VIEWS AND REVIEWS

Introduction:
Uterine adenomyosis, another
enigmatic disease of our time
Jacques Donnez, M.D., Ph.D.,a Olivier Donnez, M.D., Ph.D.,b and Marie-Madeleine Dolmans, M.D., Ph.D.c,d
a

te
Catholic University of Louvain, Socie
de Recherche pour l'Infertilite

(SRI), Brussels, Belgium; b Institut du Sein et de
Chirurgie Gyne
cologique d'Avignon, Polyclinique Urbain V (ELSAN Group), Avignon, France; c Po ^ le de Gyne
cologie
Institut de Recherche Expe
rimentale et Clinique (IREC), Universite
Catholique de Louvain, Brussels, Belgium; and
d
Gynecology Department, Cliniques Universitaires Saint Luc, Brussels, Belgium

Like endometriosis, uterine adenomyosis is another enigmatic disease and remains a source of controversy. Uterine adenomyosis is
characterized by the presence of endometrial glands in the myometrium. Two main theories may explain its pathogenesis: adenomyosis
may arise from invagination of the myometrial basalis into the myometrium; or an alternative theory maintains that it may result from
metaplasia of displaced embryonic pluripotent m€ ullerian remants or differentiation of adult stem cells. Uterine adenomyosis is respon-
sible for pelvic pain, abnormal bleeding, and infertility. Its diagnosis may be improved by high quality imaging. In this issue's Views and
Reviews, authors stress the urgent need to establish some systematic classification. Medical and surgical strategies are discussed. It
should be emphasized that treatment should be designed according to a patient's symptoms and an individual's needs. Surgical treat-
ment remains a matter of debate. Indeed, the risk of uterine rupture during pregnancy after adenomyomectomy is a reality. Therefore,
continued research into new molecules based on the pathogenic mechanisms is vital. (Fertil SterilÒ 2018;-:-–-. Ó2018 by Amer-
ican Society for Reproductive Medicine.)
Key Words: Adenomyosis, uterine adenomyosis, pathogenesis, therapy
Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-
and-sterility/posts/29570-25661

U
terine adenomyosis, histologi- its pathogenesis to its classification, amination allows direct vascularization
cally characterized by the pres- diagnosis, medical therapy, and surgi- of endometrial tissue within the myo-
ence of endometrial glands in cal management. metrium, showing a variable degree of
the myometrium, affects 20% of Adenomyosis is a commonly en- adjacent myometrial hyperplasia that
women of reproductive age and is countered benign uterine disease char- causes globular and sometimes cystic
responsible for pelvic pain, abnormal acterized histopathologically by the enlargement of the myometrium.
bleeding, and infertility (1, 2). presence of islands of ectopic endome- Some cysts are filled with hemolyzed
However, high rates of comorbidity trial tissue within the myometrium, red blood cells and siderophages. Two
with other conditions like fibroids typically found at different depths and principal forms of the disease, focal
and endometriosis makes it difficult often surrounded by hyperplastic and and diffuse, are generally described
to attribute a specific pathognomonic hypertrophic smooth muscle. It mani- but, as stressed by Gordts et al. (2), there
symptom to adenomyosis (2). Neither fests as any of a spectrum of lesions, is an urgent need for a more formal
its etiology (risk factors) nor the ranging from a slightly thickened func- categorization and comprehensive
pathogenesis is yet fully understood, tional zone to full-thickness uterine classification of uterine adenomyosis.
so information on its prevalence in adenomyosis. Gross pathology usually This should take into account its loca-
adolescent girls remains limited. reveals an enlarged and globular uterus tion in the myometrium, as well as
This issue's Views and Reviews is with areas of hypertrophic myometrial different histological variants.
devoted to uterine adenomyosis, from smooth muscle. Histopathological ex- To date, two main theories have
been proposed to explain the origin
and pathogenesis of adenomyosis (1).
Received January 24, 2018; accepted January 25, 2018.
J.D. has nothing to disclose. O.D. has nothing to disclose. M.-M.D. has nothing to disclose. The most common suggests involve-
Correspondence: Jacques Donnez, M.D., Ph.D., Director, Socie
te

de Recherche pour l'Infertilite

, ment of the tissue injury and repair
Avenue Grandchamp 143, Brussels 1150, Belgium (E-mail: [email protected]).
mechanism, claiming that adenom-
Fertility and Sterility® Vol. -, No. -, - 2018 0015-0282/$36.00 yosis arise from invagination of the
Copyright ©2018 Published by Elsevier Inc. on behalf of the American Society for Reproductive endometrial basalis into the myome-
Medicine
https://doi.org/10.1016/j.fertnstert.2018.01.035 trium. An alternative theory maintains

VOL. - NO. - / - 2018 1

that adenomyotic lesions result from metaplasia of displaced in which the uterine wall is excised in a V-shape. Thanks to
embryonic pluripotent m€ ullerian remnants or differentiation the development of more homologous and less reactive suture
of adult stem cells. The epithelial-mesenchymal transition materials provoking less severe tissue responses, as well as novel
process occurring in the early stages of progression, as well powered devices like electric, ultrasonic and high-frequency
as collective cell migration, may both be implicated in the scalpels that minimize bleeding, complication rates fell to
later events of invasion. significantly lower levels than those seen before the 1970s.
Recent improvements in imaging techniques like transva- Surgical treatment of adenomyosis remains a matter of
ginal ultrasound and magnetic resonance imaging (MRI), as debate, not only in terms of indications, but also the technical
described by Bazot et al. (3), have led to major advances in aspects of surgery. Since 1990, instead of the classic V-shaped
the field, allowing new conservative treatments to be devel- resection approach, various forms of surgical management
oped for adenomyosis. In their review, Bazot and Daraï also have been attempted. These include the uterine muscle flap
stress the need for uniform terminology and consensus clas- method involving asymmetric dissection, and a number of
sification. They clearly demonstrate the different morphology modified procedures allowing fertility preservation and
and locations of subtypes of the disease, including internal widely used in Japan, where 2,123 cases have been reported
adenomyosis, adenomyoma and external adenomyosis. since 1990.
They draw our attention to possible pitfalls in the diagnosis The triple-flap method, which involves reconstructing the
of adenomyomas, such as confusion with leiomyomas and uterine wall defect using normal uterine muscle, is carefully
myometrial contractions. Myometrial contractions can be described by Osada (5). This technique is not only effective
differentiated from leiomyomas or adenomyomas by sequen- for diffuse uterine adenomyosis, but also for nodular adeno-
tial studies thanks to their transient nature (3). Visualization myosis, and can potentially to contribute to preventing uter-
of physiological variations of the junctional zone on MRI im- ine rupture during postoperative pregnancy.
ages is dependent on the patient's age and hormonal status Out of Osada's 2,123 surgical cases, a total of 397 post-
(contraceptive pills, gonadotropin-releasing hormone agonist procedural pregnancies were reported, 337 of which yielded
[GnRHa], progestogens) as well as the menstrual cycle day. live births and 23 that ended in uterine rupture. A higher inci-
From Vannuccin and colleagues (4), messages on existing dence of placenta accretae and percreta was noted compared
medical therapy are very clear: medical management is still to cesarean section and myomectomy (5).
controversial; no drug is specifically labeled for use in case Factors causing uterine rupture during pregnancy are
of uterine adenomyosis at present; and there are no particular clearly detailed. They include the surgical technique applied,
guidelines to follow for optimal management. the extent and volume of the uterine defect, the method of
These authors do, however, provide an exhaustive review repair of the uterine wall (and sometimes the uterine cavity),
of all drugs available to treat the symptoms of this disease. postoperative wound infection and hematoma formation, and
From non-hormonal (nonsteroidal anti-inflammatory drugs) finally, as stressed by Osada (5), the skill and experience of the
and hormonal agents (progestins -delivered orally or locally, surgeon.
contraceptive pills, GnRHa) to new drugs under development, In conclusion, like endometriosis, uterine adenomyosis
such as selective progesterone receptor modulators, aroma- remains a contentious entity from pathogenesis to therapy.
tase inhibitors, valproic acid, anti-platelet therapy, and Moreover, there is an urgent need to establish some syste-
GnRH antagonist, medical therapy offers numerous possibil- matic classification, taking into account not only histological
ities, despite most of these drugs being off-label for this indi- findings but also results from the latest imaging techniques,
cation. Vannuccini et al. (4) provide a very interesting such as transvaginal ultrasound and MRI. Continued research
account in a dedicated section on medical treatment in into new molecules based on the pathogenic mechanisms of
women with uterine adenomyosis suffering from infertility. uterine adenomyosis is vital.
Summarizing existing evidence on the effect of adenomyosis
on fertility and clinical in vitro fertilization outcomes, they REFERENCES
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