Adenomyosis in pregnancy

1. Adenomyosis in
Pregnancy
DR . VIDA SHAFTI .ASSISTANT PROFESSOR,

3. Introduction
 Adenomyosis is a common benign gynecologic disorder, affecting
20%–35% of women of reproductive age, in which ectopic
endometrial glands or stroma are found within the uterine
myometrium (1). These endometrial glands may undergo cyclical
changes with the menstrual cycle and changes during pregnancy
(2).

4.  Endometriosis and adenomyosis exhibit overlapping
phenotypes. Adenomyosis has been referred to as
“endometriosis interna” due to its resemblance to
endometriosis both histologically and phenotypically.
while the diseases have many common features, they also
exhibit a number of differences. (13)

6. Theories
 (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of
endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4)
infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from
the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and
pituitary hormones; and (6) abnormal uterine development in response to genetic and
epigenetic modifications.
 (7) Numerous epidemiology and experimental studies support a role for environmental
endocrine disrupting chemicals (EDCs) in the development of endometriosis; however,
only a few studies have examined the potential relationship between toxicant exposures
and the risk of adenomyosis.

9. Prolactin

12. Pathogenesis of uterine adenomyosis:
invagination or metaplasia?
 Invagination of the endometrial basalis: hyperestrogenism,
hyperperistalsis, and TIAR( tissue injury and repair) mechanism
activation. (A) A hyperestrogenic condition in the eutopic uterus may lead
to increased proliferation in the endometrial basalis and tissue
microtrauma in the vicinity of the JZ, thus allowing endometrial
intramyometrial invagination. (B) As a consequence of tissue
microtrauma, the TIAR mechanism is activated generating a mechanism
of positive feedback whereby estrogen production promotes uterine
peristalsis and further autotraumatization, progressively worsening the
microtrauma and endometrial invagination and eventually leading to
adenomyosis establishment.(14)

15. Age
 Historically, most patients diagnosed with adenomyosis were
parous women aged 40–50 years, with rare cases in women
younger than 40 years.
 older studies that predominately used hysterectomy specimens for
diagnosis. In recent years, with use of less invasive diagnostic
criteria, adenomyosis is now recognized in younger women. In
symptomatic nulliparous women aged 18–30 years undergoing US,
diffuse adenomyosis was found in up to 34%

16. Juvenile cystic adenomyoma

17. Risk Factors
 Risk factors for adenomyosis include increasing age, increasing parity, cesarean
delivery, and pregnancy termination, as well as excess estrogen exposure states
such as early menarche, obesity, and short menstrual cycles. Adenomyosis is also
frequently associated with other gynecologic diseases such as fibroids, polyps,
and endometriosis.
 Women with adenomyosis are at higher risks of endometrial and thyroid cancers,
while women with endometriosis are at higher risks of endometrial and ovarian
cancers.(1)(12)
 According to the literature, genetic mutations, epigenetic changes, and
inactivation of specific tumor suppressor genes in adenomyosis are still poorly
understood. (12)

18. Symptoms
 Adenomyosis is a common disorder of the uterus, and is associated with an enlarged
uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility.
endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium
where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells.
While up to one-third of patients are asymptomatic, two-thirds of patients may
demonstrate a variety of symptoms associated with adenomyosis, including menorrhagia,
dysmenorrhea, and metrorrhagia
Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis,
angiogenesis, and contractile abnormalities in the endometrial and myometrial
components.

19. • Painful menstrual cramps (dysmenorrhea).
• Heavy menstrual bleeding (menorrhagia).
• Abnormal menstruation.
• Pelvic pain.
• Painful intercourse (dyspareunia).
• Infertility.
• Enlarged uterus.

20. Pathology

22. Adenomyosis and Infertility
 Although evidence is inconsistent, adenomyosis is
thought to be associated with infertility, potentially
because of impaired sperm transport from
dysfunctional uterine peristalsis or defects in
decidualization leading to impaired implantation
(3).

23. Adenomyosis Classification
 In 1908, TS Cullen classified adenomyosis into three
distinctive subtypes of adenomyosis based on
morphologic appearances [1]. He described: (i)
smooth enlargement of the uterus without disturbing
its contour, (SS, type 1 or type 3, AM) (ii)
subperitoneal or intraligamentary adenomyomata,
(SS, type 4, AM) (iii) submucous adenomyomata.
(SS, type 3, AM)

24. Different classifications of Adenomyosis
(16)

26.  Some patterns of uterine adenomyosis (AM) are more
common in China than Europe or USA. In this new
classification derived from clinical observations in
Shanghai, there are four patterns of adenomyosis, and,
three out of the four have neurologic abnormalities
associated with specific injuries to uterotubal nerves
"Shanghai system" (SS), types 1-4, AM)

28. Different types of Adenomyosis
 Concurrently, as maternal age trends toward pregnancies when
women are in their later 30s and 40s, as assisted reproductive
techniques are more successful, and as US equipment is more
advanced, adenomyosis is becoming more commonly diagnosed at
routine pregnancy US examinations and is best seen in the first
trimester. Given the hormonal changes in pregnancy, adenomyosis
has unique and variable appearances at US and MRI depending on
the diffuse, focal, or cystic pattern of adenomyosis present in the
prepregnancy state.

36. Classification with MRI

38. Type 1 AM, Diffuse, symmetric, painless
adenomyosis
 (a) all these women had, at least one, second trimester abortion,
(which can avulse both uterosacral ligaments in nulliparous
women) (b) there are no nerves of any kind at the endometrial-
myometrial nerve plexus which is continuous with the nerves in the
uterosacral ligaments (c) all uteri in this series had similar histology
of uterus, uterosacral ligaments and Fallopian tubes, and weighed
between 260g and 1160g, (d) no woman complained of pain; the
worst symptoms being “heaviness” with “pressure” on bladder and
bowel leading to frequency passing urine, and, constipation.

39. Type 2 AM, asymmetric, painful
adenomyosis (SS type 2, AM
 there is aberrant reinnervation in the myometrium in association with
asymmetric, painful, adenomyosis associated with the endometrial-myometrial
interface (SS 2, type 2 adenomyosis, Figure 2A-F). These often occur in
association with collateral sprouting of nerve bundles that is pathognomonic of
prior traumatic injury .In many cases we find evidence of over-vigorous uterine
curettage, difficult vaginal delivery, or, excessive uterine activity associated with
administration of oxytocin, prostaglandins or misoprostol – drugs that were not
available to TS Cullen in 1908 or JR Sampson in 1921. The injury is largely
confined to the body of the uterus and the clinical presentation often includes
irregular, painful bleeding at reduced uterine weights (80- 150g) that regularly
results in hysterectomy.

40.  There are two patterns of neural injury caused by, at least, two different patterns of
trauma, in type 2, AM. Firstly, there is a degree of traction to the cervix that is not
sufficient to completely avulse the uterosacral ligaments, but, allows them to reattach to
the lower uterus and cervix as scarring .that enables a “bridge” for reinnervation of the
lower uterus .Over-vigorous curettage at the same procedure causes a direct injury to the
endometrial-myometrial interface creating aberrant reinnervation at the endometrial-
myometrial interface .with subsequent, marked dysmenorrhea that often necessitates an
early hysterectomy at low uterine weights (80-150g) .Both of these specific injuries may
also result from trauma during vaginal delivery; typically uterine tachsystole replicates the
partial injury to the endometrial-myometrial interface whereas big babies (>4000g),
malpresentations, and, operative vaginal deliveries may all contribute to injuries to the
insertions of the uterosacral ligaments and their, contained uterotubal nerves.

41. Type 3 AM, painful or painless,
adenomyomas, (SS type 3, AM
 there is a circumscribed tumor that often “maps” to either the anatomic position
of the endometrial-myometrial or subserosal nerve plexi, or, most commonly the
posterosuperior myometrium of the uterus. Histologically, there is loss of nerve
fibers in myometrial nerve bundles adjacent to painless adenomyomas and
leiomyomas (SS 3, Type 3 AM), often with large numbers of narrowed arterioles
adjacent to the tumor. We believe these tumors arise from pre-uterine neural
injuries because there is no evidence of collateral sprouting in these nerve bundles
implying that a focal, pre-uterine injury to the nerve bundle had taken place
resulting in loss of specific, nerve fibers

42. Type 4, painless, intraligamentary
adenomyoma (SS type 4, AM)
 TS Cullen was aware of this least common pattern of adenomyosis though we are
aware there are also adenomyomatous patterns of uterine polyp, and,
pedunculated forms of adenomyosis that appear to have a non-neurologic origin.

51. Sonography

61.  Compared with HIFU treatment alone, HIFU combined with GnRH-a for the
treatment of adenomyosis has greater efficacy in decreasing the volumes of the
uterine and adenomyotic lesions and alleviating symptoms. However, since the
number of the included studies was too small and most of them were written in
Chinese, this conclusion needs to be referenced with caution. And the long-term
evidence of its efficacy is still insufficient.
•. 2021 Aug 16;9:688264.
doi: 10.3389/fpubh.2021.688264. eCollection 2021.
Efficacy of High-Intensity Focused Ultrasound Combined With GnRH-a for Adenomyosis: A Systematic
Review and Meta-Analysis

62. Complications of adenomysis on
pregnancy
 Recognizing the different manifestations of adenomyosis is crucial to accurately
identify this otherwise benign condition. The appearance of adenomyosis in
pregnancy can mimic myometrial and placental abnormalities and is also
potentially associated with poor pregnancy outcomes such as spontaneous
abortion, preterm birth, and even fetal growth restriction (4-5)

63. Cause, Pathogenesis, and Histopathologic
Findings
 To date, the cause of adenomyosis remains largely unknown, although two main theories are
generally accepted. The first proposed and most widely accepted and investigated theory is of
migration of endometrial tissue through the basalis layer into the myometrial junctional zone. The
migration is thought to occur because of trauma or other inciting event such as pregnancy or
surgical damage. There, the ectopic endometrial tissue (both glands and stoma) incites
inflammation and fibrosis and leads to increased uterine peristalsis. These reactions are thought to
further induce injury in a cyclical manner, recruiting additional endometrial migration (6). The
second and more recently proposed theory states that adenomyosis is a congenital disorder
arising from fetal müllerian remnants implanted in the junctional zone, or alternatively, from
differentiation of endometrial stem cells in the myometrium. Evidence to support this theory rests
in the identical histologic findings of deep endometriosis encountered in the posterior outer
uterine wall. In addition, case reports of adenomyosis in patients with Mayer-RokitanskyKüster-
Hauser syndrome, a müllerian development anomaly often with no functional endometrium,
further support this hypothesis of a congenital cause (6).

64.  During pregnancy, hormonal changes are facilitated predominantly by
progesterone along with additional complex molecular pathways, inducing
decidualization of endometrium both inside and outside the uterus, which is the
same pathophysiologic mechanism as decidualized endometriomas previously
described in the literature (7). The ectopic endometrium causes myometrial
smooth muscle hyperplasia and hypertrophy, which account for the gross
pathologic appearance of adenomyosis.
 The pathophysiologic mechanism for myometrial cyst and cystic adenomyosis
formation is thought to form as a result of cyclic hormonally controlled
proliferation and secretion (8)

65.  Occasionally, these are seen as small foci of hemorrhage. The mechanism for this
is unclear, given that adenomyosis arises from the basal, not functional, layer of
endometrium but is likely either hormonally controlled or a spontaneous
hemorrhage.

67. Sonographic Classification of Adenomyosis
 For the gravid uterus, we identify three sonographic appearances of adenomyosis:
diffuse, focal, and cystic .(10)

68. Diffuse Adenomyosis in Pregnancy
 Diffuse adenomyosis has an infiltrative appearance at US: the myometrium is
thickened and heterogeneous with echogenic islands of ectopic decidualized
tissue dispersed throughout. Even though not a focal abnormality, diffuse
adenomyosis can still cause a mass effect on the gestational sac if the entire
anterior or posterior wall is involved.
 Doppler US characteristics of adenomyosis are not specific but are often unique.
Uterine fibroids often show circumferential vascularity. However, color Doppler US
in adenomyosis typically shows increased and more diffuse flow within the
affected area as well as the normal subplacental vessels, which run parallel to the
placental attachment

71.  . More important is noting the location of adenomyosis in the gravid uterus and its
relationship to the placental implantation site. The location of the adenomyosis
within the uterine parenchyma in relation to placentation is the most useful
descriptor in pregnancy, as the placental attachment on the area of adenomyosis
can be associated with third-trimester growth restriction and preeclampsia (10)

72.  In general, myometrial disease is described by location and size. While exact
measurements are often difficult to acquire in adenomyosis, diffuse changes can
also be expressed as the subjective percentage of total myometrium involved and
by location within the uterine parenchyma (anterior wall, posterior wall, fundus,
lateral uterus, or lower uterine segment). Unlike with fibroids, descriptive terms
indicating the depth of uterine involvement such as submucosal, intramural,
subserosal, or pedunculated are not particularly useful in pregnancy. More
important is noting the location of adenomyosis in the gravid uterus and its
relationship to the placental implantation site.

74.  During pregnancy, the diffuse nature of the preexisting adenomyosis can lead to
bizarre appearances at US, causing a diagnostic dilemma .
 In the first trimester, when florid adenomyosis changes are present because of
decidualization and wall thickening, potentially eccentrically distorting the sac, it can
be difficult to distinguish the heterogeneous myometrium from decidual reaction
abnormalities. When adenomyosis underlies the placenta, it can be difficult to
distinguish myometrial or placental anatomy and disease because of a poorly defined
interface between the two structures.
 Diffuse adenomyosis can also mimic diffuse leiomyomatosis, a benign condition with
numerous small leiomyomas and smooth muscle proliferation replacing the
myometrium, resulting in heterogeneous enlargement of the uterus, which often
requires hysterectomy .

75.  Eccentric displacement of the gestational sac by adenomyosis may also mimic an
interstitial ectopic pregnancy, where implantation occurs within the interstitial
portion of the fallopian tube within the uterus

77. Focal Adenomyosis in Pregnancy
 Unlike diffuse adenomyosis, focal adenomyosis results in focal lesions from
decidualized endometrial rests within the myometrium appearing as
heterogeneous rounded masslike lesions with ill-defined margins. Typically, the
masslike area contains echogenic rests with intervening tissue that is
sonographically similar to myometrium as well as a poorly defined transition to
normal adjacent myometrium.
 Frequently, focal adenomyosis and adenomyomas exert mass effect on the
developing gestational sac in the first trimester . Depending on the size and rate
of growth from decidualization during pregnancy, these can have the appearance
of a myometrial neoplasm

79.  In the absence of cystic components, the ill-defined T2-hypointense appearance
of focal adenomyosis can also mimic placenta accreta spectrum (PAS), an
abnormal placentation disorder that may attach to or invade the myometrium,
depending on the severity.

81. Adenomyosis Cysts in Pregnancy
 Two types of cysts can be seen with adenomyosis. Myometrial cysts are usually
simple anechoic cysts smaller than 5 mm within the region of ectopic endometrial
glands and are one of the most sensitive and specific US signs of adenomyosis .
 Heterogeneous thickening of the myometrium with myometrial cysts can also
lead to misdiagnosis of gestational trophoblastic disease (GTD), namely, a
complete or partial hydatidiform mole .

84. Associated Complications and Outcomes in
Pregnancy
 Complications include but are not limited to infertility, early pregnancy loss,
growth restriction, preterm delivery, and preeclampsi. Caesarean section,
fetal malpresentation, post-partum haemorrhage and Placental abruption. (17)
 Altered uterotubal transport, anatomic distortion of the uterus, and dysfunctional
uterine peristalsis have been proposed as explanations for the association of
adenomyosis with infertility .
 early pregnancy loss is likely a consequence of the downstream effects of
abnormal uterine morphology such as impaired endometrial metabolism and its
effect on early placentation and gestational sac implantation

85.  Fetal growth restriction and preterm delivery may be associated with increased
uterine inflammation and free radicals as well as junctional zone changes, creating
a hostile environment for the placenta that restricts adequate fetal exchange with
the maternal blood supply, possibly through a vascular steal mechanism .The
implications of growth restriction and preterm delivery are significant and put the
fetus at risk for serious adverse events such as lung immaturity, brain injury, and
long-term postnatal health issues.

86.  Another known complication of adenomyosis in pregnancy is preeclampsia, which
puts maternal health at risk and predisposes her to stroke, organ failure, and
hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.
Because of the effects on maternal health, preeclampsia is also a risk factor for
fetal prematurity and demise.
 HDP was divided into gestational hypertension (GH), PE, chronic hypertension
(CH), and superimposed preeclampsia (SPE), we found that PE occurred
significantly more frequently than the others. However, other studies have not
found any increase in the rate of PE in pregnant women with adenomyosis.

87. Degeneration of Adenomyosis
 Uterine fibroids are known to degenerate during pregnancy, but it is unknown if similar pathologic
condition occurs in adenomyosis . In a case report A 38-year-old para 1 woman exhibited uterine
tenderness and a markedly elevated inflammatory response at 22 weeks of gestation. Based on
magnetic resonance imaging (MRI) findings indicative of hemorrhagic components in an
adenomyosis lesion, we judged these features resulted from degeneration of adenomyosis after
excluding the possibility of underlying infection by amniocentesis. these symptoms improved with
conservative management.(18)

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 18. Megumi Nakanishi,Takayuki Iriyama,Seisuke Sayama,Shouhei Hanaoka,Masatake
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