Three-dimensional Doppler sonography in asymptomatic and symptomatic women after medical termination of pregnancy.

OBJECTIVES: To characterize the 3D Doppler sonographic appearance of the uterine cavity in asymptomatic and symptomatic women after administration of mifepristone and misoprostol for medical termination of pregnancy. METHODS: A prospective observational study was performed. Women admitted for medical termination of pregnancy underwent transvaginal sonography 15 days after the procedure. Volumes were acquired, and offline analyses of the 3D vascularization indices were performed. Outcomes were collected at the follow-up scan and by telephone after the termination. Women were subclassified as asymptomatic or symptomatic according to the presence/absence of fever, vaginal bleeding, abdominal/pelvic pain, and infections. Spotting was defined as any episodic vaginal bleeding that was less than an expected menstruation and not regarded as a symptom. RESULTS: A total of 104 women who underwent medical termination of pregnancy between 6 and 9 weeks' gestation were enrolled in the study. The termination procedure was successful in 98% of cases; among them, 9 women (8.6%) were symptomatic due to bleeding. Two asymptomatic women required surgery; 1 had sonographic evidence of suspected retained products of conception (endometrial thickness ≥ 15 mm or power Doppler vascularization presence). Fifty-seven women (55%) presented with retained products of conception. All the women with suspected retained products regained normal menses; of these, 3 symptomatic women with retained products (2.9%) underwent a 1-month sonographic follow-up. The symptomatic status was not associated with endometrial thickness, 3D intrauterine mass volume, or 2-dimensional (2D) and 3D power Doppler appearances. CONCLUSIONS: The necessity of surgery after medical termination of pregnancy cannot be predicted by sonography. In cases with sonographic evidence of suspected retained products of conception, endometrial thickness, 2D Doppler findings, and the 3D vascularization indices correlated poorly with bleeding symptoms. Long-term follow-up should be considered in symptomatic women, and it can avoid any unnecessary surgical intervention.

Hemostasis by bipolar coagulation versus suture after surgical stripping of bilateral ovarian endometriomas: a randomized controlled trial.

STUDY OBJECTIVE: To estimate whether the suture of the ovary is superior to bipolar coagulation in preserving ovarian reserve in infertile women undergoing laparoscopic stripping of bilateral endometriomas. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: University teaching hospital. PATIENTS: 100 patients with bilateral endometriomas. INTERVENTIONS: Patients underwent stripping of bilateral endometriomas and were randomized to undergo hemostasis by use of either laparoscopic suturing (LS group) or bipolar coagulation (BC group). Changes in ovarian reserve were investigated by measuring the levels of anti-Mullerian hormone (AMH) and basal follicle-stimulating hormone (FSH) before surgery and at 3, 6 and 12 months from surgery. MEASUREMENTS AND MAIN RESULTS: At 3-month, 6-month, and 12-month follow-up, in both study groups, postsurgical AMH levels were significantly lower and basal FSH levels were significantly higher than before surgery. There was no significant difference in the mean percentage decrease of AMH levels in the BC group and LS group at 3-, 6-, and 12-month follow-up. The mean percentage increase in basal FSH was higher in the BC group than in the LS group at both 3-month (p = .023) and 6-month follow-up (p = .029), but not at 12-month follow-up. Pregnancy rate, time to conception, and rate of endometrioma recurrence was similar in the 2 study groups. CONCLUSION: Laparoscopic stripping of ovarian endometriotic cyst significantly decreases serum AMH levels and increases basal FSH levels independent from the method used to obtain hemostasis on the ovarian tissue.

The preoperative diagnosis of borderline ovarian tumors: a review of current literature.

PURPOSE: To evaluate the available information on the preoperative diagnosis of borderline ovarian tumors (BOTs). METHODS: Articles were identified through electronic databases (Medline and EMBASE, MEDLINE, PubMed), no date or language restrictions were placed; relevant citations were hand searched. RESULTS: Women with BOTs are more likely to have no symptom than women with invasive ovarian cancers; however, the type of symptoms is similar in patients with BOTs and invasive ovarian cancers. Up to 61% of women with BOTs have elevated CA-125; CA 19.9 and endoglin are not useful for diagnosing BOTs. Further studies are required to determine whether the measurements of calprotectin, oviductal glycoprotein 1 and growth differentiation factor-15 are useful for diagnosing BOTs. Ultrasonography and magnetic resonance imaging (MRI) are the mainstay for the diagnosis of BOTs. Combining MRI and positron emission tomography may facilitate the identification of BOTs. CONCLUSION: After completion of this article, the reader should be aware of the symptoms of BOTs, the potential role and pitfalls of tumor marker measurement. In addition, the reader will understand the appearance of BOTs at imaging techniques; the reader will be able to compare and combine ultrasonography, MRI and positron emission tomography in diagnosing BOTs. In clinical practice, the reader should be better able to assess whether an ovarian mass is a benign tumor, a BOT or an invasive cancer.

Clinical outcomes from a prospective study evaluating the role of ambulation during medical termination of pregnancy.

BACKGROUND: Although induced abortion is one of the most commonly performed gynecological procedures in Great Britain and medical termination of pregnancy is being used more frequently, very little is known about the role of ambulation during the procedure. We sought to compare ambulatory and non-ambulatory groups of patients undergoing medical termination in the hospital setting and determine whether ambulation impacted clinical outcomes. STUDY DESIGN: This was a prospective patient-preference study carried out among 130 women with pregnancies up to 63 days of gestation fulfilling the requirements of the 1967 Abortion Act and undergoing medical termination of pregnancy. The objective was to evaluate the effect of ambulation during medical termination of pregnancy. The women were given the choice to be ambulatory or non-ambulatory throughout the process of medical termination of pregnancy. They received 200 mg oral mifepristone and 800 mcg vaginal misoprostol for the termination procedure. Outcomes measured included time taken to pass the products of conception, first feeling of abdominal cramps, estimated blood loss, time to discharge from the hospital, pain scores and need for analgesia. RESULTS: In both ambulatory and non-ambulatory groups, the mean time taken to pass the products of conception was similar: 230.7 min (118-343.4) and 233.0 min (134.5-331.5) for ambulatory and non-ambulatory patients, respectively. Time to onset of cramps was 75.6 min (29.4-121.8) for ambulatory and 91.7 min (22.2-161.2) for non-ambulatory patients, from administration of misoprostol. Mean estimated blood loss (assessed by weighing the pads as well as blood in bed pan) was less than 100 mL in both groups, and overall, approximately 85% of patients ranked their pain score as 3 or less (on a scale of 0-5). There were no statistically significant differences in the ambulatory versus non-ambulatory groups with regard to clinical outcomes. CONCLUSION: Ambulation during medical termination of pregnancy neither appears to influence the amount of bleeding or pain nor hasten the process of medical termination of pregnancy.

Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review.

This systematic review aims to assess the efficacy of aromatase inhibitors (AIs) in treating pain symptoms caused by endometriosis. A comprehensive literature search was conducted to identify all the published studies evaluating the efficacy of type II nonsteroidal aromatase inhibitors (anastrozole and letrozole) in treating endometriosis-related pain symptoms. The MEDLINE, EMBASE, PubMed, and SCOPUS databases and the Cochrane System Reviews were searched up to October 2010. This review comprises of the results of 10 publications fitting the inclusion criteria; these studies included a total of 251 women. Five studies were prospective non-comparative, four were randomized controlled trials (RCTs) and one was a prospective patient preference trial. Seven studies examined the efficacy of AIs in improving endometriosis-related pain symptoms, whilst three RCTs investigated the use of AIs as post-operative therapy in preventing the recurrence of pain symptoms after surgery for endometriosis. All the observational studies demonstrated that AIs combined with either progestogens or oral contraceptive pill reduce the severity of pain symptoms and improve quality of life. One patient preference study demonstrated that letrozole combined with norethisterone acetate is more effective in reducing pain and deep dyspareunia than norethisterone acetate alone. However, letrozole causes a higher incidence of adverse effects and does not improve patients' satisfaction or influence recurrence of symptoms after discontinuation of treatment. A RCT showed that combining letrozole with norethisterone acetate causes a lower incidence of adverse effects and lower discontinuation rate than combining letrozole with triptorelin. Two RCTs demonstrated that, after surgical treatment of endometriosis, the administration of AIs combined with gonadotropin releasing hormone analogue for 6 months reduces the risk of endometriosis recurrence when compared with gonadotropin releasing hormone analogue alone. In conclusion, AIs effectively reduce the severity of endometriosis-related pain symptoms. Since endometriosis is a chronic disease, future investigations should clarify whether the long-term administration of AIs is superior to currently available endocrine therapies in terms of improvement of pain, adverse effects and patient satisfaction.

Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial.

BACKGROUND: When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. METHODS: Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. RESULTS: A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p=0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p=0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p=0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. CONCLUSIONS: Aromatase inhibitors reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin.

Scoring of sperm chromosomal abnormalities by manual and automated approaches: qualitative and quantitative comparisons.

It is now well known that levels of sperm disomy correlate to levels of infertility (as well as other factors). The risk of perpetuating aneuploidy to the offspring of infertile males undergoing intracytoplasmic sperm injection (ICSI) has become a hotly debated issue in assisted reproduction; however, there remain barriers to the practical implementation of offering sperm disomy screening in a clinical setting. The major barrier is the operator time taken to analyze a statistically meaningful (sufficient) number of cells. The introduction of automated 'spot counting' software-hardware combinations presents a potential solution to this problem. In this preliminary validation study, we analyzed 10 patients, both manually and using a commercially available spot counter. Results show a statistically significant correlation between both approaches for scoring of sperm disomy, but no correlation is found when scoring for diploid sperm. The most likely explanation for the latter is an apparent overscoring of two closely associated sperm heads as a single diploid cell. These results, and similar further studies that will ensue, help to inform cost-benefit analyses that individual clinics need to carry out in order to decide whether to adopt sperm aneuploidy screening as a routine tool for the assessment of sperm from men requiring ICSI treatment.

GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis.

OBJECTIVE: To determine the changes in the peritoneal fluid proteome of women with endometriosis determined by the administration of gonadotropin-releasing hormone analogues (GnRH-a). STUDY DESIGN: Peritoneal fluid samples were collected during laparoscopy from patients under GnRH-a and from women who did not receive any type of hormonal treatment in the 6 months before surgery. Samples were subjected to 2-D gel electrophoresis and compared by computerized analysis. Protein spots differentially expressed between the study groups were identified by liquid chromatography tandem mass spectrometry. RESULTS: More than 470 protein spots were analyzed. Several proteins with significant alterations were found. The down-regulated molecules were isoforms of alpha 2-HS glycoprotein, alpha 1-antitrypsin, S100-A8, haptoglobin alpha chain and vitamin D-binding protein. No protein spot had significantly higher expression in peritoneal fluid of women under GnRH-a than in untreated patients. CONCLUSION: Several inflammatory molecules present in peritoneal fluid are down-regulated during treatment with GnRH-a; administration of this drug reduces the inflammation in the peritoneal cavity.

Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis.

OBJECTIVE: To evaluate the peritoneal fluid (PF) proteome of fertile and infertile women with endometriosis. STUDY DESIGN: PF samples were collected at laparoscopy from 26 fertile women and 26 infertile ones. Samples were subjected to 2-dimensional gel electrophoresis and compared by computerized analysis. Protein spots were identified by liquid chromatography tandem mass spectrometry. RESULTS: One isoform of immunoglobulin light chain spot was more frequently present in PF of infertile women than infertile patients. Nine protein spots had significantly higher expression in PF of infertile patients than infertile controls. They were 2 isoforms of serotransferrin, 1 isoform of complement C3, serum amyloid P-component, alpha-1-antitrypsin and clusterin; 3 protein spots remain unidentified. No protein spots had significantly lower expression in PF of infertile women with endometriosis than in PF of fertile controls. Complement C3 had higher PF levels in the luteal than in the follicular phase of the menstrual cycle in both infertile and fertile patients. CONCLUSION: Among women with endometriosis, those with infertility have aberrant expression of several PF proteins; most of these molecules are involved in the immune response.

Increased expression of one isoform of leucine-rich alpha-2-glycoprotein in peritoneal fluid of women with uterine leiomyomas.

OBJECTIVE: To compare the peritoneal fluid (PF) proteome of women with and without uterine leiomyomas. STUDY DESIGN: PF samples were collected at laparoscopy from 14 women with uterine leiomyomas and 14 patients without leiomyomas who underwent tubal sterilization. PF samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by computerised analysis. Protein spots with aberrant expression in PF of women with leiomyomas were identified by liquid chromatography tandem mass spectrometry. RESULTS: One isoform of leucine-rich alpha-2-glycoprotein (LRGm), one immunoglobulin light chain, and one unidentified protein (pI: 5.62; M(r): 51.1 kDa) had significantly higher expression in PF of women with leiomyomas. Two isoforms of fibrinogen gamma chain had decreased expression in PF of women with uterine leiomyomas. Following Bonferroni correction for multiple comparisons, the aberrant expressions of LRGm and of one isoform of fibrinogen gamma chain was confirmed. The expression of these molecules was not affected by the phase of the menstrual cycle. CONCLUSIONS: Uterine leiomyomas are associated with changes in proteins present within the peritoneal fluid. The physiopathological relevance of the increased expression of LRGm in PF of women with uterine leiomyomas remains unclear.

Proteomics technologies in endometriosis.

Endometriosis is a common disorder that is associated with infertility and pelvic pain. Diagnosis is based on the visualization of endometriotic lesions during surgery as no reliable serum marker is currently available. The etiology of endometriosis is largely unknown. Over the last 20 years, several proteomics technologies have been used to research novel proteins with a potential etiological role in endometriosis, and to identify candidate serum markers for this condition. While some molecules identified by proteomics technologies may have a relevant role in the pathogenesis of endometriosis, the research of potential serum markers for this condition is still far from any clinical application. This review summarizes the state of the art and potential applications of proteomics in endometriosis research.

Peritoneal fluid proteome in women with different ASRM stages of endometriosis.

OBJECTIVE: Endometriosis has a wide range of severity but molecular factors associated with variable extension of the disease have not been widely investigated. The present study compares the peritoneal fluid (PF) proteome of 109 women with endometriosis and different disease stage as defined by the American Society for Reproductive Medicine (ASRM). METHODS: PF samples were subjected to two-dimensional gel electrophoresis; protein spots of interest were identified by liquid chromatography tandem mass spectrometry. RESULTS: Over 470 protein spots were analyzed. One isoform of haptoglobin alpha chain, alpha-1b-glycoprotein and one unknown protein had higher expression in PF of women with ASRM stage I-II endometriosis. Four isoforms of alpha1-antitrypsin, three isoforms of alpha-1b-glycoprotein, one isoform of S100-A8 and serotransferrin had higher expression in PF of women with ASRM stage III-IV disease. CONCLUSIONS: Several protein isoforms have different expression in PF of women with ASRM stage I-II endometriosis than in those with ASRM stage III-IV disease; most of these molecules are involved in inflammation and immune response.

Glycolytic enzyme expression in human granulosa cells.

OBJECTIVE: To examine the differences in specific protein expression between mural and cumulus granulosa cells following 24-hour in vitro culture. DESIGN: Laboratory study. SETTING: University Hospital. INTERVENTION(S): Human granulosa cells were collected at the time of egg collection during assisted reproduction. Cumulus cells associated with the oocyte were separated from mural cells from the periphery of the follicle before in vitro culture for 24 hours. Cells were then lysed and subjected to two-dimensional gel electrophoresis. MAIN OUTCOME MEASURE(S): Given that cumulus (cGC) and mural granulosa cells (mGC) differentiate from a single layer, it is likely that phenotypic differences between them may reflect specific molecular processes and structural adaptations. Computer-assisted analysis using dedicated software enabled the presence, absence, or relative volume of each individual protein spot to be estimated. Differentially expressed spots were identified using tandem mass spectrometry. RESULT(S): The mean number of separate protein spots detected in mGC gels was 1,105 +/- 146, and in cGC it was 887 +/- 236, although there was no statistically significant difference between the two. Five enzymes of the glycolytic pathway were never expressed in cGC after 24 hours in vitro; these were triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase 1, and two isoforms of alpha enolase. These are the first data collected in humans consistent with a recent demonstration that isolated murine cGC cultured in vitro exhibit decreased expression of mRNA encoding glycolytic enzymes, and support the suggestion that some factor or factors secreted by the oocyte may be responsible for the maintenance of glycolysis in the adjacent cGC.

Specific isoforms of leucine-rich alpha2-glycoprotein detected in the proliferative endometrium of women undergoing assisted reproduction are associated with spontaneous pregnancy.

OBJECTIVE: To examine differences in specific protein expression from the surface of the human endometrium with respect to eventual pregnancy in infertile women. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): Thirty-one women presenting for investigation into infertility at an assisted reproductive unit. INTERVENTION(S): Endometrial flushings were collected during the proliferative phase of the menstrual cycle and subjected to electrophoretic separation on the basis of isoelectric point and molecular weight. Computerized analysis of the resulting spots was performed, and the proteins were identified using tandem mass spectrometry. MAIN OUTCOME MEASURE(S): The expression of individual isoforms of leucine-rich alpha2-glycoprotein (LRG) was compared in nonpregnant patients (n = 25), those who became pregnant as a result of treatment (n = 3), and those who had treatment-independent pregnancies (n = 3). RESULT(S): A statistically significant difference was found in expression of two LRG isoforms, which were higher in the women who subsequently became pregnant independent of treatment. CONCLUSION(S): Several indirect lines of evidence suggest a role for LRG in implantation/decidualization. [1] LRG is implicated in transforming growth factor beta signal transduction. [2] Similar sequences have been identified in murine uterine tissues. [3] LRG may be involved in the infiltration of decidua by uterine natural killer cells, given that the murine homolog of LRG supports lymphocyte infiltration into secondary lymphoid tissues. [4] Human uterine natural killer cells differentiate into granular forms during early pregnancy, and LRG is known to support neutrophil granulocytic differentiation in humans.

Proteomic analysis of peritoneal fluid in women with endometriosis.

This study aims to evaluate differences in the expression of proteins present in the peritoneal fluid (PF) of women with and without endometriosis. PF samples were subjected to two-dimensional gel electrophoresis; protein spots of interest were identified by liquid chromatography tandem mass spectrometry. Several molecules had aberrant expression in PF of women with endometriosis; they may be useful for a better understanding of the pathogenesis of this disease.

Haptoglobin beta chain isoforms in the plasma and peritoneal fluid of women with endometriosis.

OBJECTIVE: To estimate the expression of haptoglobin (Hp) beta chain isoforms in the peritoneal fluid (PF) and plasma (PL) of women with and without endometriosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): Seventy-two patients with endometriosis and 35 controls. INTERVENTION(S): Peritoneal fluid and PL samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by semiquantitative computerized analysis. MAIN OUTCOME MEASURE(S): Expression of Hp beta chain isoforms. RESULT(S): No significant difference was observed in the frequency of expression of the Hp beta chain isoforms between the two groups. One beta chain isoform (HpbetaE; molecular weight, 38.40 +/- 0.94 kD; and isoelectric point, 5.63 +/- 0.17) had significantly higher expression in both the PF and PL of women with endometriosis than in the PF and PL of controls. No significant difference was observed in HpbetaE expression between women with mild (revised American Fertility Society [rAFS], stage I-II) and severe (rAFS, stage III-IV) endometriosis. In the control group, HpbetaE expression was correlated with the phase of the menstrual cycle. CONCLUSION(S): Women with endometriosis have higher PF and PL levels of HpbetaE. Further investigation should be aimed at producing antibodies against the HpbetaE-specific epitopes to determine whether its measurement may improve the clinical diagnosis of endometriosis.

Vitamin D binding protein in endometriosis.

OBJECTIVE: Two-dimensional gel electrophoresis is a powerful method for identifying post-translationally modified molecules in biological fluids. We examined the presence and expression of vitamin D binding protein (DBP) in the peritoneal fluid (PF) and plasma (PL) of women with endometriosis. METHODS: PL and PF samples were obtained from 36 women with untreated mild endometriosis (revised classification of the American Fertility Society [rAFS] stage I-II), 52 women with untreated severe endometriosis (rAFS stage III-IV), 17 women with endometriosis treated with the oral contraceptive (OC), and 40 controls (infertility, n = 23; tubal sterilization, n = 12; pelvic pain, n = 5). PF and PL samples were analyzed by quantitative, high-resolution 2-dimensional gel electrophoresis. RESULTS: The expression of one DBP isoform (DBPE) in the PF of patients with untreated endometriosis was significantly lower than in the control group (P <.05). The levels of PF DBPE in patients with endometriosis using OC were significantly higher than in women with untreated endometriosis (P <.05). No significant difference was observed in PL DBPE expression between women with and without endometriosis, while it was significantly increased in patients with endometriosis using OC (P <.05). DBP expression was not correlated with the stage of endometriosis (rAFS classification) or the phase of the menstrual cycle. CONCLUSION: The decreased level of DBPE in the PF but not in PL of women with untreated endometriosis suggests that this molecule may be relevant in the pathogenesis of this disease.