Endometriosis 1991: a discussion document.
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Biomedical subjects
Publications and source records attributed to I Brosens.
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The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.
The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age. Values were compared with protein and DNA content, as well as with lactate dehydrogenase activity, used as reference constituents. In parallel, organ cultures were established from the same endometrial specimens and the release of lysosomal enzymes into the medium was followed. The human endometrium possesses a rich lysosomal equipment, comparable to that found in the human liver. In the untreated cycles, the activities of lysosomal enzymes show a coordinate response to the hormonal changes, decreasing by about 40% from the proliferative to the mid-late secretory phase. Long-term levonorgestrel treatment causes a marked cytoplasmic atrophy, as shown by decreased protein content and lactate dehydrogenase activity, whereas DNA content remains unchanged. In contrast, N-acetyl-beta-hexosaminidase, one of the most active lysosomal enzymes studied, shows a higher specific activity upon levonorgestrel. In both untreated and treated endometria, the organ cultures provide biochemical evidence for a higher release of N-acetyl-beta-hexosaminidase than of lactate dehydrogenase, indicating active secretion of the lysosomal enzyme. During levonorgestrel treatment, there was no correlation between clinically recognized spotting-bleeding patterns and lysosomal enzyme content in, or release from, the endometrium.
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The history of endometriosis is reviewed in the light of today's clinical and pathological knowledge of this disease. Prior to Sampson's report in 1921, attention was focused on the enclosed type of endometriosis, sited deep in the pelvis and called adenomyosis externa. Sampson's first hypothesis, that rupture of an ovarian endometrioma caused superficial peritoneal endometriosis, was probably changed after this observation that the free, superficial peritoneal implants reacted like eutopic endometrium. These implants were recognized as implants from menstrual blood regurgitated into the pelvic cavity. Adenomyosis externa, ovarian endometrioma and peritoneal endometriosis then came to be regarded as the same disease. In the light of today's knowledge, it may be important to remember this progressive understanding in the nosology of what is now universally called pelvic endometriosis.
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Endometriosis is a disease affecting fertility in many women. However, the mere presence of what is defined as endometriosis cannot be accepted per se as a cause of infertility or an indication for therapy. In the minimal or mild stage the activity rather than the presence should be the criterion for diagnosis as a disease. It is also clear that the endpoint of treatment of endometriosis in infertility is not the elimination of the implants but rather the inactivation or neutralization of its activity.
A specially designed rigid salpingoscope has been developed to allow inspection of the tubal mucosa during laparoscopy. The presence and extent of intratubal adhesion formation can be evaluated more accurately by this technique than by either HSG or laparoscopy. In 22 patients with bilateral hydrosalpinges, an intrauterine pregnancy rate of 59% was achieved in the group of patients with very mild mucosal lesions and absence of mucosal adhesions.
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This study presents the patient characteristics, the reason for requesting a reversal operation, the surgical technique and pregnancy rates after a microsurgical reanastomosis following a mechanical (ring or clip) method of sterilization in 55 women. A corrected intrauterine pregnancy rate of 90% was obtained. Ectopic pregnancy occurred in 7% of the patients. Human female sterilization presently has a very high probability of being reversible on the condition that a careful mechanical sterilization has been performed.
The recovery of tubal function after restoration of patency in mechanically induced hydrosalpinges was studied in twenty sexually mature rabbits by correlating the morphological lesions of tubal damage and adhesion formation with the ovulatory function, pregnancy rate and nidation index at 2 and 4-8 weeks postoperative intervals. Two weeks after hydrosalpinx correction no implantations occurred although the oviducts had a patency rate of 63% and no or slight adhesions were present. From four weeks after hydrosalpinx correction implantations occurred. Morphological studies showed a partial or complete recovery of mucosal lesions in this group of rabbits. The number of ovulations correlated with the presence or absence of a moderate degree of postoperative adhesion formation.
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A technique of translaparoscopic salpingoscopy is utilized to evaluate the ampullary segment of the Fallopian tube in patients suffering from infertility. Comparison of this technique with hysterosalpingography in a series of 32 patients with hydrosalpinges demonstrates its superiority in the evaluation of the tubal mucosa. This new diagnostic approach allows a more accurate selection of patients for either microsurgical repair, in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT).
Endoscopy of the fallopian tube allows examination of the tubal mucosa in subfertile patients. Clinical and morphological studies have shown a high correlation between the appearance of the tubal mucosa and the ultimate outcome in terms of pregnancies. Salpingoscopy was originally performed during laparotomy for reconstructive tubal surgery. The present study describes the use of a rigid 3 mm telescope passed along the channel of the operating laparoscope to assess the mucosa of the infundibulum and ampullary segment. Lesions of the infundibulum and ampullary segment have been detected in patients with apparently normal tubes on the hysterosalpingogram and at laparoscopy. The extent of the mucosal lesions can be assessed preoperatively in patients with tubal adhesions, tubo-cornual or isthmic lesions and hydrosalpinges.
This review derives from extensive experience with the placental bed biopsy technique in three centers over the last 30 years. A placental bed biopsy, usually taken at cesarean section, must include basal decidua and subjacent myometrium from the central zone of the placental site. Attention is drawn specifically to the sampling errors and to the pitfalls in morphologic interpretation of tissues, both maternal and fetal, that are continuously changing throughout the course of pregnancy. The features of the normal placental bed and of vascular lesions in pathologic pregnancies are briefly reviewed. Extension and elaboration of the technique and its more widespread use could contribute to the elucidation of many of the unresolved problems in human pregnancy.
An examination of the maternal vascular response to placentation shows that physiological changes in the placental bed normally extend from the decidua into the inner myometrium. In pre-eclampsia and in a proportion of pregnancies with small-for-gestational age infants (SGA) the physiological changes are restricted to the decidual segments alone. In addition, complete absence of physiological changes throughout the entire length of some spiral arteries is seen in pre-eclampsia and SGA. This new observation is confirmed in a study of basal plates of placentas from abnormal pregnancies. Intraluminal endovascular trophoblast may be seen in the placental bed spiral arteries in the third trimester in pre-eclampsia and SGA, a feature not seen beyond the second trimester in normal pregnancy. These findings point to a defect in the normal interaction between migratory trophoblast and maternal uterine tissues in pre-eclampsia and in SGA.