However, the sad fact still remains that embryos are not babies. The limitation of our technology is that while we are good at making embryos in vitro , we still cannot predict which embryo will become a baby. This is true for multiple reasons, the primary one being is that while making embryos in the lab is within our control , after we transfer the embryos back into the uterus , we have no control over what will happen next. After the transfer , the embryo then has to implant in the uterus . Implantation is a biological process , which we can try to support with medications but cannot control . This is the reason why most embryos don't end up becoming babies . This is true for fresh embryos and for frozen embryos as well, because they all represent potential babies . Sadly, there’s many a slip twixt the cup and lip, as the old saying goes, and this is a barrier, which we have still not been able to overcome.
If your embryo does not implant and your pregnancy test is negative , this is extremely traumatic , because it represents to death of your dreams - and the loss of what were your potential babies. In fact, some women feel that they have killed their embryos when the IVF cycle fails - while others think that a failed IVF cycle is the same as a miscarriage. Neither of these is true. Human reproduction is an inefficient enterprise - whether the embryo is being made in the lab, or in the bedroom ! Even fertile couples take time to get pregnant when they try on their own, so it's hardly surprising that IVF does not have a 100% success rate either.
The reason most embryos do not become babies is that they have subtle genetic defects, which we still cannot identify. This is nature's defense mechanism coming into play - rather than give birth to an abnormal baby, it prevents the embryo from implanting in the first place !
I completely agree with the overall premise, an embryo is not a baby, but it still stings. We women tend to get madly sentimental!
ReplyDeleteAbout genetic defects preventing the sole cause of preventing the embryo from implanting, that I think is not open and shut. So many embryos that have gross genetic abnormalities, like entire chromosomes missing or added implant just fine. As a scientist, I can't help thinking that a very early failure has more to do with the quality of the cytoplasm of the egg- all the embryo does in the first 8-10 days is divide like crazy and needs a lot of nutrition/factors to keep it going before it gets hooked up to the maternal blood supply. Of course, there are a few key genes involved in the early hatching process etc and defects in these could also prevent reaching implantation stage. Ditto any parallel defects in the mom.
The other possible issue (though I think 3/4ths of the field is not in agreement) is other factors in the uterus-an overactive immune system could most definitely in theory prevent implantation, and there is enough anecdotal data about prednisone/intralipids and IVIG having an effect, to give one pause.
Big grey areas, all in all:)
When we don't have enough data, we all tend to fall back on our prejudices ( if implantation fails, is it the embryo ? or is it the uterus ?)
ReplyDeleteIt's the putative uterine factors which create the most controversy. The anecdotal successes just serve to muddy the waters even more.
It's hard to carry out experimental controlled studies in this area, so it's quite likely the confusion will remain for many years.
Dr Malpani
Dear Dr,
ReplyDeleteAfter undergoing many failed IVFs I used to wonder within myself, ‘what the hell is wrong with me - my egg or my uterus!?’ I personally feel adverse uterine conditions play very little role in preventing implantation, if the embryo is competent enough. It’s true that there exists a cross-talk between the embryo and the uterus which ultimately results in embryo implantation. But the main player in this scenario must be the embryo and not the uterus. If nature has given our uterus the authority to decide whether an embryo should implant and develop then there will be more genetically abnormal embryos implanting and perhaps more genetically abnormal individuals (which obviously is not good from the gene point of view!). But when the decision is taken by an embryo then it is very safe for the humankind because embryo is the one which knows about its own genetic capability (it knows whether it is normal enough to produce a competent baby which can survive all the odds!).
As an analogy consider soil and seed. When a genetically competent seed is placed in soil which provides adequate nutrition, oxygen and moisture it starts to produce shoots and roots, attach to the substrate (soil) and grow. Do seeds always need perfect soil conditions to grow or soil just plays a passive role? Whenever I see a plant growing on crevices in cement wall, when I see them growing in the meagre soil left in between the cement foot paths and when I remember how my dad has to struggle to remove a young banyan plant growing with so much resilience and producing a big crack in one of our compound wall; I am surprised by their ability to survive in such poor conditions. How did the seed that happened to fall on such unfavourable substrate conditions survive and grow? Is it sheer luck? Definitely not! The logical answer is - it is a highly competent seed, genetically!
Why can’t we connect this to human reproduction? Like a genetically competent seed growing in adverse soil conditions, a young, genetically competent embryo will grow in any uterus. It will have the capability to overcome all the adverse uterine conditions. Might be such a competent embryo can even alter the uterus environment according to its need. But what happens when a genetically incompetent embryo is seeded in a uterus which has perfect implantation favouring conditions. It just doesn’t implant or even if it implants it stops growing. This can be the reason why a young woman’s embryo can grow well in an aged woman uterus (for sure an aged uterus is definitely not a better place than a young woman’s uterus!) If all our body parts loose their optimal function with age, will a uterus be unaffected? When I hear that a 70 year old woman successfully grew a baby in her uterus I can’t stop wondering how good the embryo must have been!
In infertility bulletin boards I read about woman who are 40 plus and end up with diagnosis like immune problem. They are advised to take costly treatments like intralipids and IVIG. How could a doctor give such a diagnosis for a woman in her 40s, for her failure to become pregnant via IVF!? I recently read about a woman who underwent several IVFs but everything failed. Her NK cell counts came back very high. Her RE is not a believer of IVIG or intralipids. She later switched to donor eggs and she ended up getting pregnant. What does this incident say? This somehow supports my view that even though there is a problem with uterus, it doesn’t matter as long as the egg is competent enough. I agree that this is a single story or even if I can find few more stories too, nothing can be interpreted. But asking a 45 year old woman to undergo IVIG treatment for her recurrent IVF failure is too illogical and unethical. Actually their main problem is the genetic incompetence of their eggs and those doctors are trying to solve the problem of an aged uterus (perhaps they do not know any costly treatment to reverse egg cell aging!). Of course this approach might work for some (if they are fortunate enough to find the single good embryo to transfer!) but it doesn’t mean that it is the norm.
ReplyDeleteIt’s true that our knowledge about embryo implantation is very limited. Hope in a few decades we would be able to crack some puzzles!
Talk to Me: The Embryo Dictates Gene Expression by the Endometrium.
ReplyDeletehttp://endo.endojournals.org/content/148/9/4170.full.pdf
The Postimplantation Embryo Differentially Regulates
Endometrial Gene Expression and Decidualization
http://www.ansci.wsu.edu/personal/labs/prulab/documents/Postimplantation%20embryo%20differentially%20regulates%20endometrial%20gene%20expression.pdf
In my last FET, my beta hcg at 9dp5dt came back at 6. Does this mean implantation may have occurred? My hpt was positive that same day which was very deceiving. We transferred 2 5AA blasts which visually were perfect. My lining and all was also in good shape. We are confused as there are no answers besides potentially abnormal embryos. But does that mean the remaining 17 from that batch may have the same abnormalities even though they too are 5AA's and 4AAs?
ReplyDeleteA beta HCG of less than 10 miU/ml is negative and means your embryos did not implant, sorry
ReplyDeleteWhy good looking embryos do not implant is still one of those things we do not understand - it is
one of medicine's unsolved mysteries !
Human reproduction is not very efficient ! Don’t forget that even fertile couples take time to make a baby in their bedroom !
Please don't get disheartened - your chances remain good. Sometimes you just need to be
patient until you get lucky !
Thank you Doctor for you response. I had hope that implantation may have occurred but good to get clarity. We transferred 2 more 5AA's on Tuesday (1/29) and I am praying for the best.
ReplyDeleteDoes this mean that minimal levels of HcG is released from the body or the transferred embryo's even though implantation does not occur?
Even men can have HCG levels of 5 mIU/ml ! This is because tests do have their own limits. This is why a level of less than 10 mIU/ml is considered to be negative in clinical practise
ReplyDeleteI am a 39 yr old woman. i have two heathly pregnancies in early to mid 30's. Within the past year, I have miscarried twice in the 6th week...failure to implant. What could cause this? Should I look into fertility treatments?
ReplyDeleteThe commonest reason for a miscarriage is a genetic abnormality in the fetus, and this is Nature's defense mechanism, to prevent the birth of an abnormal baby. While these defects are often random, they are commoner in older women. This is because the eggs of older women have more genetically abnormalities, because they have "aged" and have genetic defects, which cannot be screened for.
ReplyDeleteDr Malpani
Hi Dr,
ReplyDeleteI had uterine artery emboli station in 2006 for fibroids. Later i had two myomectomy, one in may 2012 where they removed 16 fibroids biggest one of 9cm and in march 2013I had to repeat same surgery because one fibroid left behind, started to grow in a way blocking me to get pregnant. This time the RE had chance to look at my tubes and had cut part of my left tube due liuquid accumulation from my previous surgery.he took out one fibroid 5 cm in size and said thing looking better and we go ahead with ivf. I had 30 eggs retrieved of which 18 were mature and 14 got fertilized with ICSI. We had 9 blastocyst and 2 of the best grade were transferred and remaining 7 frozen. But my betahcg test came out negative and now we have todo a frozen cycle. I am not able to find what went wrong after so much pain and effort. What can I do to get positive result in this cycle?
Uterine artery embolisation is not recommended for women who want to have a baby. It blocks uterine blood flow and this can damage the uterine lining and prevent embryos from implanting.
ReplyDeleteCan you send me more details about your IVF cycle ? What were the meds which were used for
superovulation ? What was the dose used ? How many follicles did you grow ? How many eggs were collected ? What was the E2 ( estradiol) level in the blood ? What was the endometrial thickness ?
How many embryos were transferred ?
What was the embryo quality ? DO YOU HAVE PHOTOS OF YOUR EMBRYOS ? You can see what embryos should look like at http://www.drmalpani.com/embryos.htm
Can you please send me the printed treatment summary from your IVF clinic ?
Hi Dr,
ReplyDeleteI just did IVF with a so called healthy embryo (after PGD) and the embryo started to implant and then stopped. What would be the reason it would start and then stop? My hcg was 53 then 49 now 38.
My wife had 12 eggs harvested in ivf. The two best were implanted and I was just informed all the other 10 died. Does that mean the two were implanted are unlikely to survive?
ReplyDeleteThis is very unusual. Embryos don't die like this ! Was this a good lab ?
ReplyDeleteCan you send me more details about your IVF cycle ? What were the meds which were used for
superovulation ? What was the dose used ? How many follicles did you grow ? How many eggs were collected ? What was the E2 ( estradiol) level in the blood at the time of the HCG trigger? What was the endometrial thickness ?
How many embryos were transferred ?
What was the embryo quality ? DO YOU HAVE PHOTOS OF YOUR EMBRYOS ? You can see what embryos should look like at http://www.drmalpani.com/knowledge-center/ivf/embryos
Can you please send me the printed treatment summary from your IVF clinic ?
I'm going to find out and check back with you
ReplyDelete