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.

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.

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.

Family history of breast, ovarian and endometrial cancer and risk of breast cancer.

The relationship between family history of breast, ovarian and endometrial cancer and risk of breast cancer was analysed using data from a case-control study of breast cancer conducted in the greater Milan area, Northern Italy. The cases studied were 3415 women (median age 52 years, range 23-74) who had histologically confirmed breast cancer diagnosed within the year preceding the interview. The controls were 2916 women (median age 54 years; range 21-74) in hospital for a spectrum of acute illnesses excluding gynaecological, hormonal or neoplastic conditions. A total of 375 cases (11.0%) and 128 controls (4.4%) reported a history of breast cancer in first degree relatives. Compared with women with no family history of breast cancer, the RR was 2.7 (95% confidence interval [CI] : 2.2-3.3) in those with one first degree relative affected and 2.8 (95% CI : 1.3-5.7) in those with two or more affected relatives. In comparison with women without family history of ovarian cancer the RR of breast cancer was 1.4 (95% CI : 0.9-2.3) for those reporting one or more first degree relatives with ovarian cancer. However, the multivariate estimate for family history of ovarian cancer, including a term for familial breast cancer, decreased to 0.8 (95% CI : 0.5-1.4). The risk of breast cancer was similar in women reporting a family history of breast cancer (RR = 2.2) and in those reporting a family history of both breast and ovarian cancer (RR = 2.5), in comparison with women reporting no family history of breast and/or ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for ectopic pregnancy: an Italian case-control study.

OBJECTIVE: To analyze risk factors for ectopic pregnancy in a population at low risk for the disease. METHODS: Between September 1989 and February 1991 in Milan, we conducted a case-control study on 120 cases of ectopic pregnancy and 209 controls. The control subjects gave birth at term (more than 37 weeks' gestation) to healthy infants on randomly selected days at the same hospitals where the cases had been identified. RESULTS: The risk of ectopic gestation was about 40% higher in smokers than in controls, and the risk estimates increased with the number of cigarettes smoked per day (chi 2(1) trend 4.21, P = .04) and the duration of smoking (chi 2(1) trend 7.31, P < .01). However, smoking was not associated with the risk of ectopic pregnancy after adjustment for potential confounding factors (including history of pelvic inflammatory disease) in a multivariate analysis (relative risks [RRs] for ten or fewer and more than ten cigarettes per day versus no smoking were 0.8 and 1.1, respectively; chi 2(1) trend 0.10, P = not significant). Infertility problems or difficulty in conception were reported by 32% of the cases and 10% of the controls; the corresponding multivariate RR was 4.7 (95% confidence interval [CI] 2.3-9.5). A history of abdominal surgery was associated with about double the risk of ectopic pregnancy (multivariate RR 2.4, 95% CI 1.4-4.2). Similar estimates were found when the analysis was performed considering various types of surgery separately such as appendectomy, cesarean delivery, and other abdominal surgery. Finally, the risk of ectopic pregnancy was higher in women reporting a history of pelvic inflammatory disease (RR 2.7, 95% CI 0.9-8.7) and increased with the number of sexual partners (chi 2(1) trend 4.51, P = .03). CONCLUSIONS: Problems of infertility or difficulties in conception, history of pelvic inflammatory disease/salpingitis, and abdominal surgery are the main risk factors for ectopic pregnancy in this Italian study. Sexual habits also appear to have some independent effect.

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.

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.

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.

Contraceptive methods and risk of pelvic endometriosis.

The relation between contraceptive methods and risk of pelvic endometriosis has been analyzed in a case-control study. Cases were 376 women with laparoscopically or laparotomically confirmed pelvic endometriosis admitted to a network of Obstetrics and Gynecology Clinics in Lombardy, Northern Italy. Controls were 522 women admitted for acute non-gynecological and non-obstetrics conditions to the same hospitals where cases had been identified. A total 153 women (40.3%) out of the 377 cases and 154 (29.7%) out of the 522 controls reported ever oral contraceptive (OC) use: the corresponding relative risk (RR) was 1.6 (95% confidence interval, CI, 1.2-2.2). The risk was restricted to ex-OC users (RR 1.7, 95% CI 1.3-2.4), the estimated RR for current users being 0.9 (95% CI 0.5-1.9). No clear relation emerged with duration, recency and latency of OC use and risk of endometriosis. In comparison with never IUD users, the risk for ever users was 1.3 (95% CI 0.6-2.8), and no clear relation emerged with duration of use. Likewise, no association was observed between barrier method of contraception and risk of endometriosis (RR ever vs never users 0.5, 95% CI 0.3-1.4). The role of selection and other biases should be considered in the interpretation of epidemiological data on the role of OC on the risk of endometriosis.

PIP: In northern Italy, physicians compared data on 376 women with laparoscopically or laparotomically confirmed pelvic endometriosis with data on 522 age-matched controls admitted for acute nongynecologic and nonobstetric conditions to the same hospitals to examine the association between contraceptive methods and pelvic endometriosis. Cases were more likely to have ever used oral contraceptives (OCs) than controls (40.3% vs. 29.7%; relative risk [RR] = 1.6), but the risk was limited to former OC users (RR = 1.7 vs. 0.9 for current users). There was no clear association with duration, recency and latency of OC use and risk of endometriosis. The relative risk of endometriosis for ever users of the IUD was 1.3. Duration of IUD use was not associated with endometriosis risk. Use of barrier methods was not correlated with risk of endometriosis (RR = 0.5). Before making any conclusions on the association between use of contraceptive methods and pelvic endometriosis, one should consider possible selection and other biases when interpreting epidemiologic data. For example, painful menstruation is a common symptom of endometriosis and a major indication for OC use. Thus, women with endometriosis-induced dysmenorrhea tend to be ever OC users.

Past contraceptive method use and risk of ectopic pregnancy.

The relationship between past contraceptive method use and risk of ectopic pregnancy has been analyzed in a case-control study conducted in Milan, Italy. Cases were 158 women with diagnosis of ectopic pregnancy confirmed by laparoscopy or laparotomy, admitted to a network of university and general hospitals of Milan. The first control group (obstetric controls) included 243 women who gave birth at term (more than 37 weeks' gestation) to healthy infants at the same hospitals where the cases had been identified. The second control group (non-obstetric controls) was a random sample of 158 women admitted to the same network of hospitals where cases had been identified for diseases other than malignant, hormonal, or gynecological in origin. A total of 37 (23%) cases, 21 (9%) obstetric and 24 (15%) non-obstetric controls reported ever IUD use. The corresponding relative risk, RR, of ectopic pregnancy was 3.5 (95% CI 1.3-4.6) when non-obstetric subjects were considered as control group. The risk of ectopic pregnancy increased with duration of IUD use: in comparison with obstetric and non-obstetric controls, the RR were 2.3 and 2.0 for users for less than 2 years and 4.3 and 2.6 for longer users. There was no clear relation between time since last IUD use and risk of ectopic pregnancy, and no evidence of a decline of risk with increasing time since stopping use.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: The relationship between past contraceptive method use and risk of ectopic pregnancy was analyzed in a case control study conducted in Milan, Italy. Cases constituted women with a diagnosis of ectopic pregnancy confirmed by laparoscopy or laparotomy admitted to the Clinica Mangiagalli and the Obstetric and Gynecologic Clinic IV of the University of Milan between September 1989 and February 1991 and to the Obstetric and Gynecologic Clinic I between March 1991 and March 1993. The sample included a total of 158 patients (median age 32 years, range 18-43). The 1st control group (obstetric controls) included 249 women who gave birth at term to healthy infants at the same hospitals. The 2nd control group (nonobstetric controls) was a random sample of 158 women admitted to the same network of hospitals where cases had been identified for diseases other than malignant, hormonal, or gynecological in origin. A total of 37 (23%) cases, 21 (9%) obstetric and 24 (15%) nonobstetric controls, reported ever use of IUD. The corresponding relative risk, RR, of ectopic pregnancy was 3.5 (95% confidence interval, CI, 1.9-6.5) when obstetric and 2.4 (95% CI 1.3-4.6) when nonobstetric subjects were considered as control group. The risk of ectopic pregnancy increased with the duration of IUD use: in comparison with obstetric and nonobstetric controls, the RR were 2.3 and 2.0 for users for less than 2 years and 4.3 and 2.6 for longer users. There was no clear relation between time since last IUD use and risk of ectopic pregnancy, and no evidence of a decline of risk with increasing time since stopping use. A total of 80 cases (51%), 115 obstetric (47%) and 70 nonobstetric controls (44%), were ever users of oral contraceptives. These differences were not statistically significant (RR 1.1 in comparison with obstetric control and 1.2 in comparison with nonobstetric ones). Finally, 44 cases of ectopic pregnancy, 70 obstetric controls and 32 nonobstetric ones, were ever users of barrier methods of contraception; in comparison with never users, the risk of ectopic pregnancy was 1.2 and 1.9 for ever users.

Comparative efficacy of diclofenac dispersible 50 mg and ibuprofen 400 mg in patients with primary dysmenorrhea. A randomized, double-blind, within-patient, placebo-controlled study.

Sixty female out-patients suffering from moderate to severe primary dysmenorrhea, aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3-period, within-patient study, evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium), ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days. Pain relief was evaluated on a verbal rating scale (0 = none, 1 = slight, 2 = moderate, 3 = considerable, 4 = complete) at 0.5, 1,2,3,4,5 and 6 hours after the first dose; the weighted sum of pain relief scores over the 6-hour observation period was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) at baseline and at the above mentioned time points; the weighted sum of pain intensity differences at each time point was also analyzed (SPID-6). A rescue medication was permitted 1 hour or more after the intake of the test drug: in such cases the last value of pain intensity/relief scores was carried forward and used for the analysis. A global evaluation of efficacy and of trial medication as compared to her usual medication was performed by the patient at the end of each treatment period. Finally, adverse experiences were recorded throughout the study period. Analysis of covariance and Koch's adaptation of the Wilcoxon-Mann-Whitney rank sum test were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Determinants of hysterectomy and oophorectomy in northern Italy.

We analysed determinants of hysterectomy and oophorectomy using data from hospital control subjects, interviewed in a large case-control study on risk factors for breast cancer, conducted since 1983 in the Greater Milan area, Italy. Out of the 2916 women interviewed 355 (12.2%) were hysterectomized. Mean age at hysterectomy was 52. The cumulative probability of hysterectomy was similar in women born during the periods from 1900 to 1909 and 1910 to 1919. It rose steadily in each subsequent cohort for all ages till the cohort born between 1930 and 1939, then decreased in the cohort born between 1940 and 1949. The cumulative probability of hysterectomy by 60 years of age was 12.8% in women born between 1900 and 1909, and of 9.8%, 16.7% and 22.0% respectively in subsequent cohorts. Concerning determinants of hysterectomy, we found no relation with education and parity. Among the 355 hysterectomized women, 178 (50.1%) underwent unilateral (40 women) or bilateral (138 women) oophorectomy. The probability of oophorectomy was higher in more educated women. Compared with women who had had hysterectomy before the age of 45, those aged between 45 and 54 reported more frequently oophorectomy (odds ratio (OR): 1.5, 95% confidence interval (CI) from 0.9 to 2.3), but the OR was only 0.8 in those aged 55 or more (95% CI from 0.3 to 2.2). We found no relation between menopausal status or cohort of birth and oophorectomy.

Treatment with tamoxifen and progestins for metastatic breast cancer in postmenopausal women: a quantitative review of published randomized clinical trials.

The efficacy of tamoxifen (TAM) was compared to that of progestins (medroxyprogesterone acetate, MPA, and megestrol acetate, MA) in the treatment of metastatic breast cancer in postmenopausal women by a quantitative analysis of the results of published randomized clinical trials. Seven studies involving a total of 801 subjects compared TAM with MPA. Overall, the frequency of complete and partial response was 9 and 18%, respectively, in the women treated with TAM, versus 9 and 28% in those given MPA. Considering complete and partial responses together, the frequency of response was 29% in the TAM group and 39% in the MPA group, the corresponding pooled odds ratio (OR) of response being 1.5 (95% confidence interval, CI, 1.1-2.0). The median duration of response was greater in the TAM-treated patients; however, the difference was small (14 vs. 11 months). The probability of response to MPA treatment was about 3-fold higher compared with the response to TAM treatment in the subgroup with bone metastases (OR 3.4), and 2-fold higher in the subgroup with visceral metastases (OR 2.2), but the difference in the OR estimates was not statistically significant. The response to the two drugs was similar in the subgroup with metastases in soft tissues. Four studies compared TAM with MA, taking in 463 subjects. The overall frequency of complete and partial response was 35% in the patients who received TAM compared with 29% in those treated with MA. The corresponding pooled OR was 0.8 (95% CI 0.5-1.1). Analysis of the results according to site of metastases revealed no significant difference in the frequency of complete or partial response in the two treatment groups.

Risk factors for multiple births.

STUDY OBJECTIVE: To analyze risk factors for multiple births. DESIGN: A case-control study. Cases were 103 women (median age 31 years, range 20-44) who delivered multiple births not related with treatment for infertility at the 'Clinica Luigi Mangiagalli' of Milan. A total of 27 women delivered monozygotic twins and 76 dizygotic ones. Controls were 308 women (median age 30, range 17-45) admitted for normal delivery on selected days to the same clinic where cases had been identified. RESULTS: Cases tended to be less educated than controls and the relative risk of multiple pregnancy, compared with women reporting seven years of schooling or less, was 0.4 in those reporting 7-11 and 12 or more years of education. When the analysis was done separately for dizygotic and monozygotic multiple pregnancies, this relationship was restricted to dizygotic multiple pregnancies (chi 2 (1) trend for dizygotic pregnancies = 3.82, p = 0.05). A family history of multiple pregnancies was reported in 36 women (48%) with dizygotic multiple pregnancy and 13 (52%) monozygotic ones and 88 (30%) controls. The corresponding relative risks (RR) were 2.2 and 2.5 respectively for dizygotic and monozygotic pregnancies. Compared with nulliparae, the estimated RR of dizygotic multiple pregnancies was 0.5 in women reporting two or more births, but the trend in risk with number of births was not statistically significant. No relationship emerged with spontaneous or induced abortions, body mass index, oral contraceptive or IUD use, age at menarche and risk of multiple pregnancies. CONCLUSIONS: This study confirms the role of familiarity in the risk of multiple pregnancies and suggests some different epidemiological characteristics in dizygotic and monozygotic multiple pregnancies.