Etiology of adenomyosis-Solved

1-10-19.

Q.1:-What is meant by “archi myometrium “ ? These words are sometimes sometimes quoted by Sonologists in the report page in ART Centers??

Q, 2:--What is meant by Junctional Zone & what is the role of  such  J Z in the etiogenesis of adenomyosis. ,Ans:à  The area of endo-myometrial junction is known as junctional zone. 

Junctional Zone consists of three layers as detailed below from outside inwards à:

A) . Innermost part of myometrial layer

B) . and the sub vascular layer just above the above the endometrial cavity – also known as archi myometrium

C)  Outer most part of endometrial layer often called as basal endometrial layer.

We know that the normal thickness of junctional zone is 7-8 mm. But in  adenomyosis the junctional zone thickness increases to > 12mm.

 Q.3:-Why & how adenomyosis develops? In case of adenomyosis this Jun zone play a vital part and in most of the cases the disease initiates with the invagination of J  Z into myometrium due to various causes of which abnormal uterine peristalsis is mostly attributed.

Q, 4 . Abnormal peristalsis , so what?? Why invagination of junctional zone? What is the cause   ? Ans: Well , abnormal peristalsis  of any etiology cause high intra uterine pressure.   The process of invagination of this JZ( junctional zone)àinto the inner part of myometrium    is thought to be originating  either due to a) abnormal peristaltic function or wave of peristalsis originating in this J Z or  b)  local structural abnormalities in the myometrial tissue(for instance associated myoma) . It is wortnh remembering that  the  structural abnormality( etiology no 2-vide supra)  may be congenital or acquired. These two factors are the chief causes of genesis of adenomyosis –after few  years usually favour development of adenomyotic  uterus. Besides  possible etiology No 3:- abnormal hormonal and possible etiology No 4:-   immunological conditions also have a commanding role to play in the normal functions of JZ and if any one goes wild then this increased pressure induced by uterine peristalsis may cause invagination of endometrium. We have already discussed that  that the normal thickness of junctional zone is 7-8 mm. In adenomyosis the junctional zone thickness increases to > 12mm.

Q.5:-How adenomyosis cause subfertility or enhances spont miscarriage rate?

Ans:-Impediments to conception is brought about by A) increased uterine peristalsis, as mentioned earlier, which is partly governed by junctional zone. In cases of adenomyosis there is primary abnormality in junctional zone thickness à which leads to uterine dysperistalsis and therefore B) impairment of sperm transport...  In addition in adenomyosis there is also C) increased colonization by macrophages’) Secretory products of these macrophages have adverse impact on oocyte quality fertilization and implantation. These noxious products released  by macrophages trickles down to F tubeàthen via fimbrial end to the surface of ovary and it is believed that the said noxious agents / toxins liberated by endometrial macrophages is brought about via utero ovarian countercurrent systemà impedes oocyte dev environemetyt.

Q 6: What is Junctional Zone? Junctional Zone consists of three different components:-

a. On the outermost part is “innermost myometrial layer”.

B. In the middle part is “sub vascular layer deep to but adjoining the endometrial cavity – also known as archi myometrium “

C. and most inside close to uterine cavity is the “basal endometrial layer”’

We know that the normal thickness of junctional zone is 7-8 mm. But in adenomyosis the junctional zone thickness increases to > 12mm.

Q.7. what is meant by normal uterine peristalsis? How such peristlasis may go wild and may become an etiologic factor of genesis of adenomyosis? Ans: Increased peristalsis which creates increased intra uterine pressure – leading to invagination of basal endometrium into the myometrium --Uterine myometrium has a regular pattern of peristalsis regulated by endocrine and paracrine stimuli. Junctional zone thickness causes increased peristalsis which creates increased intra uterine pressure – leading to invagination of basal endometrium into the myometrium. Invagination is more commonly found on posterior wall of uterus. Invagination is also facilitated by weakness of smooth muscle tissue of uterus .Weakness may be due to high estrogen  concentration in the local area or impaired immune related growth factor.

Q8. What are the other pelvic pathologies which may be associated with adenomyosis? Apart from pelvic endometriosis adenomyosis may be associated with other pelvic pathological conditions like 1) leiomyomas 2) endometrial hyperplasia 3) endometrial polyp 4) atypical endometrial hyperplasia and rarely 5) adeno carcinoma. However presence adeno myoma or adenomyosis has no adverse effect on the prognosis of endometrial carcinoma.

Q.9. How we can confirm the clinical diagnosis of adenomyosis? There are two modalities which help us to confirm the diag of adenomyosis? Such are 1) MRI 2) USG.: In USG we should look for:-

1) Heterogeneous myometrial area.

2) Globular asymmetric uterus.

3) Irregular cystic spaces.

4) Myometrial linear striae.

5) Poor definition of endomyometrial   junction.

6) Myometrial anterior- posterior wall asymmetry.

7) Thickening of anterior and posterior wall.

8) Increased or decreased echogenecity

Most of us use only USG for cost savings while others have used all both parameters for diagnosis of adenomyosis .Hysteroscopy is more helpful in diagnosing than laparoscopy...

Q.10: How best to treat adenomyosis?? A) If Uterus exceeds 10 cm –presenting with menorrhagia and dysmenorrhea hysterectomy with preservation of ovaries for future surrogacy is considered to be the rational /effective treatment. Therefore Conservative surgery +- agonist (GnRH agonist) or one can use Danazol loaded intra uterine device. In rest cases where the uterine length is less than 10 Cm then following 7 options are available. Like 1)GnRH a for six months 2) Wedge biopsy 3) Uterine artery embolization 4) High intensity focused ultrasound

5) Ultra long GnRH followed by IVF vs. conventional Ivf. 6)

Combination of conservative surgery plus GnRH-a

7) LNG or danazol loaded IUs 8) Conservative surgery alone .9) High intensity focused ultrasound & Uterine artery embolization 10) Laparoscopic partial resection of uterus with uterine artery occlusion.

Q.11: What will the Obstetric Outcome in adenomyosis? Ans:-The obstetric outcome in an adenomyotic uterus include 1) Increased risk of preterm premature rupture of membranes 2)

Uterine rupture or perforation -29 cases from 1904 to 1984 plus an ectopic pregnancy in adenomyotic area were reported by Aziz et al 3) Rapid enlargement of adenomyotic uterus in pregnancy conceived after controlled ovarian stimulation has been reported. In fact, ART may lead to red degeneration during pregnancy and 4) PPH during and following delivery.

Q. 12: If you like to moderate a session in a CME on adenomyosis / endometriosis then may put such 11 questions as Chair person. I firmly believe the Conference Hall will be vacant and all the delegates including the panelists will be assembling there.

 Be that as it may what are those tips which will cause annoyance to audience??  :

Take home message 1:-Diag modality: The best method??  Apart from many diagnostic markers as is imaged by MRI and or USG- a) thickened endomyometrial junctional, b) anterior posterior uterine wall asymmetry c) heterogeneous myometrial areas with irregular myometrial cystic spaces are the characteristics for diagnosis of adenomyosis. It is believed that increased peristalsis which creates increased intra uterine pressure – leads to invagination of basal endometrium into the myometrium.

Take home message 2:-

Etiology? What cause adenomyosis i.e. formation of ectopic stromal tissues /glandular/surface epithelium of endometrium to go inside the deep into myometrium? Apart from being a diagnostic parameter through USG  and MRI – JZ thickness has a great impact on inducing normal myometrial contractility which creates a favorable peristaltic movement of the myometrium for sperm and embryo transport within the uterine cavity. This coordinated movement of JZ is governed by many endocrine, neuronal & paracrine and growth factors. We know that the normal thickness of junctional zone is 7-8 mm. In adenomyosis the junctional zone thickness increases to > 12mm as it is overactive and in most cases of adenomyosis the disease is initiated from this JZ.

Take home message: 3:- Why subfertility?? 1) The myometrial peristalsis of may misdirect sperm entry into the uterine cavity which may be an independent cause of infertility in women with adenomyosis. 2) Other direct cause of infertility due to adenomyosis only is migration of macrophages into the uterine myometrium leading to production of local inflammatory exudates. 3) Release of exudates within the myometrium produces adverse utero ovarian reflex signal to the developing follicle in the ovaries resulting in liberation of poor quality oocytes.

Take home message 4:-Besides subjective symptoms of dysmenorrhea and menometrorrhagia there are four other objective signs for diagnosis of adenomyosis. These are A) laparoscopy or B) hysteroscopy with or without directed myometrial biopsyà histology. C)  Transvaginal ultrasonography and 4) MRI. TVUS and MRI are non invasive and dependable diagnostic procedures. Between the two, USG is easily available and least expensive.

Take home message 5:-In initial years association of adenomyosis with pelvic endometriosis was reported to be much less than what is being reported currently. This is because of improvement of diagnostic facilities awareness of patient population and perhaps late marriage of women.

Take home message 7: TR of adenomyosis: Some without desire for babv: Currently with adenomyosis infertility is the primary problem – conservative line of treatement is the rational approach. Medical treatment with 1)GnRH a 2)danazol or 3)aromatase inhibitors , 4) LNG-IUS and recently introduced 5) dienogest are effective but not very popular for fertility restoration

Medical TR: - Adenomyosis has a negative impact on ART outcome.

With conservative surgical treatment or with ART may produce some positive outcome.

High intensity focused ultrasound or uterine artery embolization are the alternative options with questionable outcome.

Diffuse uterine adenomyosis measuring 10 cm or more with menometrorrhagia is beyond the scope of conservative management:--Such patients require abdominal hysterectomy with preservation of ovaries for future possibility of surrogacy.

Impact of adenomyosis on obstetric outcome includes – miscarriage, ectopic pregnancy within the adenomyotic foci, preterm labor, uterine perforation, and postpartum hemorrhage.