST 2019 | VOL. 1
The
Embryologist
is
a
specialized
reproductive scientist who presides over the fulfillment of infertility treatment in the laboratory for In Vitro Fertilization through the use of assisted reproductive techniques. Embryologist must be knowledgeable in basic life sciences or reproductive biology with in vitro culture techniques & familiar with ART. He/she must be either a medical graduate or a post-graduate
or
a
doctorate
in
an
appropriate area of life sciences. What are the tasks of an Embryologist? The
maintenance
laboratory
to
of
Human
ensure
reproductive
proper
culture
conditions & quality. They perform routine IVF procedures like retrieve, prepare gametes
Embryology as a career
&
produce
embryos
the
responsibility
of
selection & transfer of good quality embryos also lies under the task of embryologist. The
Written by Rahul sen The truth is that the heart of an ART clinic is its laboratory & star of laboratory is an Embryologist. In 1978 the world’s first test tube baby was born, very first reaction to welcome the miracle baby Louise Brown & the men who had worked this explicable mystery, were hailed as heroes. In Vitro Fertilization is rapidly developing field
various
advancements
&
the
research
in
Reproductive biology also falls under their domain With the increasing awareness in human biology last few decades have seen major
breakthrough
not
only
in
better
understanding of the subject but also with incorporation of other fields as Genetics, metabolomics has helped in rapid growth of this specialty. It’s important to remember
that has seen enormous growth in last 20 years & making
that Embryology is still young and a growing
a positive impact on lives of millions of infertile couples.
field.
India sees 150,000-250,000 IVF cycle annually, it is anticipated that it will continue to expand every year. Not only the private setups but also the government sector is now equipped with Assisted Reproductive Technology (ART) facilitates with increasing number of requirements for reproductive specialists will be needed as a result.It became clear from the beginning that the results of ART are not only influenced by the laboratory staff's skills to handle high-tech equipment but also affected by the understanding of human biology. Looking to the complex nature of subject a dedicated person is needed & here comes the role of Embryologist.
"We hope to have a more productive working environment with these recent employee movements and promotions."
DR.SADHANA DESAI ISAR EMBRYOLOGY COURSE
SYNGAMY ISAR SIG BULLETIN
ISAR EMBRYOLOGY COURSE DR. SADHANA DESAI UPDATE DR. VIJAY MANGOLI Considering the fact that there is a need of more trained embryologist in India, ISAR has started training program in embryology. The initiative of the program was taken by Dr.Sadhana Desai - Ex ISAR President & the funds for the same have been generated by her. As per ICMR guidelines, two courses are introduced; Embryologist graduates,
–
who
for wish
science to
post
pursue
graduates their
and
carrier
in
medical assisted
reproductive technology (ART). IVF technician for science graduates. The 13 months course of Embryologist is divided in four parts; 1. Providing detailed theory chapters in 3 modules on various aspects, with online tests for different levels in each Module. 2. A hands on training for two weeks on animal models of practical aspects, at embryology division of Manipal University. 3. 4 months observer-ship cum training at one of the ISAR approved IVF centres, with a logbook of activities to be signed by both candidate and Lab director of the centre. As a token of appreciation Rs.60,000/- is given to centers. 4. A 3 days extensive hands-on training on advanced techniques like Intra Cytoplasmic Sperm Injection in an IVF laboratory that has infrastructure for such training, followed by practical examination at Intermedics, Khar Mumbai.The 8 months course of IVF technician has two parts;
AUGUST 2019
1.Basic necessary theory covered in first Module with test at 4 levels of the Module. 2.And 6 weeks observer-ship cum training at one of the ISAR accredited IVF centres. This is followed by a VIVA examination on technical aspects. The MCQs were prepared by global experts on basic theory chapters provided by Dr. Satish Adiga and his colleagues. The first batch of ISAR embryology training course was started from 1st March, 2015 & 6 candidates were enrolled for the course. It was officially inaugurated by hodling a small function on 1stAugust, 2015 at University campus of Manipal, by Dr R.S.SharmaDeputy Director,(ICMR) in presence of Dr H.Vinod Bhat – Vice Chancellor of Manipal University, & Dr Mrs.Poornima Baliga B - Dean of Kasturba Medical college, Manipal.
Dr. Sadhana Desai Project In-charge Dr. Vijay Mangoli Project Co-ordinator Dr. Jaideep Malhotra President ISAR Chairman of Embryology Mr. Sudesh Kamat Till date 46 candidates have completed the training & currently 14 candidates are undergoing the training.Many ISAR approved Ivf centers have given training to this candidates from all over INDIA & there name are as follows; West Zone: Nirmiti Fertility & Ivf Centre- Dombivli (Dr. S.Krishna Kumar), Corion Fertility Clinic-Mumbai (Dr. Mrs.Kaushal Kadam), Fertility Clinic-Mumbai (Dr. Sadhana Desai), Safal Fertility Foundation-Gujarat (Dr. Kanthi Bansal), Ruby Hall-Pune (Dr.
Sunita
Tandulwadkar),
Nadkarni
21st Century-Gujarat
(Dr.
Purnima
K.Nadkarni), Dr.Lad’s Navjeevan Hospital –Nashik (Dr. Neha Lad & Dr. Nitin Lad), Dr. Nagori’s Institute for Infertility & IVF-Gujarat (Dr. Chaitanya Nagori), Vasundhara Hospital & Fertility Research Center –Rajasthan (Dr. Renu Makwana), Vaunshdhara Clinic & Assisted Conception CentreNagpur (Dr. Rohini Dravid), Nova Pulse Ivf Clinic Ahmedabad Pvt LtdAhmedabad (Dr. Manish Banker), Aakar Ivf Centre-Ghatkopar (Dr. Prakash Trivedi), Adwait Healthcare-Nashik (Dr. Ranjit Joshi) North Zone: Center of IVF & Human Reproduction-Delhi (Dr. Abha Majumdar), Rainbow IVFAgra (Dr. Jaideep Malhotra), Genesis Fertility & Surgical Centre-Jalandhar (Dr. Lakhvinder Singh), Javitri Test Tube Centre Pvt Ltd- Lucknow (Dr. Mrs. Rajul Tyagi) South Zone: GBR Clinic-Fertility Centre-Chennai (Dr. G Buvaneswari), Womens CenterCoimbatore (Dr. Mirudhubashini Govindarajan), Rao Hospital-Coimbatore (Dr. Asha R Rao), Dr.Patil’s Fertility & Endoscopy Clininc- Bengaluru (Dr. Madhuri Patil), Ankur Healthcare Pvt Ltd- Bangalore (Dr. Bina Vasan), Dr.Rama’s Test Tube Baby Center- Bangalore (Dr. Papolu Rama Devi), Gunasheela IVF CentreBangalore (Dr. Devika Gunasheela), GG Hospital- Chennai (Dr. Priya Selvaraj), Bloom Healthcare- Chennai (Dr. Kavitha Gautham), Dr. Rams Institute for Fertility-Telangana (Dr. Papolu Rama Devi) Central Zone: Disha Fertility & Surgical Centre- Indore (Dr. Asha Anil Baxi) East Zone: BIRTH-Kokata (Dr. Gautam Kaustagir)
We thank President, Secretary & members of managing committee – ISAR, for their cooperation & support for last 5 years.
Course Team Dr. Satish Adiga Dr. Pratap Kumar Dr. Keshav Malhotra Mr. Roshan Gaikwad Administrative Officer.
HEALTH OF THE EMBRYOLOGIST DR. RAJVI MEHTA
Embryologists are highly trained laboratory professionals who play an essential part in the diagnosis and treatment of infertility, in preventing the transmission of genetic and infectious diseases and in cryopreservation as part of infertility treatment. Unlike other clinical laboratories, the embryology laboratory presents little automation and requires the performance of numerous manual techniques. This work is associated with physical tiredness due to long periods of microscope and computer work, and may present potential health hazards including injuries from the manipulation of infectious human cells or tissues or of liquid nitrogen. Moreover, the high degree of attention needed during laboratory work in order to avoid errors of potentially severe consequences in the manipulation of samples frequently provokes mental tiredness. Other factors that aggravate this tiredness are the large amount of paperwork required by quality control and traceability systems, the inevitable periods of intense work in the embryology laboratory, the potential to confuse gametes, resulting in major ethical/legal issues, and the extreme unpredictability of the work schedule involved in most embryology laboratories. Staff who work in stressful conditions may feel anxious about themselves, their performance, how they are being treated, and about others. They may cope with these anxieties by means of psychological defences that have a major impact on interpersonal relations and work performance. Currently, one of the most important workrelated problems resulting from stress is burnout syndrome, which has negative consequences both on those who suffer from it and on the organisations for which they work. Last month, mainstream media reported on the mix-up of embryos wherein one couples embryos were transferred to another patient where they implanted and a live birth. The general public seemed scandalised how such an error could happen. As much as the ‘mistake’ seems unpardonable, we, working in the field do agree that such a mistake should not have happened – we do know that such a human error is not essentially due to callousness on the part of the embryologist but could be because of lack of coordination between the clinicians and the embryologist or due to physical and mental fatigue.Imagine the role of an embryologist often sometimes working 6 to 7 days a week, stooping over the microscope – eyes focused sometimes searching for hours at end for that evasive sperm. While one is focusing whether while screening for oocytes, injecting the oocytes or searching for sperms – the posture is always a strain on the neck, lower back and a strain on the eyes. Over the years, these body parts start expressing the discomfort. Add to that the pressure of the work. We cannot deny the fact that there is indeed a stress on the embryologists too… either due to extensive workload or just the pressure to deliver good, healthy, embryos that can lead to healthy babies. A healthy embryologist therefore is not just the one who does not miss a days work because of ill health but one who is physically fit, emotionally balanced to not get affected by the outcomes – which are not always as desired; mentally sharp and alert and clarity in thought to take the right decisions.
James Seary in his last lap.
I will describe a few of the asanas that would be helpful for the embryologists.
Paschim Baddhanguliyasana Stand straight keeping the feet slightly apart but facing the front. If you have good balance, then join the inner edges of the feet. If you feel shaky, then keep the feet slightly apart. Slightly bend your arms at the elbows and interlock the fingers behind your back. Exhale, slightly move the palms away from the trunk and straighten the arms at the elbows. Inhale, raise the head and look straight in the front. Stay in this position with normal breathing for a few seconds. Exhale, release the interlock of the fingers and release the palms. Repeat the asana by changing the interlock of the fingers. i.e, if the side of the left index finger is facing the lower back in your first attempt, then in the second attempt – the side of the right index finger should face the lower back. Stay in this position too for a few seconds.
Gomukhasana Sit cross legs on a folded blanket on the floor or sit erect on a chair. Inhale, and raise the right arm straight up. Take a normal breath. Inhale and extend the arm further up without lifting the right shoulder. Take a normal breath. Turn the right palm and lower arm inwards, keeping the upper arm close to the right ear, exhale and bend the arm at the elbow. Hold the right elbow with your left palm, extend the elbow and gently move the elbow back, so that the shoulder “opens up” further. Stay in this position for 20 to 30 seconds breathing normally. Exhale, straighten the arm at the elbow and bring it down. Do the same action by raising the left arm up and bending it at the elbow.
Bharadvajasana Sit on a folded blanket and extend the legs forward. Sit exactly on the buttock bones. Bend both the legs at the knees and move both the lower legs towards the right buttock. Place the right foot vertically over the left foot which is horizontal. Shift the blanket from underneath the right buttock and place it only underneath the left buttock. Take a few normal breaths. Keep the trunk in the centre and do not let it lean towards the left. Exhale, turn the trunk to the left side without leaning back and hold the left thigh or knee with your right palm. Take a few normal breaths and with every exhalation turn the trunk further to the left. Place the left palm behind the left buttock and also turn the head to look over your left shoulder. Stay in this position with normal breathing for 20 to 30 seconds. Then inhale, turn the head and trunk to the front, release and straighten the legs. Then, do the asana by keeping the feet towards the left.
Baddha Konasana and Supta Baddha Konasana Take a blanket and fold it four times or take a hard pillow. Sit on the pillow or blanket with your legs extended to the front. Exhale, bend the legs at the knees one by one and bring the feet closer to the pubic bone. Take a few normal breaths. Join the soles of the feet with each other. Clasp both the feet with your palms and lift the spine up. Stay in this position breathing normally for as long as you can. You an even sit in this position for 10 to 15 minutes. Then, exhale, release the palms from the feet and straighten the legs.
28th-29th