Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.

UNLABELLED: AIM. To elucidate the dynamics of FSH, LH, prolactin (PRL), TSH and insulin secretion in women with polycystic ovarian syndrome (PCOS) treated with metformin (MET). PATIENTS AND METHODS: In a prospective, controlled and randomised trial, 32 women with PCOS and 32 with normal cycle were recruited to receive MET (850 mg b.i.d.) or placebo (n: 16 for each subgroup) for an average of 40 days. Pituitary function and insulin secretion were assessed before and after intervention by GnRH-TRH tests and oral glucose tolerance test induced insulin response. RESULTS: Basal and area under the response curve (AURC) LH values were higher in PCOS than in normal controls before MET and declined following treatment in the former group (P < 0.05). Ovulatory PCOS responders had lower basal LH, AURC(LH) and AURC(PRL) values during MET than anovulatory cases (P < 0.05 for all) and AURCins was lower in ovulatory than anovulatory PCOS before and on MET (P < 0.02-P < 0.05), with a rise of QUICKY index in the former group during MET treatment (P < 0.05). FSH and TSH were similar. CONCLUSIONS: MET administration lowered LH activity in all PCOS women and in ovulatory responders and also compromised PRL stimulated secretion in the latter cases. These findings were indicative of an effect of MET on pituitary activity.

Cystic uterine tumors.

BACKGROUND/AIMS: The differential diagnosis of cystic uterine tumors includes fibroids showing cystic degeneration, cystic adenomyomas, congenital cysts, and developmental anomalies. METHODS: The incidence, clinical presentation and accuracy in preoperative diagnosis of cystic uterine tumors were studied in a university hospital population over a 6-year period. RESULTS: 29 cases were included. Of these, 8 corresponded to the diagnosis of a non-fibroid uterine cystic enlargement, and 21 to that of a fibroid with cystic degeneration. Age and parity were significantly lower in patients with non-fibroid cysts. Rates of symptomatic women (60 vs. 55.6%) were similar in both groups. The preoperative diagnosis was accurate in 20/21 (95.2%) cases with a degenerated leiomyoma. On the contrary, in 6/8 (75%) cases with a non-fibroid cystic swelling an erroneous diagnosis of an adnexal or an extrauterine mass was made preoperatively. In this group, histology of the tumor showed a cystic adenomyoma in 3, a congenital cyst in 3, and a blind rudimentary uterine horn in 2 cases, respectively. CONCLUSION: Uterine cystic tumors are uncommon. Frequently, non-fibroid swellings are erroneously diagnosed as adnexal enlargements and their true origin only becomes evident during surgery.

Insulin-like growth factor-1 isoform mRNA expression in women with endometriosis: eutopic endometrium versus endometriotic cyst.

Pathogenesis of endometriosis involves growth factors, which are synthesized locally. Insulin-like growth factor-1 (IGF-1) prevents apoptosis and has mitogenic action on endometrial cells. The IGF-1 gene undergoes alternative splicing and results in three isoforms (IGF-1Ea, IGF-1Eb, and IGF-1Ec or MGF). We analyzed the mRNA expression of IGF-1 isoforms in tissue samples of eutopic endometrium and endometriotic cyst obtained during laparoscopy from women with endometriosis. We documented that all three IGF-1 isoforms are expressed in both eutopic endometrium and ovarian endometrioma. Furthermore, we documented a significant decrease in all IGF-1 isoform expression in endometriotic cyst compared to endometrium of women with endometriosis. The reduction may correlate with the disease status and presence of fibrotic inactive tissue found in late stages of the disease.

Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH).

Improving pregnancy rates in patients with many failed attempts remains a challenge during IVF-ET or ICSI-ET programs. The availability of good-quality oocytes is a prerequisite for good results in such programs. The use of a personalized protocol for controlled ovarian hyperstimulation (COH) that gives the best possible results for the specific patient is a main factor for the success in IVF or ICSI. The response of many patients to the ovarian stimulation used is very poor, giving fewer oocytes than expected, resulting in much lower, if any, pregnancy rates. The definition of a poor responder is not clear and differs among researchers. A variety of strategies have been used to improve response in these patients, regardless of the definition used. These include various ovulation induction protocols that we believe might assist these patients achieve a pregnancy. The difficulty is greater due to the fact that poor responders are not a homogeneous group and each patient may have a different cause. More studies with large numbers of patients are needed in order to find those protocols that could provide these couples with an acceptable pregnancy rate.

Urokinase-type plasminogen activator and insulin-like growth factor-binding protein 3 mRNA expression in endometriotic lesions and eutopic endometrium: implications for the pathophysiology of endometriosis.

The peritoneal fluid of women with endometriosis contains an increased insulin-like growth factor 1 (IGF-1) bioavailability, which is produced by limited hydrolysis of urokinase-type plasminogen activator (uPA) on IGF-binding protein 3 (IGFBP-3). Recently, IGF-1 was shown to inhibit apoptosis of endometrial-like cells in vitro, suggesting that a microenvironment of increased IGF-1 bioavailability can optimize the survival of endometrial cells grown ectopically. Here the expression of mRNA of IGFBP-3 and uPA in tissue biopsies from eutopic endometrium and endometriotic lesions obtained at laparoscopy from women with endometriosis have been analyzed, and it is documented that both IGFBP-3 and uPA mRNA expression are increased from 3- to 10-fold in endometriotic lesions versus eutopic endometrium. Consequently, the necessary components (uPA and IGFBP-3 expression) of endocrine/autocrine/paracrine enhancement of local IGF bioavailability mediated by uPA hydrolysis of the IGFBP-3 were present in endometriotic lesions. These data possibly explain the origin of the increased content of uPA activity, IGF-1 bioavailability, and NH(2)-truncated forms of IGFBP-3 in the peritoneal fluid of women with endometriosis.

Laparoscopic management of patients with endometriosis and chronic pelvic pain.

Endometriosis has been traditionally included among the most important causes of chronic pelvic pain (CPP) in women of reproductive age. The main clinical manifestations of endometriosis are dysmenorrhea, dyspareunia, and chronic nonmenstrual pain. Despite the high prevalence of endometriosis in women suffering from CPP, controversy still exists regarding the true association between the stage and extent of this peculiar disease and the severity of pain. Over the last decade, advances in endoscopic technology have enabled gynecologic surgeons to recognize many atypical appearances of the endometriotic implants not known to exist before, thus allowing their complete excision or destruction. Laparoscopic surgery may offer considerable relief in patients with endometriosis and CPP. Although cases with advanced endometriosis seem to benefit the most, we also support surgical treatment in patients with early endometriosis diagnosed using laparoscopy, as many will experience improvement in their symptoms.

Tubo-ovarian abscesses in postmenopausal women: gynecological malignancy until proven otherwise?

OBJECTIVE: To investigate the incidence of gynecological malignancy in menopausal women who develop tubo-ovarian abscesses (TOAs), and to address the differences in presentation and underlying pathology between premenopausal and postmenopausal women with TOAs. STUDY DESIGN: In a retrospective study we included 93 patients with a diagnosis of a TOA and compared a premenopausal group (group 1) with a postmenopausal group (group 2). RESULTS: Group 1 included 76 (82%), and group 2 17 (18%) patients. Abdominal pain and pyrexia >38 degrees C were present in 93 and 74% cases of group 1, and in 71 and 41% cases of group 2 (P=0.016 and 0.019, respectively). Irregular vaginal bleeding and gross ascites were significantly more frequent in group 2. With respect to benign additional pathology we found no differences between the two groups. On the contrary a significant association between TOAs in menopause and malignancy was established. In 8 (47%) postmenopausal cases a concomitant gynecological malignancy was found including a variety of cancers. CONCLUSION: Postmenopausal women presenting with TOAs, should be thoroughly investigated to exclude a concomitant pelvic malignancy. Conservative treatment of TOAs has no place during the menopause.

Laparoscopy in the evaluation of women with unexplained ascites: an invaluable diagnostic tool.

STUDY OBJECTIVE: To assess whether laparoscopy is a reliable technique for the investigation of women presenting with ascites and in whom the diagnosis remains obscure. DESIGN: Prospective nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: University Departments of a tertiary referral center. PATIENTS: Women presenting in our institution with ascites in whom the diagnosis remained obscure after an extensive nonoperative diagnostic work-up. INTERVENTION: Undiagnosed cases were submitted to laparoscopy, and selective biopsy specimens were taken for histologic study. MEASUREMENTS AND MAIN RESULTS: Over a 3-year period, 73 patients were admitted to our institution with diffuse ascites. In 9 patients (12.3%), the diagnosis remained obscure, and these patients were further investigated with laparoscopy. Selective biopsy specimens obtained at laparoscopy clarified the specific cause of the ascites in all 9 patients. Peritoneal carcinomatosis was responsible in 5 patients (a metastatic gastrointestinal tumor in 1 patient, a malignant mesothelioma of the peritoneum in 1 patient, and a serous papillary carcinoma of the peritoneum and of the ovary in 2 and 1 patients, respectively). Three patients were found with miliary peritoneal tuberculosis, and the last patient had an unusual peritoneal reaction to methylene blue after laparoscopic adhesiolysis. CONCLUSION: Laparoscopy is a valuable means of assessing the peritoneal cavity in patients with unexplained ascites, where the primary cause remains unclear. The diagnosis can be accurately made with selective biopsy specimens, and appropriate treatment can be instituted without delay.

Endometriosis in patients with chronic pelvic pain: is staging predictive of the efficacy of laparoscopic surgery in pain relief?

BACKGROUND/AIMS: Endometriosis is considered an important cause of chronic pelvic pain. Despite its high prevalence, controversy still exists regarding the true association between the extent of endometriosis and the severity of symptoms. We conducted this prospective study to investigate the association between the stage of endometriosis and type and severity of pain, and to evaluate the efficacy of laparoscopic surgery in pain relief. METHODS: Ninety-five patients complaining of chronic pain were diagnosed with endometriosis and were treated with laparoscopic surgery. The severity of pain was assessed in patients with an endometriosis AFS (American Fertility Society) score less than 16 (group 1) and those with an AFS score greater than or equal to 16 (group 2), preoperatively and 6 months after surgery, using a visual pain scale. Any reduction in pain scores by 2 points or more was considered to be an improvement. RESULTS: Dysmenorrhea and deep dyspareunia, were significantly more frequent in patients of group 2. Preoperative pain scores were significantly higher for dysmenorrhea (p = 0.0022) and deep dyspareunia (p < 0.0001) but not for non-menstrual pain in group 2. Deep dyspareunia was correlated with the presence of dense pelvic adhesions. After surgery, dysmenorrhea improved in 43% of cases in group 1, vs. 66% of cases in group 2 (p = 0.0037). For deep dyspareunia, improvement was reported by 33% in group 1, vs. 67% in group 2 (p = 0.074). Improvement in non-menstrual pain was not significantly different between the two groups (67% vs. 56%). CONCLUSIONS: Advanced endometriosis is more frequently related to dysmenorrhea and deep dypareunia in comparison to early disease. Laparoscopic surgery may offer relief or improvement in the majority of patients with endometriosis and chronic pelvic pain. Cases with advanced disease seem to benefit the most.

Laparoscopic evaluation of infertile patients with chronic pelvic pain.

In this study over a 10-year period, 1584 patients complaining of infertility of more than 1 year duration were evaluated for their laparoscopic findings in relation to the presence or not of chronic pelvic pain (CPP). Infertility was the only complaint in 1215 cases (group 1), whereas 369 patients complained of infertility and CPP (group 2). All cases underwent routine infertility investigation and pelvic ultrasonography, followed by diagnostic laparoscopy, with infertility-only cases acting as a control group. At laparoscopy 76.7% of patients with CPP were found with pelvic pathology, compared with only 42.6% of cases without CPP (P < or = 0.0001). Omental-abdominal wall adhesions, advanced endometriosis, endometriomas with adhesions, pelvic venous congestion, and hydrosalpinges with pelvic adhesions were significantly more frequent in cases with CPP. Dysmenorrhoea was the most frequent type of CPP. Cases with CPP and a negative laparoscopy were further investigated using a multidisciplinary approach. In conclusion, chronic pelvic pain can be the result of several pelvic pathologies. Infertile patients with CPP are much more frequently found with an abnormal pelvis in comparison with cases without CPP. Laparoscopy is an invaluable diagnostic tool especially for symptomatic patients and should be used early in their diagnostic infertility work-up.

Primary malignant mesothelioma of the peritoneum: a clinical and immunohistochemical study.

BACKGROUND: Primary peritoneal mesothelioma is regarded as a fatal disease that presents with progressive ascites at a relatively late stage of its natural history. Differential diagnosis between this rare tumor and both serous papillary carcinoma of the peritoneum and ovary can be problematic. CASE: A 54-year-old woman presented to our institution with a 4-month history of dull epigastric pain and increased abdominal girth. Exploratory laparotomy revealed the presence of extensive intraperitoneal dissemination of a malignant neoplasm without a recognizable primary site. Suboptimal cytoreduction was carried out, and histological diagnosis was that of a malignant epithelioid mesothelioma. This was confirmed with a panel of immunohistochemical markers. The patient despite having a complete response after adjuvant chemotherapy died 18 months after primary surgery. CONCLUSION: No single immunohistochemical stain is pathognomonic of peritoneal primary malignant mesothelioma (PMM), and the results of a panel of antibodies should be interpreted to set the diagnosis.

Effect of human hydrosalpinx fluid on the development of mouse embryos and role of the concentration of growth factors in culture medium with and without hydrosalpinx fluid.

The aim of this study was to investigate the effect of human hydrosalpinx fluid (HF) on the development and blastulation of mouse embryos and the role of the concentration of growth factors in culture medium with and without HF. In total, 2100 mouse embryos were cultured. Female mice were induced to superovulate and then mated with males. Two-cell-stage embryos were recovered from the oviduct and cultured in Ham's F-10 medium with bovine serum albumin and HF. Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) were analyzed by quantitative enzyme immunoassay. Mean blastulation index of 1.11, 0.97 and 0.98 was found at HF concentration of 5%, 20% and 30%, respectively (p = 0.8). The mean value of EGF in the control culture medium without HF was 11.2 pg/ml, which was statistically significantly different from that in culture medium containing HF (p < 0.001). The mean value of IGF-I in the control group without HF was 1.30 pg/ml and was not statistically significantly different from that in culture medium containing HF. Development of the two-cell-stage embryos was not affected at low (< 30%) HF concentrations. In conclusion, the present study demonstrates that even apparently normal blastulation is affected by any concentration of HF because of low embryonic EGF.

Evidence of differential control of FSH and LH responses to GnRH by ovarian steroids in the luteal phase of the cycle.

BACKGROUND: It is known that during the follicular phase of the cycle, estradiol sensitizes the pituitary to GnRH. The aim of this study was to determine the role of ovarian steroids in the control of GnRH-induced gonadotrophin secretion in the luteal phase of the cycle. METHODS: Eighteen normally cycling women were studied during the week following bilateral ovariectomy plus hysterectomy performed in early to mid-luteal phase. Six of the women received no hormonal treatment post-operatively (group 1, control), six received estradiol through skin patches (group 2) and the remaining six received estradiol plus progesterone (group 3). In all women the response at 30 min of LH (deltadeltaLH) and FSH (deltadeltaFSH) to GnRH (10 microg i.v.) was investigated on a daily basis. RESULTS: In group 1, serum FSH, LH and deltadeltaFSH values increased progressively following ovariectomy, while in groups 2 and 3 this increase was postponed or abolished. In contrast to deltadeltaFSH, deltadeltaLH values showed the same pattern of changes in all three groups with a significant decline up to post-operative day 4 and a gradual increase thereafter. CONCLUSIONS: These results demonstrate, for the first time, that in the early to mid-luteal phase of the cycle, estradiol and progesterone participate in the control of GnRH-induced FSH, but not LH, secretion. It is possible that in the luteal phase, the response of LH to GnRH is partly regulated by gonadotrophin surge attenuating factor.