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Human endometrial stromal (ES) cells in culture express PRL, a marker of decidualization, in response to sustained activation of protein kinase A (PKA). Cotreatment with the progestin medroxyprogesterone acetate (MPA) enhanced decidual PRL gene activation in the presence of elevated intracellular cAMP levels. This synergy became apparent, at protein and promoter level, after a lag period of 2 days and increased in a time-dependent manner thereafter. Pretreatment with cAMP advanced the time at which synergy between cAMP and MPA was apparent, suggesting that PKA activation sensitized ES cells to the effects of progestins. Analysis of the progesterone receptor (PR) indicated that PR-A was the predominant form in differentiating ES cells, but its abundance decreased markedly during the course of the decidualization response. The decline in PR levels was of functional relevance, as expression of PR-B or PR-A, by transient transfection, dramatically inhibited the activity of a decidual PRL promoter-reporter construct in response to cAMP. Furthermore, the expression of endogenous PRL protein in response to cAMP or cAMP plus MPA was substantially decreased by constitutive expression of green fluorescence protein-tagged PR, which was localized in the nucleus even in the absence of added ligand. Ligand-independent PR inhibition of the decidual PRL promoter was receptor specific, independent of known PR phosphorylation sites, and required minimally a functional DNA-binding domain. Transient expression of steroid receptor coactivator-1e (SRC-1e), but not SRC-1a, allowed synergy between cAMP and MPA without the requirement of sensitization by pretreatment with cAMP. This raised the possibility that SRC-1e was a component of cAMP-dependent sensitization of ES cells, but there was no evidence of altered messenger RNA expression of either SRC-1 isoform during decidualization. In conclusion, cellular PR levels determine the onset of the decidualization response. Initiation of this process requires elevated intracellular cAMP levels that sensitize ES cells to the actions of progestins through down-regulation of cellular PR levels and possibly via modulation of function of an intermediate factor(s) such as SRC-1e.

The myometrium is usually thought of as a homogeneous mass of smooth muscle fibres. However, magnetic resonance studies of the uterus have revealed two distinct zones--the subendometrial myometrium or junctional zone and the outer myometrium. The junctional zone is not only structurally but also functionally different from the outer myometrium. For instance, myometrial contractions in a non-pregnant woman originate exclusively from the junctional zone, and their amplitude, frequency, and direction depend on the phase of the cycle. Irregular thickening of the junctional zone has been proposed as the magnetic resonance criterion for the diagnosis of diffuse adenomyosis. However, this magnetic resonance appearance relies on the disruption of the inner myometrial architecture secondary to smooth muscle hyperplasia but does not provide proof of mucosal invasion of the myometrium. We postulate that adenomyosis is a dichotomous disease characterised primarily by disruption of the inner myometrial architecture and function, with secondary infiltration of endometrial elements into the myometrium under certain circumstances. This hypothesis focuses on the inner myometrium and may explain the high incidence of superficial adenomyosis in dysfunctional uterine bleeding.

Objective: To evaluate prospectively the role of endovaginal ultrasonography in the diagnosis of adenomyosis and to identify predictive characteristics., Setting: In Vitro Fertilisation Unit, Hammersmith Hospital., Subjects: Fifty-six women with menorrhagia and dysmenorrhea., Design: Endovaginal sonography was performed and uterine body morphometry and myometrial echogenicity were assessed. The sonographic suspicion of adenomyosis was scored high or low depending on the degree of uterine enlargement, uterine asymmetry not due to fibroids and heterogenicity of myometrial echoes. The sonographic diagnosis was compared either with the histological findings after hysterectomy (n = 34) or to the appearances on magnetic resonance imaging (n = 22)., Results: Adenomyosis was diagnosed in 28 patients: 15 by histology and 13 by magnetic resonance imaging. Endovaginal ultrasound demonstrated a sensitivity of 86%, a specificity of 50%, a positive predictive value of 86%, and a negative predictive value of 77%. Uterine morphometry alone did not predict adenomyosis: although the mean length of the longitudinal, anteroposterior and transverse axis was larger in uteri with, compared with those without, adenomyosis, this did not reach statistical significance. The uterine asymmetry ratio was 1.43 (SD 0.6) and 1.34 (SD 0.4) (P = 0.26) in uteri with and without adenomyosis, respectively, but in the presence of adenomyosis the mean posterior wall was significantly thicker than the mean anterior wall: 25.6 (SD 6.6) mm compared with 21.8 (SD 5.0) mm, P = 0.02. Therefore, adenomyosis was best predicted on the basis of ill-defined myometrial heterogeneity. However, leiomyomas and various echogenic shadows and artefacts often complicate subjective assessment of the myometrial echogenicity., Conclusion: Endovaginal sonography in symptomatic patients can be a sensitive but not a specific procedure for the diagnosis of adenomyosis.

Objective: To determine the sensitivity and specificity of myometrial needle biopsies in the diagnosis of adenomyosis uteri in vitro., Design: Eight needle biopsies and 8 corresponding myometrial blocks were taken from 27 hysterectomy specimens with adenomyosis and 13 specimens with adenomyosis. Adenomyosis was graded on the basis of the depth of endometrial invasion into the myometrium: grade I, adenomyosis within the inner third of the myometrium; grade II, limited to the inner two thirds; and grade III, endometrial penetration into the outer one third of the myometrium. The sensitivity of 4 and 2 biopsies was calculated by conventional probability theory., Results: Taking 8 needle biopsies from each uterus yielded sensitivities for grade I, II, and III adenomyosis of 9%, 64%, and 100% respectively, but the calculated sensitivities of two biopsies, taken at random, were only 2.3%, 20%, and 56%, respectively. There were no false-positive biopsies., Conclusions: Myometrial needle biopsy is a highly specific technique for the diagnosis of adenomyosis uteri but the sensitivity is low and dependent on the number of biopsies and the depth of adenomyosis.

The potential value of magnetic resonance imaging as a diagnostic tool in infertility was investigated. Twenty-six women with primary or secondary infertility and symptoms of dysmenorrhoea or menorrhagia were studied prospectively using conventional T1- and T2-weighted spin-echo techniques. Positive diagnoses were obtained in 20 of 26 (76.9%) patients. Of these, 18 (69.2%) had lesions likely to be significantly contributing to infertility. Adenomyosis was detected in 14 patients (53.8%) with 11 showing the diffuse pattern while three had discrete adenomyomas. Cystic lesions typical of endometriosis were detected in seven patients (26.9%), four of these also had evidence of adenomyosis. The endometriotic lesions were also seen at laparoscopy in each case. Five patients (19.2%) had leiomyomas, one in a patient with adenomyosis and endometriosis and one in a patient with endometriosis alone. Only one patient had submucous leiomyomas causing significant distortion of the endometrial mucosa likely to affect fertility. Magnetic resonance imaging is valuable in the investigation of unexplained infertility where it provides a high diagnostic yield particularly if uterine pathology is suspected.