Kinderwunsch I Autoimmun
Endometriose & Kinderwunsch
Jährlich erkranken geschätzt etwa 40.000 Patientinnen in Deutschland an Endometriose. Die Gesamtzahl der Betroffenen beträgt soweit bekannt bis zu 10% der fertilen Frauen. Die nicht diagnostizierte Dunkelziffer, dürfe allerdings weit höher liegen. Allzu oft führen Symptome und Beschwerden zu erheblichen Einschränkungen der Lebensqualität und auch der Fruchtbarkeit.
Bei bis zu 50% der Frauen mit unerfülltem Kinderwunsch ist eine unerkannte Endometriose zu vermuten.
Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosis may not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.
PMID: 28742581
Ursachen (nach wie vor) unbekannt
So ausführlich die Beschreibung, Klassifizierung und die symptomatische Behandlung der Endometriose vorangeschritten ist, sowenig ist über die eigentlichen Ursachen bekannt, auch die die Wissenschaftsplattform pubmed hierzu mehr als 26000 Studien ausweist.
Eine Reihe von Vermutungen und Therorien zu den Ursachen bestehen: Aufgrund der versprengten Gebärmutterschleimhaut, in der Regel in den Unterbauch, liegt die Vermutung nahe, dass es sich u.a. um eine über die Eleiter in den Bauchraum fortgeleitete Menstruation handelt. Spätestens aber seit sich Endometrioseherde in von der Gebärmutter entfernten Organen wie Lunge oder Gehirn nachweisen ließen, ist die alleinige These der kontinuierlichen Fortleitung nicht haltbar. Es muss also andere komplexer auf das "Gesamtsystem" Mensch bezogene Ursachen geben. Und hier setzt eine erweiterte holistisch - integrale Vorstellung zu den Gründen der Endometriose an.
Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of endometriosis is crucial for proper diagnostic and ordering the most effective treatment. Even though there is a large body of data regarding this pathology our understanding of the pathogenesis of this disease remains incomplete. The aim of this review is to summarize contemporary data regarding pathogenesis of endometriosis. Current data regarding endometrial origin, metaplastic and Mullerian embryonic rests theory will be reviewed here. Also genetic, epigenetic, environmental factors and immunological dysfunction role in endometriosis will be summarized. To conclude, a lot of effort must be put to integrate the abundant data from genetic, epigenetic and immunological studies to propose one coherent theory for the pathogenesis of endometriosis.
Die Forschung stockt
Eine pharmazeutische Forschung zur medikamentösen Behandlung der Endometriose findet vermutlich aufgrund der komplexen Ursachen kaum statt.
Studie
Hum Reprod Update. 2018 Sep 1;24(5):577-598. doi: 10.1093/humupd/dmy020.
Is it time for a paradigm shift in drug research and development in endometriosis/adenomyosis?
Guo SW1,2, Groothuis PG3.
BACKGROUND: The drug research and development (R&D) for endometriosis/adenomyosis has been painfully slow. Most completed clinical trials on endometriosis did not publish their results, and presumably failed. ( ) Given our growing understanding of the natural history of ectopic endometrium, it is also important to make an inventory of biologicals/compounds that are currently under development to see where we stand and whether they would stand a better chance of gaining regulatory approval than their predecessors.
OUTCOMES: Despite repeated calls for more transparency, only a small fraction of completed trials on endometriosis has been published. A large number of 'novel' compounds under development are simply repurposed drugs, which seem to be ill-prepared to combat the fibroproliferative nature of endometriosis/adenomyosis. This sobering picture indicates an alarming innovation 'drought' in the drug R&D front, resulting in trickling drug pipelines. Some trials foundered owing to unanticipated serious side-effects, or because attempts were made to suppress a target that can be compensated for by redundant pathways, but many failed in efficacy, indicating that the translational value of the current models is seriously questionable. All existing animal models of endometriosis do not recapitulate the key features of human conditions.
WIDER IMPLICATIONS: The glaring innovation drought in drug R&D for endometriosis/adenomyosis should sound alarms to all stake-holders. The failed clinical trials in endometriosis also indicate that some past research had serious deficiencies. In light of the recent understanding of the natural history of ectopic endometrium, it is perhaps time to shift the research paradigm and revamp our research focus and priorities.
PMID: 29893860 DOI: 10.1093/humupd/dmy020
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Auch deswegen liegt ein integraler (ganzheitlicher) Ansatz, der nicht ausschließlich die Organ - und Symptombehandlung in den Mittelpunkt der Behandlung stellt, nahe.
Umdenken
Biologische Integrativer Ansatz
In einer integralen Denkweise ist jede Aussaat, jede Erweiterung, jedes ungerichtete Wachstum von Körperzellen eine Ausdruck von Mangelzuständen, eine Überbelastung mit körperfremden Substanzen und/oder von Regulationsstörungen.
Es bedeutet nicht selten allerdings ein völliges Umdenken und eine therapeutische Kehrwende von der rein symptomatischen Behandlung (Operation, Medikation) auf die Fähigkeit jedes biologischen Systems zu setzen, sich am Ende selbst zu regenerieren.
Auch wenn die klassisch-gynäkologische Therapie (Bauchspiegelung, Herdentfernung) jeder integralen Behandlung vorangestellt werden sollte, scheint die systematische integrale Mit- und Weiterbehandlung eine mehr als sinnvolle Option, mit hoher Wahrscheinlichkeit gar die langfristig einzig erfolgversprechende.
Biologische antioxidative Immun / Therapie
Eine ganze Reihe valider wissenschaftlicher Arbeiten zeigt signifikante Evidenz von integralen Behandlungen. Dies bestätigen zudem eigene langjährige Erfahrungen.
Recently, accumulating evidence has strongly implied that female infertility has severely deteriorated during the last few decades, particularly in Western countries.1 As a leading cause of infertility, endometriosis (EMs) remains one of the most common estrogen-dependent diseases characterized by ectopic proliferation of endometrial tissues in extrauterine sites. EMs leads to severe dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility and affects 6% to 10% of reproductive-aged women worldwide.2 However, little is known about the pathogenesis of EMs. Despite several explanations of the causes of EMs, the theory of retrograde menstruation proposed by Sampson3 is still the most widely accepted.
Recent studies have highlighted the importance of oxidative stress in the occurrence and development of various diseases, including EMs.4–6
Indeed, several studies have suggested that oxidative stress is a potential factor largely responsible for local tissue destruction and disease exacerbation in patients with EMs.7 In fact, EMs has been considered to be a complicated chronic inflammatory process associated with oxidative stress markers such as superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), and reactive oxygen species (ROS).8–11 Moreover, Ngô et al.12 found that a significant elevation of endogenous oxidative stress biomarkers resulted in promotion of the proliferative capabilities of endometriotic cells obtained from patients with EMs via MAP kinase ERK1/2 activation, leading to EMs progression. Furthermore, increasing evidence indicates that patients with EMs have lower levels of several antioxidant components such as vitamin A (VitA), VitC, and VitE and SOD in follicular fluid (FF) surrounding mature oocytes before ovulation and these lower levels reflect the reproductive performance of oocytes.13 Thus, an imbalance in ROS production in ovarian FF might lead to an adverse effect on oocyte quality, implantation, and early embryo development.
IVF-ET has been shown to be an optimal therapeutic strategy for patients with EMs-related infertility who failed to conceive with insemination.14 For example, Turocy et al.15 reported that the frequency of live birth and clinical pregnancy were relatively improved in patients with EMs undergoing frozen embryo transfer (FET).
A previous study showed that compared with antioxidant treatment, .. with antioxidant vitamin (VitC) led to a significant decrease in the peritoneal fluid concentrations of inflammatory factors, including the chemokine regulated on activation, normal T cell expressed and secreted (RANTES), interleukin-6, and monocyte chemotactic protein-1, and a reduction of chronic pelvic pain in patients with EMs.16