Why is embryo
selection important in the field of ART ?
Not all embryos which are transferred to the
uterus implant and develop into a healthy baby. This shows that not all embryos
are equal in their developmental competency. Fewer than 2 out of 10 embryos
actually implant. This scenario underlines the importance of embryo selection
before transferring them to the uterus. An ideal IVF cycle would produce a live
birth when a single embryo is transferred to a receptive uterus. But even after
3 decades of IVF invention we are still far away from an ideal IVF cycle. Most
clinics around the world have a success rate of 40-50% per cycle and this means
the chance of failure when undergoing an IVF cycle is higher than the chance of
success. During an IVF cycle several embryos are produced. The embryologist normally
selects the best looking embryo(s) to be transferred to the uterus. The
remaining embryos which are viable are frozen and are transferred to the uterus
during the subsequent IVF attempts. How does an embryologist decide which
embryo(s) should be transferred to the uterus?
There are a set of well-defined rules for selecting the best embryos (the
embryos which are viable and most likely to implant) based on their morphological
appearance under the microscope. Depending on those criteria, embryos are
graded, the best ones are selected and are transferred to the uterus. But this
technique is not fool-proof ! Fifty to sixty percent of the time , even the best
looking embryo (called a top quality embryo, selected based on the embryo
grading rules) fails to achieve a pregnancy. On the other hand, sometimes less
than optimal looking embryos implant and give rise to a healthy baby. If we are able to correctly pin-point which
embryo will implant ( by being able to assess the developmental competency of an
embryo accurately !) and become a baby then the success rate of an IVF cycle
will greatly improve. A good embryo selection technique will be able to reduce
the time taken to achieve a viable pregnancy when undergoing ART, even if it
doesn’t lead to a 100% success rate.
What criteria should a
good embryo selection tool have?
A good embryo selection technique must provide
meaningful (it should be possible to make use of this information in routine
clinical practice), quantitative information and should be non-invasive. It
must be able to differentiate between ‘viable’ and ‘non-viable’ embryos as well
as ‘normal’ and ‘abnormal’ embryos. For example an embryo which is viable need
not always be genetically normal. Many viable embryos implant but fail to
produce an ongoing pregnancy because
they are genetically abnormal . On the other hand , if the embryo is not viable
, then it fails to implant and achieve a pregnancy.
Why don’t all the
embryos produced via IVF implant and develop into a baby?
This is a million-dollar question ! Scientists
are trying hard to decipher this puzzle. As per the present state of our knowledge,
there are two major reasons for the failure of an embryo to implant:
1)
Lack of genetic competency in
embryos
It has been found that 50 – 60 % of
embryos created via IVF are genetically defective. Women of Advanced Maternal
Age (AMA) produce an even higher percentage of genetically abnormal embryos.
Such embryos are called aneuploid. Aneuploid embryos carry an abnormal number
of chromosomes in them. Chromosomes are the structures which carry the genetic information
necessary for creating a healthy baby. Abnormal chromosome number leads to
abnormal genetic content which in turn prevents the ability of an embryo to
implant and develop into a healthy baby.
2)
Lack of receptive endometrium
The endometrial layer ( the uterine
lining) plays an important role in embryo implantation. For the embryo to
implant, a successful cross-talk between the endometrium and the embryo has to
take place. If the endometrium fails to express proteins which are crucial in
assisting embryo implantation, then even if the embryo is genetically competent
, it will fail to implant in the uterus.
So, for an embryo to implant and develop into a
baby, it has to carry accurate genetic information and the endometrium should be
receptive enough to allow it to implant and grow.
What are the methods
which are employed in the field of ART to select the embryo which is more
likely to develop into a baby?
The most widely used method or ‘traditional’ method for embryo
selection is based on assessing the morphological
appearance of an embryo under the microscope (embryos are graded according
to their cell number, amount of fragmentation and cell size). You can learn here
how the embryos are graded according to their morphological appearance. The
bitter truth is that not all ‘perfect’ looking embryos survive in utero and
become a baby. On the other hand, sometimes even the worst looking embryo can
give rise to a beautiful baby. Since looks can be deceiving, as always, there
is a need to develop techniques which could accurately say whether an embryo is
viable and competent enough to develop into a baby or not. At present there are
two new developments which promises to increase the success rate of IVF. The
first one is called comprehensive chromosome screening. This technique screens
all the 23 chromosomes of the embryo for genetic abnormalities and thus
helps in selecting embryos which are genetically normal. Since genetic incompetency
of the embryo is said to be the main reason for IVF failure, this technique
theoretically should improve IVF success rate. But this technique is invasive
by nature and still in its infancy. Further clinical trials are necessary to
determine whether CCS is a panacea or a pipe dream. You can read my blog post about
CCS here.
There is one more recent invention which
promises to increase IVF success rate by improving embryo selection criteria
and this technique is based on time lapse embryo imaging. The instrument which
is used for this purpose is called an EmbryoScope.
What is an EmbryoScope
?
A new technological advance which promises to
improve IVF success rate is an EmbryoScope. It is an incubator (an instrument
which maintains ideal temperature, humidity and proper oxygenation in order to
support the optimal growth of embryos) with a built-in camera which can be used
to monitor the growth of the embryo continuously without the need to remove
them from their cosy culture conditions. The EmbryoScope thus provides a
time-lapse , slow-motion picture of your embryo’s growth, minute by minute.
What information does
an EmbryoScope provide ?
EmbryoScope provides information about an
embryo’s morphokinetics (changes in morphology with time). It can be used to
monitor the embryo’s development , minute by minute , and is capable of
generating several images of embryos growth over a period of time. As a result
an EmbryoScope can give details like - the time taken from fertilization to the
first cell division; time taken to complete first cell division; time period
between the subsequent cell divisions; how
many cells the embryo had at a particular time point; details about the cell
nuclei and so on.
How useful is the information
generated using an EmbryoScope ?
The company which developed the EmbryoScope and
many IVF specialists who own it claim that an EmbryoScope can improve IVF
success rate. It is true that an EmbryoScope generates hundreds of beautiful pictures
of an embryo’s growth. But how useful are these pictures / data in real life ? For example, if an EmbryoScope is programmed
to take pictures of an embryo every five minutes and if the embryo is monitored
continuously for 3 days, then the instrument generates 864 pictures of an
embryo, during its different stages of development. How will these pictures
help in determining an embryo’s developmental competency? The company which
sells the EmbryoScope provides software into which these pictures are fed . The
software then says whether the particular embryo complied with the ‘optimal
cell division rules’ during its development. The key question is – how many randomised
clinical trials ( not sponsored by the manufacturers) have been done to study the utility of
the Embryoscope ? What is the proof that it is better than the ‘traditional’ method
of embryo grading which relies on five or six single conveniently scheduled
observations during its in vitro development ? There are lots of unanswered questions and a
lot more has to be done before someone can claim that EmbryoScope can improve
IVF success.
Will the EmbryoScope
help me in achieving IVF success?
As patients, we should welcome any new
technological advance with utmost caution. Already the field of IVF is plagued
with flawed technologies, flawed analysis and erroneous conclusions which
affect us – the patients. We should not forget that the main aim of the company
which sells this instrument ( and of the IVF clinics which buy this costly instrument ) is to sell this technology and reap a profit. As patients, our
main aim should to get a baby with minimal expenditure. So if you are lured
into selecting an IVF clinic based on their promise to use an EmbryoScope for improving
the IVF outcome , you need to be careful. This is true especially if you have
poor ovarian reserve or if you are a poor responder to IVF drugs and yet the IVF
specialist promises that ‘come to us because we have an EmbryoScope, and can
use it to help you in attaining success’ . The best thing you can do is to
avoid that clinic because this clearly shows that even the IVF specialist is
himself not aware of the limitations of an embryoscope or he just wants to earn
more money. Remember, an EmbryoScope cannot give you more embryos or better
quality embryos. It is just an instrument to select better quality embryos. The
truth is that the selection criteria for embryos using an EmbryoScope are not
well-defined at the present moment. A poor responder normally produces few
embryos and what is the point of subjecting those embryos to monitoring using
an EmbryoScope ? With few embryos , selection often becomes unnecessary because
beggars cannot be choosers, and the doctor has very limited choices in the
first place, because of the paucity of embryos !
At present, the EmbryoScope is a novel
technological advance which might or might not prove to be helpful in improving
IVF success. It is definitely not a magical solution for conceiving a baby via
IVF. Until then , an EmbryoScope is just an instrument which provides beautiful
pictures of your embryos - and if you have to do it for an added cost , it is
definitely not worthwhile to use it!
One thing i wud ask if u can share incidents or feelings abt gud n bad things happen in ur life, if u want to share only then.
ReplyDelete