4DryField vs. hyalobarrier gel for preventing the recurrence of intrauterine adhesions - a pilot study.

INTRODUCTION: This was a single-center pilot study that sought to describe an innovative use of 4DryField® PH (premix) for preventing the recurrence of intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis in patients with Asherman's syndrome (AS). MATERIAL AND METHODS: Twenty-three patients with AS were enrolled and 20 were randomized (1:1 ratio) to intrauterine application of 4DryField® PH (n = 10) or Hyalobarrier® gel (n = 10) in a single-blind manner. We evaluated IUAs (American Fertility Society [AFS] score) during initial hysteroscopy and second-look hysteroscopy one month later. Patients completed a follow-up symptoms questionnaire three and reproductive outcomes questionnaire six months later. RESULTS: The demographic and clinical characteristics, as well as severity of IUAs, were comparable in both groups. The mean initial AFS score was 9 and 8.5 in the 4DryField® PH and Hyalobarrier® gel groups, respectively (p = .476). There were no between-group differences in AFS progress (5.9 vs. 5.6, p = .675), need for secondary adhesiolysis (7 vs. 7 patients, p = 1), and the follow-up outcomes. CONCLUSION: 4DryField® PH could be a promising antiadhesive agent for preventing the recurrence of IUAs, showing similar effectiveness and safety to Hyalobarrier® gel. Our findings warrant prospective validation in a larger clinical trial. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN15630617.

The fertility sparing therapy in ectopic pregnancy.

OBJECTIVE: A review of current knowledge on the possibilities of fertility sparing therapy in case of ectopic pregnancy. METHODS AND RESULTS: Ectopic pregnancy is defined as implantation of an embryo outside the endometrial cavity, most often in the fallopian tube. This dia-gnosis is very common among young women. Ectopic pregnancies can be treated using the following three approaches, which can be combined: expectantly, pharmacologically or surgically. Fertility-sparing salpingostomy may be performed during surgical treatment. Medical (pharmacological) treatment consists in the application of methotrexate with a success rate of 75-96%, depending on the initial level of the free beta subunit of human chorionic gonadotropin (b-hCG). This is a safe treatment with minimal side effects. There is no standardization of the blood b-hCG level limits or of the size of the ectopic pregnancy mass for choosing expectant, surgical or medical treatment. A considerable increase in the rate of Cesarean sections over the last decades has led to an increase in the occurrence of the implantation of the gestational sac in the hysterotomy scar. There are several options to address this dia-gnosis, but none is clearly preferred. This issue is also discussed in the article. CONCLUSION: The goal of ectopic pregnancy treatment is to choose a safe and effective therapy with a low incidence of side effects and maintaining the maximum fertility of women. Properly set indication criteria are most important when choosing the right option.

Are we better off using multiple endometriosis classifications in imaging and surgery than settle for one universal less than perfect protocol? Review of staging systems in ultrasound, magnetic resonance and surgery.

There are multiple classifications in imaging and surgery of endometriosis and in this article, we offer a review of the main evaluation systems. The International Deep Endometriosis Analysis group consensus is the leading document for ultrasound assessment, while magnetic resonance imaging is guided by the European Society for Urogenital Radiology recommendations on technical protocol. In surgery, the revised American Society for Reproductive Medicine classification is the oldest system, ideally combined with newer classifications, such as Enzian or Endometriosis Fertility Index. Recently, The World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project introduced detailed proforma for clinical and intraoperative findings. There is still no universal consensus, so the initial emphasis should be on the uniform reporting of the disease extent until research clarifies more the correlations between extent, symptoms and progression in order to develop a reliable staging system.Impact StatementWhat is already known on this subject? There have been several reviews of surgical classifications, comparing their scope and practical use, while in the imaging the attempts for literature review has been scarce.What do the results of this study add? This is the first up to date review offering detailed analysis of the main classification systems across the three main areas involved in endometriosis care - ultrasound, MRI and surgery. The mutual awareness of the radiological classifications for surgeons and vice versa is crucial in an efficient multidisciplinary communication and patient care. On these comparisons we were able to demonstrate the lack of consensus in description of the extent of the disease and even further lack of prognostic features (with the exemption of one surgical system).What are the implications of these findings for clinical practice and/or further research? Future attempts of scientific societies should focus on defining uniform nomenclature for extent description. In the second step the staging classification should encompass prognostic value (risk of disease and symptoms recurrence).

Uterus sparing surgery in adenomyosis and its impact on reproductive outcomes.

OBJECTIVE: The purpose of this study was to evaluate the appropriate surgical treatment of adenomyosis and its impact on reproductive outcomes. CONCLUSION: Patients with adenomyosis and fibroids may show a lower pregnancy rate and higher miscarriage rate than healthy individuals. However, there is no standard protocol for their optimal treatment, particularly in pregnancy-seeking or infertile women. Myomectomy is generally a commonly performed procedure that preserves fertility. On the other hand, the role of surgery in extensive uterine adenomyosis remains controversial, because adenomyosis often involves the whole uterus diffusely. It is almost impossible to remove all pathological tissue from the surrounding myometrium. Therefore, this procedure is called debulking/cytoreductive surgery. However, adenomyomectomy has also become a more common type of surgical intervention in recent years.

Hysteroscopic management of endometrial polyps and submucous leiomyomas in women using a levonorgestrel-releasing intrauterine system.

INTRODUCTION: This study was designed to evaluate the feasibility and effectiveness of hysteroscopy in the management of symptoms related to endometrial polyps and submucous leiomyomas in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: Twenty-three LNG-IUS users presenting with endometrial polyps and/or submucous leiomyomas and irregular uterine bleeding were recruited for hysteroscopic examination and surgery. Intrauterine pathology was investigated and treated by hysteroscopic resection with the LNG-IUS in situ, and the effect of the procedure on symptoms was evaluated after three to six months. RESULTS: Intrauterine pathology was successfully resected by hysteroscopy in 23 (100.0%) out of 23 cases. Following hysteroscopy, 18 (78.3%) women reported amenorrhea, one (4.3%) regular spotting, three (13.0%) irregular spotting and one (4.3%) patient resumed normal menstrual cycle. We conclude that 19 (82.6%) patients were postoperatively asymptomatic. All procedures were uncomplicated and 4 (17.4%) were carried out without general anesthesia as office procedures. CONCLUSION: Endometrial polyps and submucous leiomyomas can develop in LNG-IUS users, and this can cause irregular uterine bleeding. Hysteroscopic resection of these pathologies is a feasible method in the clinical management of symptoms.

Malignant endometrial polyp in woman with the levonorgestrel intrauterine system - a case report.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is widely used and recommended as a reliable contraceptive. It also acts by opposing the effects of estrogen on the endometrium, thereby preventing development of endometrial hyperplasia and its possible malignant transformation. This case describes a 52-year-old multiparous amenorrhoeic patient who was seen in the gynecology outpatient department for a routine control 46 months after the insertion LNG-IUS as contraception. Hysteroscopy with a target biopsy following suspicious ultrasound scan confirmed well-differentiated endometrioid adenocarcinoma. Ultrasound scan prior to inserting LNG-IUS revealed normal 5 mm thin endometrium with the sharp edges. Uterine bleeding before the LNG-IUS insertion was regular and not excessive and the woman has remained amenorrhoeic after the LNG-IUS insertion. We present a case of the growth of a polyp-shaped endometrial carcinoma in a LNG-IUS asymptomatic user.

The utility of fasting plasma glucose to identify impaired glucose metabolism in women with polycystic ovary syndrome.

We evaluated the utility of impaired fasting plasma glucose as defined by ADA to identify women with polycystic ovary syndrome (PCOS) affected by impaired glucose metabolism (i.e. impaired fasting glucose, impaired glucose tolerance and diabetes mellitus). In 330 women with PCOS, according to ESHRE criteria, an oral glucose tolerance test was done. Impaired fasting glucose was present in 36 women (12%), impaired glucose tolerance in 29 women (8.8%) and diabetes mellitus in 10 women (3%), 4 of them have fasting glucose higher than 7 mmol/l. The combination of impaired fasting glucose and impaired glucose tolerance was seen in 5 women (1.5%). The sensitivity of impaired fasting glucose for the detection of impaired glucose tolerance was 24% and specificity 91.8%. When fasting glucose above 5.6 mmol/l was used as the screening criterion, 28/35 subjects (80%) would have been missed. We conclude that fasting plasma glucose is not sufficiently sensitive for the detection of impaired glucose tolerance and diabetes mellitus type 2 in women with PCOS.

Is polycystic ovary syndrome, a state of relative estrogen excess, a real risk factor for estrogen-dependant malignancies?

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of fertile age. It is associated with several risk factors and long-term health consequences. Chronic anovulation combined with relative estrogen excess and consequent prolonged stimulatory effect on the endometrium can lead to the pathogenesis of hormonal dependant carcinoma. PCOS is thus traditionally reported to be associated with increased risk of endometrial, as well as breast and ovarian cancers. This article provides a critical literature review of the relationship between PCOS and the incidence of estrogen-dependant gynecological tumours, and it then discusses whether the commonly cited risk factor association can be substantiated by high quality studies which comply with the requirements of "evidence-based medicine."

Comparison of complications in very obese women undergoing hysterectomy - Abdominal vs laparoscopic approach with short- and long-term follow-up.

BACKGROUND: Surgical treatment of obese female patients represents a real challenge. Over the last decade, minimally invasive techniques for hysterectomy have emerged. These approaches reduce the invasiveness of standard surgical procedures while maintaining efficacy and feasibility. OBJECTIVE: To evaluate the rates of perioperative, early, mid-term and late postoperative complications in very obese [body mass index (BMI) ≥ 35 and < 40 kg/m2] and severely obese (BMI ≥ 40 kg/m2) women who underwent total (non-radical) hysterectomy. DESIGN: A prospective comparative multi-centre non-randomized study. METHODS: In total, 328 consecutive total (non-radical) hysterectomies were performed at seven teaching gynaecological centres. Of these, 153 (46.6%) were performed using an open laparotomy (LT) approach and 175 (53.4%) were performed laparoscopically (LS). All data were collected by medical specialists at the pre-operative examination prior to surgery, during surgery and three times postoperatively (during hospital stay, at 6-week follow-up and 6 months following surgery). Another analysis considered a total of 206 women who underwent laparoscopic hysterectomy. The subjects were divided according to BMI into 120 very obese women (BMI ≥ 35 and < 40 kg/m2) and 86 severely obese women (BMI ≥ 40 kg/m2). RESULTS: The total number of composite perioperative complications was significantly lower in the LS group (p = 0.006). Composite complications occurred significantly more often in patients in the LT group compared with the LS group in the early (p < 0.001) and mid-term (p < 0.001) postoperative periods. In the late postoperative period, the total number of composite postoperative complications did not differ significantly between the groups (p < 0.396). Among 206 patients who underwent laparoscopic hysterectomy, the number of complications was generally low; the rates of composite perioperative (p = 0.393), early (p = 0.642), mid-term (p = 0.738) and late (p = 1) postoperative complications were generally low; and frequency did not differ significantly with BMI. CONCLUSION: The LS approach does not increase intra-operative morbidity associated with surgery, and has significantly better outcomes in terms of the postoperative complication rate.

Comparison of corticoid substitution versus combined oral contraception administration in the treatment of non-classic adrenal hyperplasia: a prospective study.

OBJECTIVE: The clinical symptoms of non-classic adrenal hyperplasia (NCAH) are the same as those in patients with polycystic ovary syndrome (PCOS). The aim of our study was to compare conventional corticoid treatment of NCAH with the effect of combined oral contraception (COC) administration (used in treatment of PCOS) on clinical and laboratory parameters of NCAH. DESIGN: A prospective clinical study, cross-over design. MATERIAL AND METHODS: Since 1999 from 298 hyperandrogenic women, eight patients having 21-hydroxylase deficient NCAH have been identified. They were divided equally into two groups according to the order of application treatment modality (hydrocortison vs. COC). Effect of treatment of both modalities on clinical symptoms (hirsutism - FG score, acne, menstrual cycle) and laboratory parameters (testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, sex hormone binding globulin (SHBG)) were evaluated. RESULTS: We observed the decrease of plasma androgens in both groups, which did not differ significantly. Significant increase of SHBG (i.e. decrease of free androgens) was, however, documented in each period with COC administration. Not surprisingly, improvement of the most frequent clinical symptom of NCAH in our study group, oligomenorrhea, was also more apparent in COC. Hirsutism was only a minor problem in our group that did not allow to evaluate treatment effect of both the modalities CONCLUSION: Our results indicate that ovarian suppression by COC administration can effectively suppress androgen production and improve the most frequent clinical symptom (irregular cycle) in patients with NCAH, so can be successfully used for the treatment at least under basal conditions. Whether corticosteroid substitution can be limited to patients with inadequate response to COC on plasma androgen levels or with signs of adrenal insufficiency requires further data.

Insulin sensitivity in women with polycystic ovary syndrome.

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 +/- 1.8 kg/m2 and 30 obese with BMI of 29.6 +/- 3.7 kg/m2] and in 15 healthy women with BMI of 21.6 +/- 1.8 kg/m2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women.

High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma.

BACKGROUND: Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. OBJECTIVE: The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2-IIIB tumours and correlate findings with histopathology. STUDY DESIGN: The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group. RESULTS: The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. CONCLUSIONS: Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort.

Prevalence of nonclassic adrenal hyperplasia (NCAH) in hyperandrogenic women.

OBJECTIVE: The clinical symptoms of nonclassic adrenal hyperplasia (NCAH) are identical with polycystic ovary syndrome (PCOS). The aim of our study was to determine the prevalence of nonclassic adrenal hyperplasia (21-hydroxylase-deficiency) in hyperandrogenic women, its biochemical, endocrine and clinical characteristics and to compare them with parameters of patients with ovarian hyperandrogenism. METHODS: Since 1999, 298 patients with elevation of at least one androgen and manifestation of one of the clinical androgenic symptoms (oligo/amenorrhea, hirsutism or acne) have been identified in our database. A diagnosis of NCAH was considered when the basal or stimulated 17-hydroxyprogesterone was elevated. RESULTS: Only eight patients were identified as having 21- hydroxylase deficient NCAH in the whole group of 298 hyperandrogenic women. Hirsutism and acne were found only in three, two patients, five of them had oligo/amenorrhea. Seven patients had both elevated basal and stimulated 17-hydroxyprogesterone, while in one case only elevation of stimulated level was found. All of the NCAH patients had elevated concentrations of testosterone, six DHEA, lower SHBG was found in four patients. Surprisingly, none of the NCAH patients had increased DHEAS. CONCLUSION: In our study, the prevalence of NCAH in hyperandrogenic women was 2.68%. Their leading symptom was oligomenorrhea, skin androgenic disorders were a minor clinical problem. None of the NCAH patients had an elevated DHEAS, the androgen dominantly produced by the adrenal glands.