Dr. Smith, I'm not sure if this is a question for you or Dr. Jacobs so I posted my question to both of you.
I had my first IVF cycle this past Feb. with 3 embies that were 95, 75 snd 75. They all made it to 8 cells at the time of my 3 day transfer. They did not implant. One thing I did question was my uterus lining. It was at 7mm. For my cycle day 9, it was at 7 and they said they like for it to be between 8 and 10 and put me on Viagra supp. along with Terbutaline Sulfate 5mg. 3x a day. At the beginnning on my cycle, they also had me on Estradiol supp. 2mg. one at bedtime. However, when I questioned my lining and how it was still at 7 mm at the time of retrieval, the nurse said it was fine. The fertility center that I go to has centers nationwide and the founder is at a different location than the one I go to. They also have a chat where you can ask any of the doctors a question. The founder has on his website repeatedly that a linng of less than 8 mm has decreased implantation rates. In a chat, I asked the founder if 7mm was ok. He said "in his opinion, 7mm does not cut it". When I went to my RE and asked her, she said "I dont know where he comes up with those numbers". My RE said that I had a triple lining and she felt my lining was fine. Now I am back for another cycle, they put me on the Viagra and Terbutaline a week early to try and get my lining a jump start. When I went for my cycle day 9 check, it is again at 7mm.
I'm not sure who to believe--the founder or my RE. My question for you is: 1.Is there a decrease in implantation rates at 7mm vs. 9mm? 2.Is the triple lining more important than the lining thickness? 3. While we are getting the US, are we being too aggressive if we ask to see the triple lining on the US screen? 4. Do you know anything about using Viagra and Terbutaline to increase the thickness of a linng?
A1. Yes. Several studies have shown that the likelihood of implantation is decreased when the endometrium is less than 8mm. That is not to say that patients with an endometrium 7mm will not have implantation, just that it is less likely. 7mm is the lower limit and I agree with the "founder" that 8-10mm is optimal.
A2. It is a combination of the triple pattern AND the thickness. A triple pattern alone is not enough if the endometrium is thin. Conversely, a thick endometrium without a triple pattern is not optimal either.
A3. No. You are entitled to see anything you want. If you ask and they are reluctant to show you, it is red flag. Especially in view of your previous cycles with a thin endometrium.
A4. In one clinical study, Viagra was shown to to improve blood flow to the uterus and increase endometrial thickness. A single study is not conclusive. That being said, we use Viagra suppositories on FET and donor egg cycles. The rationale being it can't hurt and it may help. I have heard of terbutaline being used to decrease uterine contractions and improve the chances of implantation by reducing movement of the embryos within the uterine cavity after transfer. I do not know if it also improves endometrial thickness.
You say that several studies have shown that the likelihood of implantation is decreased when the endometrium is less than 8 mm. Is that measurement on the day of retrieval or on the day of the hCG shot or for some other day?
My husband and I went back for our US and she wasnt supportive on us looking at the US screen. She didnt stop us but you can tell she didnt like it. She never showed us what we were looking at. Her workers have said that other patients have complained on her demeanor. I was cancelled because she said my follicles were not growing. She said it was because my FSH was elevated-it went from 6.7 to 9.4 after a 30 day menstraul cycle. But it always elevates when I have a 30 day cycle. I always have a 30 day cycle after an IVF cycle. She said once my FSH goes back down, it will be a good time to try again. She said my lining will not grow unless my ovaries have follicles in them growing and prog. in them.
While I am waiting, I am considering other options:
natural IVF--because of stims being too high. She has me on the max protocol. My E2 in January reached 2680 then they reduced my meds and it went down two days later to 780. When I went to a different clinic last year, they had me on a standard protocol and my E2 reached 1730 and my lining was at 9mm. But they retrieved when the follicles were under 16mm except one. So we switched to the present one now. She is good on when to retrieve but we are in disagreement on the lining being only at 7mm. I am afraid that the stims could be jeopardizing my lining's receptivity. here some studies I found: http://www.pubmedcentral.gov/articlerender.fcgi?artid=1266397
I also found one on using Doppler US.to check the blood flow in the uterus: http://www.fertilitydirectory.org/news_updates_ivf_clinical01.html Please look under Ultrasound Obslet Gynecol 2002 May;19 Evaluation of cycle-to cycle variation of endometrial resp. using transvaginal sonography.
I am really confused on which direction to take. I will be seeing her this Thurs. to discuss her trying to remove the fibroid that is blocking the left tube. But since I turned 41 last month, maybe natural IVF would be better. Are these studies credible and worthwhile to show her. she used prog. supp. the day of retreival. Is this their way of trying to rescue the uterus because of the high E2 levels.
Well... I'm not suprised that your are confused. The publications you have been looking at a quite complex for the layperson. Heck, they're complex for for me too. Its difficult to sort through all the information to find what you're looking for, and even then, to be sure that you can trust it.
The first link is a lengthy review of the literature surrounding the effect of E2 on everything imaginable. Although informative, the authors are a little biased in their interpretation. They have selected a multitude of references that support their argument, but came up a little short on studies that refute their position.
The general consesus is that very high levels of estrogen can have a negative impact on endometrial receptivity. This is most common in PCOS patients (hyper-responders) that get up in 5-6000 pg/ml range. The question is how high is too high. I think it is generally accepted that levels in excess of 5000 pg/ml are too high, but many patients run E2s in the 3-4000 range become pregnant and carried to term. So its less clear what effect the intermediate values will have. Also, one must consider that circulating levels of any hormone are only half the story. These hormones must also bind to receptor molecules on the outside and inside of the cell to be effective in facilitating a response from the cell. Once all the receptor molecules for a given cell are occupied by the hormone, having more hormone around won't have any additional effect. The cell is "maxed out" so to speak. One hormone will induce the cell to make additional receptors or make receptors for another hormone. This is what makes it so complex to interpret.
The second linked article basically says the same thing. There are pros and cons to any manipulation of nature. Ovarian stimulation is no exception. An increased number of follicles means that the E2 will go up to supraphysiological levels. As with most things, its a trade off. The trick is to balance the stimulation so that the E2 does not get too high, but still allow the follicles to reach a size that will allow the eggs inside to mature and be of good developmental potential. You need to keep in mind that endometrial thickness is not directly tied to E2 levels (i.e. the higher the E2, the thicker the endometrium). Once all the endometrial E2 receptors have homone bound (i.e. saturated), more E2 doesn't have any additional stimulatory effect.
From what I know and read in the linked articles, the E2s in the 1700-2600 range that you had wouldn't have a detrimental effect on the endometrium. It is more troubling that your E2 dropped so precipitously when they lowered your medication on the first cycle. Not a good sign. The following cycle, they kept the E2 down, your endometrium was of adequate thickness, but (da) the follicles weren't mature.
The paper concluding that endmetrial biospy in the same cycle improves implantation has been discussed at length in the IVF community, but so far, has not been confirmed. The dogma is that an endometrial biopsy in the same IVF cycle is one of the worst things you can do since it may cause a blood clot in the uterine cavity that would prevent implantation. The authors of this study are out on a limb, but I try to keep an open mind.
Dopper US is another one of these "flash in the pan" things that everybody thinks is interesting, but doesn't really pan out. As expected, blood flow is correlated with implantation and ongoing pregnancy. The problem is that medications that increase blood flow to the endometrium do not improve implantation rates significantly. Clearly, there's more to the story than just blood flow to the endometrium.
When the Fallopian tubes are patent (open) and the psrm is fine, natural cycle IVF has the same pregnancy rates as timed intercourse. Save your money.
The progesterone suppositories are standard progesterone replacement following an IVF retrieval. It was not done to "rescue" the endometrium from a high E2. Progesterone is necessary to "turn on" endometrial recitivity that will allow implantation to occur.
I think (if I may be so bold) you are driving yourself crazy with all this stuff. I relaize that you want as much information as posible (and that's a good thing), but biology has a lot of variation and it is a very difficult beast to tame. Sometimes we are at the mercy of the beast and there's nothing we can do.
I hope you get some clear answers from your RE on Thursday. I think you should ask what she plans to do about the endometrial thickness on any subsequent cycle. 7mm is not that great and she knows it.
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