Diana Obidniak, MD, Head of International Cooperation Department at AVA-Peter, is talking about endometriosis in the context of IVF and answers questions on how to manage this condition during IVF treatment.
Firstly, according to the doctor, the history of endometriosis is described to be ancient since some similar conditions and clinical manifestations have been detected for centuries. By comparison, endometriosis is still considered to be a mysterious disease even in the 21st century because of a general shortage of etiology information regardless of evidence-based investigations.
Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility.
In addition to that, endometriosis is still regarded as an actual problem as there are verifications that take place every 10 years due to clinical manifestations that delay a diagnosis. What is more, the average of verified endometriosis is 27 years old. According to the World Health Organization, more than 176 million women are believed to be affected by endometriosis.
Then, based on the session, a series of theories are analyzed in detail.
“The theory of retrograde menstruation” ( J.A. Sampson, 1921).
By that time, It was believed that having a retrograde flow of menstruation into the abdomen could provoke the formation of heterotopic endometriosis. Also, it was added that endometrial translocation during surgical interventions on the uterus could also cause the base for the formation of heterotopics. However, a great investigation was performed in 2005 by Marsh. E.E. and Leufer M.R. demonstrated that this theory did not apply to endometriosis.
Both of these theories involve an explanation of the appearance of endometriosis tissue outside of the reproductive system as other organs can also be affected such as the lungs. On the one hand, the appearance of endometrial tissue can be due to peritoneal and mesothelial metaplasia (Coelomic metaplasia). On the other hand, in dysontogenetic theory, endometriosis was explained as compromised embryogenesis with the development of endometrial tissue from abnormally located rudiments of the muller channel. Neither of these theories responded to the etiology of endometriosis in the reproductive system.
As a result, it was determined by worldwide investigators that investigation of the local disruptions was the focus of endometriosis as it was later revealed that certain hormonal disorders were involved:
In conclusion, these certain hormonal disruptions provide local hyperestrogenemia which results in enhanced elevated proliferation activity.
It is still a compromised theory that explains the formation of endometriosis as a result of epigenetic changes in one cell and affects the process of methylation and regulation of activity using micro RNA. Moreover, It is also said that microRNA shuts down a specific gene.
According to the doctor, it is known that many mechanisms and tools affect the fertility system through endometriosis. These are described to be not only simple things as disruptions of the egg transport process due to adhesions that ultimately produce a mechanical obstruction of the fallopian tubes and disruptions of sperm transportation but also to the growth of oxidative stress markers in the follicular fluid that eventually result in compromised endometrial receptivity and its implantation process among others.
All in all, the endometrium is compromised not only in morphological ways but also considering its functionality and so, the implantation process is always in discussion.
Unfortunately, a lower survival rate of embryos is perceived in patients with endometriosis along with a lower number of blastocysts at the end of embryo cultivation although there is much evidence that embryo quality is the same as in generation.
The endometrium is known as a biosensor that receives the signaling and quality of the embryo, providing a result for the whole organism if the embryo is good enough for implantation and pregnancy. These processes are related to receptivity and selectivity and can be altered either morphologically or functionally.
Regarding receptivity, due to progesterone resistance, pretreatment of different medications such as GnRH proved to be effective in improving ART outcomes. As regards morphological disruptions and alterations are called chronic endometritis, which is strongly associated with endometriosis despite being a separate disease. The difference between both is that chronic endometritis is an inflammation as the result of a micro bacteria, while endometriosis is the inflammation that results from our own epigenetic changes.
In addition, speaking of the diagnosis of external genital endometriosis, the gold standard to go is a laparoscopy while a hysteroscopy is said to be the most effective standard regarding internal genital endometriosis (adenomyosis).
Stages of restoration of reproductive function in endometriosis:
Above all, according to the doctor, the first goal is the removal of endometroid foci, which is the tissue growing outside the reproductive system as a means of reducing pain. Afterwards, the following steps should be considered:
It is believed that the most important thing in surgery and ART for endometriosis is age as performing surgery on a patient below the age of 28 years old enhances the possibility of natural conceiving while assisted reproductive technology would be highly suggested for patients over the age of 28 years old because of better results concerning the number of embryos. Finally, with patients over 43 years old surgery is the standard recommendation although not highly suggested because of the likelihood risk of cancer.
Case 1 – a 29-year-old woman, with endometriosis at stage IV, she already had surgical treatment of endometrioid cysts of both ovaries, with AMH= 0.31
After the surgery, she did not receive conservative treatment. After she came to the clinic, the patient and her partner were once again screened, and sperm analysis was normal, however, after performing the MAR test, which is used to detect IgG and IgA class anti-sperm antibodies in semen, it was at 80%. Another thing suggested and conducted was the application of Dienogest during 4 cycles and after that, a controlled ovarian stimulation and short protocol with an antagonist was performed through IVF/ICSI. Four oocytes were received, and one embryo was transferred on day 5. Another two embryos were vitrified. The patient got pregnant after her first attempt.
Case 2 – a 41-year-old woman, with endometriosis at stage IV, had a combined surgical treatment of endometrioid cysts of both ovaries and hormonal treatment with GnRH agonist for 6 months without add-back therapy.
The treatment was however stopped due to the severity of side effects. There was no response to controlled stimulation. Her AMH = 0.31, FSH = 22.3. When she came to the clinic (Ava Peter), Dienogestan for 3 cycles was suggested, and then IVF/ICSI treatment in the natural cycles was performed as part of the embryo banking (embryo accumulation) program. Three viable embryos were vitrified, one was transferred and once again the patient got pregnant after her first attempt.- Questions and Answers