Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study.

PURPOSE: In a series of publications, we had developed the concept that uterine adenomyosis and pelvic endometriosis as well as endometriotic lesions at distant sites of the body share a common pathophysiology with endometriosis constituting a secondary phenomenon. Uterine auto-traumatization and the initiation of the mechanism of tissue injury and repair (TIAR) were considered the primary events in the disease process. The present MRI study was undertaken (1) to corroborate this concept by re-visiting, in view of discrepant results in the literature, the association of adenomyosis with endometriosis and (2) to extend our views concerning the mechanisms of uterine auto-traumatization. PATIENTS AND METHODS: MRI was performed in 143 women attending our center, in whom, on the basis of transvaginal sonography (TVS) and historical data, such as documented endometriosis and dysmenorrhea of various degrees of severity, the presence of uterine adenomyosis was suspected. In addition to the measurement of the diameter of junctional zone (JZ) of the anterior and posterior walls in the mid-sagittal plane, the diagnosis of adenomyosis was based on visualization, in that all planes were analyzed with scrutiny. By this method of "visualization" all transient enlargement of the JZ, such as peristaltic waves of the archimyometrium and sporadic neometral contractions that might mimic adenomyotic lesions could be excluded. At the same time, this method allowed to lower the limit of detection in terms of thickness of the JZ for assured diagnosis of adenomyosis. Furthermore, the localizations of the individual lesions, their shapes and patterns were described. RESULTS: With the method of 'visualization', the diagnosis of uterine adenomyosis could be verified in 127 of the 143 patients studied. The prevalence of endometriosis in adenomyosis was 80.6% and the prevalence of adenomyosis in endometriosis was 91.1%. As concluded from their localization within the uterine wall, the adenomyotic lesions predominantly developed in the median region of the upper two-thirds of the uterine wall. Cystic cornual angle adenomyosis was a distinct phenomenon that was only observed in patients suffering from extreme primary dysmenorrhea. Aside from this, the majority of the patients complained of primary dysmenorrhea (80%). On the basis of these findings and the fact that particularly extreme primary dysmenorrhea is associated with high intrauterine pressure, menstrual 'archimetral compression by neometral contraction' has to be considered as an important cause of uterine auto-traumatization in addition to uterine peristalsis and hyperperistalsis. Both mechanical functions of the non-pregnant uterus exert their strongest power in the upper region of the uterus, which is compatible with the predominant localization of the adenomyotic lesions. CONCLUSIONS: The data confirm our previous results of a high association of adenomyosis with endometriosis and vice versa. Our view of the mechanism of uterine auto-traumatization by mechanical functions of the non-pregnant uterus has to be extended, in that 'archimetral compression by neometral contractions' could be realized as the predominant cause of mechanical strain to the non-pregnant uterus. The data of this study confirm our concept of the etiology and pathophysiology of adenomyosis and endometriosis in that the process of chronic proliferation and inflammation is induced at the level of the archimetra by chronic uterine auto-traumatization. Furthermore, with respect to the diagnosis of uterine adenomyosis (and consequently endometriosis) this study shows a high degree of accordance between the findings in real-time TVS and MRI.

The pathophysiology of endometriosis and adenomyosis: tissue injury and repair.

INTRODUCTION: This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women affected with the disease. METHODS: In women suffering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology as well as clinical aspects. The relevant molecular biologic aspects were compared to those of tissue injury and repair (TIAR) mechanisms reported in literature. RESULTS AND CONCLUSIONS: Circumstantial evidence suggests that endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatizations with the activation of the mechanism of 'tissue injury and repair' (TIAR). This results in the local production of estrogen. With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with the ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis. In late premenopausal adenomyosis, such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life leads to the same extent of microtraumatization. With the activation of the TIAR mechanism followed by infiltrative growth and chronic inflammation, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principle the same pathophysiology. In conclusion, endometriosis and adenomyosis result from the physiological mechanism of 'tissue injury and repair' (TIAR) involving local estrogen production in an estrogen-sensitive environment normally controlled by the ovary.

Duration of dysmenorrhoea and extent of adenomyosis visualised by magnetic resonance imaging.

OBJECTIVE: Enlargement of the junctional zone (JZ) on T2-weighted resonance imaging of the uterus has recently been established as the major criterion for adenomyosis in patients with endometriosis. This study was conducted to analyse the extent of adenomyosis using magnetic resonance imaging (MRI) and relate it to the duration of dysmenorrhoea. STUDY DESIGN: This was a prospective study of 70 patients presenting with the complaint of severe dysmenorrhoea. Forty patients (57%) reported dysmenorrhoea as their major complaint and 30 patients (43%) suffered additionally from infertility. Group I (n=40) consisted of patients with dysmenorrhoea of between 1 and 10 years' duration, group II (n=30) consisted of patients with dysmenorrhoea of longer than 11 years' duration. All patients underwent laparoscopy to detect the presence and degree of endometriosis, and all patients underwent T2-weighted resonance imaging of the uterus to detect the extent of adenomyosis by measurement of the "junctional zone". RESULTS: In group I, adenomyosis could be detected via MRI in 21 patients (52.5%), while 19 patients (47.5%) showed no signs of adenomyosis. By contrast, in group II a distinct enlargement of the JZ, as the major radiological criterion of adenomyosis, could be observed in 26 patients (87%), while only 4 patients (13%) revealed no signs of adenomyosis (p=0.04). The mean thickness of the JZ was significantly enlarged in group II (11.07 mm) compared with group I (6.38 mm; p<0.0001). The prevalence of adenomyosis in endometriosis after dysmenorrhoea of more than 11 years' duration was 87%. CONCLUSIONS: In deep infiltrating endometriosis, a correlation between a specific localisation and dysmenorrhoea can often not be found. Recently, endometriosis and adenomyosis have been believed to result from a common uterine disease, the dislocation of the basal endometrium. Our data clearly show that dysmenorrhoea of long duration in patients who have had endometriosis for over a threshold value of 11 years is significantly related to adenomyosis of the uterus. Hence, evaluation of adenomyosis using MRI should become a standard procedure in cases of dysmenorrhoea and endometriosis. Severe dysmenorrhoea of long duration should always focus clinical interest on adenomyosis of the uterus.

Adenomyosis as a disorder of the early and late human reproductive period.

Magnetic resonance imaging (MRI) allows the diagnosis of adenomyosis in vivo with a high sensitivity and specificity. Usually the diagnosis of adenomyosis is obtained from women in their fourth to fifth decade of life. However, recent data suggest that adenomyosis may develop much sooner in life, particularly in women with endometriosis. In order to test these suggestions, MRI of the uterus in 227 women with and without endometriosis was performed and the results were related to the age of the subjects (age groups: 17-24, 25-29, 30-34 and >34 years). The study revealed that the process of the development of adenomyosis, represented by an increased diameter of the dorsal junctional zone of the uterus as the imaging correlative of the invasion of basal endometrium into the junctional zone, had already commenced early in the third decade of life and progressed steadily during the fourth decade in women with endometriosis. Women without endometriosis showed almost no signs of adenomyosis up to the age of 34 years. Surprisingly, parallel in both groups of women, a marked increase in the incidence of adenomyosis could be observed beyond the age of 34 years, thus representing a common phenomenon in the age-related pathophysiological continuum of adenomyosis.

Physiology of upward transport in the human female genital tract.

The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).

Oxytocin--a stimulator of directed sperm transport in humans.

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus, as well as rapid sperm transport from the vagina to the Fallopian tubes, have long been documented by means of vaginal sonography and hysterosalpingoscintigraphy. Uterine peristaltic activity reaches a maximum before ovulation and is controlled via oestradiol secretion from the dominant follicle systemically and into the utero-ovarian countercurrent system; it is also enhanced by oxytocin. In this study, the effect of oxytocin and its receptor antagonist atosiban on uterine peristalsis and thus directed sperm transport during the mid and late follicular phases was examined. Atosiban did not show any effect either on frequency or on pattern of the peristaltic contractions. However, oxytocin significantly increased the rapid and directed transport of radiolabelled particles representing spermatozoa from the vagina into the Fallopian tube ipsilateral to the site of the dominant follicle (P = 0.02, 0.04 and 0.02 after 1, 16 and 32 min of documentation respectively). It seems reasonable to assume that oxytocin plays an important, although not critical, role in the mechanisms governing rapid sperm ascension that, at least in humans, were developed to rapidly preserve an aliquot of spermatozoa following intercourse.

Control and function of uterine peristalsis during the human luteal phase.

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus can be demonstrated throughout the menstrual cycle, with a maximum just before ovulation. However, not only during the follicular phase but also during the luteal phase, the uterus shows remarkable contractile activity. The present study was conducted in order to examine uterine peristaltic activity and its function during the luteal phases of the human menstrual cycle. The results of vaginal sonography of uterine peristalsis, of hysterosalpingoscintigraphy and of the documentation of the sites of embryo implantation in natural and artificial cycles have shown that uterine peristalsis during the luteal phase is controlled by systemic and probably even more by local hormonal secretion from the fresh corpus luteum, and facilitates the fundal implantation of the blastocyst predominantly ipsilateral to the site of the dominant ovarian structure. Furthermore, this study suggests that the defence against the infiltration and inflammation of the upper genital tract, and thus the degradation of the implanted embryo, represents a further and phylogenetically old and genuine function of the archimetra, which in placentalia was modified in order to participate in the control of invasion of the endometrium by the trophoblast.

Uterotubal transport disorder in adenomyosis and endometriosis--a cause for infertility.

OBJECTIVE: Uterine hyperperistalsis and dysperistalsis are common phenomena in endometriosis and may be responsible for reduced fertility in cases of minimal or mild extent of disease. Since a high prevalence of adenomyosis uteri has been well documented in association with endometriosis, we designed a study to examine whether hyperperistalsis and dysperistalsis are caused by the endometriosis itself or by the adenomyotic component of the disease. DESIGN: A prospective observational study. SETTING: University hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 300 in vitro fertilisation/intracytoplasmatic sperm injection cycles and 350 intrauterine insemination cycles/year. POPULATION: Forty-one subjects with infertility and with laparoscopically proven endometriosis and patent fallopian tubes. Thirty-five subjects (85%) additionally showed signs of adenomyosis. METHODS: All subjects underwent T2-weighed magnetic resonance imaging (MRI) and hysterosalpingoscintigraphy (HSSG) during the subsequent menstrual cycle. MRI revealed the extent of the adenomyotic component of the disease and the integrity of uterotubal transport capacity was evaluated by HSSG. MAIN OUTCOME MEASURES: Influence of adenomyosis on uterotubal transport capacity in endometriosis. RESULTS: In 35 of the 41 subjects (85%) with endometriosis, signs of adenomyosis were detected using T2-weighed MRI. Two of six (33%) subjects with no adenomyosis (group I) showed dysperistalsis and hyperperistalsis, compared with 14 of 24 (58%) women with focal adenomyosis (group II) and 10 of 11 (91%) women with diffuse adenomyosis (seven showed a failure in transport capacity and two contralateral transport). CONCLUSIONS: Our data suggest that endometriosis is associated with impeded hyperperistaltic and dysperistaltic uterotubal transport capacity. However, adenomyosis is of even more importance, especially when diffuse adenomyosis is detected. Both forms of adenomyosis are commonly found in subjects with mild to moderate endometriosis. We suggest that the extent of the adenomyotic component in subjects with endometriosis explains much of the reduced fertility in subjects with intact tubo-ovarian anatomy.

[Endometriosis and adenomyosis]. / Endometriose und Adenomyose -- Neue Sichtweisen der Uterus(patho)physiologie.

Peristaltic activity of the non-pregnant uterus serves fundamental functions in the early process of reproduction. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have an increased potential of implantation and proliferation resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of about 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. The principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary thus resulting in hyperperistalsis. Minimal endometriosis of the fertile women, endometriosis and adenomyosis of the infertile women and adenomyosis of the parous peri- and postmenopausal women are considered as phenotypes of a pathophysiological continuum with uterine peristalsis playing a prominent role.

Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging.

BACKGROUND: The hypothesis is tested that there is a strong association between endometriosis and adenomyosis and that adenomyosis plays a role in causing infertility in women with endometriosis. METHODS. Magnetic resonance imaging of the uteri was performed in 160 women with and 67 women without endometriosis. The findings were correlated with the stage of the disease, the age of the women and the sperm count parameters of the respective partners. RESULTS: The posterior junctional zone (PJZ) was significantly thicker in women with endometriosis than in those without the disease (P<0.001). There was a positive correlation of the diameter of the PJZ with the stage of the disease and the age of the patients. The PJZ was thicker in patients with endometriosis with fertile than in patients with subfertile partners. The prevalence of adenomyotic lesions in all 160 women with endometriosis was 79%. In women with endometriosis below an age of 36 years and fertile partners, the prevalence of adenomyosis was 90% (P<0.01) CONCLUSIONS: With a prevalence of up to 90%, uterine adenomyosis is significantly associated with pelvic endometriosis and constitutes an important factor of sterility in endometriosis presumably by impairing uterine sperm transport.

Endometriosis results from the dislocation of basal endometrium.

BACKGROUND: The hypothesis is tested that both adenomyotic and endometriotic lesions are derived from basal endometrium. METHODS: Normal uteri and uteri with adenomyosis obtained by hysterectomy, excised endometriotic lesions and menstrual blood of women with and without endometriosis were used. Estrogen receptor (ER), progesterone receptor (PR), progesterone receptor B isoform (PR(B)) and P450 aromatase (P450A) immunohistochemistry was performed with the use of specific monoclonal antibodies. RESULTS: With respect to the parameters studied there was a fundamental difference between the cyclical patterns of the basalis and the functionalis of the eutopic endometrium. The endometrium of endometriotic and adenomyotic lesions mimicked the cyclical pattern of the basalis. The peristromal muscular tissue of endometriotic and adenomyotic lesions displayed the same cyclical pattern of ER and PR expression as the archimyometrium. There was a significantly higher prevalence of fragments of shed basalis in menstrual blood of women with endometriosis than in healthy controls. CONCLUSIONS: These data suggest that ectopic endometrial lesions result from dislocation of basal endometrium. Dislocated basal endometrium has stem cell character resulting in the ectopic formation of all archimetrial components such as epithelial and stromal endometrium as well as peristromal muscular tissue.

Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging.

In women with endometriosis, the peristaltic activity of the uterus is significantly enhanced and may even become dysperistaltic at midcycle. Since uterine peristalsis is confined to the endometrium and the subendometrial myometrium with its predominantly circular arrangement of muscular fibres it was assumed that this dysfunction might be associated with structural abnormalities that could be visualized by high resolution ultrasonography and magnetic resonance imaging (MRI). Therefore, the uteri of women with and without endometriosis were subjected to endovaginal sonography (EVS) and to MRI. In EVS, women with laparoscopically proven endometriosis and infertility exhibited an infiltrative expansion of the archimetra in that the halo surrounding the uterine endometrium and representing the subendometrial myometrium was significantly enlarged compared with controls. The expansion was more pronounced in older than in younger women. There was, however, no relationship between the width of the expansion and the severity of the endometriotic disease. Similar data were obtained by MRI in that the 'junctional zone' in women with endometriosis and infertility was expanded in comparison with controls. The results of this study provide further support to the notion that endometriosis is primarily a uterine disease.

The cyclic pattern of the immunocytochemical expression of oestrogen and progesterone receptors in human myometrial and endometrial layers: characterization of the endometrial-subendometrial unit.

Immunocytochemistry of oestrogen receptor (ER) and progesterone receptor (PR) expression of the whole uterine muscular wall and the endometrium was performed in order to obtain morphological and functional insights into the regulation of cyclic uterine peristalsis, which is confined to the endometrium and the subendometrial myometrium and serves functions such as rapid and sustained sperm transport. The study revealed that the subendometrial myometrium or stratum subvasculare with a predominantly circular arrangement of muscular fibres exhibits a cyclic pattern of ER and PR expression that parallels that of the endometrium, whereas the outer portion of the uterine wall composed of the stratum vasculare and supravasculare, which represents the bulk of the uterine musculature, does not exhibit a cyclic pattern of ER and PR expression. According to ontogenetic and phylogenetic data from the literature, the outer myometrium is of non-paramesonephric origin with functions confined to parturition, while the inner myometrial layer together with the glandular epithelium and the stroma of the endometrium is of paramesonephric origin with various functions during the cycle in addition to those during pregnancy and parturition. The inner quarter of the stratum vasculare adjacent to the stratum subvasculare constitutes a transitional zone in that the cyclicity of receptor staining becomes, in radial direction, gradually less expressed. Morphologically this zone corresponds to the inner part of the stratum vasculare where its muscular fibres blend with those of the stratum subvasculare.

Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin.

Uterine peristalsis, directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Chlomiphene tended, though insignificantly so, to suppress the frequency of peristaltic waves in the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system.

Sonographic evidence for the involvement of the utero-ovarian counter-current system in the ovarian control of directed uterine sperm transport.

Sperm transport from the cervix into the tube is an important uterine function within the process of reproduction. This function is exerted by uterine peristalsis and is controlled by the dominant ovarian structure via a cascade of endocrine events. The uterine peristaltic activity involves only the stratum subvasculare of the myometrium, which exhibits a predominantly circular arrangement of muscular fibres that separate at the fundal level into the fibres of the cornua and continue into the circular muscles of the respective tubes. Since spermatozoa are transported preferentially into the tube ipsilateral to the dominant follicle, this asymmetric uterine function may be controlled by the ovary via direct effects utilizing the utero-ovarian counter-current system, in addition to the systemic circulation. To test this possibility the sonographic characteristics of the uterine vascular bed were studied during different phases of the menstrual cycle. Vaginal sonography with the measurement of Doppler flow characteristics of both uterine arteries and of the arterial anastomoses of the uterine and ovarian arteries (junctional vessels) in the cornual region of both sides of the uterus during the menstrual phase of regular-cycling women demonstrated significant lower resistance indices of the junctional vessels ipsilateral to the side of the dominant ovarian structure as compared with the corresponding arteries contralaterally. By the use of the perfusion mode technique, it could be observed that vascular perfusion of the fundal myometrium was significantly increased ipsilateral to the dominant follicle during the late follicular phase of the cycle. These results show that the endocrine control of the dominant ovarian structure over uterine function is not only exerted via the systemic circulation but also directly, most probably utilizing the utero-ovarian counter-current system.

Endometriosis: a dysfunction and disease of the archimetra.

Endometriosis is considered primarily a disease of the endometrial-subendometrial unit or archimetra. The clinical picture of endometriosis characterises this disease as a hyperactivation of genuine archimetrial functions such as proliferation, inflammatory defence and peristalsis. While the aetiology of the disease remains to be elucidated, a key event appears to consist in the local production of extraovarian oestrogen by a pathological expression of the P450 aromatase. The starting event may consist in a hyperactivity of the endometrial inflammatory defence, a hyperactivity of the endometrial oxytocin/oxytocin receptor system or in the pathological expression of the P450 aromatase system itself. Regardless of which of these levels the starting event is localized in, they influence each other on both the level of the archimetra and the endometriotic lesions. Locally elevated oestrogen levels inevitably up-regulate the endometrial oxytocin mRNA and increased levels of oxytocin result in uterine hyperperistalsis, increased transtubal seeding of endometrial tissue fragments and finally subfertility and infertility by impairment of the uterine mechanism of rapid and sustained sperm transport. Locally increased levels of oestrogen lead, on both the level of the endometrial-subendometrial unit and the endometriotic lesion, to processes of hyperproliferation. These processes result, on the level of the uterus, in an infiltrative growth of elements of the archimetra into the neometra and, on the level of the endometriotic lesion, in infiltrative endometriosis. There is circumstantial evidence that trauma might be an important initial event that induces the specific biochemical and cellular responses of the archimetra. This model is able to explain both the pleiomorphic appearance of endometriosis and the, up until now, enigmatic infertility associated with mild and moderate endometriosis.

The uterine peristaltic pump. Normal and impeded sperm transport within the female genital tract.

Rapid as well as sustained sperm transport from the cervical canal to the isthmical part of the fallopian tube is provided by cervico-fundal uterine peristaltic contractions that can be visualized by vaginal sonography. The peristaltic contractions increase in frequency and presumably also in intensity as the proliferative phase progresses. As shown by placement of labeled albumin macrospheres of sperm size at the external cervical os and serial hysterosalpingoscintigraphy (HSSG) sperm reach, following their vaginal deposition, the uterine cavity within minutes. In the early follicular phase a large proportion of the macrospheres remains at the site of application, while a smaller proportion enters the uterine cavity with even a smaller one reaching the isthmical part of the tubes. In the mid-follicular phase of the cycle with increased frequency and intensity of the uterine contractions the proportion of macrospheres entering the uterine cavity as well as the tubes has significantly increased. In the late follicular phase with maximum frequency and intensity of uterine peristalsis the proportion of macrospheres entering the tube increases further at the expense of those at the site of application as well as within the uterine cavity. The transport of the macrospheres into the tube is preferentially directed into the tube ipsilateral to the dominant follicle, which becomes apparent in the mid-follicular phase as soon as a dominant follicle can be identified by ultrasound. Since the macrosphere are inert particles the directed sperm transport into the tube ipsilateral to the dominant follicle is not functionally related to a mechanism such as chemotaxis but is rather provided by uterine contraction of which the direction may be controlled by a specific myometrial architecture in combination with an asymmetric distribution of myometrial oestradiol receptors. Women with infertility and mostly mild endometriosis display on VSUP a uterine hyperperistalsis with nearly double the frequency of contractions during the early and mid- as well as midluteal phase in comparison to the fertile and healthy controls. During midcycle these women display a considerable uterine dysperistalsis in that the normally long and regular cervico-fundal contractions during this phase of the cycle have become more or less undirected and convulsive in character. Hyperperistalsis results in the transport of inert particles from the cervix into the tubes within minutes already during the early follicular phase, and may therefore constitute the mechanical cause for the development of endometriosis in that it transports detached endometrial cells and tissue fragments via the tubes into the peritoneal cavity. Moreover, dysperistalsis may contribute to the infertility in these patients since it results in a break down of sperm transport within the female genital tract.

[Comparison of laparoscopically assisted vaginal hysterectomy with abdominal hysterectomy. Technique and results]. / Vergleich der laparoskopisch assistierten vaginalen Hysterektomie (LAVH) mit der abdominalen Hysterektomie. Technik und Ergebnisse.

Technique and Results: The aim of this prospective randomised study was to compare laparoscopy-assisted vaginal hysterectomy (LAVH, group A) with abdominal hysterectomy (abd. HE, group B). Therefore, 35 hysterectomies due to non-malignant diseases such as uterine fibroma were performed in each group. A rather simple technique of LAVH was developed. In respect of the indication for hysterectomy, mean duration of operation and the size of the excised uteri there were no statistical differences between the two groups. One severe complication of haemorrhage was observed after LAVH in a patient suffering from a coagulopathy. The requirements for analgesics were significantly lower after LAVH compared to abd. HE during the postoperative period. A significantly lower serum concentration of the c-reactive protein on the first and third days after operation was found in group A. The patients of group A were discharged on the average 5 days after operation and 11 days in group B, respectively. Hence LAVH should replace abd. HE in most cases with the advantages of shorter hospitalisation, minimised requirements for analgesics and cost reduction.

Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility.

Women suffering from infertility in association with mostly mild endometriosis were subjected to vaginal sonography of uterine peristalsis during the menstrual period, the early, mid- and late follicular phases, and the mid-luteal phase of the menstrual cycle. The data obtained were compared with those of healthy controls. Women with endometriosis displayed a marked uterine hyperperistalsis that differed significantly from the peristalsis of the controls during the early and mid-follicular and mid-luteal phases. During the late follicular phase of the cycle, uterine peristalsis in women with endometriosis became dysperistaltic, arrhythmic and convulsive in character, while in controls peristalsis continued to show long and regular cervico-fundal contractions. Hysterosalpingoscintigraphy during the early, mid- and late follicular phases revealed that hyperperistalsis in the early and mid-follicular phases of patients with endometriosis resulted in a dramatic increase in the transport of inert particles from the vaginal depot, through the uterus into the tubes and also into the peritoneal cavity. During the late follicular phase of the cycle, the dysperistalsis observed in women with endometriosis resulted in a dramatic reduction of uterine transport capacity in comparison with the healthy controls. We consider uterine hyperperistalsis to be the mechanical cause of endometriosis rather than retrograde menstruation. Dysperistalsis in the late follicular phase of patients with endometriosis may compromise rapid sperm transport. Uterine hyperperistalsis and dysperistalsis are considered to be responsible for both reduced fertility and the development of endometriosis.