Melanie Cole (Host):  Problems with the endometrial lining are one of the leading causes of infertility in women. If you’ve had implantation failure, there is a test available that can help evaluate a woman’s endometrial receptivity from a molecular perspective. This advanced technology is a personalized genetic test to diagnose the state of endometrial receptivity in the window of implantation. My guest today is Dr. William Ziegler. He’s a specialist in reproductive endocrinology and infertility and is the medical director of the Reproductive Science Center in New Jersey. Welcome to the show. We’ve got a heck of a topic here today. Let’s start by explaining to listeners what the endometrial lining is. What really is that and how is that related to fertility or infertility?

Dr. William Ziegler (Guest):  We have to understand that when an embryo into the uterine cavity, whether it is put there through in vitro fertilization or whether it gets there naturally, the uterine lining really needs to be prepared and has to have the right components so the embryo can basically, as I refer to it, zipper into the uterine lining. When an embryo breaks out of its shell – because we actually do hatch, there is a shell around an embryo – it does break out and if you think about a zipper, those teeth have to mesh together. The question that we always have is how prepared is the uterine lining. In the past, the way we used to look at the uterine lining through in vitro fertilization cycles or even other fertility treatment cycles is we used to look at the lining through using an ultrasound. We want the living to be a certain thickness, we want it to be a certain pattern and those are indirect measurements of what this lining means to us. If it’s too thin, then we think it’s not going to be a good lining and we have to change a patient’s medications or protocol to improve it to make sure that it gets the right thickness and the right pattern. We’re finding that now even if the lining looks okay, it may not be ready yet. You basically have a very small window that the embryo has to implant and you want to make sure that the uterine lining is right where it needs to be, so the embryo can implant.

Melanie:  You explained a little bit about how you used to look and see if it was ready. What are you doing now? What is this ERA biopsy – the endometrial receptivity analysis? How does that help determine if the living is ready as it were?

Dr. Ziegler:  Years ago, we used to look for adhesion protein. These were molecules called cadherins and integrins. That test that we initially used years ago was not an accurate test. At this time, we’re able to look at the uterine lining on a molecular level and to see whether or not it has the DNA or the markers to tell us that lining is receptive. We use this test to assess the uterine lining in those women that have had recurrent pregnancy losses or those that are just having implantation failures with in vitro fertilization. By augmenting or adjusting or supplementing a woman’s hormones, we can basically make that lining receptive, so it does help improve implantation rates, pregnancy rates and pregnancy outcomes.

Melanie:  What technology is used with ERA and how does it take to get results?

Dr. Ziegler:  We have to really take a step back and the way that we actually used the endometrial receptivity is we put a patient through what's called a frozen embryo transfer cycle where we basically shut down their ovaries and we give the patient back estrogen and progesterone. They're on a certain protocol and after a certain number of days of progesterone, we when sample the uterine lining and that’s by taking a little cath that’s called a pipelle and we scratch the uterine lining. We then send that sample to a lab and they analyze it for DNA markers to see if the appropriate DNA markers are actually present. We get the result back usually within 10-14 days. When it actually comes back, the report will tell us whether or not the lining is receptive – meaning it’s right where we need it to be – or it could be post-receptive – meaning that we missed the window – or its pre-receptive – meaning it’s just not ready yet. The report that we get actually tells us what to do with those medications – how do we adjust them so we make the lining perfect so when we put back embryos with in vitro fertilization or with the frozen embryo transfer cycle that we know that lining is perfect, that we know we’re putting the embryo back at the right time, the right components are there, so that maximizes the implantation of that embryo.

Melanie:  When is this receptivity cycle recommended? You mentioned that if there was implantation failures or unexplained recurrent pregnancy losses, when would a woman be able to request or would you suggest this type of procedure?

Dr. Ziegler:  Like I mentioned, we do it for our patients that are really undergoing a frozen embryo transfer, which they have embryos frozen with us, and if they had a prior cycle and they did not get pregnant, then we’re able to freeze embryos and then we discuss proceedings with this type of analysis or if they went through an IVF cycle and they had a pregnancy loss. This is a way of us really determining what is the recipe for a woman’s uterus. We know that not every woman’s uterine lining is the same. By doing this test, we have found that there’s marked variability of receptivity – when is the uterine lining receptive for each woman – so this is another way for us taking a look at what I refer to as the “black box” of implantation because we can put back embryos and we can make sure that the lining looks good and still implantation does not take place. By looking at receptivity, now we’re putting back a good looking embryo into a uterine lining which is receptive, so you're maximizing those two windows for implantation.

Melanie:  Clearly as what you have explained to us, that this assay can give you the information that you need to help with the endometrial lining. Does the ERA analysis itself help with the lining based on the procedure of the biopsy what you're doing in there?

Dr. Ziegler:  I think what you're getting at is does disturbing the uterine lining help with implantation?

Melanie:  Yes.

Dr. Ziegler:  There's been some studies out that have shown about the scratched technique and the data is really just all over the place. There's more data out use frozen eggs and how implantation rates may be higher in using frozen donor eggs. It’s true that it may be beneficial that scratching the uterine lining increases growth factors that may help with implantation, but those studies were done when the scratched technique is done around two or three weeks prior to somebody going through a treatment cycle. The endometrial biopsies that we do for the ERA is done probably around a month to a month and a half prior to us putting back embryos. The data on that is less clear, but could it benefit implantation by just scratching the uterine lining? That is a possibility and with the additional information that we need to adjust hormones to improve implantation, I think it’s just beneficial for the patient to have that test done whether it’s from the effects of the scratch technique or whether it’s us adjusting their protocol based on the ERA aspect.

Melanie:  That’s so interesting. Are there certain women for whom this is not an available procedure?

Dr. Ziegler:  That is available for everybody; however, for somebody who is going through IVF for the first time, I don’t think this is really a necessary task. I think you have to look for an indication to do this. Insurance does not cover for the analysis to be run and that runs around $800. Most patients have coverage for fertility treatment and therefore this would be covered, and even if they have a diagnostic policy only, then this would also be covered mainly because you're trying to diagnose something. It’s just another test that we have to take a look at areas that we can basically fix if there is a problem.

Melanie:  Give us a summary of this particular procedure, test or whatever they're calling it, it’s an ERA biopsy, so it’s an analysis. Explain to the listeners what you want them to know about the availability of this test. Who should have it and why they should come to the Reproductive Science Center of New Jersey for their care?

Dr. Ziegler:  Our practice strives to be on top of the most current treatment and the most current diagnostic testing that’s out there, so we can improve pregnancy outcomes for patients. This test was developed around seven years ago, and around two or three years ago, biggest centers started to use it and the studies started coming out where this may be beneficial for some patients. For those patients that should be offered this test are those that have had unexplained recurrent pregnancy failures, those that have had failed IVF cycles, even those that just may have only one or two embryos left frozen – you want to give them best opportunity to implant. This is another way to just facilitate implantation and to improve outcomes for a couple. I think this test is beneficial in those patients in which have a limited number of embryos and those in which who are concerned that could be an implantation issue and it may be stemming from the uterine lining. Also, those that have had prior surgical procedures – they've had multiple fibroids removed that were close to the uterine cavity. Those that have had curettage – or scraping of the uterus – that may be beneficial also. There are some OB outcomes. If you’ve had what's called a placenta accreta – where the placenta is very much embedded into uterine lining and they had to manually remove it – then again, there may be a problem with the uterine lining. This is another way of assessing that. We’ve had cases where we did this test and those DNA markers were not there, despite altering medications. We have beautiful looking embryos cryo-preserved, but their lining can never get to the point where those markers are there that facilitate implantation. It’s another test that’s out there to help us help patients.

Melanie:  Thank you so much for being with us today. You're listening to Fertility Talk with the Reproductive Science Center of New Jersey. For more information, you can go to fertilitynj.com. That’s fertilitynj.com. This is Melanie Cole. Thanks so much for listening.