BEYOND: a randomized controlled trial comparing efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus antagonist protocol during the first ovarian stimulation cycle.

STUDY QUESTION: How does a gonadotrophin-releasing hormone (GnRH) agonist versus a GnRH antagonist protocol affect ovarian response when using an individualized fixed daily dose of follitropin delta for ovarian stimulation? SUMMARY ANSWER: The BEYOND trial data demonstrate thatindividualized fixed-dose follitropin delta is effective when used in a GnRH agonist protocol, compared with a GnRH antagonist protocol, in women with anti-Müllerian hormone (AMH) ≤35 pmol/l and no increased risk of ovarian hyperstimulation syndrome (OHSS). WHAT IS KNOWN ALREADY: The efficacy and safety of an individualized fixed daily dose of follitropin delta (based on body weight and AMH) have been established in randomized controlled trials (RCTs) using a GnRH antagonist protocol. Preliminary study data indicate that individualized follitropin delta is also efficacious in a GnRH agonist protocol (RAINBOW trial, NCT03564509). There are no prospective comparative data using individualized follitropin delta for ovarian stimulation in a GnRH agonist versus a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: This is the first randomized, controlled, open-label, multi-centre trial exploring efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus a GnRH antagonist protocol in participants undergoing their first ovarian stimulation cycle for IVF/ICSI. A total of 437 participants were randomized centrally and stratified by centre and age. The primary endpoint was the number of oocytes retrieved. Secondary endpoints included ongoing pregnancy rates, adverse drug reactions (including OHSS), live births, and neonatal outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants (18-40 years; AMH ≤35 pmol/l) were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway, and Switzerland. The mean number of oocytes retrieved was compared between the GnRH agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. Analyses were based on all randomized subjects, using a multiple imputation method for randomized subjects withdrawing before the start of stimulation. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 437 randomized subjects, 221 were randomized to the GnRH agonist, and 216 were randomized to the GnRH antagonist protocol. The participants had a mean age of 32.3 ± 4.3 years and a mean serum AMH of 16.6 ± 7.8 pmol/l. A total of 202 and 204 participants started ovarian stimulation with follitropin delta in the GnRH agonist and antagonist groups, respectively. The mean number of oocytes retrieved was statistically significantly higher in the agonist group (11.1 ± 5.9) versus the antagonist group (9.6 ± 5.5), with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, P = 0.0185). The difference in number of oocytes retrieved was influenced by the patients' age and ovarian reserve, with a greater difference observed in patients aged <35 years and in patients with high ovarian reserve (AMH >15 pmol/l). Both the GnRH agonist and antagonist groups had a similar proportion of cycle cancellations (2.0% [4/202] versus 3.4% [7/204]) and fresh blastocyst transfer cancellations (13.4% [27/202] versus 14.7% [30/204]). The estimated ongoing pregnancy rate per started cycle was numerically higher in the GnRH agonist group (36.9% versus 29.1%; difference: 7.74% [95% CI: -1.49; 16.97, P = 0.1002]). The most commonly reported adverse events (≥1% in either group; headache, OHSS, nausea, pelvic pain, or discomfort and abdominal pain) were similar in both groups. The incidence of early moderate/severe OHSS was low (1.5% for the agonist group versus 2.5% for antagonist groups). Estimated live birth rates per started cycle were 35.8% and 28.7% in the GnRH agonist and antagonist groups, respectively (treatment difference 7.15%; 95% CI: -2.02; 16.31; P = 0.1265). The two treatment groups were comparable with respect to neonatal health data for singletons and twins and for incidence of congenital malformations (2.7% and 3.3% for the GnRH agonist versus antagonist groups, respectively). LIMITATIONS, REASONS FOR CAUTION: All participants had AMH ≤35 pmol/l and were ≤40 years old. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/l (i.e. those with an increased OHSS risk). The incidence of OHSS in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Outcomes of transfers with cryopreserved blastocysts were not followed up, therefore the cumulative live birth rates and neonatal outcomes after cryotransfer are unknown. WIDER IMPLICATIONS OF THE FINDINGS: In women with AMH ≤35 pmol/l, an individualized fixed daily dose of follitropin delta resulted in a significantly higher number of oocytes retrieved when used in a GnRH agonist protocol compared with a GnRH antagonist protocol, with no additional safety signals observed and no additional risk of OHSS. Live birth rates following ovarian stimulation with individualized follitropin delta were not statistically different between the GnRH protocols; however, the trial was not powered to assess this endpoint. There were no safety concerns with respect to neonatal health after ovarian stimulation with follitropin delta in either protocol. STUDY FUNDING/COMPETING INTEREST(S): The trial was funded by Ferring Pharmaceuticals. EE, EP, and MS have no competing interests. AP has received research support from Ferring, and Gedeon Richter, and honoraria or consultation fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, Merck A/S. BC has received consulting fees from Ferring and Merck, and his department received fees from Ferring to cover the costs of patient enrolment. MBS has received support to attend meetings and/or travel from Ferring, and was a board member for FertiPROTEKT e.V. until 2023. JS has received honoraria or consultation fees from Ferring and Merck, and support for attending meetings and/or travel from Ferring, Merck, and GoodLife. TS has received support/travel expenses from Ferring for attending a congress meeting, and participated in an advisory board for Merck. YS has received grants/research support from Ferring and support to attend a professional society congress meeting from Merck. RL and PP are employees of Ferring Pharmaceuticals. PP is a BOD member of PharmaBiome and owns stocks of Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT03809429; EudraCT Number 2017-002783-40. TRIAL REGISTRATION DATE: 7 April 2019. DATE OF FIRST PATIENT'S ENROLMENT: 2 May 2019.

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.

[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.

Cervical tissue changes in women with miscarriage: a morphological and biochemical investigation.

OBJECTIVE: To evaluate morphological and inflammatory events in the uterine cervix in first trimester miscarriages. DESIGN: Experimental study. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION: Nulliparous women with first trimester symptomatic (n = 7) or silent (n = 11) miscarriage scheduled for surgical evacuation and nulliparous women scheduled for surgical termination of first trimester pregnancies (control group n = 11). METHODS: Before evacuation, biopsies were obtained from the cervix. The specimens were either fixed in glutaraldehyde for electron microscopy or snap-frozen in liquid nitrogen and stored at -70 degrees C until analyses of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs). MAIN OUTCOME MEASURES: Ultrastructure of cervical tissue, cervical tissue levels of IL-8, immunohistochemistry of MMP-1, MMP-8, MMP-9 and IL-8. RESULTS: The organization of the cervical collagen framework was deranged, the fibroblasts were reactive and the number of activated mast cells appeared to be increased in specimens from women with miscarriage compared with controls. IL-8 was significantly increased in women with miscarriage. Immunohistochemistry of MMP-1 and MMP-8 did not demonstrate any significant difference between the groups. MMP-9 was significantly lower in specimens from women with symptomatic miscarriage compared to women with silent miscarriage and women in the control group. CONCLUSIONS: An inflammatory-like response takes place in the cervix both in women with symptomatic and silent miscarriage. The intensity of the inflammatory response seems to be similar in the two groups. Therefore, inadequate cervical remodeling does not seem to be the reason why some miscarriages remain silent.

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.

[Ovulation induction by means of letrozole]. / Ovulasjonsinduksjon ved bruk av letrozol.

BACKGROUND: Clomiphene citrate is a first line treatment of infertile anovulatory women. Although the treatment induces ovulation in most women, only one in four achieve uncomplicated pregnancy after treatment over several cycles. During recent years several clinics have started to use letrozole tablets for ovulation induction. This paper gives a short presentation of letrozole, mechanisms of action are explained, and pros and cons of letrozole versus clomiphene citrate are discussed. MATERIAL AND METHODS: The paper is based on more than two years of clinical experience with use of letrozole for ovulation induction before timed sexual intercourse or intrauterine insemination and the use of letrozole during ovarian stimulation for in vitro fertilization. In addition, a non-systematic search in Pubmed has been performed to give an overview of what is known about letrozole for ovulation induction. RESULTS: Use of letrozole is associated with a higher chance of uncomplicated pregnancy and a lower risk of multiple pregnancy than clomiphene citrate. In addition, more than 60 % of the women who are resistant to clomiphene citrate ovulate after treatment with letrozole. Letrozole combined with gonadotropin may also be beneficial in some women during in vitro fertilization. INTERPRETATION: Studies of letrozole use in reproduction have so far been promising. However, large randomized studies are warranted before it can be concluded that letrozole should become a first line treatment for ovulation induction.

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.

Sublingual nitroglycerin seems to be effective in the management of retained placenta.

BACKGROUND: A common approach in the management of retained placenta is administration of oxytocin followed by controlled cord traction. Previously it has also been demonstrated that intravenously administered nitroglycerin facilitates manual extraction of retained placenta. The purpose of the present trial was to examine the success rate and safety of sequential administration of intravenous oxytocin in combination with sublingual nitroglycerin for the delivery of retained placenta. METHODS: The report is a chart review of 24 women with retained placenta despite intravenously administered oxytocin. The women were given sublingual nitroglycerin (1 mg) to promote detachment of the placenta. Some 5 min after resorption of the tablets, controlled cord traction was carried out for a maximum of 5 min. In addition, changes in blood pressure following treatment with nitroglycerin and total blood loss during delivery were registered. RESULTS: Twenty-one of the women delivered the placenta successfully following sublingual administration of nitroglycerin. The procedure failed in 3 women and operative manual removal under regional or general anesthesia was undertaken. No complications due to nitroglycerin were registered. CONCLUSIONS: Sequential administration of oxytocin and nitroglycerin seems to be an effective and safe procedure in the management of retained placenta. However, larger studies are needed to confirm the encouraging results of the present trial.

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 in men with Klinefelter syndrome]. / Assistert befruktning ved Klinefelters syndrom.

BACKGROUND: Klinefelter syndrome is the most common chromosomal aberration in men with azoospermia. The revision of the Norwegian biotechnology law in 2004 allows infertile couples with this diagnosis to become genetic parents. Surgical sperm extraction has to be performed to enable identification of possible sperm production. The preliminary approval to use this procedure (stated in the biotechnology law) was extended in 2007. This paper presents a short overview of the infertility investigation and treatment in men with Klinefelter syndrome. MATERIAL AND METHODS: The paper is based on more than 10 years of clinical experience in workup and treatment of infertile couples with the diagnosis Klinefelter syndrome. In addition, a non-systematic search in Pubmed and Medline has been carried out. RESULTS: Use of a microscopy during testicular sperm extraction increases the possibility of finding sperm in men with Klinefelter syndrome. The microsurgical procedure also reduces the risk of complications. If the diagnostic recovery has identified testicular sperm, there is a high predictive value of finding sperm in a subsequent surgical procedure. INTERPRETATION: The optimal method for successful sperm recovery in men with Klinefelter syndrome implies the use of microsurgery. This surgical method should therefore be considered established in Norway.

Outpatient vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening and labor induction postterm: a randomized controlled study.

OBJECTIVE: Our aim was to examine the efficacy, safety, and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting. STUDY DESIGN: Two hundred pregnant women of at least 42 weeks' gestation with an unripe cervix were randomly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets. RESULTS: Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group (P < .05). In women who did not go into labor, cervical status was similar in the 2 groups the next day. Headache was a common side effect. No maternal or fetal side effects of clinical importance were registered. CONCLUSION: Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective, safe, and well tolerated procedure. The definitive clinical efficacy and safety needs to be evaluated in larger series of patients.

[Preimplantation genetic diagnosis]. / Preimplantatorisk genetisk diagnostikk.

BACKGROUND: The revised Norwegian biotechnology law implies restrictive use of preimplantation genetic diagnostics--a highly specialised procedure, which is still in an early phase of development. MATERIAL AND METHOD: The paper is based on more than 10 years of clinical experience in preimplantation genetic diagnostics and on literature retrieved through PubMed/Medline. RESULTS: According to the biotechnology law, preimplantation genetic diagnostics can only be carried out when strict medical indications are present. Genetic counselling and a fertility work-up are compulsory for couples who wish to receive preimplantation genetic diagnostics. INTERPRETATION: Few disorders have an indication for preimplantation genetic diagnostics. It will therefore take time to build up adequate national expertise. For couples with a known risk of serious hereditary disease, preimplantation genetic diagnosis is useful in achieving an uncomplicated pregnancy and a healthy child.

A Case of Chronic Ectopic Pregnancy Manifested by Rectal Bleeding.

Ectopic pregnancy resulting in perforation of the rectum and rectal bleeding is clinically rare. We report an extremely rare case of chronic ectopic pregnancy with decreasing low levels of serum ß-HCG resulting in rectal bleeding. A 31-year-old woman, gravida 3, para 3, with moderate abdominal pain and rectal bleeding was diagnosed with a tubal pregnancy. The tube was adherent to the rectum. Following salpingo-oophorectomy, the perforation of the rectum was sutured. Biopsies from the rectum as well as the tube confirmed chronic ectopic pregnancy. This case illustrates that diagnosing ectopic pregnancy is sometimes extremely challenging and it underlines the importance of follow-up consultations when the final diagnosis has not yet been reached.

[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.

An ultrasound-based approach to the assessment of infertility, including the evaluation of tubal patency.

An optimal initial infertility investigation protocol would be a process that is diagnostically accurate, expeditious, cost-effective, reliable and as minimally invasive as possible. In addition, the investigation should provide the clinician with useful prognostic information regarding possible future treatment. At present, extensive use of invasive procedures such as diagnostic hysteroscopy and laparoscopy is the standard at many fertility centres. Recent advances in gynaecological ultrasonography have shown that ultrasound can replace routine invasive investigative procedures. An ultrasound-based approach would make the basic infertility investigation less time-consuming and less expensive, but at the same time more acceptable to the majority of patients. This chapter describes an ultrasound-based approach to the assessment of infertility. In addition, the role of ultrasonography for assessment of the pelvic organs as a basic part of the initial investigation of an infertile couple is discussed and compared to more traditional invasive methods.