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.
