Evidence for nitric oxide acting as a luteolytic factor in the human corpus luteum.

The aims of the present study were to characterize the expression and cellular localization of isoforms of nitric oxide synthase (NOS) in the human corpus luteum (CL) and to determine the effects of nitric oxide (NO) on CL steroidogenesis. Immunoblotting analyses revealed that endothelial NOS (eNOS) is the most abundant isoform in human CL with highest values during the late luteal phase. Immunoreactive eNOS was localized predominantely in the theca lutein layer, being particularly abundant in endothelial cells, but with positive staining also in some steroidogenic cells. Immunoreactive inducible NOS (iNOS) was also detected, but to lesser degree, and did not display apparent phase-specific changes. The effect of NO on CL steroid synthesis was examined using human chorionic gonadotrophin (HCG)-stimulated dispersed CL cells cultured in vitro. Progesterone production was significantly decreased (P < 0.05) by the NO donor spermine NONOate (10(-5) mol/l) in cells of the late, but not mid-, luteal phase. To investigate a potential link between NO and the local prostaglandins (PG), concentrations of PGF(2alpha) and PGE(2) were measured in culture medium. NO significantly increased (P < 0.05) concentrations of both PGF(2alpha) and PGE(2) during the late luteal phase. It is concluded that NO may be luteolytic in the human CL of menstruation.

Exon deletions and variants of human estrogen receptor mRNA in endometrial hyperplasia and adenocarcinoma.

Estrogen receptors (estrogen receptor alpha, ER) belong to a family of ligand-modulated transcription factors that play an important role in the progression of such tumors as breast and endometrial cancers. Functional domains, a set of mutations and variants produced by internal deletions of ER mRNA, have mainly been identified in breast cancer. Experimental results suggest that the presence of variants may result in different proteins which differ in activity and modulate the ER signaling pathway differently. We analyzed samples from 21 cases of endometrial hyperplasia and from 29 cases of endometrial cancer for the presence of internal exons and exon deletion variants of ER mRNA. ER and progesterone receptor (PgR) proteins were measured using Western blot technique in all endometrial cancer samples. We found that absence of the wild-type exon PCR product of ER mRNA in a sample increased in parallel with malignant potential in both sample types, whereas the number of exon deletion variants detected in the same sample decreased in cases of malignancy. The precise deletions of the respective exons suggest that they are probably the result of splicing errors. A relatively high number of variants in hyperplasia samples may indicate the important role of ER mRNA variants in the physiologic regulation of transcription in estrogen-sensitive genes. Eleven of 29 adenocarcinomas expressed a 62-kDa ER protein, truncated at the amino terminal, whereas all but one sample expressed a short 52 kDa variant ER protein. Our results suggest that differing ER proteins are generally present in human endometrial adenocarcinomas and that they may influence the estradiol signaling pathways.

Randomised trial comparing expectant with medical management for first trimester miscarriages.

OBJECTIVE: To compare the efficacy of antiprogesterone (mifepristone) in combination with a synthetic prostaglandin E1 analogue (misoprostol) for outpatient treatment of miscarriages. PARTICIPANTS: One hundred and twenty-two women with first trimester miscarriages. METHODS: The women were randomised to treatment with mifepristone 400 mg orally followed by a single oral dose of 400 microg misoprostol 48 hours later (n = 60) or expectant management (n = 62). Women were re-evaluated five days later. If retained intrauterine products of conception were found with an antero-posterior diameter above 15 mm on transvaginal ultrasound, surgical evacuation was performed. RESULTS: Eighty-two percent of the women randomised to pharmacological treatment and 76% of those randomised to expectant management had an empty uterine cavity after five days. Convalescence time was 1.8 days longer for women randomised to pharmacological treatment. Pain, bleeding, complications, and satisfaction with the treatment did not differ between the groups. CONCLUSIONS: Most cases of spontaneous incomplete miscarriage will become a complete miscarriage without intervention. This study shows that outpatient treatment with a combination of antiprogesterone and a prostaglandin E1 analogue did not increase the rate of complete miscarriage, compared with expectancy alone, by a clinical important degree.

Cell characteristics and function of two enriched fraction of human luteal cells prolonged culture.

Two subpopulations of steroidogenic cells exist in the corpus luteum of most species. The aims of the present study were to characterize these cells and to study their function during long-term culture. Human corpora lutea from early and late luteal phases were treated by mechanical and enzymatic digestion, followed by density sedimentation. Five distinct cell bands were obtained, two of which produced large amounts of progesterone. These were characterized according to density, size, steroidogenic enzymes, and numbers. More than 75% of cells expressed immunoreactive 3beta-hydroxydehydrogenase (3beta-HSD). Cells of higher density/smaller size were obtained in increasing numbers during the luteal phase and were more numerous compared with large cells. Under basal, human chorionic gonadotrophin (HCG)-, and prostaglandin E(2)-stimulated culture conditions, progesterone synthesis was greater in large cells of the early, but not late, luteal phase. Both cell fractions obtained from late, in contrast to early, luteal phase increased their basal progesterone production during the culture period of 9 days. We conclude that this technique for luteal cell isolation in the human yields two distinct subpopulations of steroidogenic cells, which respond differently to luteotrophic stimuli. We also conclude that cells of late luteal phase readily increase their progesterone synthesis over a period of 9 days, indicating a transition to longevity.

The conservative management of first trimester miscarriages and the use of colour Doppler sonography for patient selection.

This study of patients with first trimester miscarriage evaluates whether conservative management is a feasible strategy and assesses the value of colour Doppler ultrasonography for patient selection. After confirmation of the diagnosis by transvaginal sonography all patients were offered the choice of immediate dilatation and curettage or conservative management. The presence of a gestational sac, the occurrence of spontaneous complete miscarriage within 28 days, detectable pulsatile blood flow within the placenta in the presumed region of the intervillous space and post-treatment complications were the main end-points. Out of a total of 108 women recruited, 23 (21.3%) elected to undergo immediate dilatation and curettage and 85 (78.7%) chose conservative management. The treatment groups were similar in age, gestational age, gestational sac diameter, serum concentrations of human chorionic gonadotrophin (HCG) and progesterone, and proportion of patients who had post-treatment complications (12-13%). Of patients in the conservative management group, 71 out of 85 (84%) had a spontaneous, complete abortion, while 37 out of 46 cases (80%) with detectable presumed intervillous pulsatile blood flow had a complete, spontaneous abortion within 1 week; this occurred in 23% of cases with no detectable flow. This suggests that conservative management is a successful approach for many patients with first trimester miscarriage; colour Doppler ultrasonography can be used to select the most suitable patients for this strategy, and thus reduce the need for hospital admission and surgery.

Pain and pulmonary function following laparoscopic and abdominal hysterectomy: a randomized study.

BACKGROUND: The aim of this study was to evaluate pain and pulmonary function the first two days after abdominal and laparoscopic hysterectomy. METHODS: Women scheduled for abdominal hysterectomy were prospectively randomized to either laparoscopic (n=20) or abdominal (n=20) hysterectomy. Analgesics were self-administered by the patients by means of a programable infusion pump containing morphine. Postoperative pain was evaluated using a visual analog scale. Oxygen saturation was measured with an oxymeter. Pulmonary function was assessed using a peak flow meter measuring peak expiratory flow and a vitalograph measuring forced vital capacity and forced expiratory volume in one second. RESULTS: Pain scores were lower after laparoscopic hysterectomy at the first (p<0.05) and second postoperative day (p<0.01). Lung function was impaired on days 1 and 2 postoperatively, measured as peak expiratory flow, forced vital capacity and forced expiratory volume in one second, in both groups compared to the preoperative values. The patients undergoing laparoscopic hysterectomy had less impairment of lung function measured by peak expiratory flow (p<0.01), forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.05) the first postoperative day compared to the patients undergoing abdominal hysterectomy. The second postoperative day differences between the groups remained for peak expiratory flow (p<0.05) and forced expiratory volume in one second (p<0.05). CONCLUSIONS: Laparoscopic hysterectomy results in less pain and less impairment of respiratory function compared to abdominal hysterectomy.

Integrated multimodality therapy for embryonal rhabdomyosarcoma of the lower genital tract in postpubertal females.

Embryonal rhabdomyosarcoma of the female lower genital tract is generally regarded as a neoplasm occurring in childhood, but has also been reported in adults. The philosophy of therapy, largely based on data obtained from pediatric patients, has evolved slowly from ultraradical surgery, without adjuvant therapy, to neoadjuvant chemotherapy followed by less radical surgery and postoperative radiation. We report here three cases of lower genital tract rhabdomyosarcoma in postpubertal females. A failure to observe complete responses from any single treatment modality suggests that for embryonal rhabdomyosarcoma in adult and adolescent women a multimodality approach to therapy is essential.

[Aids in the management of pathological pregnancies. Advances in current knowledge of corpus luteum function]. / Hjälp vid handläggning av patologiska graviditeter. Ny kunskap om gulkroppens funktion.

Technological advances during the past decade have yielded new knowledge of luteal function and its regulation. A number of new substances with luteotrophic and lutcolytic properties have been identified in the corpus luteum, and the picture which emerges of the mechanisms responsible for physiological luteolysis is becoming increasingly complex. As luteal function/regulation during the menstrual cycle in the absence of pregnancy differs both from that in normal pregnancy, and from that in pathological pregnancy, these advances in our knowledge should prove clinically useful, particularly with regard to the early diagnosis and management of pathological pregnancy.

A randomized trial with a cost-consequence analysis after laparoscopic and abdominal hysterectomy.

OBJECTIVE: To perform a cost-consequence analysis after total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH). METHODS: Women scheduled for TAH were randomized prospectively to undergo the procedure by laparoscopic (n = 71) or abdominal (n = 72) surgery. Postoperative health status was assessed using The Medical Outcome Trust 36-Item Short-Form Health Survey questionnaire. The financial accounting system at the hospital and information from the local national health insurance office were used for the economic analysis. We evaluated changes in direct costs (hospital costs) and indirect costs (loss of production value) when performing a laparoscopic hysterectomy instead of an abdominal hysterectomy. RESULTS: Postoperative health status improved significantly faster after TLH than after TAH. The direct costs were 1.7% higher and the indirect costs 50.3% lower for patients undergoing laparoscopic surgery. The total costs were 23.1% lower after laparoscopic hysterectomy. CONCLUSION: A change in surgical technique from abdominal to laparoscopic hysterectomy was possible without compromising the health status of the patients, and it provided substantial financial benefits to society.

Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandin E1 analogue.

In a prospective clinical trial the effectiveness of a combination of 400 mg of mifepristone (antiprogesterone) and 400 g misoprostol (synthetic prostaglandin E1 analogue), both taken orally, was evaluated for the treatment of missed abortion. Of the 31 patients included, 16 (52%) had an empty uterine cavity at follow up six days after inclusion, 11 (35%) required surgical evacuation for retained intrauterine products of conception found at follow up, and four (13%) required emergency surgical evacuation due to severe pain or bleeding. The results do not support the use of mifepristone and misoprostol for women wishing the miscarriage to be resolved quickly.

PIP: A prospective clinical trial involving 31 Swedish women failed to demonstrate the effectiveness of a combination of 400 mg of mifepristone and 400 g of misoprostol for the treatment of missed spontaneous abortion. Transvaginal ultrasound examination showed intrauterine products of conception with an antero-posterior diameter of 15-50 mm in all study participants. 6 days after treatment, only 16 women (52%) had an empty uterine cavity. Surgical evacuation was required in the remaining 15 women, 11 because of retained products of conception (mean diameter, 26.7 mm). An additional 4 women underwent emergency surgical evacuation due to severe pain or bleeding. Women who successfully aborted after treatment had a significantly greater number of prior pregnancies than women who failed to abort. There were no differences between groups, however, in gestational length, size of the pregnancy products, or serum levels of human chorionic gonadotropin and progesterone. These results do not support the use of mifepristone and misoprostol for pharmacologic treatment in women who want their spontaneous abortions to be resolved quickly.

Ultrasound in gynecology: endometrium.

With the development and clinical application of transvaginal transducers/probes (TVS) the sonographic imaging of the endometrium was greatly enhanced compared with abdominal ultrasound. Also, the discomfort of a full bladder associated with abdominal ultrasound could be avoided. A shorter distance between probe and target allowed the use of higher frequency transducers, thereby achieving improved imaging. This review will only discuss the use of TVS, but it does not mean that abdominal ultrasound should not or cannot be used when dealing with the postmenopausal uterus. Transvaginal sonography (TVS) provides a valuable tool for the diagnosis of a wide range of gynecological disorders including those of the uterus and endometrium. The ability of TVS to depict the thickness and morphology of the endometrium has been established in both office and hospital settings. This article will discuss and illustrate the clinical and research applications of transvaginal sonography in relation to the endometrium in both symptomatic and asymptomatic postmenopausal women. The article is of particular relevance today given the number of women who are undergoing transvaginal ultrasonography in the absence of symptoms as a part of their routine check ups. There is a paucity of data relating to the management of apparent ultrasound abnormalities in such women. In symptomatic women or for women at risk of developing endometrial pathology, a technique that could reduce the number of biopsy procedures would be of value. Hysteroscopy, dilatation and curettage (D & C) as well as other endometrial sampling methods are all invasive, thus it would be of benefit if a way could be found to assess the endometrium using a relatively non-invasive approach. Such a technique would need to be relatively easy to learn and perform, as well as being well accepted by the patients. We believe that transvaginal sonography fulfills many of these requirements, the following review will attempt to put forward some of the evidence to support this view.

Using a logistic model to identify women with first-trimester spontaneous abortion suitable for expectant management.

OBJECTIVE: To design a method to identify women with first trimester spontaneous abortion suitable for expectant management. DESIGN: A stepwise logistic regression analysis based on retrospective analysis of clinical and biochemical variables. SETTING: Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Gothenburg, Sweden. PARTICIPANTS: One hundred and three women with inevitable or incomplete spontaneous abortion at < 13 weeks of gestation were chosen for expectant management. Eighty-one women with complete spontaneous abortion (i.e. complete expulsion and/or resolution of pregnancy products within three days of expectant management) were compared with those (n = 22) who underwent surgical evacuation of the uterus, most commonly owing to retained products of conception after three days. RESULTS: Employing a stepwise logistic regression procedure, five diagnostic variables possessing prognostic power were identified: serum progesterone, daily serum hCG change, serum CA125, serum alpha fetoprotein and intrauterine diameter. The logistic regression analysis was also applied to three diagnostic variables chosen for routine clinical use: serum progesterone, serum hCG and intrauterine diameter. The probability of complete spontaneous abortion within three days of expectant management in each woman could be calculated. CONCLUSION: We have used a logistic model to calculate the probability of complete spontaneous abortion within three days in women with first trimester miscarriages. Such information may be of clinical use in caring for women, as well as for development of management guidelines for those with miscarriages.

Increased concentrations of neopterin in plasma, ascites and ovarian cyst fluid in malignant tumours compared with benign ovarian tumours.

Neopterin is a marker of the activation of cell-mediated immunity. The aim was to determine whether the concentrations of neopterin differ in plasma, ascites and ovarian cyst fluid between patients with ovarian cancer and patients with benign ovarian tumours. Neopterin was measured in 29 patients with cystic ovarian tumours of unknown histology. 14 ovarian cancers and 15 benign ovarian tumours were diagnosed histologically. Patient age and tumour size did not differ significantly between the groups. Neopterin levels were determined in plasma, and in ascites and cyst fluid by ELISA. The neopterin concentration in plasma, ascites and ovarian cyst fluid was significantly higher in patients with ovarian cancer compared with patients with benign ovarian tumours of the same size. The study shows that activation of cell-mediated immunity, defined as increased formation of neopterin, was increased in patients with ovarian cancer compared with patients with benign ovarian tumours.

Bereavement, grieving and psychological morbidity after first trimester spontaneous abortion: comparing expectant management with surgical evacuation.

Early pregnancy loss is a profound adverse life event for many women, and increased psychiatric morbidity has been shown to occur after spontaneous abortion. Dilatation and curettage (D&C) has been the cornerstone in the treatment of first trimester spontaneous abortion over the last few decades. During recent years the possibility of conservative management has, however, been increasingly discussed. In a prospective randomized trial, we compared psychological reactions and morbidity, after either expectant management or D&C, for miscarriages of < 13 weeks gestation in which a transvaginal ultrasound examination showed intrauterine tissue and/or blood clots with an antero-posterior diameter of between 15 and 50 mm. Of the 86 patients included, 58 were randomized to expectant management and 28 to primary D&C. In patients randomized to expectant management, pregnancy products shown by transvaginal ultrasound disappeared within 3 days in 43 cases (74%), whereas 15 patients (26%) underwent D&C owing to retained products of conception after 3 days. At 2 weeks after inclusion, all patients answered self-administered questionnaires, including visual analogue scales, concerning their experience of the pregnancy loss, the present situation and concerns about the future. A brief anxiety status inventory was included. This study showed no increase in anxiety or depressive reactions 2 weeks after a first trimester spontaneous abortion when these patients were compared with non-pregnant healthy working females 19-39 years of age. Moreover, there were no significant differences in psychological reactions between patients managed either expectantly or by D&C.

Tissue Trauma after Laparoscopic and Abdominal Hysterectomy Measuring Inflammatory Response

It is suggested that laparoscopic surgery reduces postoperative pain and shortens hospital stay and convalescence because of the small amount of tissue trauma. We evaluated the inflammatory response during abdominal hysterectomy (AH, 12 women) and laparoscopic hysterectomy (LH, 12 women) by measuring interleukin (IL)-6, neopterin and terminal C5b9 complement complex (TCC). Blood samples were drawn preoperatively, perioperatively, 1 minute, 24 hours, and 7 days postoperatively. Levels of IL-6 were determined to evaluate cytokine release, neopterin was determined as a marker for macrophage-monocyte activation, and TCC was determined to assess complement activation. The IL-6 concentrations, as a percentage of preoperative level, were significantly elevated postoperatively in both groups, and also perioperatively in the LH group. Neopterin concentrations, as a percentage of perioperative level, were significantly increased in the LH group preoperatively and postoperatively. No elevation was seen in the AH group. There was no sign of complement activation in either group. Our results indicate significant tissue trauma during both LH and AH. The extent of trauma might be greater in laparoscopic surgery. Despite this, the LH group had a shorter hospital stay and convalescence than the AH group. The proposed advantages to the patient of laparsocopic surgery thus seem to be attributable to other factors than the amount of tissue trauma.

Cost Effectiveness and Health Status after Laparoscopic and Abdominal Hysterectomy

Laparoscopic hysterectomy has rapidly become a routine procedure without a preceding evaluation of its cost effectiveness in comparison with abdominal hysterectomy. Economic analysis must include an assessment of patients' health status. Direct costs (hospital costs) and indirect costs (value of production loss) were calculated for 20 women randomized to total laparoscopic hysterectomy (TLH) and 20 to total abdominal hysterectomy (TAH). Health status was evaluated by scoring responses to standardized questions 1, 3, and 12 weeks after the operation. Direct costs were 7% lower for TLH than for TAH. The shorter hospital stay after TLH more than compensated for the increased costs due to longer operating time. Indirect costs were 52% lower for TLH than for TAH. One and 3 weeks after the operation, limitations in physical and social activity were less pronounced, general mental health was better, and pain less pronounced after TLH compared with TAH. Fewer women considered their hospital stay and sick leave as too short after TLH compared with TAH. We conclude that, compared with TAH, TLH offers economic advantages to the patient, hospital, and society.