Roberto Matorras

Epidemiology of endometriosis in infertile women

OBJECTIVE To assess the epidemiological factors linked to endometriosis in infertile women. SETTING Academic tertiary hospital. DESIGN Case-control study. PATIENTS One hundred seventy-four infertile women with endometriosis and 174 infertile women without endometriosis, all of them studied by laparoscopy. RESULTS Women with endometriosis and infertility had a higher frequency of cycles < or = 27 days (26.4% versus 16.7%). A trend to a protective effect of smoking was detected. Social class, reproductive history, infertility history, previous abortions, age, family history, age at menarche, and duration of menstrual flow were similar in both groups. CONCLUSION Cycles < or = 27 days was the only risk factor that seemed to be associated to endometriosis in infertile patients. However, predictive values were low. A trend to a protective effect of smoking was detected.

Comprehensive Proteomic Analysis of Human Endometrial Fluid Aspirate

The endometrial fluid is a noninvasive sample which contains numerous secreted proteins representative of endometrial function and reflects the state of the endometrium. In this study, we describe, for the first time, a comprehensive catalogue of proteins of the endometrial fluid during the secretory phase of the menstrual cycle. To achieve this objective, three different but complementary strategies were used: First, in-solution digestion followed by reverse phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS); second, protein separation by denaturing one-dimensional electrophoresis (SDS-PAGE) followed by HPLC-MS/MS analysis. Finally, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) followed by MALDI-TOF/TOF analysis. The combination of the three strategies led to the successful identification of 803 different proteins in the International Protein Index (IPI) human database (v3.48). An extensive description of the endometrial fluid proteome will help provide the basis for a better understanding of a number of diseases and processes, including endometriosis, endometrial cancer and embryo implantation. We believe that the thorough catalogue of proteins presented here can serve as a valuable reference for the study of embryo implantation and for future biomarker discovery involved in pathologic alterations of endometrial function.

Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy

OBJECTIVE To estimate the risk of recurrence after administration of hormone replacement therapy (HRT) among women who have had endometriosis and who underwent bilateral salpingo-oophorectomy (BSO). DESIGN Prospective randomized trial (115 women receiving HRT and 57 not receiving HRT). SETTING; Public university hospital. PATIENT(S) Women with a histologic diagnosis of endometriosis in whom BSO was performed; 91.8% had a total hysterectomy. INTERVENTION(S) Periodical clinical examination, vaginal ultrasound, and CA-125 levels; surgical evaluation and histologic study. MAIN OUTCOME MEASURE(S) Recurrence rate, prognostic factors, and a mean follow-up time of 45 months. RESULT(S) There was no recurrence among women who did not receive HRT, versus a 3.5% rate (4 out of 115), or 0.9% per year, in women who received HRT. Two recurrences required abdominal surgery. There was one additional patient who required surgery, but the relationship to the endometriosis recurrence was controversial. Among women receiving HRT, the following risk factors were detected: peritoneal involvement > 3 cm (2.4% recurrence per year vs. 0.3%) and incomplete surgery (22.2% per patient vs. 1.9%). CONCLUSION(S) Patients with a history of endometriosis in whom total hysterectomy and bilateral salpingo-oophorectomy have been performed have a low risk of recurrence when HRT is administered. In those patients, HRT is a reasonable option. However, in cases with peritoneal involvement > 3 cm, the recurrence rate makes HRT a controversial option; if HRT is indicated, it should be monitored closely.

Sperm morphology analysis (strict criteria) in male infertility is not a prognostic factor in intrauterine insemination with husband's sperm.

OBJECTIVE To assess the prognostic value of strict sperm morphology analysis in intrauterine insemination with husbands sperm (IUI) cycles performed because of male infertility. DESIGN Prospective study. SETTING Academic tertiary hospital. PATIENTS Seventy-four consecutive couples subjected to 271 IUI cycles because of male infertility. MAIN OUTCOME MEASURE Strict morphology analysis 1 month before the beginning of IUI following the criteria of Kruger et al. RESULTS Pregnancy and no pregnancy couples were similar regarding strict normal forms (2.85% +/- 2.07% versus 3.13% +/- 2.63%), slightly amorphous forms, and the morphology index (11.79 +/- 6.06 versus 12.04 +/- 7.13). Pregnancy rates (PRs) were similar when normal forms were <4% (39.1%) or > 4% (35.7%). The PR, although higher in the group with morphology index > 10% (41.4%) than in the group < 10% (33.3%), lacked statistical significance. In pure male infertility group, mean values of morphology were similar in pregnancy and nonpregnancy group. A not significant trend was detected toward higher PRs in morphology index > 10% (50.0%) than in the group < 10% (33.3%). CONCLUSION Strict morphology analysis 1 month before the beginning of IUI is not a useful prognostic factor in IUI performed because of male infertility.

Endometrial fluid is a specific and non-invasive biological sample for protein biomarker identification in endometriosis

BACKGROUND The development of non-invasive diagnostic methods for endometriosis requires sensitive and disease specific biomarkers. Here, we describe the use of aspirated endometrial fluid from women with and without endometriosis as a novel biological sample for biomarker discovery. METHODS Differential protein expression profiling of aspirates from women with early endometriosis (n = 14), advanced endometriosis (n = 32) and without evidence of the disease (n = 32) was assessed by two-dimensional gel electrophoresis (2-DE). A biomarker validation study was performed in an independent cohort (early endometriosis n = 6 and advanced endometriosis n = 14, controls n = 15). RESULTS The analysis resulted in the identification of 31 proteins showing statistically significant differences in expression. The proteins identified are related to cell signalling, cell death and cell movement, processes that may be involved in the onset and/or progression of endometriosis. The differences in expression observed for 14-3-3 (signal transduction) and moesin (cytoskeletal structure) were confirmed in an independent group of endometriosis patients. CONCLUSIONS Endometrial fluid represents a novel sample for proteomic analysis offering reliable, disease specific information on protein expression, facilitating the discovery of biomarkers for endometriosis. The results described here complement previous proteomic studies, providing new endometriosis-related proteins to be validated as diagnostic markers.

Are there any clinical signs and symptoms that are related to endometriosis in infertile women

OBJECTIVE Our purpose was to assess the physical signs and clinical symptoms associated with endometriosis in infertile women. STUDY DESIGN This case-control study was carried out in an academic tertiary hospital. There were 174 infertile women with endometriosis and 174 infertile women without endometriosis, all of them studied by laparoscopy. Before laparoscopy a standard interview and a standard physical examination were performed. RESULTS Cul-de-sac nodularity was more frequent in infertile women with endometriosis than in infertile women without endometriosis (6.3% vs 0%). Although uterosacral tenderness was also more frequent in infertile women with endometriosis (7.5% vs 1.7%), uterosacral tenderness without nodularity was similar in both populations. Uterine retroversion and cul-de-sac obstruction frequencies were somewhat higher in the endometriosis group (p<0.10). The remaining signs and symptoms analyzed, including pelvic pain and dysmenorrhea, were similarly frequent in both populations. Symptoms were similarly frequent in all American Fertility Society stages, although adnexal mass was higher in stage IV. CONCLUSION Uterosacral nodularity was pathognomonic of endometriosis in infertile women. Uterosacral nodularity and uterosacral tenderness (associated with uterosacral nodularity) were the only symptoms or signs of value to indicate endometriosis in infertile patients. The remaining clinical signs, as well as clinical symptoms, were of no value in diagnosing endometriosis in infertile women.

Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study.

This single-centre, randomized, parallel group, comparative study aimed to identify potential benefits of mid-follicular recombinant human LH (r-HLH) supplementation in women aged 35-39 years undergoing ovarian stimulation for intracytoplasmic sperm injection (ICSI). The main endpoint was the number of metaphase II oocytes retrieved. After pituitary suppression with a gonadotrophin-releasing hormone agonist, ovarian stimulation was initiated with recombinant human FSH (r-HFSH; 300-450 IU/day). On stimulation day 6, patients were randomized to receive r-HFSH alone or r-HFSH + r-HLH (r-HLH 150 IU/day) for the remainder of the stimulation period. Final follicular maturation was triggered with 250 mug of recombinant human chorionic gonadotrophin. After assessing oocyte nuclear maturity, oocyte were fertilized by ICSI and afterwards embryo quality was analyzed. Of the 131 women enrolled, 68 were allocated to r-HFSH alone and 63 to r-HFSH + r-HLH. No significant differences were observed in markers of either oocyte or embryo quality or quantity. However, higher rates of implantation and live birth per started cycle were observed with r-HLH supplementation than with r-HFSH alone. Although additional large studies are required to further investigate these findings, r-HLH supplementation for women aged 35-39 years undergoing ICSI is recommended as it may have a beneficial action on implantation.

Supplementation with docosahexaenoic acid in the last trimester of pregnancy: maternal-fetal biochemical findings.

The nutritional significance of long-chain polyunsaturated fatty acids (LCPS) during the perinatal period is becoming increasingly important. There are currently very few studies on dietary intervention during gestation. The aim of the study was to analyze the effect of docosahexaenoic acid (DHA) supplementation during pregnancy on levels in both the newborn and the mother. A randomized placebo controlled study was carried out on 20 pregnant women in study group receiving 200 mg/day of docosahexaenoic acid-(DHA) during the last trimester of pregnancy. Results in both groups (A supplemented, B non-supplemented) highlighted a decrease in plasma arachidonic acid (5.99 +/- 0.91 vs. 4.51 +/- 0.71 p<0.001 for group A and 5.84 +/- 0.71 vs. 4.80 +/- 0.51 p<0.01 for group B) in the baseline-final intra-group comparison. The intergroup comparison revealed a significant difference in plasma DHA at delivery: it was found to be higher in the population of supplemented pregnant women (3.17 +/- 0.26 vs. 2.77 +/- 0.31). The neonate population displayed no significant differences between the two groups. The results show that LCPS are consumed during the final stages of pregnancy and that oral supplementation with 200 mg/day of DHA is reflected in an increase in the plasma level of this fatty acid in the mother. One could speculate that there would be a corresponding increase in DHA bioavailability for the fetus.

Intake of long chain w3 polyunsaturated fatty acids during pregnancy and the influence of levels in the mother on newborn levels

OBJECTIVE To assess the relationship between the free intake of long chain w3 polyunsaturated fatty acid (w3 LCP) during pregnancy and the levels in the mother with the levels in the neonate. DESIGN Cross-sectional study. SETTING University hospital. SUBJECTS One hundred and sixty-two mother-neonate pairs from normal at-term pregnancies. MAIN OUTCOME MEASURE Dietetic interview in order to assess the w3 LCP intake. w3 LCPs were analyzed by capillary gas chromatography in plasma (expressed as percentage and as total amount) and in erythrocyte phospholipids (expressed as percentage) from mothers and neonates. RESULTS The w3 LCP intake assessed by the dietetic interview was significantly correlated with w3 LCP levels in the plasma of both mothers and neonates. The levels of w3 LCPs in mothers and neonates were significantly correlated both in plasma fatty acids (expressed both as a percentage and absolute values) and in erythrocyte phospholipids (in percentage) (r=0.49-0.22). CONCLUSION In an apparently well-nourished population the w3 LCP levels of the newborn infants are clearly influenced by those of their mothers. The higher the levels in mothers, the higher those in the neonates. The w3 LCP intake assessed by an interview also showed a significant influence, but to a lesser extent.

Endometriosis and spontaneous abortion rate: a cohort study in infertile women

OBJECTIVE To ascertain if there is an association between endometriosis and spontaneous abortion. DESIGN Prospective cohort study. SETTING Medical School Hospital. POPULATION 174 infertile women laparoscopically diagnosed with endometriosis and 174 infertile women in which endometriosis was ruled out by laparoscopy, in the same period of time. MAIN OUTCOME MEASURE Spontaneous abortion. Non-progressive gestational sac and/or histological study. RESULTS Per woman abortion rate was 7.47% (13/174) in the endometriosis group, similar to 5.74% (10/174) in the infertile women without endometriosis (RR=1.32: CI=0.53-3.36). Nor were there any differences in the per pregnancy abortion rate: 20.96% (13/62) in endometriosis vs. 16.94% (10/59) in non-endometriosis (RR=1.3; CI=0.47-3.57). The abortion rate was similar in the different AFS stages: 22.86% (8/35) in stage I, 16.67% (3/18) in II, 25% (1/4) in III and 20% (1/5) in IV. In stage I no differences were observed in patients who were managed expectantly or with medical treatment. CONCLUSION Endometriosis is not associated with an increased abortion rate. The severity of disease expressed by AFS staging is not associated with an increase in the abortion rate. In stage I the treatment of endometriosis did not decrease abortion rates.