Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations.

INTRODUCTION: Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. MATERIAL AND METHODS: Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. RESULTS: Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. CONCLUSIONS: Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.

Mast cell involvement in human cervical ripening.

OBJECTIVE: Cervical ripening resembles an inflammatory process in many aspects, involving invasion of inflammatory cells, collagen breakdown and remodelling of the extracellular matrix. Mast cells produce a variety of inflammatory agents and are attributed a functional role in cervical ripening. The aim of this study was to examine if cervical mast cells are increased in number and stimulated during pregnancy. STUDY DESIGN: Cervical biopsies were obtained with a biopsy needle prior to surgical termination of pregnancy in the first trimester, surgery for first-trimester miscarriage, elective caesarean section, and benign gynaecological surgery in non-pregnant women. After fixation, semithin sections were prepared and stained with toluidine blue. The number of mast cells was counted under a light microscope and their secretory activity was scored (0.5-4) according to specified criteria and further visualised with electron microscopy. For pairwise comparison between groups Fisher's nonparametric permutation test was used. RESULTS: The number of mast cells was increased from 3.4 ± 1.65 mast cells per 10 visual fields in non-pregnant women to 7.70 ± 0.35 per 10 visual fields in first trimester control women (p < 0.05). The highest number of mast cells was observed at term with 10.8 ± 2.1 per 10 visual fields, a number that was significantly higher than in first trimester control women (p < 0.05). At term mast cell activity scores were 3.39 ± 0.37 compared with 2.69 ± 0.27 in control first trimester women and 2.21 ± 0.86 in women with missed miscarriage (p < 0.05). The percentage of mast cells with activity score 4 was significantly higher at term compared with in the first trimester. Free mast cell granules were predominantly observed in areas with disorganized collagen fibres. CONCLUSION: The findings confirm that an increased influx of mast cells to the cervix occurs during pregnancy. The stimulated mast cell secretory activity in conditions associated with cervical tissue remodelling, such as term pregnancy and symptomatic miscarriage, provides further evidence that mast cells play a physiological role in cervical ripening.

[Use of GnRH antagonist for in vitro fertilization]. / Bruk av GnRH-antagonist ved in vitro-fertilisering.

BACKGROUND: For many patients, the typical treatment protocol for in vitro fertilization (IVF) is both physically and psychologically demanding. An alternative approach to use of gonadotropin-releasing hormone (GnRH)-agonists traditionally used to prevent premature ovulation, is use of GnRH-antagonists. The aim of this article is to describe advantages and disadvantages of using GnRH-antagonists in IVF. MATERIAL AND METHODS: The paper is based on literature identified through a non-systematic search in PubMed, and more than ten years of clinical experience with use of GnRH antagonists in IVF. RESULTS: To maintain a similar pregnancy rate as that with GnRH-agonists, one can use GnRH-antagonists at an earlier time-point during stimulation of the ovaries and a lower dose of follicle stimulating hormone (FSH). A less intensive stimulation implies a lower risk of complications and side effects and a shorter treatment period before egg collection (from four-five weeks to less than two weeks). The main disadvantage of the GnRH-antagonist protocol is that ovarian stimulation cannot be programmed to the same extent as that with use of a GnRH-agonist. INTERPRETATION: Stimulation with a GnRH-antagonist instead of a GnRH-agonist in IVF, is less physically and psychologically demanding for the patients and maintains the same birth rate.

Abnormal uterine bleeding refractory to medical therapy assessed by saline infusion sonohysterography.

OBJECTIVE: The primary aim of the study was to assess the incidence of intracavitary pathology visualized by saline infusion sonohysterography (SIS) in premenopausal women suffering from abnormal uterine bleeding refractory to medical therapy. Secondary aims were to evaluate the clinical course when a minimally invasive therapeutic approach was applied and to examine the need for hysterectomy in this group of women over a follow-up period of two years. DESIGN: Prospective cohort study. SETTING: Tertiary referral university hospital. POPULATION: Between February 2004 and June 2006, 104 premenopausal women suffering from abnormal uterine bleeding refractory to medical treatment were included. METHODS: Transvaginal ultrasonography and SIS were performed as first line procedures of the investigation. Hysteroscopy was undertaken for removal of focal intrauterine anomalies. Hysterectomy was only carried out when other approaches failed or were regarded as unsuitable. Women who did not undergo hysterectomy had regular follow-up consultations for at least two years. MAIN OUTCOME MEASURES: Incidence of intrauterine focal anomalies, clinical course, and need for hysterectomy. RESULTS: Following saline infusion sonohysterograhy intracavitary anomalies were visualized in 58 (55.8%) women. Over the follow-up period 80 women had successful minimally invasive treatment, while 24 women underwent hysterectomy. CONCLUSIONS: The study shows that focal intracavitary lesions are common in premenopausal women with abnormal uterine bleeding refractory to medical treatment. By applying minimally invasive diagnostic and therapeutic approaches acceptable bleeding patterns can be re-established in most cases, thereby resulting in a low rate of hysterectomies.

The management of pelvic abscess.

The optimum treatment for pelvic abscess would be an approach that is safe, efficacious, cost-effective, minimally invasive, and which affects the woman's fertility potential as little as possible. In women of reproductive age tubo-ovarian abscess is one of the most common types of pelvic abscess. Tubo-ovarian abscesses are classically treated with broad-spectrum antibiotics. Frequently this approach fails and surgical intervention becomes necessary in about 25% of all cases. Surgical procedures include laparotomy or laparoscopy with drainage of abscess, unilateral or bilateral salpingo-ophorectomy, and hysterectomy. However, surgery for tubo-ovarian abscess is often technically difficult and associated with complications. An alternative approach is the use of imaging-guided drainage of abscess in combination with antibiotics. Combined data from several studies indicate that ultrasound-guided transvaginal drainage with concomitant antibiotics is especially safe and efficacious. This chapter discusses the management of pelvic abscess with a special focus on transvaginal ultrasound-guided drainage of tubo-ovarian abscess.

Cervical priming in the first trimester: morphological and biochemical effects of misoprostol and isosorbide mononitrate.

OBJECTIVE: To evaluate morphological changes and inflammatory events in the uterine cervix following presurgical treatment with the prostaglandin analogue misoprostol or the nitric oxide donor isosorbide mononitrate (IMN). DESIGN: Experimental study. SETTINGS: Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION OF SAMPLE: Primigravid women (n=32) scheduled for surgical termination of first trimester pregnancy, treated vaginally overnight with either misoprostol (200 microg), IMN (40 mg) or no treatment (controls). METHODS: Before evacuation, cervical biopsies were obtained with the use of a Tru-Cut biopsy needle. Morphology was studied by electron microscopy. For assessment of inflammatory events the expression of the matrix metalloproteinases MMP-1 and MMP-9 was estimated by immunohistochemistry and interleukin IL-8 was quantified by ELISA. RESULTS: Misoprostol induced splitting and disorganization of the collagen fibres. Compared to specimens from women who had received no treatment, the granular endoplasmatic reticulum appeared enriched and dilated and the nuclear chromatin was clearly dispersed. Similar changes of a lesser degree were observed in specimens obtained from IMN-treated women. Staining intensity for MMP-1 and MMP-9 was more evident in specimens obtained from IMN-treated women compared to women who had received treatment with misoprostol or no treatment. The levels of IL-8 were higher following treatment with misoprostol compared to IMN and controls. CONCLUSION: The study demonstrates that misoprostol as well as IMN induces morphological changes and inflammatory events of the cervix. Changes of the collagen network were more pronounced in samples obtained from women treated with misoprostol compared to IMN.

Efficacy of percutaneous needle aspiration and open biopsy for sperm retrieval in men with non-obstructive azoospermia.

OBJECTIVE: To assess the efficacy of the two most common sperm retrieval procedures, testicular sperm aspiration (TESA) and testicular sperm extraction (TESE) as part of the diagnostic work-up in men with non-obstructive azoospermia. Design. Retrospective cohort study. SETTING: Center for Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. SAMPLE: Three hundred fifty men who underwent diagnostic surgical sperm recovery between January 1997 and December 2006. METHODS: A diagnostic TESA was initially performed in 281 men with testes of >12 mm(3). If no spermatozoa or an insufficient number of spermatozoa was found, most of the men underwent a diagnostic TESE. Diagnostic TESE was performed as the only surgical procedure in 69 men who had at least one testis < or =12 mm(3). MAIN OUTCOME MEASURES: Success rates of diagnostic TESA and diagnostic TESE. RESULTS: Spermatozoa were found in 129 (45.9%) of the 281 men who underwent TESA. However, in 29 of these men too few spermatozoa were identified for the men to be accepted for IVF/ICSI. The subsequent TESE resulted in 26 additional men being accepted for IVF/ICSI. In men with testes < or =12 mm(3) a sufficient number of spermatozoa were found in 27 out of 69 men following TESE. CONCLUSIONS: The study shows that in 52% of the men with non-obstructive azoospermia spermatozoa useful for ICSI can be identified. For at least one-third of the men with testes >12 mm(3) TESA is a sufficient procedure. Sperm retrieval rate is further increased following a subsequent TESE.

[Infertility treatment of men with azoospermia]. / Infertilitetsbehandling av menn med azoospermi.

BACKGROUND: Treatment of infertile couples with diagnosed azoospermia is a new medical field in Norway. The operative methods used for identification of sperm are not well known. The aim of this paper is to give an overview of the etiologies of azoospermia, to describe the surgical methods, and to discuss important aspects of this topic. MATERIAL AND METHOD: The paper is based on a search in Pubmed/Medline and more than ten years of clinical experience in workup and treatment of this patient group. RESULTS: Blood tests may indicate the type of azoospermia. For identification of sperm, either surgical recovery of testicular tissue or epididymal fluid is necessary. If the diagnostic sperm recovery is successful, the predictive value of finding sperm in subsequent in vitro fertilisation cycles is high. INTERPRETATION: When azoospermia is diagnosed, the couple should be given the opportunity to discuss the following with their doctor; possible causes of why there was no sperm in the ejaculate, the possibility for further investigation and treatment, and the possibilities of finding sperm if further investigation is carried out. In order to give adequate answers to these questions the doctor needs to be updated. In addition, a strategy for further investigation and treatment should be established, in order to fulfil the couple's legal rights.

Transvaginal ultrasound-guided aspiration for treatment of tubo-ovarian abscess: a study of 302 cases.

OBJECTIVE: Our purpose was to evaluate the effectiveness and safety of transvaginal ultrasound-guided aspiration together with antibiotic therapy for treatment of tubo-ovarian abscess. STUDY DESIGN: A review of women treated with transvaginal ultrasound-guided aspiration for tubo-ovarian abscess at Haukeland University Hospital, Bergen, Norway, between June 1986 and July 2003 was performed. Immediate clinical response and longer-term follow-up results were assessed. RESULTS: A total of 449 transvaginal aspirations were performed on 302 women. A total of 282 women (93.4%) were successfully treated for transvaginal aspiration of purulent fluid, together with antibiotic therapy. In the other 20 women (6.6%), surgery was performed. The main indications for surgery were diagnostic or therapeutic uncertainty, such as suspected residual tubo-ovarian abscess or pain. No procedure-related complications were diagnosed. CONCLUSION: Transvaginal ultrasound-guided aspiration combined with antibiotics is an effective and safe treatment regimen for tubo-ovarian abscess. The high success rate indicates that it should be a first-line procedure.

[Polycystic ovary syndrome]. / Polycystisk ovariesyndrom.

INTRODUCTION: In May 2003, leading American and European experts reached a consensus for the definition of polycystic ovary syndrome (PCOS). This consensus implies that the same criteria can be used when research on PCOS is performed, which is fundamental to further knowledge development. MATERIAL AND METHODS: The present review is based on a search in PubMed/Medline and personal clinical experience. RESULTS AND INTERPRETATION: Based on existing knowledge, women with PCOS have an increased risk of overweight, insulin resistance, type 2 diabetes mellitus, cardiovascular disease, and most likely certain types of gynaecologic cancer. Treatment of PCOS should therefore not only be symptomatic, focusing on existing symptoms. In addition, prophylactic measures should also be initiated. This change in treatment philosophy is a huge challenge to all doctors. In order to correctly diagnosing PCOS, general practitioners need to co-operate with gynaecologists. For optimal management of PCOS, general practitioners as well as gynaecologists have to be aware of the diagnostic criteria; the syndrome should be diagnosed as early as possible and the patient informed about the syndrome. The doctor and the patient should decide upon a long-term follow-up strategy together.

Prevalence and histologic diagnosis of adnexal cysts in postmenopausal women: an autopsy study.

OBJECTIVE: The purpose of this autopsy study was to examine the prevalence and histologic condition of adnexal cysts in postmenopausal women. STUDY DESIGN: Adnexa of 234 postmenopausal women who had died from nongynecologic diseases were examined by the team pathologist. RESULTS: Ovarian cysts were found in 36 of the women (15.4%). Nine women (3.8%) had ovarian cysts with a diameter between 20 and < or =50 mm; 4 women (1.7%) had cysts that were >50 mm in diameter. Four women had bilateral ovarian cysts. Paraovarian cysts were found in 11 women (4.7%). All cysts were benign, except for 1 woman, who had bilateral serous cystadenoma of borderline type. Macroscopically, the borderline cysts were multilocular with mean diameters of 60 mm and 15 mm, respectively. CONCLUSION: Because of the high prevalence of benign adnexal cysts, the identification of small unilocular cysts in postmenopausal women should be regarded as a normal finding.