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One of the first steps in the pathogenesis of endometriosis is the attachment of the endometrium to the peritoneal lining. Since the peritoneum is extremely fragile and hard to obtain, amnion has been used as an in-vitro model to study adhesion. Scanning and transmission electron microscopy was applied to evaluate the adhesion of endometrial cells isolated in the proliferative and secretory phases of the menstrual cycle. Endometrial fragments obtained in either phase of the cycle were able to adhere to the extracellular matrix of the amnion. Fragments from proliferative phase endometrium showed active spreading and growth over the matrix surface, whereas fragments from secretory phase endometrium did not. Fragments from proliferative as well as secretory phase endometrium were able to adhere to the epithelial side of the amnion, but only at locations where the amniotic epithelium was damaged or partly absent. These observations indicate that the basement membrane and extracellular matrix provide a suitable substrate for endometrial cell attachment and growth and that endometrial cell adhesion occurs preferentially to subepithelial structures, whereas an intact epithelium prevents the adhesion of endometrial fragments to the amnion.

A long waiting list for in-vitro fertilization (IVF) offers the possibility to study treatment-independent pregnancy rates in patients with severe reproductive disorders. We performed a retrospective cohort study with a nested case-control design in which the cases achieved a spontaneous pregnancy while on the waiting list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the controls did not become pregnant while on the waiting list. Spontaneous pregnancies occurred in 76 of 1391 patients on the waiting list. Significant differences between pregnant and non-pregnant patients were found for duration of subfertility (couples on the IVF waiting list), and for progressive sperm motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12 months cumulative pregnancy rate for patients on the waiting list was 2.4% (95% CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of unexplained subfertility patients, and 17% of male subfertility patients achieved a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the treatment-independent pregnancy rate in patients with severe reproductive disorders is low. More than 75% of the spontaneous pregnancies in the tubal subfertility and unexplained subfertility couples occurred during their first three months on the waiting list, whereas spontaneous pregnancy rate in male subfertility couples showed a more gradual but persisting increase. We conclude that one cycle of IVF or ICSI is superior to 12 months of expectant management in patients with severely impaired fertility due to tubal, unexplained or male factors.

This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation.

Summary.In 25 rabbits (Group E) endometrium from the right uterine horn was transplanted onto the peritoneum. In 25 rabbits (Group C) fat was transplanted. After a recovery period of 12 weeks the does were mated, and killed 24 h later. In Group E the implants had changed into cysts of 5–15 mm in diameter. Histological examination revealed endometrial glands and stroma in every specimen. Periadenexal adhesions did not develop in any animal. No differences were found between Groups C and E in the number of corpora lutea, the recovery rate, the fertilization rate and the transport of fertilized ova. These findings indicate that endometrial implants in the rabbit have no influence on the ovulatory mechanism, the pickup function of the oviduct, the fertilization rate or on the transport of fertilized ova. Taking into account the restrictions of a rabbit model, it is suggested that the decreased fecundity in mild endometriosis in the human may be caused by disturbances in post-fertilization events, i.e. development of the pre-implantation embryo or implantation.Keywords:endometriosis; ovulation; ovum pickup; fertilization; tubal transport

Summary.Peritoneal fluid volume was determined and concentrations of C-reactive protein, α1-antitrypsin, acid-α1-glycoprotein, α2-macroglobulin, haptoglobin, complement factors C3and C4, IgG, IgA and IgM were measured in the supernatant of the peritoneal fluid and in serum by means of a radial-immunodiffusion technique in 25 patients with and in 45 patients without endometriosis. Peritoneal fluid volume was not different between the two groups. The peritoneal fluid:serum ratios for the proteins determined showed a significant inverse correlation with their molecular weight in both groups, indicating that their presence in peritoneal fluid is governed by exudation according to their molecular weight, rather than by active production in, or selective release into, the peritoneal cavity. In control patients only, the ratios of most of the individual proteins studied were significantly higher in the luteal than in the follicular phase. We suggest that the high values of peritoneal fluid:serum ratios in endometriosis patients in the follicular phase reflects an additional contribution by endometriotic tissue and peritoneal macrophages. In the luteal phase, the cycle-dependent increase of protein exudation obscures this additional contribution.We conclude that endometriosis does not cause marked intra-abdominal inflammatory changes. If the presence of endometriosis lowers fecundity, the mechanism probably does not involve acute-phase protein synthesis.Keywords:endometriosis; acute-phase proteins; peritoneal fluid; man

Objectives. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo.

To qualify and quantify endometrial waves in regularly cycling women.

Data on the thermal expansion coefficients of some Morpholinium-TCNQ salts are presented. Measurements were carried out with the help of a Michelson interferometer.

Objectives. This study was conducted to test the hypothesis that angiotensin-converting enzyme (ACE) inhibition reduces myocardial ischemia and related events after myocardial infarction (MI).

Objective: To evaluate whether the predictive ability of a normal FSH level on cycle day 3 can be enhanced by levels of estradiol-17β (E2) on cycle day 3.

Sampson's transplantation theory for the pathogenesis of peritoneal endometriosis is widely accepted. The events that take place, however, on the cellular and subcellular level during the transition of endometrial tissue in the abdominal cavity into peritoneal endometriosis remain controversial. The mesothelium plays a central role in the debate on this subject. The interaction between endometrium and peritoneum has been studied in an in-vitro model using amnion, peritoneum and mesothelial cells in culture on the one hand and cyclic and menstrual endometrium on the other hand. The results of these studies indicate that (i) an intact mesothelial lining prevents adhesion of shed endometrial tissue, (ii) shed endometrial tissue adheres to the peritoneal extracellular matrix and (iii) menstrual effluent creates its own adhesion sites by damaging the mesothelial lining thus exposing the extracellular matrix. Therefore we conclude that the mesothelium has the properties of Teflon, while the extracellular matrix resembles Velcro.

Oestrogen receptors (ER) and progesterone receptors (PR) were measured in the rabbit model of endometriosis in eutopic and ectopic endometrium of pregnant animals (n = 7) and controls (n = 7). Immunostaining of cryostat sections of ectopic and eutopic endometrium was performed using monoclonal antibodies against ER and PR. Levels of ER and PR were 'evaluated' in a semi-quantitative manner using a modified histoscore. The ER and PR content in stromal and glandular cells was not different in eutopic and ectopic endometrium in either pregnant or non-pregnant control animals. There was a significant difference between the PR content of the glandular epithelium of pregnant animals and controls for both eutopic (P less than 0.02) and ectopic (P less than 0.001) endometrium. The disappearance of glandular PR and the persistence of stromal PR suggest that the function of the glandular endometrium is mediated by the paracrine and autocrine action of stromal cells. The decidual cells are likely to produce substances that may be of importance in embryo implantation and early pregnancy.

The reasons for sub-fertility in patients with mild endometriosis remain unclear. Peritoneal fluid constituents may alter tubal transport and embryonic cleavage, with subsequent implantation disturbances. We used an animal model to study the influence of endometrial implants on early embryonic development. In 25 rabbits, endometrium from the right uterine horn was transplanted onto the peritoneum (Experimental group = Group E). In 25 rabbits, fat was transplanted (control group = group C). After a recovery period of 12 weeks the does were mated, and killed 24 h later. In the experimental group the implants had changed into cysts of 5-15 mm in diameter. Histological examination revealed endometrial glands and stroma in every specimen. Periadnexal adhesions did not develop in any animal. No marked differences were found between Groups E and C in embryonic cleavage stage, 24 h after mating. Additional culturing of the embryos for 48 h in a suitable culture medium revealed normal further development of the embryos. Bearing in mind the restrictions of extrapolating a rabbit model to the human, it is suggested that the decreased fecundity in mild endometriosis is not caused by altered early embryonic cleavage rate. The results of this study offer indirect evidence for implantation disturbances as a cause of endometriosis-associated sub-fertility.

To study the isolated influence of peritoneal endometrial implants on fertility in an adhesion-free rabbit model.

Felodipine (FEL) is a vasoselective dihydropyridine calcium antagonist that has shown promising results in smaller congestive heart failure (CHF) studies. Angiotensin converting enzyme inhibitors (ACEI) are the cornerstone of CHF therapy, but many patients can not be treated with these drugs because of side effects or contraindications. We compared the effects of FEL. 10mg b.Ld., and enalapril (ENA), 10mg b.Ld., in a double blind, parallel study in 50 patients with CHF. At baseline and after 16 weeks treatment cardiopulmonary exercise test, neurohormone sampling, Holter recording and quality of life questionaires were assessed.