Andreas Abraham, MD, MBA
Head of Eugin International, Eugin Clinic
Failed IVF Cycles, Success Rates
‘Adenomyosis is more, and more diagnosed because we have more and more advanced age patients. 55%, in our case, of the IVF patients who go ahead with their own eggs are 40 years and older, so this accounts for a big part of our patient population.’
I assume that you had four unsuccessful IVF cycles with your own eggs. Endometrial scratching is a very interesting topic that came up around about five, six years ago by accident. A group in Israel noted that in patients where they did a hysteroscopy before the IVF cycle, there were higher implantation rates. Endometrial scratching means irritation of the endometrium before the IVF cycle.
In the beginning, everybody was very excited about this finding, it triggered a lot of studies all around the world, hoping to have found a very potent means to increase the implantation rate. That means you irritate the endometrium, scratch the endometrium, you do that with a little catheter, you use the speculum, get into the womb scratch around the clock. You will irritate the endometrium without provoking bleeding, and then you’d have the IVF cycle.
If you look at evidence-based medicine, all the studies that have been performed and there were a lot in the last five, six years now recently have shown that there is not a measurable effect. It doesn’t hurt, but if you look at the evidence-based data, we can’t tell that it will improve your chances. In our clinic, we try to be very strict and be as evidence-based as possible. We used it at the beginning, after having heard about this in the last two years, we refrained from it since the latest data doesn’t support it anymore. Don’t worry, it is something your doctors tried since you had four unsuccessful tries so far, and I know how frustrating it is in terms of infertility in general, it’s very tricky to find a sole responsible factor. It is a multi-factorial procedure and process, so it’s very rare to find the one solely responsible factor.
The first step, as I told you, is the ultrasound. Polyps are tricky, and on the ultrasound, you can see very tiny structures, but sometimes you see artefacts. It might be, and it’s not the fault of your gynaecologist or the sonographer, it might show up and seem to be a polyp but then if you dig deeper into it, do the sonohysteroscopy or even hysteroscopy, you might not find it because it was an artefact.
Polyps are not always visible on ultrasound that’s why you have to do this three-step diagnosis. If you see a polyp on an ultrasound, you might want to verify it with the ultrasound using the injection of the cell line. That might make it more visible, and if you confirm it, then you go and get it out with the hysteroscopy.
Usually, if you block the ovarian function, it’s reversible. The artificial menopause that’s created is reversible, it would not put you in a permanent state of menopause, and it won’t lower your antral follicle count or AMH level. This is age-dependent. Usually, the effect of these injections is around two months. These injections are used in the treatment of endometriosis. All the alterations and problems that are triggered by estrogens, endometriosis, adenomyosis and fibroids, the concept of treatment is at some stage to block the production of estrogen to run down the system in the ovaries, but this is reversible, so it is temporary.
The presence of ectopic endometrial tissue, which is by definition what I told you in the context of adenomyosis which is closely or very much linked to deep endometriosis, goes together but can contribute to ectopic pregnancy. If you have this problem, the transport of the egg or the embryo can be impaired, it’s a mechanical thing. There can be a link between them. The pelvic pain is also related to that, so the symptoms to have pelvic pain are related to what you described, so yes.
AMH can show some fluctuations as well, yes that is something which you can regard as in the normal range.
Yes, the differential diagnosis is quite tricky. Sometimes, it’s just a slight septum, or it’s a very long septum. Differentiating between a septate uterus and a bicornuate uterus is not that easy. Since you had a hysteroscopy, some of this septum has been cut off. The best way is to combine both. Look from the inside of your abdomen to the outside of the uterus and inside by hysteroscopy. Working from both ways would be the way to go. Remember, bicornuate uterus very rarely requires an operation. The spontaneous conception rate in women with a bicornuate uterus does not decrease. It is a problem later on in pregnancy, second trimester, third trimester, preterm labour, prematurity.
The topic of adhesions post-op is very tricky. Adhesions play a part not just in reproductive medicine, we do not know why some patients form adhesions and other patients do not. There are attempts to inject hyaluronic acid into the cavity after an operation or into the abdominal cavity, liquids, patches. There’s a lot of options, they do not prove to be very effective. Some patients are very resistant to these measures, but since they don’t hurt, surgeons try to use them because they don’t have big side effects or no side effects at all.
Any operation can cause adhesions, the more invasive it is, the more likely you might have them. A normal diagnostic laparoscopy is not very invasive, it’s minimally invasive. If you remove hydrosalpinx, it’s not very invasive and would not cause a lot of adhesions. There are very few therapeutic means to prevent adhesions, injecting hyaluronic acid, putting in some net-like structures. Usually, the minimal invasive laparoscopy with the clipping or resection of the hydrosalpinx is not very invasive and should not cause problems.
Anything that alters the endometrium can contribute to some problems with getting pregnant, so yes, if there are any infections, long-lasting infections, chronic infections, untreated conditions, they can negatively impact fertility. That’s why in the pre-IVF workup, all this is included the HPV test, the pap smear before you start going into this journey. If you’re under 35 and trying to conceive naturally, your doctor would let you try for 12 months to get pregnant if everything checks out fine. If you’re over 35, they would give you 6 months, but they want to know beforehand, yes, infections like that can negatively impact the outcome.
There is some controversy about that, and you’ll find tons of publications where the academics fight about thresholds. What is big in terms of the intramural fibroids, the ones trapped in the wall, you don’t touch them if they do not distort the endometrium. What is big in that context? The threshold is 4 to 5 centimetres, and again you have to consider two things.
If you operate, and it’s very invasive, you leave a scar, scar tissue can again impact implantation, so you have to walk the fine line and decide case by case. The cut-off, I would say, is 5 centimetres. The other fibroids, which are outside, the subserosal fibroids, can be bigger, you don’t care about them if you don’t have symptoms. Those you do not touch, only if they cause symptoms or are big, but the huge ones nowadays are very rare, you don’t see them anymore.
No, it doesn’t affect it because the cavity is unaffected by an outside fibroid. There are discussions about the fact that fibroids cause some metabolical issues, they produce factors that might impair, but that is controversial as well so an outside fab fibroid that does not distort or touch or affect the cavity is not a cause or problem or explanation for miscarriage.
A big chunk of our patients is over 40. First thing in the context of reproduction in nature or IVF, the egg is more important than the sperm cell. The maternal age defines egg quality, egg quality defines embryo quality, so the most important contributing factor for not having had success with two transfers of visually very good embryos, morphologically speaking, good embryos is maternal age. If you imagine you have a 32-year-old patient who has the same embryos, the same classification and let’s say this patient has the same uterus, cavity and the same everything, then from the outside, you don’t see anything. You just know that there’s a 10-year age difference that is the most defining, most impacting factor. Maternal age is something unfortunately, we don’t have treatment for anything that really could improve age, we can’t improve egg quality.
There are some studies to show, but if you look at the context, we know that there are some studies that claim that the usage of DHEA, which is not a drug at least in Germany it’s not considered a drug, it’s like a nutrition supplement that this might increase egg quality, but the studies show not. Some studies say it might increase egg quantity, but there is very little to do in this case. Being 42 or younger, you want to be sure that the uterus cavity is okay, but I suppose your doctors did that, but other than there’s not a lot you can do and that would be a topic for another talk.
Some clinics, especially, in the U.S., would then tell you to do a PGT-A, formally called PGS, which screens for aneuploid embryos. Be very careful there because data shows it’s not the case, and ESHRE, the European Society and the American Society, for the time being, do not recommend aneuploidy screening in advanced maternal age.