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Wednesday, October 17, 2012

What can I do if my IVF doctor does not show me photos of my embryos? Why is it important to see and get photos of your embryos when undergoing IVF ?

What is an embryo and how it is formed?

We all began our life as a microscopic embryo.  An embryo is formed when a sperm produced by the male enters into the egg (when the sperm fuses with the egg) which is produced by the female. The sperm carries half of the information (genetic information) needed for creating a baby and the egg carries the remaining information. The sperm’s function is to deliver the genetic information it is carrying in the form of chromosomes to the egg so that a new life can be created. When a sperm successfully delivers the information it is carrying to the egg by entering inside it, an embryo is formed. On the first day of its genesis (formation) an embryo is called a zygote. The process which results in the formation of an embryo is called fertilization and when couples copulate (have sex) they provide their sperm and the egg a chance to meet each other ( this event takes place inside the fallopian tube of the female) which might or might not end in successful fertilization. The life of your baby begins the moment when an embryo is formed. All living organisms develop from an embryo. All babies come from an embryo but not all embryos have the potential to develop into babies.  This is the reason for IVF failure – not all embryos transferred into the uterus implant; and not all the embryos which implant in the uterus continue to grow. In humans, the term ‘embryo’ is used to refer to the new life that is created as a result of fertilization upto the end of the eighth week of pregnancy. After this, the embryo is called a fetus.

The above picture is just a dust particle resting in the ear of a needle. This can be used as a pictorial representation of an embryo’s size. You cannot see an embryo with your naked eye. You need a microscope which could magnify the embryo several times to have a closer look at it.

How does an IVF clinic create embryos?

For couples who fail to conceive naturally (in their bedroom) IVF technique comes as a boon.  When couples undergo IVF treatment their eggs and sperms are brought together in a petri dish (a sterile plate) which contains appropriate fluids to nourish them. The sperm and the egg which normally meet each other in a fallopian tube are thus allowed to meet each other in an artificial laboratory environment and this facilitates fertilization which ultimately results in the formation of an embryo. During ICSI treatment a single sperm is picked up and injected into a single egg –you can call it ‘assisted fertilization’ which in turn , leads to the formation of an embryo. The embryo or embryos which are formed in such a manner are transferred into the uterus usually after 3 days or 5 days of fertilization. The transferred embryos , if they are competent enough and all goes well, implant in the uterus and develop into beautiful babies. So the entire work of an IVF clinic revolves around creating embryos which are good enough to be transferred into the uterus.

How does your doctor decide which embryos should be transferred into your uterus?

Many women produce several eggs when their ovaries are stimulated with hormones and a good IVF clinic will be able to successfully fertilize most of your eggs (provided your egg quality is good) using your husband’s sperm.  As a result couples undergoing IVF will end up with many embryos. It is a well-known fact that not all embryos result in a baby. If this is the case , how does your doctor decide which embryos should be transferred into your uterus?  Just imagine a beauty pageant , where your embryos are the contestants , and your IVF doctor or embryologist is the judge of that beauty contest. The beauty contest judge has a set of rules to rank the embryos according to their external appearance (by observing them under a microscope) so that the most beautiful embryos are selected to enter the ‘sanctum sanctorum’ (your uterus) , where they originally belong. The remaining embryos , which occupy the next ranks , are frozen so that they can be transferred back to your uterus if the current IVF cycle fails. If you want to know how embryos are graded during their beauty contest please visit this link.

What does an embryo look like during different stages of development?

You can see how your embryo appears during its different stages of development by following this link.

Will my IVF clinic show me my embryos?

It is the duty of your IVF clinic to show you ‘YOUR EMBRYO’ before they transfer it into your uterus. You pay so much money to create beautiful embryos and it is their duty to display their embryo creating skills!  Watching your embryos under the microscope will be a wonderful experience. You will finally get a feeling that the entire process is so real and worth the effort. It is also also your duty to know the basics of embryo development (how an embryo looks during its different developmental stage) so that you can ask the embryologist some reasonable questions. This will help you to judge the clinics competence in creating good quality embryos. For example, a good quality embryo will have 2 pronuclei on day 1 (after 18h of fertilization), 4 cells on day 2, and 8 cells on day 3. On day 4 the embryo will start to compact, so that the individual cells are no longer discernible . On day 5,  embryo becomes a blastocyst which contains approximately 100 cells.  The individual cells (called blastomeres) which make up the embryo should be equal in size and should be free of fragments or with minimum amount of fragments. If you know this basic information and study the ‘beautiful’ and ‘ugly’ embryo pictures on the internet, you can very well become the beauty pageant judge yourself ! If your embryos don’t look as good as expected, ask the embryologist for an explanation. This will keep them on their toes to do their duty well and will also help you to understand whether everything is going on properly with your treatment! So never compromise on your right to have a look at your embryos. If you ask your IVF clinic to show your embryos and if they are reluctant to do so , then it should raise a red flag in your mind. Your clinic should provide you with an opportunity to view your embryos. You are the customer and they are working for the money you pay for them. If they say that embryology lab should be sterile and hence you are barred from entering inside – as a biologist I find this excuse too lame! Going inside and watching your embryos under the microscope will not harm your embryos or the sterile environment of an embryology lab!

Should my IVF clinic provide me with the picture of my embryos?

Definitely! Your embryo pictures are your property. Imagine, when you become pregnant after the embryo transfer and give birth to your much desired baby, won’t it be nice to show your child how he/she looked as embryo? How many people will get the chance to do it?  Won’t the baby album look better with the embryo picture in it? Isn’t the embryo your prospective baby? How can you let go of such a beautiful memory just because your clinic does not provide you with the embryo picture? OK, forget the emotional part, what will happen if you do not succeed and plan to switch clinics? The embryo pictures you can give your new IVF doctor will help him understand whether your embryo quality is good or not. This will give him information about whether the problem is with your fertility or with your previous clinic’s ability to create good-quality embryo. This can also help him to decide whether he must tweak your ovary stimulation regime used by the previous IVF clinic. Why should you lose such invaluable information? If your IVF clinic says that taking a picture of your embryo can damage the embryo do not believe them! Taking a photo of your embryo will not damage them or compromise your IVF success!

What should I do if my clinic doesn’t show me my embryos or provide me with my embryo photos?

Do not be afraid to fight for your rights. First request them, and then demand them. If your IVF clinic is not yielding to your demands , submit your demand in the form of writing. Patients should take a proactive role in their treatment so that they are treated with care and respect. IVF clinics should keep your best interest in mind (you are the customers and they are serving you! They depend on you for their survival) and not theirs.  Remember, the most important work of an IVF clinic is  to produce good-quality embryos and it is their duty to provide you with proof that they are able to do so.  After transferring the embryos inside your uterus , nothing you do can improve your chance of success , but getting good quality IVF treatment is in your hands.  The field of ART is growing into a huge business and as a patient it is your responsibility to get the best out of it.  Being knowledgeable about IVF treatment will protect you from less than optimal medical care you might receive in the field of ART.

Tuesday, October 16, 2012

A comparison of CCRM's publication about blastocyst tranfer and blastocyst transfer after Comprehensive Chromosome Screening - are they biased?

I found two different publications of CCRM, one from the year 2000 and it talks about the importance of blastocyst transfer over day 3 embryo transfer. The other publication is a very recent one (2010) where they talk about the supremacy of comprehensive chromosome screening (CCS). Their published implantation rate caught my attention. They showed that when blastocyst transfer was performed they obtained an implantation rate of 70% (in 2000) in their patients and when blastocyst transfer was performed after CCS testing (in 2010) (that is transferring only euploid embryos) they obtained an implantation rate of 68.9%. But in control group where no CCS testing was performed they got only an implantation rate of 44.8% (in 2010). This means CCRM is able to get the same high implantation rate using blastocyst transfer (without performing CCS on them, that is, without selecting for euploid embryos) almost 10 years ago. But in 2010 when they performed blastocyst transfer without CCS (control group) they got only an implantation rate of 44.8%! I hope people get my point!!! So I decided to compare patient selection criteria used in both the studies and found not much difference.
 
2000, CCRM,  PMID: 10856474 ( publication on blastocyst transfer)
 
 
 
 
Patient selection criteria
 
 
FSH ≤ 15 mIU/ml,
age ≤ 45 years
atleast  10 follicles ≥ 12 mm on the day of HCG administration
 
Mean age
 
 
34 years
 
Age range
 
 
25-43
 
Mean number of blastocysts on day 5
 
 
8.6
 
Implantation Rate
 
 
70%
 
No of blastocysts transferred
 
 
2
 
 
 
 
 
 




















2010, CCRM,  PMID: 19939370
( publication on CCS)
 
 
 
 
Patient selection criteria
 
 
FSH  7.3-7.6 mIU/ml , patients with  AMA, RPL and RIA
 
 
Mean age
 
 
37.7 years
 
Age range
 
 
30-43
 
Mean number of blastocysts on day 5 (CCS group)
 
 
6.3
 
Implantation Rate (control group)
Implantation Rate (CCS group)
 
 
44.8%
68.9%
 
No of blastocysts transferred
 
 
2 .7 (control group)
2 (CCS group)
 
 
 
 
 
 























In their 2000 publication they used blastocysts scored using morphological appearance (no selection for chromosomally normal embryos). There is not much information about the patient characteristics (like whether there are patients who underwent recurrent pregnancy loss (RPL) and implantation failure). But definitely there are patients with Advanced Maternal Age (AMA) as evidenced by the age range of patients given in the publication. But nowhere had they mentioned that the above said patients are first time IVFers! So naturally there would have been patients with previous IVF failures. 68 patients underwent 2 blastocyst transfers (top scoring blastocyst).

In 2010 publication where they applied CCS using aCGH to screen embryos, they say they have included patients with AMA, patients who underwent RPL and patients with recurrent IVF failure (RIF) (more than 2 failed IVF cycles!). They had 48 patients in CCS group and their control group consisted of 113 patients undergoing blastocyst transfer in the same center. They say that the patients were matched for age, day 3 FSH, previous unsuccessful attempt etc. But there is no mention whether there are patients with RPL in control group! It must be noted that the day 3 FSH in two groups is very less when compared to day 3 FSH of patients from 2000 paper. They said the selection criteria for including patients for blastocyst transfer (2000 publication) is day 3 FSH 15 mIU/ml. It does imply that they used patients who had FSH upto 15 mIU/ml.

If this is the case how come they got an implantation rate (with fetal heart tone) of 70% in 2000 (the same group and the same author too!) with the transfer of 2 good quality blastocyst and when they performed 3 blastocyst transfer (2.7 mean) in control group in 2010 they are able to achieve only an implantation rate (with fetal heart tone) of only 44.8%. In the CCS group they got an implantation rate of 68.9%. 

Even if they argue that they have included only the difficult patients (as per AMA, RPL and RIF) – the FSH level in patients and the blastocyst formation rate do not show much difference between the patients selected in 2000 and in 2010. Actually in 2010 paper the day 3 FSH level of patients seems to be lower than in 2000! 

The only question in my mind after comparing both their publications is - ARE THEY BIASED? 
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