Endometriosis Foundation of America
Endometriosis 2013 / Economic Burden of Endometriosis Infertility Treatment in the United States -
David Adamson, MD
In terms of dollars and cents I think this will be the right segue into what are the fertility options today for patients with endometriosis. I decided to give you what I think is the top ten, kind of stealing from Letterman a little bit. What we will try to do is ask ten questions that pertain to the treatment of endometriosis and see if we can answer them one by one. Maybe you can take home some of those messages
The first question is does ovarian suppression help? Just giving suppression I think some physicians have the notion that if they give OCPs, GnRH analogues or Danazol, which is kind of an older drug, for a period of time that by itself will help their patients conceive and in a Cochrane data base review this was not found to increase pregnancy rates. So that settles that. Ovarian suppression is not recommend today in the treatment of infertility and should not delay effective treatment. You do not want your patient to age through the process. I always tell my patients whenever they come to me at any stage I do not want you to age under my watch. As we said on Saturday the three main factors affecting fertility are age, age and age. You always have to keep that in mind. It is no different for the endometriosis patient.
The second question is how successful is fertility treatment? That pertains - Dr. Adamson had quite a few very good slides on that but cumulative pregnancy rates for IUI alone is 18 percent, The gonodotropin/IUI, which we do not recommend that much anymore, we want it to be replaced by IVF, we feel it is safer, is 33 percent for stages one and two. Stages one and two are not that different than...endometriosis patients.
So, does endometriosis reduce success in IVF? There was a study, quite a well known study in our field by Dr. Kurt Barnhart from Penn in 2002. They did a meta-analysis of 27 trials and they showed in that study the chance of conception was much reduced compared to if your infertility was a tubal factor. They looked at all the parameters, all the things that physiologically we can learn about the patient; the fertilization rate, the implantation rate and the number of eggs. However, if you look at another study by Omland this is a European study, they actually show that endometriosis pregnancy in IVF was similar, almost identical, to tubal factor but both of them were still less than unexplained infertility. Implantation rates were the same for all three groups and just for those of you who do not do IVF here implantation rates are probably a more important way to judge fertility success in IVF than just pregnancy rates. Implantation rates is actually the number of pregnancies per embryo that you implanted.
More good news came from the SART registry. This is the registry that actually encompasses almost all the IVF programs in the United States and 2010 was the last one published. If you look at every age group, it is always reported by age, again, to underline how important age is, you see the pregnancy rate, not only pregnancy rates but implantation rates, everything is pretty much the same between all diagnoses and patients with endometriosis. You see in young patients less than 35 years of age the delivery rate was 36 percent, almost 37 percent. Then between 35 to 37 it is about 27 percent and it goes on to 18 percent and ten percent in the higher age groups. Again, good news, this is all stages.
So now comes the question, well wait a minute - okay you showed that pregnancy rates for the whole group of endometriosis is the same but does the level of endometriosis, does the severity matter? Well, it seems to be that the only real thing that matters that reduces pregnancy rates is deeply infiltrative disease versus superficial disease in this study from 2002. You see a significant drop of 58 percent when it is invasive versus 83 percent for superficial lesions.
So then the question is, okay, does surgery improve IVF success? This is a study from a group that did a lot of surgeries but is also very well known in our field for their success in IVF out in Colorado. As you can see here the ongoing pregnancy rate, as well as implantation rate, did not differ. And just as an aside comment; you know when you saw David Adamson's slide about the cost of a baby based on an algorithm that includes laparoscopy if let's say chlomid...does not work, I would like to make a comment that I do think that for endometriosis, and I know there are a lot of surgeons here so I have to be careful, but for endometriosis mild and minimal it has never been shown that there is a benefit of laparoscopy in pregnancies. So I would vouch that in my patients who I do not think have a more severe disease than that I go directly from chlomid... to IVF. I bypass it, I shorten the time to pregnancy and I reduce the cost.
What about an endometrioma? Does it affect IVF success and should it be removed prior to IVF? Most studies show, again, this is a Ballister and very recently that there is no impact on the IVF outcome of the number of endometriomas, of the size of endometriomas, which was a question we got on Saturday from one of the patients, and whether the endometrioma is on one side or both sides. However, what was significant, what was the deleterious again was if there was concomitant deep infiltrating disease and AMH was highly predictive. That is one of the things I would like to urge everybody to do. Of course my suggestion is that if you are an endometriosis doctor who deals with endometriosis a lot, a surgeon, a gynecologic surgeon, I would suggest that you work together with a fertility specialist on your patient. Evaluate, even if you are planning on doing surgery, do a pre-surgical evaluation of the patient's fertility potential. What is her FSH on day three and estradiol? What is her AMH? Consult with a fertility doctor. Have her see that person to make a plan, even if you are planning on significant surgery so you can jump right onto treatment.
What are the proposed indications for removing an endometrioma? First of all for diagnosis, as we know, a very small proportion has cancer. If you are seeing a big, complex cyst in the ovary and you do not know what it is, obviously the patient has significant pain. If the cyst has grown rapidly, if the sonographer tells you that the lesion is suspicious and compromised access to the remaining follicles, sometimes it helps actually IVF and concern for rupture in pregnancy due to size. Obviously we have to be reasonable in deciding who, actually which, endometrioma, not to operate on.
Then the question is we said that just medical treatment without anything else does not really help fertility. But medical treatment suppression before IVF does it increase? The results and the answer are actually many studies show yes. You see this comparison of ongoing pregnancy rate and implantation from long term Lupron or GnRH agonist did benefit. The length of time you see here all the different studies vary between three months to six months. I think there is more consensuses on the three months. I would not prolong it more. There is also the problem that if you gave the patient six months of Lupron their response in IVF will be/can be quite sluggish and that could be a problem for us.
Does IVF, this is actually a question that came up again from patients on Saturday, does IVF make endometriosis worse? The good news is there is no worsening in symptom scores and the size of the endometriomas or peritoneal nodules. Actually, 22 percent of patients reported improvement in symptoms while 11 percent reported worsening. I think the weight of the evidence right now is no, you do not have to worry about that. This is just one of the studies where people have tried to look into the role of the endometrium. Does endometriosis really affect the endometrium adversely and they looked at all kinds of markers, one of them is the beta integrin and this study shows you that there was no difference.
What can we learn from the egg donation model? Now this is very interesting. This study from 1994 from Spain did the following. They divided the patients into three groups. They had egg donors who gave eggs to recipients, both donors and recipients did not have endometriosis. The second group was donors that had endometriosis and donated to patients who did not have endometriosis. The third one was donors who did not have endometriosis who donated to patients who had endometriosis. Did I confuse you already? This model is very interesting because you are trying to figure out where is - it is not the chicken and the egg - but, you know, where is the endometriosis affecting adversely? When you use donor eggs on patients firstly without endometriosis you see the pregnancy rate was fantastic - 61 percent. The same pregnancy rate if you are using donors who are healthy and the recipients have endometriosis. But where the pregnancy rate drops precipitously is when the donors have endometriosis. What does that teach us? You see it drops to half, to 29 percent.
So those who have been looking at the endometrium and endometriosis have been barking up the wrong tree. I hope the physiologic talk that follows me will not fight that notion. If you are looking at the weight of the evidence it is the egg.
How successful is egg donation with endometriosis? It kind of showed you already one statistic. A retrospective analysis of 10,000 egg donations over a ten year period showed the cumulative pregnancy rate to be the same regardless of the indication or the diagnosis.
The last thing is donor eggs and donor banking. I said it on Saturday, today is a little bit of a different crowd, so I will say that your patients will run out of fertility potential. A few of them spoke to us on Saturday, actually came up with questions, and it is obvious that they have been fighting with fertility for years and are not getting pregnant. They need to turn on that switch that I showed them Saturday, an actual switch in the women's brain on extra donor eggs. It is not an easy switch for them to turn on. Once they do donor eggs I showed you the pregnancy rate is fantastic. They go from being in the worst pregnancy chance group to the best pregnancy chance group, which is donor eggs. So now the new concept is egg banking. We have contracted the egg bank from Atlanta and egg banking using the frozen eggs from an egg bank it is much cheaper, about $10,000 cheaper. It is available. It is immediate. Logistics of synchronization between donor and recipient does not exist and is potentially safer. We have that contract in our office here at Lenox Hill. We will provide you with this service.
To recap: Ovarian suppression does not improve fertility. Chlomid IUI and gonadotropin IUI are all effective treatments of endometriosis. Overall, IVF pregnancy rates with endometriosis is the same as all other categories. Deeply infiltrative disease lowers success rates. Surgery on non-ovarian endometriosis does not improve IVF outcomes. Endometriomas do not affect results. Pre-IVF resection is not indicated routinely and may reduce the response. However, there are indications where you should do it, which we have mentioned before. Pre-IVF medical suppression does improve the results. IVF does not make endometriosis worse. Studies from egg donations show that the main problem in endometriosis is the egg, not the endometrium. And egg donation is as successful with endometriosis patients as with all other patients and the egg bank is an exciting new option, much cheaper and simpler.