Epidemiology of endometriosis and its comorbidities.

Genetic profile, inflammation, hormonal activity, menstrual cyclicity, organochlorine burden, prostaglandin metabolism and immunological factors have been suggested to play a role in the establishment and development of endometriosis. From the epidemiological perspective, several risk factors have been studied to suggest or support the different aetiological hypotheses. Social class and family history apart, the factors most consistently associated with endometriosis are early age at menarche and long and heavy menstrual cycles. These menstrual characteristics (together with nulliparity) reflect increased exposure to menstruation. The other main risk factors are pigmentary traits and sun habits, alcohol intake, use of oral contraceptives, and environmental factors such as exposure to polychlorinated biphenyls and dioxin. All of these factors support a potential role of hormonal mileau and inflammation in the pathogenesis of endometriosis. There is a clear association between endometriosis and gastrointestinal and immunological diseases, ovarian cancer and other gynaecological cancers, and thyroid cancer.

Retained versus resected posterior cruciate ligament in mobile-bearing total knee replacement: a retrospective, clinical and functional assessment.

PURPOSE: Fully conforming, mobile-bearing total knee replacement (TKR) was initially designed using a posterior cruciate-sacrificing (CS) technique. Rotating-platform TKR that could also be performed retaining the posterior cruciate developed afterwards. The purpose of this study was to compare the clinical and functional outcomes of patients who had either cruciate-retaining (CR) or cruciate-sacrificing (CS) TKR at a minimum follow-up of 2 years with the same prosthetic design. METHODS: One hundred and two consecutive TKR (88 patients) were performed at the same institution either with CS (56 TKR-49 patients) or with CR (46 TKR-39 patients) technique. Patients were followed at a minimum of 2 years. Patients were evaluated for articular range of motion, complication rate (infection, loosening) and clinical outcome measures included the pain and functional components of the Knee Society Score. RESULTS: The two groups (CS, CR) were homogeneous. At final follow-up, no significant difference was seen between the two surgical techniques in terms of ROM, pain and functional level, and revision rate. CONCLUSIONS: This study showed that for this given mobile-bearing, fully conforming prosthetic design, sacrificing or resecting the PCL does not influence the clinical and functional outcomes at a minimum of 2-year follow-up. Surgeons may indifferently choose one of the two options (CS, CR) according to their preferences. LEVEL OF EVIDENCE: Case series, level IV.

Postchemotherapy residual masses in germ cell tumor patients: our experience.

BACKGROUND: The nature of post-chemotherapy tumor residuals can be determined only by excision and histological examination, but at present no consensus has been reached as to whether all patients with residual masses should undergo adjunctive surgery. PATIENTS AND METHODS: Between August 1991 and September 2004, 120 patients with metastatic germ cell tumors were diagnosed at our hospital and 35 of these patients (30%) underwent adjunctive surgery after cisplatin-based chemotherapy. If serum tumor markers were still raised salvage chemotherapy was administered. RESULTS: At the time of surgical intervention 30 patients (86%) had a partial remission with normal markers. Necrosis, differentiated teratoma and undifferentiated tumor were found in nine (30%), 19 (63%) and two (7%) of all patients. Five patients (14%) underwent postchemotherapy resections after second-line cisplatin-based combination chemotherapy. Four of the 35 patients died as a result of their malignant germ cell tumor. The median observation time after the initial diagnosis was 99 months (range 15-172 months). CONCLUSIONS: Secondary resection of residual masses after first or second-line chemotherapy is still an essential part of the treatment of metastatic testicular cancer. Resection of mature teratoma or viable cancer adds to long-term event-free and overall survival in these patients.

Coffee drinking and risk of preterm birth.

OBJECTIVES: We analysed the association between coffee drinking before and during the three trimesters of pregnancy and the risk of preterm birth of babies normal for gestational age (NGA) or small for gestational age (SGA). METHODS: Case-control study conducted in University clinics of North Italy. Cases were 502 women who delivered at <37 weeks of gestation. The controls included 1966 women who gave birth at term (>or=37 weeks of gestation) to healthy infants on randomly selected days at the hospitals where cases had been identified. RESULTS: There was inverse association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA (heterogeneity test between OR: chi1(2)=5.6811 P<0.05). In comparison with not drinkers, all the ORs of overall intake of caffeine were closed near the unity for both SGA and NGA preterm birth. CONCLUSION: Compared with no consumption, a low consumption of coffee during pregnancy may not have significant effects on preterm birth.

Maternal coffee drinking in pregnancy and risk of small for gestational age birth.

OBJECTIVE: We have analysed the association between coffee drinking before and during the three trimesters of pregnancy and risk of small for gestational age (SGA) birth. METHODS: Cases were 555 women who delivered SGA births (ie <10th percentile according Italian standard). The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight. RESULTS: In comparison with nondrinkers, the ORs for SGA birth were 1.3 (95% confidence interval, CI, 0.9-1.9) for consumption of four or more cups of coffee/day before pregnancy, and 1.2 (95% CI 0.8-1.8), 1.2 (95% CI 0.8-1.8) and 0.9 (95% CI 0.6-1.4) for consumption of three or more cups of coffee/day during the first, second and third trimester of pregnancy, respectively. CONCLUSION: These findings were consistent in women who delivered preterm and at term births and were not affected by potential confounding such as smoking.

Moderate alcohol drinking and risk of preterm birth.

OBJECTIVE: We have analysed the association between alcohol drinking before and during the three trimesters of pregnancy and risk of preterm birth of babies with normal weight for gestational age or with low weight for gestational age (SGA). DESIGN: Case-control study. SETTING: General and university hospitals in Italy. SUBJECTS: Cases were 502 women who delivered preterm births <37 weeks gestation. The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight (ie between 10th and 90th centile according to the Italian standard) on randomly selected days at the hospitals where cases had been identified. INTERVENTIONS: Interview. RESULTS: No increased risk of preterm birth was observed in women drinking one or two drinks/die in pregnancy, but three or more drinks/die increased the risk (multivariate odds ratios (OR) 2.0 for >/=3 drinks during the first trimester, 1.8 during the second and 1.9 during the third). When the analysis was conducted separately for preterm births with normal weight or SGA, the increased risk was observed in preterm SGA only (multivariate OR for >/=3 drinks/die during the first trimester=3.6, 95% confidence interval (CI) 1.3-11.1); the estimated multivariate OR for >/=3 drinks/die during the first trimester of preterm babies with normal weight for gestational age was only slightly above unity and not statistically significant (multivariate OR 1.4, 95% CI 0.5-3.7). CONCLUSIONS: The study shows an increased risk in mothers who drink >/=3 die units alcohol in pregnancy of preterm births.

Selected food intake and risk of multiple pregnancies.

In order to explore the association between multiple birth risk and diet, data were analysed from a case-control study on risk factors for multiple births conducted in Italy between 1988 and 1998. A total of 185 cases (median age 30 years) were interviewed: 36 women delivered monozygotic and 149 delivered spontaneous dizygotic multiple births. The control group comprised 498 women who gave birth at term (>37 weeks gestation) to healthy infants on randomly selected days at the same clinic. Women were specifically excluded if they reported a history of multiple pregnancy or they had received treatment for infertility for the index pregnancy. No marked differences emerged in daily intake between cases and controls and a total of 35 foods items, including the major sources of beta-carotene, retinol, ascorbic acid, vitamin D, E, methionine folate and calcium in the Italian diet. Likewise intake of selected micronutrients was largely similar in dizygotic cases, monozygotic cases and controls, with the only exception of a slightly lower intake of folates in dizygotic pregnancies in comparison with controls: this difference was statistically significant (P < 0.05), but limited in quantitative terms (mean daily intake of folate 192.4, 183.2 and 191.4 microg respectively in monozygotic, dizygotic cases and controls). In conclusion, the results of this study do not support the role of diet in the development of multiple births.

Gonadotropin-releasing hormone agonist treatment for endometriosis of the rectovaginal septum.

OBJECTIVE: This study was undertaken to evaluate the effectiveness of a 6-month course of gonadotropin-releasing hormone agonist treatment for patients with symptomatic endometriosis of the rectovaginal septum. STUDY DESIGN: Fifteen patients with rectovaginal endometriosis and moderate to severe pain symptoms were the subjects of the study. None of these patients had either clinical or objective evidence of ovarian endometriosis, nor was there evidence of any obstructive lesions of the intestine or ureters. All patients were given leuprolide acetate depot at 3.75 mg, 1 ampule intramuscularly every 28 days, and treatment had a planned duration of 6 months. Follow-up evaluations were set every 2 months during the treatment phase and every 3 months thereafter until the completion of 1 year after discontinuation of medical therapy. At each follow-up visit pain symptoms were recorded, and clinical exploration, transvaginal ultrasonography, and transrectal ultrasonography were performed. RESULTS: Two patients stopped the treatment early after the second and fourth leuprolide doses; in both cases the reason was persistence of pain, and both requested a surgical solution. The other 13 patients showed a marked improvement with respect to pain during the 6-month treatment course but had early pain recurrence after drug suspension; 11 of them required further treatment within the first year of follow-up. The failure rate of gonadotropin-releasing hormone agonist therapy to produce 1-year pain relief after treatment discontinuation was 87% (13/15) on an intent-to-treat basis. The endometriotic lesions showed a slight but significant reduction in size during therapy but had returned to the original volume within 6 months after cessation of the gonadotropin-releasing hormone analog treatment. CONCLUSION: Our results suggest that gonadotropin-releasing hormone analogs should not be considered a real therapeutic alternative to surgical treatment for patients with symptomatic endometriosis of the rectovaginal septum, except possibly in a limited and unpredictable number of cases.

Phase I - II study of oral idarubicin, tegafur and levo-folinate in patients with pretreated advanced breast cancer.

Thirty patients with pretreated advanced breast cancer were enrolled in a study aimed to establish the maximum tolerated dose and to evaluate the efficacy of oral idarubicin (12 mg/m2/day for 3 days every 4 weeks) with tegafur and levo-folinate (200 mg/m2/day and 50 mg/day, respectively, for a minimum of 6 days, increasing the dose and duration according to a modified Fibonacci scheme). The maximum tolerated doses identified were 200 mg/m2 days 1-30 for tegafur and 50 mg days 1-30 for levo-folinate. We obtained 2 partial remissions (7%) and 12 stable disease (45%) in 27 objectively evaluable patients. The main toxicity was gastrointestinal, with no hematologic toxicity. Median time to progression was 4 months (range 2-14), median survival was 10 months (3-30). A median number of 4 cycles (1-13) was administered. The results seem to support the use of this combination in elderly and pretreated patients.

Intramesosalpingeal injection of oxytocin in conservative laparoscopic treatment for tubal pregnancy: preliminary results.

The objective of this study was to evaluate the efficacy of the local use of oxytocin as adjuvant treatment in conservative surgery for tubal pregnancy. The patients were 25 women with laparoscopic diagnosis of tubal pregnancy who were candidates for salpingotomy. Before salpingotomy, each patient was randomly allocated to intramesosalpingeal injection of 20 IU oxytocin diluted to 20 ml with saline solution or 20 ml saline solution. The surgeon then proceeded with salpingotomy and removal of the pregnancy according to the usual technique. The main outcome measures were bleeding during salpingotomy, ease of removal of the pregnancy, bleeding at the site of the pregnancy, and need for recourse to salpingectomy. Twelve women were randomized to the oxytocin group and 13 to the control group. Examination of the surgeons' assessments of the difficulties encountered at the different stages of surgery revealed statistically significant differences between the oxytocin group and controls in each variable. In particular, the amount of endosalpingeal bleeding after removal of the pregnancy was less in the oxytocin group. In one control patient, persistent bleeding due to incomplete trophoblast removal forced the surgeon to perform salpingectomy. Our results indicate that intramesosalpingeal injection of oxytocin facilitates the performance of conservative laparoscopic treatment for tubal pregnancy.

Induced abortion in the first trimester of pregnancy and risk of miscarriage.

OBJECTIVE: To analyse the relation between induced abortion and risk of subsequent miscarriage. DESIGN: Case-control study conducted between February 1990 and May 1995. PARTICIPANTS: Case group included 782 women (median age 32 years, range 14-46) admitted for spontaneous abortion (within the 12th week of gestation) to a network of obstetric departments in the greater Milan area. The control group was recruited among women who gave birth at term (> 37 weeks of gestation) to healthy infants on randomly selected days at the hospitals where cases had been identified. A total of 1543 controls (median age 30 years, range 14-45) were interviewed. RESULTS: A total of 102 cases (13%) and 181 controls (12%) reported one or more induced abortions. No clear relation emerged between miscarriage and induced abortions. In comparison with women reporting no induced abortion the odds ratio (OR) for miscarriage were 1.1 (95% CI 0.8-1.4) in women reporting one induced abortion and 0.9 (95% CI 0.4-1.8) in women reporting two or more. Likewise, there was no association between time since last and age at first induced abortion and risk of miscarriage. CONCLUSIONS: This study did not find any strong association between induced and spontaneous abortion.

PIP: The association between induced abortion and the risk of miscarriage in subsequent pregnancies was assessed in a case-control study conducted in Italy in 1990-95. 782 women (median age, 32 years) admitted to hospital obstetrics departments in Milan with spontaneous abortion in the first trimester of pregnancy were enrolled as cases, while 1543 women (median age, 30 years) who had a live, full-term birth at the same hospitals served as controls. Compared to controls, women with a spontaneous abortion were significantly more likely to be unmarried, to have a low educational level, and to have a history of pelvic inflammatory disease and previous miscarriage. 102 cases (13%) and 181 controls (12%) reported 1 or more induced abortions. Compared with women reporting no induced abortion, the odds ratio for miscarriage was 1.1 (95% confidence interval (CI), 0.9-1.4) in women reporting 1 induced abortion and 0.9 (95% CI, 0.4-1.8) in women reporting 2 or more induced abortions. Thus, this study failed to document a significant association between induced and spontaneous abortion. Moreover, there was no relationship between time since last induced abortion or age at first induced abortion and risk of miscarriage.

Determinants of risk of spontaneous abortions in the first trimester of pregnancy.

Several factors, such as socioeconomic status, obstetrical and menstrual history, and contraceptive methods, have been associated with risk of spontaneous abortion. We conducted a hospital case-control study to analyze risk factors for spontaneous abortion during the first trimester. Cases were 782 women admitted for spontaneous abortion. Controls included 1,543 women who gave birth at term in the same hospitals. Adjusted odds ratios (ORs) for spontaneous abortion were 0.9 and 0.6, respectively, for women reporting 7-11 and > or = 12 years of schooling, compared with women reporting < 7 years of education. A history of pelvic inflammatory disease increased the odds ratio fivefold [OR = 5.1; 95% confidence interval (CI) = 1.0-26.2]. The OR for spontaneous abortion was 1.7 (95% CI = 1.4-2.1) in women reporting previous spontaneous abortions.

Dietary habits, reproductive and menstrual factors and risk of dysmenorrhoea.

In order to analyze risk factors for dysmenorrhoea, we conducted a case-control study. Cases were 106 women (median age 27 years) with moderate or severe dysmenorrhoea lasting 12 months or more. Controls were 145 women (median age 26 years) without dysmenorrhoea, admitted for routine gynecological examination at the outpatient gynecological services of the same clinic where cases had been identified. In comparison with women reporting short menstrual cycles (every 25 days or less) the relative risk (RR) of dysmenorrhoea was 2.0 and 2.6, respectively, in those reporting their menstrual cycles of 26-30 days and of 31 days or more, and the RR was 3.6 (95% confidence interval (CI): 1.0-13.4) for women reporting totally irregular menstrual cycles. The estimated RRs were, in comparison with women reporting menstrual flows lasting 4 days or less, respectively 2.2 and 1.9 in those reporting menstrual flows lasting 5 and 6 days or more. Fourty-four (58%) cases but only seven (5%) controls reported heavy menstrual flows (RR in comparison with women reporting slight or normal menstrual flow 12.6, 95% CI: 5.0-32.1). As regards dietary factors, no associations emerged between the various food items, with the exception of cheese and eggs, which tended to be more frequently consumed by cases than controls. The results of this study suggest that the risk of dysmenorrhoea is higher in women with irregular, long and heavy menstrual flows. No association emerged between reproductive history and dysmenorrhoea. Likewise, no clear relationship emerged between intake of several dietary factors and risk dysmenorrhoea.

A new laparoscopic procedure for creation of a neovagina in Mayer-Rokitansky-Kuster-Hauser syndrome.

OBJECTIVE: To evaluate the results of a new laparoscopic technique for the creation of a neovagina in women with Rokitansky syndrome. DESIGN: Open noncomparative clinical study. SETTING: Tertiary care center. PATIENT(S): Fourteen patients with Rokitansky syndrome, aged 15 to 34 years, desiring to have sexual relations. INTERVENTION(S): The patients underwent creation of a neovagina at laparoscopy by a modification of Vecchietti's technique. MAIN OUTCOME MEASURE(S): At the clinical examinations performed during the follow up (ranging from 6 to 24 months), the patients reported the frequency, satisfaction, and any difficulties found at intercourse. At each examination, the depth and diameter of the neovagina was determined. The characteristics of the neovaginal mucosa were investigated by vaginoscopy. RESULTS(S): No intraoperative and postoperative complications were observed. The patients considered the discomfort caused by the Vecchietti's device and the daily tractions acceptable. In all the patients the mucosa was pink, trophic, and moist 3 months after the operation. Two fingers were introduced easily into the neovagina in all cases, and the mean length was 8.1 +/- 1.1 cm. All but one patient defined their sexual intercourse as satisfying within 6 months from the intervention. CONCLUSION(S): In light of the results obtained in the present series, we consider that, because of its efficacy, rapidity, and safety, the laparoscopic surgical method used by us may be suggested as the treatment of choice to correct Rokitansky syndrome.

Coffee and alcohol intake, smoking and risk of multiple pregnancy.

We analysed the relationship between coffee and alcohol intake, smoking and risk of multiple pregnancies using data from a case-control study on risk factors for multiple births conducted in Italy. Cases were 133 women who delivered multiple births not related to treatment for infertility (33 monozygotic and 100 dizygotic twins). Controls were 395 women admitted for normal delivery at the same clinic where cases had been identified. The odds ratios (OR) of multiple pregnancy were 1.5[95% confidence interval (CI) 0.8-2.8] and 2.0 (95% CI 1.0-3.7) for women drinking respectively one to two or three or more cups of coffee per day in comparison with non-coffee drinkers. Considering separately dizygotic and monozygotic pregnancies, the estimated OR were respectively for women drinking three or more cups of coffee, 1.7 and 3.1 for dizygotic and monozygotic pregnancies. The risk of multiple pregnancy tended to be higher in women drinking >or= 15 alcohol drinks per week: in comparison with tea-totallers the estimated OR for drink > or = 15 glasses per week were 2.3 and 2.6 respectively for dizygotic and monozygotic pregnancies. Heavy smokers (> or = 10 cigarettes per day) were at increased risk of multiple pregnancy: in comparison with never smokers, the estimated OR for multiple pregnancy was 1.6 (95% CI 0.9-2.7). Considering separately the two groups of multiple pregnancy, the OR of dizygotic and monozygotic pregnancy were 1.4 (95% CI 0.8-2.5) and 2.4 (95% CI 0.9-6.1) for women smoking > or = 10 cigarettes/day, but the trend in risk with number of cigarettes smoked per day and duration of the habit was not significant.

Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study.

OBJECTIVE: To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility. STUDY DESIGN: We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins. RESULTS: The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05). CONCLUSION: Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility.

Ultrastructural aspects of endometrium in infertile women with septate uterus.

OBJECTIVES: To evaluate the endometrial surface morphology in patients with septate uterus and primary infertility in an attempt to throw light on the question of whether endometrial anomalies are involved in the pathogenesis of infertility in women with mullerian malformations. DESIGN: Endometrial biopsies were performed in eight women with septate uterus and primary infertility during hysteroscopy scheduled in the preovulatory phase of the cycle (when a follicle > 17 mm was identified by ultrasonography and E2 levels were >200 pg/mL [conversion factor to SI unit, 3.671]). Two samples were obtained from each patient, one from endometrium covering the septum and the other from endometrium lining the lateral wall of the uterus. All specimens were examined by scanning electron microscopy. MAIN OUTCOME MEASURES: The number of glandular ostia, the ciliated:nonciliated cell ratio, and the number of cilia on ciliated cells were analyzed in endometrial specimen from both the covering of the septum and the corresponding uterine lateral wall. RESULTS: In five patients septal endometrium showed the following defective preovulatory changes with respect to endometrium of the lateral uterine wall: a reduced number of glandular ostia, irregular nonciliated cells with rare microvilli, incomplete ciliogenesis on ciliated cells, and decrease in the ciliated:nonciliated cell ratio (1:52 +/- 11 versus 1:21 +/- 8). CONCLUSIONS: Our results indicate a decrease in the sensitivity of endometrium covering the septa of malformed uteri to preovulatory hormonal changes. This could play a role in the pathogenesis of primary infertility in patients with septate uterus.

Residual uterine septum of less than 1 cm after hysteroscopic metroplasty does not impair reproductive outcome.

The objective of this study was to ascertain if incomplete correction leaving a residual uterine septum of < or = 1 cm affects fertility outcome. Reproductive outcome in 17 women with a residual septum of between 0.5 cm and 1 cm after hysteroscopic metroplasty was compared to that in 51 women with no residual septum or one of < 0.5 cm. Septal lysis was performed with microscissors or resectoscope. One month after operative hysteroscopy, abdominal ultrasonography was performed on all the women and those with a residual septum of > 1 cm then underwent a second operative hysteroscopy to complete the lysis. The cumulative pregnancy and birth rates were calculated and the curves compared using the log-rank test. The cumulative 18 month probability of becoming pregnant was 44.5% in the patients with residual septum and 52.7% in those with no residual septum (not significantly different), and the cumulative 18 month probability of giving birth to a child was 27.5 and 36% respectively (also not significant). The presence of a residual uterine septum of between 0.5 and 1 cm as shown by ultrasonography appears not to worsen the reproductive prognosis compared with that in women in whom the septum has been completely or almost completely corrected.

Urinary tract anomalies associated with unicornuate uterus.

PURPOSE: We investigated the association between the various subclasses of the unicornuate uterus and urinary tract anomalies. MATERIALS AND METHODS: We studied the urinary tract of 37 patients with a unicornuate uterus by urography and/or ultrasonography. Unicornuate uterus was diagnosed at laparoscopy or laparotomy. RESULTS: A total of 15 patients (40.5%) had urinary tract anomalies, including ectopic kidney in 4, renal agenesis in 6, double renal pelvis in 2, horseshoe kidneys in 2 and unilateral medullary sponge kidney in 1. No differences were observed in the frequency of urinary anomalies among the various subclasses of unicornuate uterus. CONCLUSIONS: Our results indicate the need to suspect a urinary tract anomaly, particularly of the kidney, in all women with a unicornuate uterus.