Questions Flashcards

1
Q

Why do you want to do the MSc in Clinical Embryology?

A

The reason I’d love to study a masters in Clinical Embryology is that this will ultimately help me in pursuing a PhD and thus help me achieve my end goal of becoming a fertility specialist and researcher in the field.

More specifically, the masters would be ideal in providing a theoretical grounding of clinical embryology and related topics including human reproductive biology and fertility. For instance, exploring topics from the processes of gamete formation, fertilisation and early embryonic development, and also what can go wrong in those processes and how ART can help, I think through learning this I will have a deeper understanding of the building blocks of this field which will help me in future studies and also specialisation in fertility medicine.

And I think through the masters I will be able to explore the various areas of clinical embryology, and thus be better informed on which specific area of this field I would like to focus in on and which area I would like to take forwards in my future PhD studies.

Also, this masters will equip me with the necessary practical skills for my future career
– hands-on training, exposure to cutting-edge technologies involved in general research but also specifically in relation to assisted reproductive technologies

Ultimately, my decision to pursue a masters in clinical embryology is driven by my aspiration to become a fertility specialist and researcher and is a crucial stepping stone in that direction.

If its alright with you I’ll answer this question in 3 quick parts - firstly why I’d like to do this masters, then why I’d like to study the topic and lastly why id like to study at Oxford specifically

I would love to do the masters in clinical embryology because ultimately this will help me in pursuing a PhD and thus help me achieve my end goal of becoming a fertility specialist and researcher in the field. More specifically, I think it would give me the theoretical grounding and building blocks of the field and by exploring the different areas of embryology and reproduction, I will be better informed on which topic I would like to focus in on and take on board onto my PhD studies.

The masters will also equip me with the necessary practical skills not only general transferable research skills, but also skills directly related to ART.

Looking into the reason why I would like to study the topic of embryology and related topics including reproductive science and fertility, - I think that working in this field has a huge impact on peoples lives - there are still 1 in 6 people affected by infertility, and not only that but also the effect it has on women in terms of their biological clock and the fact that women still dont have full autonomy to decide when they want to have children - they are still limited by this and this has a prevailing impact on their lives and careers among other things. And I think this is a field in which there is still so much to discover and one that is more recently rapidly evolving, and I really hope to contribute to it in the future.

And finally, I would love to study the course at Oxford because firstly looking at the course itself, I think its great that you start of learning about what should happen normally in reproduction at Michaelmas term, though to Hilary term where you learn about what can go wrong and how art can help and I think building on knowledge like this is great and the fact that you are learning about research skills in ART in tandem with the theory is great to be able to see how the theory applies into practice.
And of course, a big reason for which I wanted to apply to Oxford was the emphasis this course places on the practical skills, such as the use of integrated 3 micro manipulator, or also other vital techniques in Hilary term such as learning about in-vitro maturation.

And not only the course, but also the location is something that really drew me to apply to Oxford - the fact that we are learning by TFP Oxford fertility means we have teaching, research and clinical practice all in the same place and I think as a clinician this is really valuable for me to see how the theory and research applies to clinical practice and I also remember during the virtual open day dr coward saying we could have a chance to speak to the academic doctors which would be a great to give a further insight into career progression and options.

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2
Q

Why do you want to study the masters at Oxford?

A

The masters at Oxford would be ideal because of several reasons.

Firstly, looking at the course itself – it is designed in a way that suits my stage of learning best. The way the modules are laid out starting in Michelmas term where you learn about what should happen normally in reproduction, to hilary term where you look at what can go wrong and how ART can help, — this kind of set up is ideal in building on knowledge and will allow me to gain a solid understanding of the basis of reproduction and development before embarking on the extended lab research project in trinity term.
Not only that but I really like the fact that you develop research and lab skills in tandem with theoretical knowledge in michelmas –And learning these two in parallel I think is excellent in terms of being able to apply the theoretical knowledge to practical research skills, which better prepares students for the research project in trinity term and also to better prepare us for a future research orientated career.

Another aspect of the course that really drew me towards Oxford is the emphasis on the practical lab skills. This was something that I have been really looking to expand as a clinican, for example looking at integra 3 micromanipulator, or also looking into other vital techniques in hilary term such as learning about in-vitro maturation. IVM was first done in the oxford fertility center and it would be absolutely amazing to be in a place where such techniques are being developed.

Aside from the course content itself, the location is another aspect that was very attractive to me. As students, we are learning by TFP oxford fertility – so this is really unique because you have clinical practice, research and education all under one roof and the attachment to TFT means you can see the theory being applied to practice.
It’s great for me because I have the ability to speak to clinicans and attend clinic – this is particularly important for the clinical diagnosis aspect for me as a clinician - but at the same time merging the clinical aspect with the teaching and research which is essential to progress the diagnosis and treatment side of it.
Also, when I attended the virtual open day, I recall that we also have the opportunity to speak to academic doctors Becca and Christy which would be hugely valuable to discuss career options and further steps to take as a scientist practitioner. I think this ability to discuss with specialist and clinicans in the field is a huge advantage of this course for me personally and will give me a further insight into the field and career progression.

And finally, Oxford is a world class institution and I would be honoured to be a part of a community that simulates thinking and progress, and to be taught by such esteemed faculty as yourselves in an area of science that I am really interested in.

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3
Q

Tell us more about the research you did in the kisspeptin lab

A

I worked with the kisspeptin team at imperial under dr abbara and professor dhillo. There were several research projects looking into neuropeptide kisspeptin and its use both diagnostically and therapeutically in infertility.
One of the main areas I was involved in was in the use of kisspeptin in diagnosing the underlying cause of women presenting with menstrual disturbance.
Kisspeptin is a neuropeptide that stimulates GnrH production and thus LH and FSH production.
the two most common causes of anovulation and menstrual disturbance are PCOS and Hypothalamic amenorrhoea. It is found in the literature to be very hard to differentiate between these two causes of amenohrrhoea, and sometimes these conditions can co-exist.

The kisspeptin group had previously shown that women with HA show an exagrerated response to KP compare to eumennorhaic women. we looked at the effects of kisspeptin on the LH and FSH
secretion of women with these two common ovulation disorders and compared them to healthy women.

We found large LH surges in women with HA thus serving as a diagnostic tool for women with underlying menstrual disturbances.

I worked both in the hormonal analysis lab and also in a clinical setting, carrying out patient interviews and blood tests.

I felt completely integrated within the team, and really felt that through my day to day work I was making a direct contribution to such a vital piece of research which can further increase our understanding of the underlying pathophysiology of menstrual disturbances and in general, of disorders affecting fertility.

I think this experience was vital in developing my practical research abilities through operating hormone analysers and other machinery. Importantly, as well, this is when my understanding of this area of research had developed significantly and I was contributing to team research meetings and reading around and exploring the different sub fields of reproductive biology. Through a deeper understanding of the subject area, I was gaining a grasp on the limits of current knowledge.
For instance, reading more about the use of kisspeptin in treating polycystic ovary syndrome, I read about the state of FSH deficiency in pcos and with kisspeptin increasing the surge of LH more than FSH, this can push patients with pcos into more of an FSH deficiency, possibly limiting the use of kisspeptin in restoring folliculogenesis in women with PCOS. A greater knowledge base allows me to understand what we know and what we don’t know and where the gaps for further research are.

direct action via ovarian kisspeptin receptors to suppress the release of VEGF from the ovary and reduce the risk of OHSS

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4
Q

Tell us more about what you did during your Bsc

A

I completed my BSc in neuroscience at Imperial. I worked at the UK dementia research institute and my final research project consisted of evaluating the role of lipid droplet accumulation in diseased microglia, the immune cells of the brain, also referred to as the “policemen of the brain.” We used lipopolysaccharide to replicate neuroinflammation and neurodegeneration in the microglia, and based on previous literature, wanted to see whether there was an increase in lipid droplets in the diseased microglia, in order to understand whether these lipid droplets could be a potential therapeutic target in neurodegenerative diseases.

So I spent the initial six weeks of my research project in the lab culturing the rodent microglia cells. I learned how to split cells and trialled different ways of growing them at optimum conditions and at different cell densities. We used a dye called BODIPY, that attaches to lipid droplets and with the use of fluorescence-activated cell sorting which captures signals depending on wavelength, we were able to quantify the lipid droplets. I learnt how to titrate the dye and carry out several experiments to determine the correct concentration of BODIPY. Through trial and error, and looking at the lipid droplets under fluorescence microscopy, it was identified that the larger the lipid droplet size, the less BODIPY was needed and so the concentration of the dye was adjusted accordingly.
Another part of the experiment was to investigate the effect of translocator protein on lipid droplet accumulation in the microglia - so we used ELISA to to quantify TNF alpha, which is a marker of neuroinflammation - we wanted to identify whether the addition of the translocator protein reduced the neuroinflammation through measurement of TNF alpha.

Once I became more confident with culturing and staining the cells, using the dye and the fluorescence microscope, time keeping and organisation was vital. I had developed a system or rota based on the proliferation rate of the cells in order to analyse the lipid droplet accumulation at different time points of lipopolysaccharide activation as well as the translocator protein addition. I was culturing the cells with many replicates per plate with untreated, lipopolysaccharide and BODIPY dye, and translocator protein with BODIPY dye. I think overall I spent a lot of time figuring out and adjusting my methods through trial and error and I think this process taught me a lot about how you get data and the methods behind data, and realised that if you get data by face value you’re not able to critically evaluate the data.

Alongside the more practical aspects, I was able to analyse the data that came from the FACS – using SPSS statistics and prism to create histograms. Running the flow cytometry data and displaying the data was something that I had to teach myself using tutorial videos. This took some time, but meant I really understood the data and was able to really communicate this in my written report and viva voce.

research skills - culture fix and stain cells - use electron microscopy as well as fluorescence microscopy
use ELISA as well FACS

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5
Q

What do you think makes you well suited to this MSc?

A

I think accepting me into this master’s programme would bring a unique perspective to the master’s community, particularly through my healthcare background.
I believe I would offer my peers a perhaps different view on embryology and reproductive science, looking into the clinician standpoint of the practical process of reproduction and fertility, and how a patient-centred approach to reproductive science and technologies is extremely beneficial.

I think another thing is also my previous research experience - which has equipped me with the necessary tools to undertake this masters programme. I have developed these skills through both my BSc and also during my medical elective where I worked with the reproductive endocrinology team at Imperial in the Charing Cross clinical research facility. I developed my critical analysis and literature search skills through writing up projects, as well as practical wet lab techniques and further developing my communication skills in the form of oral presentations or viva voce. I am also currently working with a member of the reproductive endocrinology team, Dr Abbara, on publishing a paper in endocrinology.

And I also think in terms of my experience, I’ve had quite a varied research experience from my neuroscience BSc to my research experience in reproductive endocrinology and through these two experiences I really gained an appreciation for the importance of a multidisciplinary approach to research, - when I was working with the kisspeptin team I found myself revisiting the hypothalamic pituitary gonadal axis and neural circuitry that I learnt about during my neuroscience BSc. And this really highlighted to me how disciplines merge to advance progress and thinking. And I think this varied knowledge base will allow me to make a good contribution to discussions and the masters community.

Lastly, I am committed to a career in reproductive science and fertility and have plans to take this master’s further by pursuing a PhD alongside specialist training in obstetrics and gynaecology, in the aims of becoming a fertility specialist and scientist.

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6
Q

How will the MSc help with your future career

/what do you want to do in the future with your career?
Describe your dream job in the future

A

So I think firstly, I’ll talk about what I want to do in my future career and then I will speak about how the masters will help me get there.

I want to specialise in obstetrics and gynaecology and become a fertility specialist and scientist practitioner in the field

To get to that end goal, I hope to firstly pursue the masters in Clinical Embryology, after which I would like to apply for an academic clinical fellowship in obstetrics and gynaecology, which I would love to do in Oxford. This is a three year training post which combines specialist training with 25% protected research time. After the 3 year post, you apply to an external funding body to pursue a PhD. And once the PhD ends, you are guaranteed to go back into obstetrics and gynaecology training. After this I can apply for a clinical lectureship position which has a 50/50 split between clinical work and research. And it’s through this academic route I hope to specialist in fertility medicine and become a researcher in the field as well.

Now, the masters at Oxford would help me in pursuing a PhD in the field, and more specifically, it would be ideal in providing a theoretical grounding of the topics and building blocks of reproductive science. And through this theoretical grounding, I will be able to explore the different areas of reproductive and developmental biology, and thus be better informed on which area of reproductive science I would like to focus on and which area I would like to pursue a PhD in.

Practically, I will also be better equipped, in terms of further developing my research skills, including hands on training in ART techniques - which will be vital for further research studies and also for future practice as a fertility specialist.

And not only this, but I will be in a world-renowned institution and be able to delve into research that I have a real interest for.

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7
Q

What is FACS and why did you use fluorescence microscopy?
What were the results?i

A

Fluorescence activated cell sorting is based on the principle that cells can be labelled with fluorescent dyes and sorted according to their fluorescence intensity. FACS is carried out using a flow cytometer, which is a machine that can measure the fluorescence of cells as they pass through a laser beam.
We used fluorescence microscopy in our preliminary work to ensure that the BODIPY dye was staining the cells.
There was approximately a 75% increase in fluorescence intensity from untreated microglia to 24 hour lipopolysaccharide treated microglia.

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8
Q

Where do you see yourself in 5 years time?

A

In five years time, I will hopefully be carrying out my PhD in the field of reproductive science.

To get to this point I will have hopefully completed my masters degree. Following this I hope to apply to an academic clinical fellowship post in obstetrics and gynaecology. This is a three year training post which combines specialist training with 25% protected research time. During the protected time I would essentially be learning research techniques and generating preliminary data towards a research proposal. After the 3 year post, the goal is to apply to an external funding body like the Wellcome Trust for a research training fellowship leading to the PhD.

So the PhD involves 3 years of time out of medical training, but then you are guaranteed to return to training as an ST4 after the PhD. Once an ST4 I can apply for a three year clinical lectureship which has a 50/50 split between clinical work and research.

So in summary - the masters, academic clinical fellowship, PhD and clinical lectureship, are all stepping stones to the end goal of becoming a fertility specialist and scientist practitioner in reproductive science.

To add to this, alongside my medical and research focussed career ambitions, I also hope to integrate teaching in my future career. I have already began integrating teaching in my current practice through my academic foundation programme post in medical education, and I really hope I can continue this in the future. I hope to teach students in subject areas that really excite me and hopefully I can inspire or transfer that enthusiasm onto them, in the same way that my teachers did for me!

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9
Q

Tell me about yourself

A

So I gained a first class honours BSc in Neuroscience at Imperial, after which I completed my MBBS in medicine where I got a merit in Obstetrics and gynaecology as well as in psychiatry. And once I graduated from Imperial I became a junior doctor and now am currently in the second year of the two year foundation programme.

I got accepted into the specialised foundation programme in medical education where I spend 60% of my time clinically in the hospital, and the remaining 40% involves me teaching and also undertaking my postgraduate certificate in medical education.

Now, throughout my undergraduate degrees until now, apart from my pursuit of medicine of course, my other interest are research and teaching.

As examples of research, during my Neuroscience BSc I worked at the UK Dementia Research Institute under Professor Paul Matthews team, where I investigated the role of lipid droplets in diseased microglia, which are the immune cells of the brain, with the goal of identifying whether these lipid droplets could be a therapeutic target in neurodegenerative conditions.

At the end of my MBBS I also had some research experience, and I think throughout my MBBS my interests actually evolved from neuroscience to obstetrics and gynaecology. I carried out my medical elective with the reproductive endocrinology research team at Imperial under professor dhillo and dr Abbara, where we evaluated the use of neuropeptide kisspeptin in diagnosing the underlying cause of women presenting with menstrual disturbances and infertility disorders. Following the time I spent in the lab, I now continue working with Dr Abbara from the kisspeptin team and we are currently in the process of publishing some work in endocrinology.

In terms of teaching, throughout both my MBBS and BSc I was heavily involved in near-peer teaching to younger year medical students, helping them prepare for practical and written examinations. I think my interest in teaching particularly took off when I initiated an online course for students in their fourth year of med school around over 20 med schools in the UK. I delivered fortnightly lectures for students throughout a year. This did take a lot of time and effort, and I even set up a website with resources for students and opened up an online forum where students could discuss questions they had, and every so often I would post new practice paper questions and resources for students to have a look at. It was quite time consuming but honestly was really rewarding to see students engaging and enjoying the teaching and ultimately this raised over £2300 pounds for a charity providing feeding and hygiene equipment for babies living in poverty.
And now I continue teaching and I think my teaching has evolved as an academic foundation trainee in medical education - I deliver teaching daily to the Cambridge medical students, I lead the simulation teaching to the final year students as well, and have started developing an educational project, as well as studying for my pgcert in medical education.

And this summarises my journey so far and what ive been doing the past few years

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10
Q

What are your strengths and weaknesses?

A

weakness: focus too much on one task perfectionist etc. But now through juggling AFP clinical work and teaching and PGCert have learnt to better prioritise tasks etc.

Strengths:
Hardworking, and driven individual and I think I’ve shown that through my previous achievements
I thrive working in a team, I work in a team every day in my career through working with other doctors, nurses, physiotheraists and other members of the multidisciplinary team
I also have good organisational skills that I have developmed throughout my career, especially in research settings in both my bsc and medical elective research experience I have been able to develop this through good record keeping – making sure I keep correct accounts of concentrations and timings of different soluitons

And the other area I think I have developed substantially is the ability to recognise patterns in different areas which I think really relates to a career in research. In my day to day work I use pattern recognition in patient diagnoses, and I think this applies to research where we create patterns and find the pattern between things that initially seem unrelated.

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11
Q

Any questions you have?

A

What would graduates say was the most valuable thing about the masters programme?

How do we choose our research project? What areas are there

I understand that the process for choosing your research project is through a list of projects after which you choose which you rank your choices - is there a possibility of meeting professors and discussing projects with them

And also I saw some examples of publications that MSc students contributed to, and I understand some of the research in the department is relating to improving techniques such as in-vitro maturation - is there any research in this topic that a student has previously done?

do you have any examples on what types of projects have been done by MSc students bef

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12
Q

Why do you want to do research?
What would you like to research?

A

I have wanted to do research for a while and I’ve always thought about the importance of research in advancing thinking and progress in the medical field - without research were not able to improve current diagnostic and management techniques and I’d really like to carry out that research from bench to bedside and take that research into my clinical practice. I also think it allows people to understand more about their academic interests and also ask questions that no one else has asked.

I think specifically looking into research in embryology and fertility, this is a field that is advancing at such a rapid rate and advancing so recently that I would love to be a part of and is a field that is making such a drastic impact on peoples lives - 1 in 6 people are affected by fertility and women still dont have full autonomy to decide when they would like to have children which can affect them both personally and professionally. And so I would really love to advance current technologies in this field.

I think I would love to explore various areas of embryology and reproductive science in order to make an informed decision about what I specifically want to research.
But at the moment I would love to carry out research in methods that improve the safety profile of fertility treatments and reduce burden. I would love to carry on from my research experience with the kisspeptin team at Imperial, where I learnt about the use of kisspeptin in reducing the risk of OHSS.
In my personal and professional life I have seen first hand the burden and impact that fertility treatments can have on a persons life.
During my research experience, alongside the research side of things, I was also involved in the clinical aspect, in which I would speak to patients undergoing the trial, we would take their history, examine and do take their blood samples. I had many amazing conversations with these patients, and many times they would talk about how fantastic it would be to be able to limit the several injections patients had to endure and how this could have such a profound impact on patient lives. They were so grateful to be a part of a trial that would improve the safety of fertility treatments such as IVF and reduce the burden.

I think it would be absolutely amazing to be able to carry on in that line of research, either looking into further ways kisspeptin can be used in fertility treatments, or looking into other techniques such as in-vitro maturation which essentially removes the risk of OHSS - it would be amazing to do this at Oxford where IVM was first performed, and further look into improving this technology.

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13
Q

hy do you want to obstetrics and gynaecology/fertility specialist?

A

I want to pursue a career in obstetrics and gynaecology and become a fertility specialist and researcher because of the impact that working in this field has and the way it can drastically improve peoples lives- reproductive science has a huge impact on people who want to have children and there are still many women and men who can’t have children around 1 in 6 people are affected by infertility. But also the effect it has on women in terms of their biological clock and the fact that women still dont have full autonomy to decide when they want to have children - they are still limited by this and this has a prevailing impact on their lives and careers among other things. And I think this is a field in which there is still so much to discover and more recently has been evolving rapidly, I find it extremely interesting and I hope to go into this area so that hopefully yin the future I am able to contribute to the field of reproductive science and improve current knowledge and technologies that exist to help these women and men.

problem:
there are still many women and men that can’t have children
and women can’t choose when they want to have children
there is still a lot of areas which haven’t been reserched
from the moment I was exposed to this area, research is very recent and knowledge is only growing now, there’s still a lot to be learnt, and I find it really interesting, especial because it has a huge imact on people who want to have children, limited in their biological clock
I want to go into this area sot hat hopefully in the future I am Abel to contribute in this area and improve.

I have both personal and professional reasons for this. Personally, my closest friend was born through IVF when her parents were not able to conceive through other means. I was so intrigued by the process that led to this miracle and began reading about it because I couldn’t quite believe that through a series of steps, it was possible to replicate the process that brings new life. That to me was truly fantastic. I began reading around the subject of IVF to try and get an idea of how this happens.
Professionally, I thoroughly enjoyed my few months in my obstetrics and gynaecology rotation in medical school, and loved the Wednesday teaching by one of the fertility specialists at Imperial, where he would go through different case scenarios and possible treatments for disorders of infertility. I also really enjoyed the new introduction of the reproduction module during my MBBS which was delivered in a highly intuitive format and made me understand the underpinnings of gametogenesis. I hope I can deep dive into this topic further through this masters.

I chose to do my elective in reproductive endocrinology with the kisspeptin team (after reading about a new treatment used in IVF – kisspeptin by Prof Dhillo!). I honestly could not believe I was working under Prof Dhillo’s team and just hearing them talk about new exciting findings during lab meetings or just in the corridors, that was when I really thought that I could see myself doing this. I found a huge sense of reward when I was working in the lab, alongside clinical research, carrying out patient interviews and blood tests. When speaking to these women who we were giving kisspepting and gnrh injections to, they talked to me about how grateful they were that they could be a part of this study to further understand how to improve diagnostic capability as well as management of the various menstrual disturbances and disorders causing infertility. Many of the participants of the trial had quite traumatic experiences through failed IVF cycles and OHSS which can be fatal in some situations. This trial was hope for these women. We were also trialling MVT, which causes a longer hormonal release of LH and acts for longer, which reduces the risk of OHSS but also means fewer injections for the patients, reducing burden. It was great to parallel these two together and directly see how much of an impact we were already having.

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14
Q

Tell me about a recent book/article you have read

A

preconceptions is a book that I have been reading which shares intimate stories about people who have perhaps deviated from the heteronormative nuclear family, and in this book, the author combines reproductive science research and innovations with personal stories to reconsider ideas about parenthood and a new version of the meaning family.

George murdock - nuclear families

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15
Q

ethical issue

A

IVG - genetic modification or selection of embryo or genetic modification of germ cells using crispr
or pre implantation genetic testing on the embryos. - parents choosing embryos even not based on disease - just off preferred genetic traits

somatic cells -> induced pluripotent stem cells -> in vitro gametogenesis into gametes

(premature ovarian failure, pcos, cancer, azoospermia)

determinable genetic and epigenetic aberrations in in vitro-derived gametes and IVG-derived embryos

ynthetic mouse embryos developing organ progenitors such as brain and heart together with complex extra-embryonic compartments could be developed ex utero entirely from murine PSCs

insights to obtain a more comprehensive picture of early mammalian embryogenesis

and with IVG you could technically use a skin cell to produce gametes and an embryo and surely then you’d be able to produce an infinite amount of embryos
IVG could allow same sex couples to have a child

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16
Q

article about cohesion

A

whole genome sequencing on consaguiinous family with inherited premature ovarian failure identified a mutation in STAG3 on chromosome 7 which encodes a meiosis specific subunit of the cohesin ring - with allows for correct sister chromatid cohesion - oocytes arrest at early prophase I.

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17
Q

Human genome editing

A

preimplantation genetic testing can produce off targets

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18
Q

Mitochondrial transfer

A

2015 - law to allow mitochondria transfer — swapping the eggs mitochondrial DNA with healthy mitochondrial dan

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19
Q

14 day rule

A

UK’s Human Fertilisation and Embryology Act 14 day limit
14 day rule on how far in development embryos can be cultivated in the lab
- dates back to 1990
formed synthetic embryos from mouse cells

14 days is when a physical milestone happens which is called the primitive streak when the embryo organises itself from a ball of cells into a definite top back and bottom.

pros: can help us determine what goes wrong in the early stages of development of an embryo - could lead to improvements in IVF success rates and also spina bifida research
IVF success rates is 1 in 4 - often the failure occurs after the second week of development but we know very little about what happens then.
the neural tube closes at week 4 - can look into spina bifida research

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20
Q

AFP project

A

teaching sessions to junior doctors and ward team members on obstetrics and gynae emergencies
and also high fidelity sim that is multidisciplinary involving midwives to help junior doctors and trainees

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21
Q
  • Integrated Foundations of Medical Education
A

Integrated Foundations of Medical Education at Cambridge university - Associate Fellowship of the Higher Education Academy

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22
Q

BSc modules

A

in cellular neurobiology, neurological diseases and pathophysiology and neurodevelopment

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23
Q

critical appraisal surrounding available drug therapies for Alzheimer’s disease

A

meantime vs donepezil and rivastigmine — looking at why therapies directed against a protein called amyloid aren’t working - and the fact that perhaps they are targeting the wrong protein - looking at different studies and their findings and critically appraising them and the methods used in the studies - for instance the fact that most studies use mice models which are not wholly representable of humans.

24
Q

receiving a data set

A

carrying out data analysis that seemed appropriate for instance doing one way ANOVA when trying to determine the impact of an independent on a dependent quantitative variable

25
Q

presentation on psilocybin

A

summary of the study of a study on the effects of psilocybin in treatment resister depression - summary of study and also critical appraisal looking into power calculations, hypothesises, biases
was a non randomised
and proposed varied study that was randomised, with longer term follow up and various psilocybin doses rather than jut one

26
Q

lipid droplets microlgila

A

radical oxygen species in tressed state

27
Q

A Response to Widening Participation in Medicine: The Impact of Medical Student-Led Conferences for Year 12 Pupils

A

looking into a widening participation event led by medical students on the confidence of year 12 pupils applying for med school - looking at the questionnaires they used and different aspects of their conference.

28
Q

univariate and multivariate analysis

A

univariate - looking at histograms of flow cytometry data - the frequency of lipid droplets
multivariate looking at LPS and lipid droplet accumulation

29
Q

recent paper you read

A

paper in CELL:
mamalian oocytes store proteins on cytoplasmic lattices that are needed for early embryonic development

Loss of cytoplasmic lattices leads to reduced levels of maternally supplied proteins and embryogenesis failure

These proteins are needed for epigenetic reprogramming of the embryo

The study used super-resolution light microscopy and electron tomography to show that cytoplasmic lattices are composed of filaments and proteins called PADI6
Mutations in PADI6 genes are causes of infertility
Loss of cytoplasmic lattices by knocking out PADI6 prevents the accumulation of these proteins and results in early embryonic arrest. Performed mass spectrometry analysis of wild type oocytes and of oocytes with knocked out PADI6 gene

30
Q

Describe the curriculum

A

Michaelmas – learn about the reproductive pathways and what should happen normally in reproduction– 5 modules (each module 1-3 weeks) (total 10 weeks) - so you learn about fundamental reproductive science and weave this in with laboratory methods/practical skills - using for eg integrated 3 micro manipulator
Hilary – Applied and clinical aspects where clinical embryologists go through what can go wrong and how ART can help and in which ways it can’t – 5 modules (another 10 weeks)
–10 modules comprise of core content–
Trinity – extended for lab research project - 13 weeks

31
Q

Which assessments?

A

are five summative assessments in total:
* A computer-based multiple choice examination at the end of Michaelmas term.
* An extended essay submitted during Hilary term.
* A short essay written examination in Trinity term.
* A dissertation based on a laboratory research project submitted during the extended Trinity term.
* A viva voce examination, normally conducted in September of the year in which the candidate is examined.

32
Q

Comparative array hybridisation

A

is a molecular cytogenetic technique for the detection of chromosomal copy number changes on a genome wide and high-resolution scale
In a way similar techniques to what I did in BSc with fluorescence labelling - you are using fluorescence to label patient and control DNA and then the microarray detects fluorescence signals – based on colour you see whether there is a mixture of colour, if one overpowers the other there is more or less colour

33
Q

Pathophysiology of hypothalamic amenorrhoea

A

GnRH deficiency - normally the hypothalamus secretes pulsatile GnRH which stimulates the pituitary to produce LH and FSH - in HA this doesn’t happen either due to a functional cause such as low weight, stress and exercise, or due to a structural cause such as a tumour in the hypothalamus

34
Q

More info about kisspeptin research

A

KP causes a higer surge of LH than FSH - makes sense because FSH relies less on GnRH pulsatility as based on the literature

previous work about OHSS - The group treated with KP54 had a
33.6-fold reduced odds ratio for OHSS compared to women receiving hCG

Reason for an exaggerated response is because in hypothalamic amenorrhoea there have been previous studies that have shown a higher expression of KISS1 receptors which means this upregulatio of receptors in GNRH deficiency cause a greater response to kisspeptin as there are more receptors for it to target

The team were doing different research in tandem and the one where I was analysing the blood samples etc was where we were looking at the diagnostic use of kisspeptin
but there were other studies looking at the effect of kisspeptin in oocyte maturation and reduction of OHSS - and they’ve shown that no women actually developed OHSS and they all had PCOS. They were randomly assigned KP

35
Q

if they ask about if you’ve seen any research in the topic of safety of OHSS and in-vitro maturation at Oxford

A

There has been 1 or 2 papers comparing the safety of in-vitro maturation where ovaries are not being stimulated to normal IVF - and the risk of OHSS was lower but the pregnancy rate also lower.

I also saw a paper that is not directly related but looks into IVM and the support cells of the oocytes, the cumulus cells and the effect of these cells in improving IVM rates and reducing the risks of aneuploidy

36
Q

research article

A

listening to fertilpod podcast came across the use of platelet rich plasma in reproduction and read an article about using platelet rich plasma to “rejuvenate oocytes” I think this is so cool because many times we are trying to use ART to treat the problem of fertility, but what if we tackle the actual issue that is then causing the fertility. So we are using this technology to rejuvenate the oocytes, which then allows for fertility- And its amazing because this is a step also towards women being able to have children later if they so wish - one of the reasons I’ve wanted to go into fertility is due to the prevailing impacts we can have on women’s autonomy and control over their own biological clock.

from a non-randomised interventional study involving 83 subfertile women, 46 of whom opted for several infusions of 200 µl of autologous PRP into each ovary, and 37 who opted for no treatment. These two arms were further subdivided into groups who opted for IVF, and those who continued with unassisted conception. Overall, significantly higher antral follicle counts were observed in women who received PRP infusion compared to those women who received no treatment. In addition, embryo quality was scored higher from those obtained through PRP therapy, although there was no difference in the fertilisation rate of oocytes from either group. The authors concluded that ovarian injection of PRP did lead to increased egg yield in subfertile women and prompted changes within the oocyte which may lead to increased ‘quality’ of subsequent embryos

platelets release a range of cytokines which are used in signalling for angiogenesis and is used in folliculogenesis as well
proagniogienc VEGF- PRIMORDIAL FOLLICLES NEED stromal blood vessels and have an increase in VEGF

This non-randomized controlled pilot study compared the effect of PRP versus no intervention upon ovarian reserve parameters in women with low ovarian reserve prior to ART. Our findings showed that a 3-month treatment course with PRP improved ovarian reserve markers when compared with no intervention. In addition, the use of PRP was associated with a significant increase in biochemical and clinical pregnancy rates. Nevertheless, our data revealed no effect of PRP on the rates of oocyte fertilization in IVF/ICSI, miscarriage and live birth.

37
Q

What makes a good researcher?

A

organisation, team work, pattern recognition

38
Q

Any particular topics or research you’d want to do

A

talk about kisspeptin and how you saw the impacts their research was having on women with higher risk of OHSS - and you thought about looking into ways to improve current assisted reproduction techniques- and for example another way to reduce OHSS is IVM - which was founded in Oxford- I would love to research topics in this area of improving safety and reducing risks in fertility treatments

Not long ago systematic review by Dr Child - To determine the effectiveness and safety of hCG priming in subfertile women who are undergoing IVM treatment in the context of assisted reproduction.

no conclusive evidence that hCG priming had an effect on live birth, pregnancy, or miscarriage rates in IVM

Mild-stimulation IVF combined with IVM treatment may represent a viable alternative to the standard treatment.

I think there are many areas of clinical embryology and fertility that I would love to learn more about, which I think the masters will be ideal for.
But if I had to choose one area of research I would love to look into developments in improving safety of current assisted reproductive technologies. Looking back at my research experience with the kisspeptin team, I was looking mainly at the diagnostic use of kisspeptin, but read around the topics of kisspeptin in reducing the risk of OHSS in IVF, and this was something that really interested me , because it would be amazing to be able to reduce the risk of patients undergoing fertility treatments anduce the risk and burden of these women undergoing fertility treatments - aside from kisspeptin, IVM essentially eliminates the risk of OHSS, and is a technique that was first carried out in the Oxford fertility unit. I would love to look into this research further and have seen some work by Dr Timothy child who looks into the use of HCG in IVM.

39
Q

More about IVM

A

In vitro maturation (IVM) is a fertility treatment that involves the transvaginal retrieval of immature oocytes, and their subsequent maturation and fertilisation. Although the live birth rate is lower than conventional in vitro fertilisation (IVF) with ovarian stimulation, it is a useful treatment, as it avoids the risk of ovarian hyperstimulation syndrome (OHSS). Women with polycystic ovaries (PCO) or polycystic ovarian syndrome (PCOS) are at an increased risk of OHSS. Thus, IVM may be a more useful treatment in this patient group.

Strategies to maximise the maturation rates of the immature oocytes are important. This review focuses on the administration of human chorionic gonadotrophin (hCG) prior to immature oocyte retrieval.

During the normal menstrual cycle, a surge in luteinising hormone (LH) triggers oocyte maturation and ovulation. Human chorionic gonadotrophin has a similar structure to LH, and can mimic its biological activity. Therefore, it can be used to promote the start of oocyte maturation, when given as a trigger prior to oocyte retrieval. This is called hCG priming.

40
Q

Kisspeptin and OHSS

A

A randomised controlled study investigated whether the use of kisspeptin as trigger of oocyte maturation could avoid OHSS in 60 women at high a priori risk (defined as total antral follicle count (AFC) of >23 or a serum anti-Müllerian hormone (AMH) level ≥40 pmol/L) (18). This study observed a dose-dependent increase in the mature oocyte yield 53% at 3.2 nmol/kg, 86% at both 6.4 nmol/kg and 9.6 nmol/kg, and 121% at 12.8 nmol/kg (18). The live birth rate per transfer was 45%, and importantly without any clinically significant (moderate or severe) OHSS (18).

OHSS is predominantly an iatrogenic condition that arises due to the aberrant release of vasoactive substances such as vascular endothelial growth factor (VEGF) from the ovary after excessive ovarian stimulation (33). This causes leakage of fluid from the vascular compartment and third-spacing of fluids, for example into the abdomen leading to ascites, or into the lungs causing pleural effusions (19).

41
Q

process of IVF

A

During IVF, a pharmacological dose of a preparation containing follicle stimulating h ormone (FSH) is used to induce multi-follicular growth in the ovaries (7). Thereafter, premature ovulation is prevented either by using a competitive gonadotrophin releasing hormone (GnRH) antagonist, or by chronic administration of a GnRH agonist (GnRHa) to down-regulate pituitary GnRH receptors thereby preventing a premature luteinising hormone (LH) surge This allows follicles the time to grow to the required size whilst avoiding ovulation from occurring prematurely. Once 2-3 follicles of 17-18mm are reached, a hormonal inductor (frequently called the ‘trigger’) of oocyte maturation is used to provide the LH-like exposure needed to mature the oocytes and enable their surgical retrieval. Oocyte maturation refers to the process by which oocytes gain competence for fertilisation by sperm as they traverse from the metaphase I to the metaphase II stage of development by extruding half of their genetic material as the polar body (which is used to identify that successful nuclear oocyte maturation has occurred

GnRHa shorter half life than HCG less effect but the less LH can hamper pregnancy rates

hCG is the most widely used ‘ovarian trigger’ to induce oocyte maturation. Unfortunately, it is also the most frequent cause of OHSS secondary to its long half-life, potent LH receptor activity and long duration of intracellular effect (5). GnRHa is used as an alternative agent particularly in females deemed ‘high risk for OHSS’ however implantation rates have been reported as lower due to luteal phase insufficiency. A small dose of hCG is sometimes used to rescue the luteal phase insufficiency, however this approach can also increase the rate of OHSS

Kisspeptin is part of the physiological mechanism for instigating ovulation (12), and induces LH levels of an amplitude more similar to that of the natural midcycle LH surge than by currently available triggers

future- direct comparison with other methods
kisspeptin regulates the activity of GnRH neurons in the hypothalamus and thus the downstream hypothalamo-pituitary-gonadal axis

42
Q

more about BSc project

A

The translocator protein (TSPO) is an outer mitochondrial membrane protein that is widely used as a biomarker of neuroinflammation, being markedly upregulated in activated microglia in a range of brain pathologies – so wanted to see whether this protein would increase lipid droplets because microglia are activated and also measured TNFa

43
Q

Univaraate and multivariate with binary logistic regression

A

Univarate looking at the range of lipid droplets and median etc. of the lipid droplets in each time point - looking at it through the histogram

cluster analysis was an example of multivariate where we are grouping different objects based on characteristics so with flow cytometry we were grouping lipid droplets vs other particles.

binary logistic regression is used to see whether there will be an increase or not in lipid droplets with lips

44
Q

Flowjo software for facs data

A
45
Q

grids meaning using electron microscopy to count cells using a haemocytometer

A

cell culture media +. trypsin from fridge and place in incubator to warm

Look at cells to be counted under elecontr microscope to check for bacteria

Suspension cells - agitating flask to ensure cells well mixed
take sample and pittpet into epindorf tube
Wash with PBS (prevents osmosis) and add trypsin EDTA to detach the cells
adequate volumes of PBS and trypsin
incubate the cells
give growth media to neutralise the cells
resuspend the cells, and transfer into tube, centrifuge the cell suspension
remove supernatant using pipette and resuspend with growth media
transfer a bit to epindorf
add trypan blue – drop into well of counting chamber to count the cells in haemocytomeer - inverted microscope - focus on 4x4 grids and count cells that are negative for trypan blue

46
Q

Hayashi IVG

A
47
Q

assessment

A

A computer-based multiple choice examination at the end of Michaelmas term.
An extended essay submitted during Hilary term.
A short essay written examination in Trinity term.
A dissertation based on a laboratory research project submitted during the extended Trinity term.
A viva voce examination, normally conducted in September of the year in which the candidate is examined.

48
Q

ethical approval

A

applying to a research ethics committee

49
Q

Jesus college

A

Jesus College was one of the first men’s colleges to admit women, in 1974, but nowadays, our student intake is evenly balanced between men and women

50
Q

NGS can sequence hundreds and thousands of genes or whole genome in a short period of time.

A
51
Q

Gardner and Veeck grading systems - embryo grading - development and potential for implantation

A
52
Q

time lapse imaging of embryo

A
53
Q

Unlike egg and embryo freezing where it is necessary to stimulate a menstrual cycle and so can take a few weeks to complete, ovarian tissue freezing can be performed at very short notice

A
54
Q

flow cytometry

A

difference is that FACS isolates the particles whereas flow cytometry only separates them
forward scatter indicates cell size
side scatter indicates granularity

55
Q

ISO

A

quality management system