October 13, 2010 Blog Post
Most fertility treatment focuses pretty intently upon the sperm and the egg. Unmistakably, these are essential factors in initiating a pregnancy. But even the best quality embryos cannot survive more than 7 days outside of the womb. Therefore, a healthy uterus is an essential bridge between conception and delivery. In fact, more recent studies suggest that even impaired implantation can result in a pregnancy but one that may be fated to problems avoidable complications. So taking steps to optimize uterine receptivity—the term used to describe how inviting the environment is for the embryo—represent a critical link to take full advantage of your fertility treatment.
Since many fertility treatment centers don’t focus on uterine issues, it is uncertain what percentage of patient’s have a “uterine factor” as their sole obstacle to conception. However, most centers do use ultrasound to measure the endometrial thickness as an estimate of receptive the woman’s uterus is to implantation. In a seminal paper [G1] published in the journal Human Reproduction in 1991, Dr. Geoffrey Sher demonstrated that when this thickness was less than 9 mm, the chance for a successful pregnancy was dramatically reduced—typically to less than 10%. He later went on to demonstrate [G2] that for many women (~70% in our clinic) this failure of endometrial receptivity is due to poor blood flow. This identified a treatable problem that can potentially be reversed with the use of well-known erectile dysfunction drug name Viagra. By implementing the Viagra Protocol, we have been able help many women successfully carry their own pregnancy even when they had previously been told that this was not possible. Even with a thick enough endometrial lining, some additional attention to receptivity may be warranted.
Multiple studies [G3] have demonstrated that the medications used to optimize egg development can cause a hormone imbalance that interferes with endometrial receptiveness. In fact, some studies [G4] suggest that the very high estrogen levels often associated with IVF cycles may have a negative impact upon implantation even while promoting the number of embryos produced. Various strategies have been created to overcome these obstacles and since there is no simple answer, I feel that it is best to inform patients and offer them options when creating a treatment plan. Here’s what you should consider when you discuss this with your doctor:
- Ask about your endometrial thickness. If it is less than 9 mm, discuss the possibility of freezing your embryos and/or consider the Viagra Protocol.
- Talk to your doctor about your highest estrogen level. If it was above 3500 pg/mL discuss whether or not it may be in your best interest to freeze all of your embryos. Doing so may not only improve implantation but can also reduce your risk of developing Ovarian Hyperstimulation Syndrome (OHSS).
- Consider the use of a steroid. There have been several studies that demonstrate that various forms of the hormone called cortisol, can off-set the impact the impact estrogen has upon your immune system. The end result may be a greater chance that your immune cells will welcome an embryo and foster its implantation.
- Request “luteal support” through the use of progesterone. The process of IVF can reduce implantation unless steps are taken to support implantation. Whether it is because of an imbalance between estrogen and progesterone, residual effects of medications used to block ovulation or due to a loss of hormone producing cells at the time of egg retrieval remains a subject of debate. But it is pretty widely accepted [G5] that the use of progesterone helps improve your chances of becoming pregnant. Which form of progesterone to use (injections, pills or suppositories) and how long [G6] to use it for are another topic that can/should be tailored to your unique situation.
Enhancing Fertility 
Dear Dr Greene,
During my last (2nd) IVF ICSI cycle, my endo thickness was 19mm during ET. It was very thick. Two blasts transferred did not implant. After my period came, my RE did a Day 2 scan for me and the lining was back 3-4mm. He was concerned if there was some polyp for that thick lining but said all was fine. He had also done a hysteroscopy last December, all fine except a tiny polyp which he removed. Is a lining that thick of any concern to you at all?
My E2 level was 5328 right before my egg retrieval. I had 11 eggs retrieved. I saw that you mentioned if it goes above 3500 to have embryos frozen instead. If that high level was a concern, I wonder why my RE did not highlight it to me. I always thought the higher E2 the better until I read your blog. I thought E2 level just coincides with folicle growth and numbers? Is too high something to be very concerned about??
Also, you mentioned about using cortisols, are they immunosuppressants? Are they antibiotics? Are predisolone and dexamethosone examples of them? Just want to clarify what sort of medications they are.
Thanks!
Dear mum2oneds,
More of something good is not always better. What I try to stress in my practice–based upon both my experience and the published research–is that biology is typically about balance. There is significant data that if the E2 level gets too high and peaks too early, it can create changes in the endometrium that may decrease the chance of successful implantation. Estrogen needs to be balanced against progesterone and various other hormones. Keep in mind that this is not an absolute fact. There have been many studies (and I have seen several patients) become pregnant with very high E2 levels. However, that situation is less than ideal. Hope this explanation helps.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Dear Dr Greene,
Yes your explanation helps! Thank you so much. I would want to ask my RE about it now because he did not even went into this with me. I was the one who requested my nurse to post the reports to me and brought it along to see him. The IVF facility and my RE are in two different locations as my RE is an OB with his own private practice but he treats IVF patients.
And when I saw him, I was ignorant about the E2 and thought it was great level. He did not even show me any report, nothing at all except a brief summary! If I did not request for the blood & embryo reports or our embryo pictures or scan results, my RE has only that pathetic brief summary and would only use that to see us. I cannot believe how superficial they can get.
Thank you so much!
Hi Dr Greene,
I noticed you mentioned about progesterone. When I had my IVF my progesterone was never monitored. Do you monitor P4 level in your IVF patients? Can I know if there is such thing as too high a level of this hormone that can cause implantation failure? Or is it always a too low a level that causes problem, rather than being too high? Thanks!
Dear mum2oneds,
Progesterone levels can be helpful but they are not always necessary. If you are using a vaginal progesterone supplementation (like Crinone or Endometrin) then measuring your blood level is not necessary. These products have been so thoroughly tested and their absorption has been so well documented that it is not required. If you are using compounded progesterone (like the “progesterone in oil” injections) then I feel that measuring the progesterone level can be very informative. Regardless of which method you are using; there is no data having a high progesterone level can be detrimental to the outcome of your cycle. It is simply important to make certain that you have enough progesterone to support implantation and initial development. Hope this information is helpful and reassuring to you.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Dear Dr Greene, yes very helpful! Thank you so much!
How do you thicken the uterine wall????
Please check out the following blog post: http://bit.ly/alKvl5
Best thoughts,
~Robert
Robert Greene, MD, FACOG
A lot of helpful information here. Thank you for posting. I do have some questions. I just had a failed IVF cycle. My Dr transfered two embryos on day three. I questioned why they don’t wait until day five for a higher success rate. I only had five eggs fertilize and in case i didn’t have any make it to freeze status they wanted to get the two best ones back in my uterus. I had a lot of discomfort after retrieval and I was wondering if the swelling of my ovaries and the pain I was in assisted in the failed IVF?
I was on the protocol of crinone in the morning and estridol three times a day. I rested the day of transfer and the next day. I went back to work after that on light duty. I do a lot of walking, some stairs and light lifting. I experienced nausea and pressure for two days and then nothing. I could tell it didn’t work by day five after transfer. We did get two embryos that reached freeze status. If we do transfer again, will taking it easy for longer help?
I do not remember them saying anything about my uterus other than “it looks good” or what my E2 level was. I hope I can get that information from them still.
One last question…we might want to use a different dr if we transfer again. Do we own the embryos and is it ok to do that?
Thank you for being here!
Dear Jilly20,
Thank you for your kind comments. I am so glad that you have found this blog to be helpful. Unfortunately, it is set up as an information site. I am not able to give specific medical advice. There are so many variables involved with each of the decisions/recommendations that you outline that it would be unfair to both you and your current provider. Worse still, without access to the details of your case, I might provide you with misguided advice. I would encourage you to present these same questions to your doctor. If you find that you are not satisfied with their response then you should seek a second opinion. You might find that the perspective of another provider will reinforce the original recommendation or it may provide you with another route for pursuing treatment. Either way, you will come away feeling empowered. Does this make sense? If you do have any general questions about the diagnosis of or treatment of fertility problems; I will gladly respond. If you’d like to set up a consultation, we can arrange that as well. Whatever you do, you should not proceed until you are comfortable with the path that you choose to pursue.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Dear Dr Greene,
I am half way through my ivf process and my scan this morning show the endometrium (uterus?) blood flow was not good and they do not think they should put the egg’s back in this cycle. I have responded well to the drugs and they say i have a very could cultivation of follicles which they should be able to take at least 5 from. They have recommended a continue with taking the eggs this week, putting them with the sperm and when they are ready freezing them. They then have recommended putting them pack in during a natural cycle as they think my uterus has been affected by the drugs during this process. What is your opinion of this procedure? What else can i do during my ‘natural cycle’ to help with the blood flow in my uterus?
Hannah from London
Dear Hannah,
Unfortunately, I do not feel comfortable providing specific advice but I would be more than happy to comment on the concept you propose of freezing embryos and transferring them in a subsequent cycle. We refer to this as a “staggered cycle.” I have been an advocate for this strategy for quite some time. Having seen the benefit of this in my own practice, I have been further encouraged by recent studies demonstrating the validity of this practice. In fact, I am in the process of writing a blog post in support of this based upon a recent study. Please check back in a week or so. Better still, let me know of your pregnancy as your treatment proceeds!
Best thoughts,
~Robert
Robert Greene, MD, FACOG
CNY Fertility Center
Dear Dr Greene,
Thank you so much for your very helpful advise. things turned around for us last week and we ended up with 8 embryo’s and my hormone levels being good enough for 2 to be put back in tomorrow. I am on blood thinning injections, steroids and progesterone.
If unsuccessful they will follow up with a ‘staggered cycle’ with 2 of the remaining embryo’s. I have 6 in category 1 and 2.
Thanks again for your advise. The information you have published has been very useful for me so far.
Hannah from London
Dear Dr Green,
I wonder if you can help me. I am about to embark on IVF my next cycle as I have very low AMH (0.07). The problem I have is I am having an unusually long cycle and my period has not started for me to begin treatment. I am currently on day 47 of my cycle. I have been undergoing TCM for the last 7 months, taking DHEA for the last 2 months. I have been averaging 31 days before this for my cycle. Could you offer any advice on why this might be happening and anything I can do to expediate my period. And – I am definitely not preganant unfortuanately. The nurse at the IVF clinic says it should not stop me starting IVF when my period does start.
Best wishes.
Jas from London
Dear Jas,
Thank you for seeking my input on your pathway to parenthood. Unfortunately, I am not able to provide specific advice through the internet–current regulations forbid it. That is probably a good thing as there is not nearly enough information for me to guide you accurately. I would feel terribly if I misguided you by assuming aspects of your care that are not included. With that in mind, it is vital that you discuss all of the steps you have taken with your current provider. For instance, some TCM can actually cause temporary disruption in menstrual cycles. Even a hormone like DHEA–a precursor to both estrogen as well as testosterone–can trigger a hormone imbalance rather than replace a deficiency. So I would encourage you to have a sincere and detailed discussion with your current provider and redirect your plan in the way that is most suitable to your needs and your personal preference. If any other questions arise during the process, I’d be delighted to assist you further.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
CNY Fertility Center
I have strange things happen to me. My period is regular but eversince my miscarriage, my period has shortened to a mere 1.5 days in total. However during ultrasound scans, my lining is always very thick. In my last two IVF cycles, my endometrial thickness is about 20mm! I was very concerned if this will affect implantation and was puzzled by short periods and yet thick lining. Yet amazingly in the last cycle one embryo attached and I am currently 30+ weeks pregnant. Sometimes some things are just beyond medical explanation. I still dont have an answer but it doesnt matter anymore cos I am having my baby.
Dear Dr Greene,
I was wondering if you can advise me on my progesterone level:
I asked for a bloodtest of Progesterone and Estradiol on 3dpo when I had my transfer.
The result was Progesterone: 166 nmol/l, – and Estradiol was 1.03 nmol/l.
Are these levels ok good?
From what I can googled progesterone seems high?
And Estradiol could be low seeing that I had 4 follicles retrieved.
4 eggs retrieved from 4 follicles, had been on Elonva for 6 days, then 150 Pergoveris and 75 Gonal for 3 days, then Pregnyl.
Im taking 3 x 100 mg of Lutinus per day sine ER, nothing else, no HCG-support, no Estradiol.
In your opinion should I take some estradiol pills from today? Im 6dpo.
Thanks very much!
Dear Ada,
I do not enough about your history to provide you with specific medical advice. In reality, the question that you pose about supplementing estradiol remains a very active debate in our field because there is not a definitive answer. My opinion at this point is that adding estradiol provides no additional benefit and may actually create some problems. That said, it would be up to you to discuss your concerns with your provider and arrive at a decision that you’re both comfortable with.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Thank you very much! Mean while Ive researched some more, and it seems that my 1.03 nmol/l ( 1030 pmol/l) on transfer day should be in the ideal frame, im very confused, since some IVF-docs on the internet say that it is too low. (the blood test was taken on transfer day, not around retrieval when I understand that estradiol peaks.) If you can put my mind at rest id be very grateful indeed!! Yours x
There is much discussion and on-going debate about whether there is any meaning or usefulness from the early progesterone level. I am of the belief that if it has any value whatsoever, it may indicate the readiness of the endometrium for implantation. Even that use however remains to be firmly established. Since the embryo has already been transferred, I would focus on the pregnancy test and stay positive.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Thanks Dr Greene! If Im not pregnant this time and my progesterone is as high before next transfer, would you say I shouldnt take the progesterone suppositories cause this might over-mature the endometrium? Have a lovely Sunday!
Dear Dr Greene, I have a question about hypothyroidism and ivf: I fell pregnant 3 years ago naturally the first time me and my ex tried for it. At this point my hypothyroidism was undiscovered and I only started taking Eltroxin AFTER I knew I was pregnant. My TSH is now well regulated or maybe a bit OVER-regulated, it has been around 0.55 or 0.60 the last times it was tested. Im doing IVF and am wondering if an overregulated thyroid might cause a hormonal imbalances in me that makes my otherwise thick endometrium unreceptive to the perfect embryos Ive had transferred the last 3 IVFs? This is a real and serious concern of mine, and I hope so much that you can help me. My TSH was around 6.0 when I became pregnant 3 yeas ago, and my sister who is not hypothyroid has a natural TSH of around 2.5. Im only writing from an instinctive feeling that I might be better of taking a lower dose of eltroxin and getting my TSH up to 1.5 or 2, what is your take on this?
Best thoughts! And thank you!
Dear Greta,
Thyroid levels are quite dynamic. That is why they often need to be checked and at times dosage may need to be adjusted. I think that it is also important to consider the nutritional ways to help support healthy thyroid functioning. For instance, obtaining adequate levels of iodide and eating foods with selenium (like Brazil nuts) can often help a woman’s thyroid gland adjust naturally the hormonal shifts. There is also some new data (see recent “Hormone Happenings entry in this blog) that over treatment of thyroid can possibly have a negative impact on the developing child’s cognitive development. So this is not a simple question. I would encourage you to speak with your healthcare provider about your unique situation.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Thank you very much! Do you know how doses of 10-25 mg prednisone over a month can affect my thyroid and does it enhance the effect of my thyroid medication? Im thinking there is something ‘going on there’. Sincerely
Again, there are different opinions on what to do in such situations. My recommendation is that the embryos should be frozen at the blastocyst stage (if your center has mastered the technique to do so safely) and you should then consider a frozen embryo transfer. In a “programmed cycle” attention is taken to optimize the uterine environment since the embryos have already been created and stored. Many centers in the USA have adopted this strategy.
Best always,
~Robert
Robert Greene, MD, FACOG
Dear Dr Greene, Thank you for a great blog, and your generous help!
I have to questions:
1. How often do you see that eggs retrieved from follicles that measure 14-15 mm fertilize?
2. I had a cycle where I stimmed faster than usual, fewer eggs too, my biggest follicle was already 16 mm on day 7 of stim. Does a fast stim in anyway indicate lower egg quality?
Thank you very much!!
Dear Mimi,
Thank your kind comments and for sharing your experience.
I have recovered mature eggs from follicles as small as 10 mm. Routinely, I find that with a properly timed protocol most follicles greater than 12 mm will be mature. There are patients that vary from this however and when I have encountered such individuals, I will adjust my plan of when to trigger on their next attempt if they do not become pregnant.
I do believe that most patients do best with at least 8 days of stimulation and I prefer to have them complete 9. Therefore, I would rather go a bit longer rather than trigger too soon. I have found premature egg release or “post maturity” to be exceedingly rare. That said, my experience may be based upon the protocols that I choose so your provider may have different recommendations for you.
Please let me know if I can be of further guidance.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Thank you very much Dr Greene! Well the smaller egg didnt fertilize, but the bigger one, the one that was already 16mm on day 7 of stim did, and yielded a top grade embryo when fertilized. However, I didnt fall pregnant this time.
I have another question for you if you dont mind:
Ive done 6 IVFs and 6 transfers. Im using donor sperm, and have been using 2 different donors for the 6 cycles, 3 cycles each. Ive had top grade embryos with both of them. With the one donor Ive had 2 biochemical pregnancies, and with the other donor only negatives. My sperm bank says they think I should use one of their ‘top 5 donors’ next time, donors who consistently have much higher pregnancy rates than the rest. What is your experience? Can changing donor be a sensible thing to do?
Thank you!!
Dear Mimi,
Typically, the sperm donor should not be a determining factor of a cycle’s success or failure. Considering that the sperm provides only DNA whereas the egg has to provide many other anatomic and chemical structures to the developing embryo; it has much less impact. More importantly, any reputable sperm bank would reject any donor that had any factor that could limit success. You may wish to consider having a meeting with another provider to review your records and provide some additional insights.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Conceptions Reproductive Associates of Colorado
Hi i have under go 2 fresh emryo transfer n 1 frozen embryo transfer but it fail.. recently in july i did my ivf, there withdrawn 10 egg- 3 fertilize (gd quality embryo) 3th day after my embryo transfer the thikness of my endometrium lining was 10mm and dr say my overies oso gd enough, ovaroes are functining well he said but still failure.. can some 1 help me y implantation doea not occur plz.. im spouse to do my FET on coming sept but b4 tat i qould like to know hw can i prapare my uterus well to implant the embryo????
Dear Theelorthanam,
I am sorry that I cannot comment on your situation specifically but there are too many details that I do not know about your case. In general terms I can tell you that like many other leading centers, we almost never perform a fresh embryo transfer any longer. We have come to believe that the conditions necessary to optimize the egg collection are very different from the those that are ideal for embryo implantation. So we split our cycles into two phases. After we collect the eggs and freeze the embryos; we then work to creating the embryo transfer cycle. In fact, another important consideration is if the embryos are judged to be “good quality” based upon their appearance or genetic testing. If it is based upon appearance that means that typically means that they embryo has about a 30-40% chance if it is a blastocyst (less if it is a day 3 embryo). If it has undergone the latest in comprehensive genetic screening then the embryo has a 70 to 80% chance. So this means that most embryos that “look good” aren’t as high quality as they appear. If you would like a more comprehensive and formal discussion/review, please consider phoning our office to set up a consultation.
Best thoughts,
~Robert
Robert Greene, MD, FACOG
Conceptions Reproductive Associates of Colorado