endometriosis and adenomyosis Flashcards
How to diagnose endometriosis? (ESHRE + RANZCOG)
ESHRE (2022): Laparoscopy is no longer the diagnostic gold standard and it is now only recommended in patients with negative imaging results and/or where empirical treatment was unsuccessful or inappropriate.
RANZCOG (2021): Still considers laparoscopy and biopsy the gold standard. Can be reasonably suspected and empirically managed. Imaging is also used in the diagnosis - TVUS and MRI.
Abnormalities in the endometrium caused by adenomyosis
- Progesterone resistence (KRAS mutation caused reduced Progesterone receptors)
- Abnormal contractility (driven by Prog resistence)
- Hyperinflammation +/- chronic endometritis (Pro-inflam cytokines - IL-1beta, IL-6, IL-8 then increases STAT3)
- Impaired decidualisation (decreased HOXA10 HOXA11)
- Hyperproliferation - epithelial cells sustained (Ki67+ve)
Adenomyomectomy - what and pros and cons
Surigcal procedure to resect adenomyosis. Not performed in NZ or Australia.
Pros:
Decrease in pain symptoms, ?miscarriage, pPROM, PET, SGA, degeneration of adenomyosis.
Cons:
Increases placenta accreta spectrum quite considerably, increases caesarean and caesarean hysterectomy, clinical evidence on benefit in infertilty is poor, uterine ruptures increased.
How does endometriosis lead to infertility
Multifactorial,
Social determinants (pain, access to care, inability to engage in penetrative intercourse)
Factors associated with lesions (adhesions, inflammation, distortion of anatomy, tubal dysfunction)
Those not related with lesions – factors at the level of HPO and reproductive tract (decreased ovarian reserve, oocyte quality, sperm-oocyte interaction, decreased endometrial receptivity, increased uterine contractions).
Aetiology of adeomyosis
Poorly understood.
1. endomyometrial invagination of the endometrium.
2. de novo development from embryologically misplaced pleuripotent mullerian remnant
3. Invagination of the basalis proceeding along the intramyometrial lymphatic system.
4. Originating from bone marrow stem cells that are displaced through the vasculature.
Gut and uterine microbiome and endometriosis
Gut microbiome = shown to be changes in the gut microbiome in those with endometriosis
Disrupts immune function, exacerbates chronic inflammation, exacerbates gut symptoms.
Gut estrobolome – bacterial genes present within the gut are able to metabolise oestrogens, produce enzymes that can then modify the bioavailability of oestrogen.
Variations in the gut microbial community can impact oestrogen metabolism.
Uterine microbiome
Fusobacterium may facilitate endometriosis through inflammatory effects on eutopic endometrial fibroblasts.
High Hz of fusobaceterium in euptoic endometrial and ovarian endometriotic samples relative to those without endometriosis.
TVUS for endometriosis - key components
Must be experienced endometriosis scanner must include:
1. scans though the posterior vaginal forni
2. assessing the sliding sign
3. identifying the USLs.
proposed etiology theories of endometriosis development
Sampson’s theory (retrograde menstruation) (90% of women have retrograde menstruation and only 11% develop endometriosis - why? - likely immune abberations)
Coelomic metaplasia (originates from the metaplasia of specialised cells that are present in the mesothelial lining of the visceral and abdominal peritoneum).
Induction (results from the differentiation of mesenchymal cells, activated by substances released by the degenerating endometrium that arrives in the abdominal cavity)
Embryonic rest (defect of embryogenesis – mullerian duct maldevelopment could cause the spread of endometriotic cells across the posterior pelvic floor and the persistence of embryonic cell rests).
Stem cell theory (Stem cell theory posits that the cells responsible for the regeneration of the endometrial lining during one’s menstrual cycle play a role in the development of endometriosis. The spreading of these stem cells to ectopic regions can then lead to the differentiation of endometrial cells and cause endometriosis.)
pathophysiology of endometriosis and infertility
Distorted pelvic anatomy
Altered peritoneal function
Altered hormonal and cell mediated function
Endocrine and ovulatory abnormalities
Impaired implantation
Oocyte and embryo quality
Abnormal uterotubal transport
Drugs recommended for endometriosis-associated pain
ESHRE:
1. Analgesia (NSAIDs alone or in combo with other analgesia) (WEAK)
2. COCP (STRONG)
3. Progestogens (depot MPA, cyproterone acetate, MPA, northisterone acetate/norethindrone, desogesterl, dienogest, gestrinone. (NB - danazol no longer recommended).
4. LNG-IUS or etonogestrel-releasing subdermal implant (implanon)
(NB Jadelle is levonorgesterol and not recommended in guideline) (STRONG)
5. GnRH agonists as second line (due to side effect profile - VMS and BMD loss), add back combined therapy can reduced side effects and should be considered. (STRONG)
5. GnRH antagonists second line option -oral formulations now available (WEAK)
6. Aromatase inhibitors (STRONG???)
Surgical interruption of pelvic nerve pathways - two types used in endometriosis and ESHRE recommendation
Laparoscopic uterosacral nerve ablation (LUNA) - not recommended
Presacral neurectomy (PSN) - beneficial in treating midline pain as an adjunct to conventional laproscopic surgery, requires a high degree of skill and is assoc. with higher operative risk ( bleeding/constipation/urinary urgency/painless first stage of labour)
Evidence for surgically removing endometriosis to improve pain (stage 1/2)
Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. (2 small RCTs only, very low quality evidence).
Currently a registered trial (Esprit2) looking at randomising patients with CPP and superficial endo to diagnostic lap versus.
Evidence in improvement in QoL scores have stronger evidence to support excision. Improved mental componenet score but not physical component score. Sexual satisfaction scores also improved.
Excision recommended over ablation
EHP-30 - what is it?
Endometriosis Health Profile is a health related Quality of Life (HRQoL) patient self-reported outcome tool. (Has been validated). Also a short version (EHP-5)
Covers;
Pain (11)
Control and powerlessness (6)
Social support (4)
Emotional well-being (6)
Self-image (3)
Evidence to support removal of advanced DIE/endometrioma for pain
Surgical removal of deep endometriosis may reduce endometriosis-assicated pain and improve QoL.
Removing endometrioma has not been studied using RCTs for reducing pain symptoms.
Nerve sparing operative laparoscopy should be performed and these surgeries should be done by experts.
No RCTs for hysterectomy improving pelvic pain, but ESHRE states can consider it (+/- ovaries) + all visible endometriosis. Must be aware it may not help cure the disease.
Ovarian suppression treatment to improve infertility in endometriosis
Based on the results of the Cochrane review, suppression of ovarian function (by means of danazol, GnRH agonists, progestogens, OCP) to improve fertility in women with endometriosis is not effective and should not be offered for this indication alone (strong recommendation).
Hormonal therapy post surgery in those TTC
Women seeking pregnancy shouldn’t be prescribed postoperative hormonal suppresion with the sole surpose to enhance future pregnancy rates.
Those not planning to conceive after surgery can be offered hormonal suppresion therpay as it doesn’t negatively impact future fertiltiy and improves the immediate outcome of surgery for pain.
Other medication treatments to improve fertility in those with endometriosis?
None that should benefit - pentoxifylline, NSAIds, letrozole outside of ovulation induction shouldn’t be prescribed to improve pregnancy rates.
Evidence of stage 1/2 excision and natural fertility
Peritoneal endometriosis
Although the Cochrane review does not specifically address endometriosis subtypes, it could only identify and include trials on rASRM stage I/II endometriosis (Bafort, et al., 2020). Therefore, their findings could be extrapolated to peritoneal endometriosis (or at least the absence of large endometrioma and/or deep lesions with extensive adhesions). Although laparoscopic surgery was found to increase (natural) viable intrauterine pregnancy rates, no data were found on live birth rates. It should also be noted that none of the studies discussed were stratified according to the Endometriosis fertility Index (EFI).
Endometriosis Fertility Index
An end-of-surgery scoring system that predicts non-ART pregnancy rates (natural conception or IUI) after surgery. It was derived from prospective analysis of clinical data and has since been (externally) validated in over 30 studies, of which the majority were evaluated in a meta-analysis (Vesali, et al., 2020) confirming its good performance despite substantial heterogeneity between studies. By scoring patient-related factors (age, duration of subfertility and history of prior pregnancy) and surgical factors (‘least function score’ of the tubes and ovaries, endometriosis lesion and total score as extracted from the rASRM staging) factors, a score between 0 and 10 is generated. This score is strongly correlated with postoperative non-ART pregnancy rates and can therefore be used to counsel patients on their reproductive options, although it assumes normal gamete function.
IVF and endometriosis
- Stage1/2 endometriosis - same number of oocytes retrieved, lower fertilisation rates, no reduction in implantation, clinical pregnancy or live birth rates compared to women without endometriosis.
- Stage 3/4 endo - lower number of oocytes obtained, lower implantation, clinical pregnancy and trend to lower live birth was seen.
- Endometriomas - number of oocytes and M2 oocytes retrieved were lower, blastocysts, clinical pregnancy rates, live birth rates were all the same as controls.
FIGO MUSA group features of adenomyosis on TVUS
Asymmetrical myometrial thickening
Myometrial cysts
Hyperechoic islands
Fan shaped shadowing
Echogenic subendometrial lines and buds
tranlesional vascularity
Irregular junctional zone
Interrupted junctional zone
*junctional zone may be best evaluated with 3D USS
* presence of 2 or more is highly associated with adenomyosis.
ENZIAN scoring system
comparing enzian, rASRM and EFI
rASRM
Separated into 4 stages:
Minimal (1-5) -
Mild (6-15) -
Moderate (16-40) -
Severe (>40) –
Broken down into endometriosis, posterior cul-de-sac obliteration, adhesions
Endometriosis further broken down into superficial or deep and into peritoneum, ovary.
Adhesions separated into filmy or dense and described for ovary and tubes. Broken down to <1/3 , 1/3-2/3 or >2/3
