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FEI – a new approach in the therapy of implantation failure?

Robert Najdecki, MD, PhD
Co-Founder & Scientific Director at Assisting Nature , Assisting Nature – Human Reproduction & Genetics

Category:
Embryo Implantation, Failed IVF Cycles

FEI - new aproach for implantation failure
From this video you will find out:
  • What is hysteroscopic scratching and how it works?
  • What is the timeline of this procedure?
  • Why there is no common consensus on endometrial scratch among doctors?
  • How does Hysteroscopic Fundus Endometrial Incision work?
  • What are the benefits of FEI?
   

FEI – a new approach in the therapy of implantation failure?

What is Hysteroscopic Fundus Endometrial Incision?

In this session, Dr Robert Najdecki, Co-Founder & Scientific Director at Assisting Nature, Thessaloniki, Greece has introduced a new technique called FEI (Hysteroscopic Fundus Endometrial Incision) that is aspiring to replace the traditional endometrial scratching. FEI method means Fundus Endometrial Incision aspire to replace the traditional endometrial scratching. Nowadays, despite the scientific progress and advances in knowledge on human reproduction, the process of embryo implantation in the human uterus remains the most undiscovered part of the whole process of pregnancy. The fact that after using ART techniques, only 25-30% of transferred embryos seem to be successfully implanted leaves a huge area to be investigated. The term implantation failure can be used to describe a patient who never had an increased level of hCG or clinically confirmed pregnancy via ultrasound. Implantation failure can be applied to patients undergoing assisted reproduction technology therapies (ART) and patients trying to conceive without any fertility treatment. Repeated implantation failure (RIF) refers to when transferred embryos repeatedly fail to implant despite numerous attempts via assisted reproductive technology treatments. The implantation failure means there is no evidence of implantation or no visible formation of the gestational sac despite detectable hCG (biochemical pregnancy). Recurrent implantation failure means that we have over 3 high-quality embryo transfers without any pregnancy. Successful implantation in an ART cycle is influenced by many complex factors, such as:
  • endometrial environment
    • intrauterine pathologies (submucosal fibroids, uterine septum, polyps)
  • endometrial thickness and pattern
  • endometrial decidualization
  • embryo quality and euploidy
  • embryo-endometrium crosstalk and immune regulation
  • embryo-endometrium synchrony
  • embryo transfer technique and expertise/use of abdominal ultrasound guidance
The prevalence of congenital uterine anomalies has been reported to vary depending on the population and the diagnostic technique used. It has been shown that such anomalies affect 4.3- 6.7% of the general population and 3.4-8% of the infertile population. In women who suffered from several failures, the figure has been reported to be 12.6-18.2%. We need to be aware that diagnosis of small uterine anatomical variations based on high hysterosalpingography imaging and 2D or 3D ultrasound scans is still difficult, and often results in misdiagnosis. Even during hysteroscopy, the gold standard in uterine assessment, the diagnosis depends on operator experience and is therefore not always objective.

Congenital abnormalities

Big congenital abnormalities, such as polyps, and fibromas have been investigated, and their negative influence on the implantation process is statistically confirmed. Smaller anatomical variations can cause different degrees of uterine and endometrial dysfunction. Their influence on the implantation process is probably under-investigated, it is partially unknown and underestimated. The first papers that remarked that small, not diagnosed anatomical abnormalities may play a significant role in implantation failure came with the presentation of Venetis and Gribiziz in 2013. ESHRE consensus on the classification of female genital tract congenital anomalies brought a new taxonomy system, helping to understand their implication in reproduction better.

Endometrial scratching (ES) and implantation

There are several hypotheses on endometrial scratching supporting the positive effect on pregnancy rates. Over the past decade, endometrial scratching was proposed to improve implantation, but the exact mechanism remains unclear. In a preceding cycle, it improved clinical pregnancy and live birth rates in women with recurrent implantation failure, but not in an unselected subfertile woman undergoing IVF. Endometrial scratching is an intervention leading to enhanced endometrial receptivity by some mechanisms, such as inflammatory reaction, better synchronization of the endometrium, and inducing decidualization. There are a few types of scratching procedures, starting from using the curette with different catheters and finishing with hysteroscopic scratching. The techniques of hysteroscopic scratching are not sufficiently described in the literature. There isn’t any common consensus according to the technique and surgical tools. There is also confusion about the timeline of the procedure. Some authors support the follicular phase for the procedure, but others think that the luteal phase is more appropriate. There is no common consensus, and there are several points, such as many techniques described in the literature, it is usually performed using a soft plastic pipelle, endometrial biopsy catheter, differences in the number of times the procedure has been performed, variation in stimulation protocols, differences in timing.

Hysteroscopy

Hysteroscopy allows reliable visual assessment of the cervical canal, and uterine cavity for intrauterine adhesions, endometrial polyps, submucous fibromas, endometritis or uterine malformations that could interfere with implantation. One of the most beneficial impacts of hysteroscopy is the correction of specific uterine cavity abnormalities. Endometrial polyps and different degrees of septum or adhesions are the most common findings in women with implantation failure. Hysteroscopy is currently the only direct method for observing physiological and pathological changes of the endometrium, as well as accurate scratching and treatment.

FEI (Fundus Endometrial Scissors Incision)

FEI technique is always performed:
  • in a cycle with oral contraceptive pills (OCP)
  • one or two cycles before embryo transfer
  • in the follicular phase of the cycle (from day 6-10)
  • on the line from the right opening of the fallopian tube to the left
  • the incision is continuing within the connective tissue until the appearance of the first vessels
The main benefits of this technique are:
  • always in the cycle before the embryo transfer cycle which is giving the stability and the time for the inflammatory reaction
  • in the same, follicular part of the cycle and under the control of contraceptive pills
  • the technique is detailed described allowing operators to perform the procedure, in the same way, every time
  • it is performed under direct ‘eye’ procedure in contrast contraindication to all other ‘blind’ scratching techniques
It has been reported that the prevalence of minor intrauterine abnormalities identified by hysteroscopy is as high as 30 to 45% under normal transvaginal sonography, and abnormalities found by hysteroscopy are significantly higher in patients with previous failures. The results shown by Dr Najdecki (Assisting Nature) show a statistical significance with a p-value of 0.015 and a better result of pregnancy. In the group of hysteroscopy, it was about 73.7 compared to the non-hysteroscopy group with 57.34%. The live birth rate was higher in the hysteroscopy group than in the non-hysteroscopy group, at 56.14%.
At Assisting Nature, we try to create an ideal personalized donation program and using euploid blastocysts, we significantly increase pregnancy rate by over 60% per embryo transfer. Using euploid blastocyst and hysteroscopic fungus endometrial incision (FEI) and enhancing endometrial receptivity by inducing decidualization through inflammatory reaction leads to real pregnancy.

Conclusions

Recurrent Implantation Failure is a complex problem with a wide variety of etiologies and mechanisms, as well as treatment options. The recommendations for women with RIF vary depending on the source of their problem. The best, yet most complex answer is personalized medicine, a personal approach to each patient depending on a unique set of characteristics. Adding PGT and hysteroscopic Fundus Endometrial Incision (FEI) to egg donation cycles seems to be the state-of-the-art procedure leading to the highest possible results. Endometrial preparation regimens that incorporate antithrombotic agents, immunosuppressive drugs, and intralipid infusion could aid in the development of an optimal endometrial environment for implantation.

What is Hysteroscopic Fundus Endometrial Incision? - Questions and Answers

Can we use this method with our own eggs and not donor eggs?

Absolutely, the method is used for all purposes. We are using the fundus endometrial incision in every case, although we prefer to use this method after one embryo transfer failure. We propose a hysteroscopic examination and fundus endometrial incision to every patient. When we have the leftover embryos or blastocysts after a failed embryo transfer, and hysteroscopy was not done. It works in every case, not only in the case of egg donation. Before the second embryo transfer, it is absolutely necessary to use this technique.

I am 36 years old, I have one endometrial cyst. I had one failed PGT tested FET. I have 2 embryos left, which are PGT tested. How Hysteroscopic Fundus Endometrial Incision (FEI) is different than standard hysteroscopy? As I have already gone through hysteroscopy.

Some steps need to be taken. The first is the synchronization with your future embryo transfer cycle, we are performing the hysteroscopy before the embryo transfer, and the embryo transfer must be done in the next cycle or the third cycle. Only then the influence of the fundus incision gives the best results. After two cycles probably, this method is not going to work well. Secondly, this is a technique, which is very well performed, and with this, we have a very good view of the uterus, but it’s not only to see it, the point is to perform this incision in the fundus. This is the reaction from the endometrium, and due to this reaction, we have these benefits. It’s impossible to compare this technique with every simple diagnostic hysteroscopy. This is an advanced technique and more sophisticated. I try to cooperate with some doctors in the UK who can follow our steps and follow our advice. We performed some hysteroscopies this way with quite good results. After that, our transfers here in Thessaloniki were successful. The technique is not very difficult, but some points are required, like performing in the follicular phase of the cycle, from day 6 to day 10, and the embryo transfer must be performed in the second one, or the third cycle measuring from this point.

Can a patient do FEI with a natural cycle?

It’s also possible to perform this technique in the natural cycles, but it is better to use frozen embryos in this case. We collect the eggs and embryos afterward in the natural cycle, vitrify them at the blastocyst stage, and we perform this hysteroscopy procedure in the next cycle, and then in the third cycle, we try to transfer the embryos.

Could this technique be used for women with fibroids?

This technique is possible to be used in a woman with fibroids. However, it depends on the location of the fibroid, and if the fibroids are very close to the cavity. This is a general problem with embryo transfers, but if fibroids are endo-muscular or are in the uterus wall, there is no reason to connect the hysteroscopy with embryo transfer and not extracting these fibroids. Very small submucous, it’s no problem, we also have 2,3 cases with extracting small submucous fibroids during the hysteroscopy, it depends on the operator experience.

What about Platelet Rich Plasma therapy? Do you use that?

Yes, we use it but very rarely. If there is a case where the patient needs to use this technique, yes, we do it.

Do you know the increase in success rates with own eggs using this FEI method? Is it +10% as well?

Absolutely, it’s the same, but in every case, I would like to say it again, that the better way and the better results we get if we have the euploid embryos. In every case that we are going through IVF failure cycles or failure with embryo transfer, it is a very smart step to use the PGT-A technique to be absolutely sure that you are using the euploid embryos. If we have the euploid embryos, then the hysteroscopic procedure is very important, and we are talking about 10% and more.

Is this technique available in the US (FEI)?

Generally, the technique is available everywhere. Anyone who wants to perform this procedure is able to do it. I’m sure that it will be very popular next year after our presentations and after our research, it will be more popular, and probably it will be available in every country.

During the last transfer, the doctor was having a problem with opening my cervix as it is too tight, which resulted in pain during the FET transfer. Could it be the reason for the failed transfer? Is this technique (FEI) beneficial in such a scenario?

This is another issue. We are absolutely sure of using a hysteroscopy before the embryo transfer for cervix opening, and it will be performed with sedation, it’s very comfortable for the patient, without any pain, and this is also the experience for the operator. In the case of embryo transfer having all this information about the cervix and about the uterus is very important for the operator, it’s helping him to perform the embryo transfer, properly, and without any pain for the patient.  It’s possible to have lower implantation rates after a very difficult embryo transfer with difficulties in opening the cervix or going through into the cavity, yes, absolutely it’s possible, and we also prefer to use the hysteroscopy before.

Is there any risk for scars using these FEI techniques?

Generally, we haven’t got any problems until now using these techniques. It depends on the operator experience but using these modern hysteroscopies with a very thin injection needle, it’s about 4 millimeters.It’s very rare to have some complications during the hysteroscopy.

What are the costs of this procedure (FEI)?

In our unit, the cost is 1200EUR per procedure, all in the package.
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Authors
Robert Najdecki, MD, PhD

Robert Najdecki, MD, PhD

Robert Najdecki MD, Ph.D. is a Reproductive Gynaecology Specialist. His experience in diagnosis and treatment of fertility disorders, such as endoscopic surgery is long and extensive and includes more than 6000 stimulated cycles. Dr. Najdecki’s vast experience in reproductive gynaecology and embryology has contributed greatly to his achievements in the field, e.g. the second baby birth through IVF technique in Poland and the first transvaginal, ultrasound OPU (oocyte retrieval), which resulted in second IVF baby being born in the nation. These successes opened new doors to a new era in IVF techniques that continues till now. Assisting Nature IVF clinic provides international couples who are struggling to conceive with the most advanced donor egg programs in Greece.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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