Patterns of changes in glycoproteins, polypeptides, and steroids in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle.

During laparoscopy peritoneal fluid samples were collected for FSH, LH, PRL, 17 beta-estradiol, progesterone, and total protein determinations in 100 women with a normal menstrual cycle. The samples were collected between cycle day -6 and cycle day +9, with the serum LH peak as a point of reference (day 0). The period investigated was divided into seven phases. FSH and LH concentrations in the peritoneal fluid varied in a cycle-dependent pattern that reflected the pattern in serum. In every phase of the cycle, however, peritoneal fluid FSH and LH concentrations were higher than or equal to the serum levels. This finding contrasts with the physiological behavior of other proteins in the peritoneal fluid. Peritoneal fluid 17 beta-estradiol and progesterone levels also varied in a cyclic pattern, with an increase in concentration immediately after ovulation and a decrease after the midluteal phase. With the exception of 17 beta-estradiol levels during the preovulatory phase of the cycle, peritoneal fluid levels of 17 beta-estradiol and progesterone were always equal to or higher than serum levels. The increase in 17 beta-estradiol concentration in the postovulatory phase was more gradual than that in the progesterone concentration. The elevated peritoneal fluid levels of gonadotropins in the preovulatory phase of the menstrual cycle were the most striking finding of the present study. This together with the finding of high peritoneal fluid to serum ratios of steroid hormones after ovulation shed new light upon the surroundings in which follicular development, ovulation, and fertilization take place.

Achievement of therapeutic concentrations of cefuroxime in early preterm gestations with premature rupture of the membranes.

OBJECTIVE: To determine whether therapeutic cefuroxime concentrations can be achieved in maternal plasma, amniotic fluid (AF), neonatal plasma, placenta, and membranes in women with premature rupture of the membranes (PROM) at 27-33 weeks' gestation. METHODS: In an open nonrandomized, dose-response study, nine patients with PROM at 27-33 weeks' gestation received 1.5 g of cefuroxime intravenously three times daily. Maternal plasma and AF specimens were collected during pregnancy, and umbilical cord plasma, placenta, and membrane specimens were collected after delivery to assay cefuroxime concentrations using high-performance liquid chromatography. RESULTS: A high rate of placental transfer of cefuroxime was found. Bactericidal concentrations could be demonstrated in maternal plasma and in AF leaking from the vagina. A concentration-time curve in AF could be detected, with a peak concentration 3-4 hours after infusion. Therapeutically active levels were present in the newborns. The resorption of cefuroxime by the fetal membranes was high. CONCLUSIONS: Therapeutic concentrations of cefuroxime were found in all body fluids and tissues studied. Further study to establish the clinical utility of cefuroxime prophylaxis in PROM seems appropriate.

Detection of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in pregnant Dutch women.

A prospective study was performed to determine the prevalence of endocervical infection by Chlamydia trachomatis and vaginal colonization by Mycoplasma hominis and Ureaplasma urealyticum in pregnant women seeking routine obstetrical care in two clinics in the southern part of the Netherlands. C. trachomatis was detected using the direct immunofluorescence staining technique. For the genital mycoplasmata, generally accepted culture methods were used. Evaluable samples were obtained from 691 of 770 women in the first trimester of pregnancy. C. trachomatis was detected in 2.3%, M. hominis in 5.2% and U. urealyticum in 23.9% of the women. The isolation percentages of C. trachomatis and U. urealyticum were almost equally distributed in the different age groups. The prevalence of all three micro-organisms did not seem to be related to parity. Smoking and alcohol consumption seemed to influence the isolation rate of M. hominis and U. urealyticum.

The acute-phase response in endometriosis of women.

Peritoneal fluid volume was determined and concentrations of C-reactive protein, alpha 1-antitrypsin, acid-alpha 1-glycoprotein, alpha 2-macroglobulin, haptoglobin, complement factors C3 and 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 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.

Is there a solution for recurrent endometriosis?

Endometriosis may be either symptomatic or asymptomatic. Recurrence rates are mostly calculated on the basis of symptomatic patients re-presenting to their doctor. Based on the number of patients who experience recurrence of symptoms after medical or surgical therapy, recurrence rates of up to 45% after five years have been calculated. Whether the symptoms are due to real recurrence of disease or expanding, previously microscopic, endometriotic implants has not yet been established. Therapy should be tailored to the patient's complaints, but does not necessarily have to differ from that in patients with primary disease.

A rabbit model of endometriosis.

Since not all problems in endometriosis can be studied in the human, there is need of an animal model. We transplanted endometrial tissue of the rabbit into the peritoneal cavity and studied the changes after 12 weeks. At that time the endometrial implants in the rabbit had become cystic structures. The macroscopic and histologic appearance was consistent with endometriosis. Hormonal supplementation turned out not to be necessary. Microsurgical techniques prevented the formation of tubo-ovarian adhesions. This makes the rabbit model suitable for studying the influence of endometrial implants on fertility.

Pharmacokinetics of cefuroxime in pregnant patients with preterm premature rupture of the membranes.

To 6 pregnant patients with preterm premature rupture of the membranes, cefuroxime prophylaxis was given 1,500 mg three times daily intravenously. Cefuroxime concentrations were assayed in maternal plasma and amniotic fluid during pregnancy and in umbilical cord blood, placenta, and membranes after delivery. Our results showed a high rate of transplacental transfer of cefuroxime. Bactericidal levels could be demonstrated in maternal plasma, and in amniotic fluid leaking from the vagina. Therapeutically active levels were present in the newborns. The absorption of cefuroxime by the foetal membranes was high. Although the neonatal morbidity in this high-risk population was low, the data are still too preliminary to advise the routine prophylactic use of cefuroxime to pregnant patients with preterm premature rupture of the membranes.

Effect of endometriosis on ovulation, ovum pickup, fertilization and tubal transport in the rabbit.

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 mechanisms, 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.

Functional aspects of peritoneal macrophages in endometriosis of women.

Peritoneal fluid was collected in the periovulatory phase of the cycle from 25 women undergoing laparoscopy. Endometriosis was diagnosed in 13 patients (AFS score 1, N = 9; AFS score 2, N = 4) and 12 patients without endometriosis served as controls. In endometriosis patients the total peritoneal fluid cell number and cell concentration was significantly higher than in controls, indicating peritoneal irritation by endometrial implants. Peritoneal fluid macrophages in patients with endometriosis showed significantly increased erythrophagocytosis and lower chemiluminescence than in controls, suggesting an advanced differentiation of the macrophages in endometriosis patients. The macrophages in this stage of differentiation may interfere with gametes and embryos and thus contribute to endometriosis-associated subfertility.

Patterns of changes in proteins in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle.

During a laparoscopy that was performed between Day -6 and Day +9 of the cycle as related to the day of the LH peak (Day 0), the peritoneal fluid of 100 healthy female volunteers of proven fertility was collected and analysed. Peritoneal fluid volume and concentrations of total protein, albumin, alpha 1-, alpha 2-, beta- and gamma-globulins, IgA, IgG, IgM, haptoglobulin, acid-alpha 1-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C3-, C4- and C-reactive protein were determined. The peritoneal fluid volume and the concentrations of most proteins analysed showed an increase during the post-ovulatory phase of the period investigated. The peritoneal fluid:serum ratio of each individual protein showed a significant inverse correlation with its molecular weight. This confirms the assumption that peritoneal fluid is mainly an exudation product, most probably of ovarian origin.

Fibrinolytic properties of peritoneal fluid in endometriosis.

A decreased intraabdominal fibrinolytic activity has been proposed as an etiological factor in the development of endometriosis. To test this hypothesis plasminogen, fibrinogen, alpha 2-antiplasmin, alpha 2-macroglobulin, plasminogen activator (t-PA) and its inhibitor and the degradation products of fibrin were determined in the peritoneal fluid of 25 patients with and 45 patients without endometriosis. No significant difference was found for any of the parameters. Therefore, a role for the fibrinolytic system as an etiological factor in the development of endometriosis is unlikely. A high concentration of t-PA was found in comparison to normal blood levels, leading to a high concentration of fibrin degradation products in the peritoneal fluid, indicating an active system of intraabdominal fibrinolysis. A high concentration of fibrin degradation products further indicates the presence of fibrinogen and its turnover secondary to thrombin action.

Congenital cytomegalovirus infection in a twin pregnancy: a case report.

A case of congenital cytomegalovirus infection in a twin pregnancy is described, causing neonatal death in one of the infants whereas the other survived without major complications. The possible mechanisms involved are discussed.

The impact of peritoneal trauma on intra-abdominal fibrinolytic activity, adhesion formation and early embryonic development in a rabbit longitudinal model.

Intra-abdominal adhesions may interfere with fertility following gynaecological surgery and injury to the peritoneum plays a central role in the pathogenesis. Tissue plasminogen activator and its antagonists play a pivotal role in the intra-abdominal balance between fibrinolysis and adhesion formation. This process may be cycle-dependent in women. In order to establish the impact of the fibrinolytic activity on adhesion formation after a standardized trauma, a rabbit longitudinal model was developed, which allowed the study of possible differences between the periods before and after ovulation. The influence of extra-genital adhesions on early embryonic development was investigated. No cycle-dependent changes in fibrinolytic activity of the peritoneal fluid (PF) or of the serum could be demonstrated. No correlation was found between post-operative adhesion formation and the fibrinolytic activity during surgery. Three weeks after surgery, a significant increase in fibrinolytic activity of the PF was observed. The rank order of sampling is suggested to account for these differences. Extra-genital adhesions did not markedly influence ovulation, ovum pick-up and fertilization in this hormonally controlled rabbit model.

Effect of endometriosis on early embryonic development in the rabbit.

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.

Haemostatic and fibrinolytic properties of peritoneal fluid in the menstrual cycle.

The haemostatic and fibrinolytic properties of peritoneal fluid aspirated during laparoscopy were studied in a group of 49 women, 12 patients during the follicular phase of the menstrual cycle, and 37 during the luteal phase. Haemoglobin concentration and platelet count were low and similar in the pre- and post-ovulatory groups. Factor VIII was present in low concentrations both in the pre- and post-ovulatory period. The fibrinolytic and antifibrinolytic activity as judged by measurements of plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, fibrinogen and antithrombin III, rose significantly in the postovulatory period. It is concluded that the fibrinolytic activity of the peritoneal fluid depends on the stage of the menstrual cycle and is higher during the luteal phase.

Oculoauriculovertebral spectrum and cerebral anomalies.

We report on three Dutch children with a clinical diagnosis of oculoauriculovertebral spectrum (OAVS) and hydrocephalus. The clinical features are compared to 15 published cases of OAVS and hydrocephalus. Several other cerebral abnormalities were present in the whole group. About half of the cases had cleft lip/palate, anophthalmia/microphthalmia, or a cardiac defect. Mental retardation was found in five of the surviving 11 patients and early death occurred in one-third. We compared the cases with OAVS and hydrocephalus with published reports of OAVS and other cerebral anomalies and found no significant clinical differences. However, the clinical characteristics were clearly more severely expressed than generally found in patients with OAVS. Children with OAVS and more severe clinical features, especially anophthalmia/microphthalmia and cleft lip/palate, seem to be at an increased risk for cerebral malformations and for mental retardation.