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.

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.

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.

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.

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.

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.