Localization of renin gene expression to monkey ovarian theca cells by in situ hybridization.

To investigate the sites of renin gene expression and localization of renin in primate ovaries, five cynomolgus (Macaca fascicularis) and one rhesus (Macaca mulatta) monkey were treated with gonadotropins to induce multiple follicle development. One ovary was removed before hCG injection (1200 IU) from three monkeys and one ovary was removed 36 h after hCG administration from three monkeys. In three monkeys, the remaining ovary was removed 3, 5, and 7 days after injection of hCG. To detect and localize renin messenger RNA, 35S-radiolabelled 1.1 kb length complementary DNA and RNA probes of human renin were used for in situ hybridization. To compare the synthesis with the presence and the storage of renin or prorenin, renin antigen was assessed by immunohistochemistry in the same tissues using a polyclonal antibody against human renin (R15). Renin mRNA was detected by in situ hybridization only in ovaries collected within 5 days of exposure to hCG. All such ovaries exhibited a positive signal. Renin mRNA was localized to the theca interna and theca lutein cells. Positive cells were observed in a few growing antral follicles, in occasional mature preovulatory follicles, in corpus luteum, and most strikingly in atretic follicles. No signal was detected in primordial, primary, or in small antral follicles of ovaries exposed to hCG. In contrast with the in situ hybridization data, no signal was detected by immunohistochemistry using antirenin antibodies which exhibited a positive signal in monkey kidney. These results indicate that hCG turns on renin gene expression. Renin is synthesized without significant intracellular storage in monkey ovarian theca interna cells and in corpus luteum. The absence of storage of renin is consistent with the high concentrations of prorenin found in ovarian follicular fluid of hCG stimulated primates and with our knowledge of cellular renin processing which indicate that prorenin is secreted constitutively as it is synthesized.

Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.

To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 +/- 255 pg/mL (8430 pmol/L); P4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 +/- 28 micrograms/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 +/- 283 ng angiotensin-I/mL (n = 8) to 3682 +/- 607 (n = 8) on day 7 and to 5353 +/- 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth and development of children conceived by in vitro fertilization.

To assess the physical and mental development of infants born after in vitro fertilization (IVF), we performed a general physical and developmental examination (Bayley and Stanford-Binet scales) on a cohort of 116 IVF children, conceived and born at our institution between February 1985 and March 1989, and on 116 non-IVF matched controls. Study and control groups were each composed of 66 singletons, 19 pairs of twins and 4 sets of triplets, whose age at examination ranged from 12 to 45 months. The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls. The indices were positively correlated to gestational age, birth weight, head circumference at birth and at examination, and mother's education. Mean birth weight, gestational age, and birth weight percentile of IVF infants were lower than the mean of the healthy population. Mean percentiles of weight and length at examination (mean age 22.4 months) were equally low but did not differ from those of the matched controls. However, mean percentiles of head circumference at birth and at examination compare well with the normal mean, both in IVF and control groups. Twins and triplets (IVF and controls) had significantly lower physical and mental indices as compared to singletons.

Renal artery flow velocity waveforms in normal and hypertensive pregnant women.

Pregnancy is associated with marked changes in renal functions. Hypertensive disorders in pregnancy are frequently accompanied by deteriorated renal functions and by pathological lesions in the glomeruli. Using a pulsed Doppler ultrasound, we measured the resistance to flow in the renal artery in normal and hypertensive pregnant patients. We performed 176 pulsed Doppler ultrasound measurements of the renal arteries at various stages of gestation in 60 low risk pregnant patients. Another 111 Doppler measurements of the same vessels were obtained from 80 hypertensive pregnant patients throughout the third trimester. Twenty-six patients had preeclampsia, 35 patients had pregnancy-induced hypertension, and 19 patients had chronic hypertension. The resistance to flow in the renal arteries (expressed by the resistance index, RI) did not change significantly during pregnancy. The renal artery RI was not significantly different between the hypertensive group (RI = 0.61 +/- 0.06) and the low risk group (RI = 0.605 +/- 0.04). The RI values were also similar in all hypertensive patient categories: preeclampsia (RI = 0.62 +/- 0.07), pregnancy-induced hypertension (RI = 0.60 +/- 0.06), and chronic hypertension (RI = 0.61 +/- 0.05). The renal artery RI did not correlate with the severity of the hypertensive disease or with the status of renal functions. The outcome of pregnancy was worse in patients with abnormally elevated resistance index in the renal arteries. Patients with abnormally elevated resistance to flow in the uterine arteries also had a significant increase in the resistance index in the renal vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension.

The effect of isosorbide dinitrate (ISDN) on maternal and fetal circulation was assessed in 23 women with pregnancy induced hypertension (PIH). A double-blind randomized design was employed. Each woman was given a sublingual tablet of ISDN (5 mg) or placebo. Maternal blood pressure (BP) and heart rate (HR) were measured before and every 2 min after the medication or placebo, for a total of 20 min. Flow velocity waveforms in the uterine and umbilical arteries were recorded at the same time periods, using pulsed Doppler ultrasound. The ratio of peak systolic to end-diastolic flow velocity (S/D) in those vessels was calculated. After ISDN mean maternal BP fell from 103 +/- 1.8 mm Hg to 90.5 +/- 2.9 mm Hg at 14 min (P < .0001) and mean maternal HR increased from 97.3 +/- 3.8 beats/min to 115.7 +/- 3.5 beats/min at 12 min (P < .0001). The mean S/D in the umbilical artery fell from 3.07 +/- 0.33 to 2.58 +/- 0.23 at 8 min (P < .0007). The mean S/D in the uterine artery fell from 3.27 +/- 0.6 to 2.38 +/- 0.28 at 10 min (P < .0001). In seven of 12 women with an early diastolic notch in the uterine artery flow velocity waveform the notch diminished or disappeared within the first 6 min after the medication. No significant change in any of the measured parameters was observed in the placebo group. Our finding that ISDN altered maternal and fetal hemodynamics in PIH lends support to the further exploration of nitric oxide donors in the treatment and prevention of pregnancy induced hypertension.

Systolic or diastolic notch in uterine artery blood flow velocity waveforms in hypertensive pregnant patients: relationship to outcome.

To identify the relationship between a systolic or diastolic notch in uterine artery flow velocity waveforms and pregnancy outcome, we studied 140 hypertensive pregnant women with transvaginal, image-directed pulsed Doppler ultrasound. The subjects were classified according to the presence or absence of a systolic or diastolic notch. In 14 with a systolic and 25 with a diastolic notch, the resistance indexes in the uterine arteries on both sides of the uterus were significantly higher than in 101 subjects without a notch. Those with notches had significantly higher rates of fetal growth retardation and cesarean delivery because of fetal distress. Significantly more infants born to women with a notch spent longer than 48 hours in the neonatal intensive care unit. Subjects with a systolic notch also had significantly higher rates of abnormal fetal heart rate patterns during labor and low Apgar scores at 5 minutes. Fifty-one women with elevated resistances indexes in both uterine arteries were divided into two groups according to the resistance index in the umbilical artery. Each group was subdivided according to the presence or absence of a systolic or diastolic notch in the uterine artery flow velocity waveforms. In the group with a normal resistance index in the umbilical artery, five women had growth-retarded fetuses when a notch was present (N = 8), compared with none in women without a notch (N = 11) (P less than .005). The respective figures for the group with abnormal umbilical artery resistance indexes were 14 of 19 (73.7%) and two of 13 (15.4%) (P less than .002).(ABSTRACT TRUNCATED AT 250 WORDS)

Anticardiolipin antibodies in patients with recurrent pregnancy wastage: treatment and uterine blood flow.

The interest in autoimmune pregnancy loss has increased recently with the discovery of the association between the presence of antibodies to phospholipids and cardiolipin and habitual abortion. To evaluate the prevalence of anticardiolipin antibodies in patients with recurrent fetal loss and the effect of low-dose aspirin and corticosteroid treatment, we examined 67 women for anticardiolipin antibodies with an enzyme-linked immunosorbent assay. Increased levels of anticardiolipin antibodies were found in 34 of these women (50.7%) and in none of 12 normal pregnant controls. Seventeen of these 34 patients conceived and were treated with aspirin, 100 mg/day, and fluocortolone, 10 mg/day. Twelve gravidas reached term, all delivering live infants with good Apgar scores and normal birth weights. Three others delivered prematurely, two of them because of premature rupture of membranes and the other because of severe fetal growth retardation. This latter woman delivered at 31 weeks, and the 1000-g infant died neonatally. The neonatal survival rate was 82% in the treated patients, versus 18% in the same group of subjects in their previous, untreated gestations. The umbilical artery resistance index of the treated subjects was not different from that of anticardiolipin-negative hypertensive women who did not receive aspirin and corticosteroid therapy. However, the uterine artery resistance index was significantly lower in the hypertensive treated group than in the untreated group. Whether this difference reflected a beneficial effect of low-dose aspirin and corticosteroid therapy on pregnancy outcome and survival rate remains to be evaluated.

The effect of isosorbide dinitrate on uterine artery and umbilical artery flow velocity waveforms at mid-pregnancy.

OBJECTIVE: To study the effect of isosorbide dinitrate, a nitric oxide donor, on the maternal cardiovascular system and on uterine and umbilical artery blood flow velocities in mid-pregnancy. METHODS: Eighteen women with low-risk pregnancy at 17-24 weeks' gestation were given a single 5-mg dose of sublingual isosorbide dinitrate, a nitrovasodilator. Blood flow velocity waveforms in the ascending uterine artery and in the umbilical artery were measured by an image-directed, pulsed color Doppler ultrasound scan before and after the medication was administered. Maternal blood pressure (BP) and heart rate were also obtained. RESULTS: The mean arterial BP decreased from 86 mmHg (95% confidence interval [CI] 72-99) to a nadir of 73 mmHg at 6 minutes (95% CI 61-85, P < .04). Mean maternal heart rate increased from 85 beats per minute (95% CI 80-90) to 96 beats per minute at 6 minutes (95% CI 87-105, P < .01). Mean systolic-diastolic flow velocity ratio (S/D) in the umbilical artery rapidly declined from 4.18 (95% CI 3.80-4.56), reaching a nadir of 3.12 at 6 minutes (95% CI 2.65-3.84, P < .001). The S/D in the uterine artery decreased from 4.83 (95% CI 3.99-5.56) to a nadir of 4.02 at 10 minutes (95% CI 3.41-4.63, P < .001). CONCLUSION: Isosorbide dinitrate, a donor of nitric acid, lowers mean maternal BP and reduces the Doppler impedance in the umbilical and uterine arteries. This drug could prove to be beneficial when endothelial cell dysfunction leads to insufficient synthesis and release of endothelium-derived relaxing factor, resulting in generalized vasoconstriction and increased resistance to flow in the uteroplacental circulation.

Differentiating malignant from benign ovarian tumors with transvaginal color flow imaging.

The impedance to blood flow was examined by transvaginal color flow imaging in 53 ovarian masses before exploratory laparotomy. Serum CA 125 levels were measured in all subjects. Thirty-six had benign ovarian tumors and 17 had malignant ovarian tumors confirmed by histopathologic examination. Intratumoral blood vessels, detected in 16 of the malignant tumors, consistently demonstrated low impedance to flow, with a pulsatility index (PI) always below 1. The PI of the intraovarian or intratumoral blood vessels was greater than 1 in 35 of the 36 benign tumors, although 11 had suspicious sonographic findings (P less than .01) and 14 had elevated CA 125 levels (P less than .001). The sensitivity and specificity of the preoperative PI in detecting malignant ovarian tumors were 94 and 97%, respectively. The sensitivity and specificity of preoperative suspicious sonographic findings in detecting malignant ovarian tumors were 94 and 69%, and those of elevated preoperative serum CA 125 levels were 82 and 61%, respectively. Our results suggest that transvaginal color flow imaging may be a useful clinical tool in the preoperative evaluation of ovarian masses.

Treatment of ovarian hyperstimulation syndrome: the physiologic basis for a modified approach.

A case of severe ovarian hyperstimulation syndrome (OHSS) secondary to human menopausal gonadotropin-human chorionic gonadotropin therapy is presented. Draining 4000 ml of exudate by abdominal paracentesis under real-time B-scan imaging induced a marked improvement in the patient's condition. Fluids from the third space were rapidly excreted, renal function improved, and the patient's weight decreased substantially. The underlying physiologic factors responsible for these changes are discussed. Other modes of treatment, including salt and water restriction and the use of volume expanders and diuretics, had no significant effect on the course of the syndrome. Paracentesis has a definite therapeutic value and is recommended in cases of OHSS with tense ascites.

Assessment of ovarian and uterine blood flow by transvaginal color Doppler in ovarian-stimulated women: correlation with the number of follicles and steroid hormone levels.

OBJECTIVE: To study the changes that occur in vascular resistance to flow in the utero-ovarian circulation and their correlation with the number of follicles and steroid hormone levels in patients undergoing ovarian stimulation with gonadotropin. DESIGN: In a prospective study, the impedance to flow in the intraovarian and uterine vessels was measured by means of transvaginal color flow Doppler imaging throughout the cycle. SETTING: University-based IVF program. PATIENTS: Eleven infertile patients undergoing ovarian stimulation with gonadotropin in preparation for IVF and ET. MAIN OUTCOME MEASURES: Intraovarian, uterine, and arcuate artery blood flow velocity waveforms, follicular growth, and serum E2 and P concentrations throughout the cycle. RESULTS: Pulsatility index (PI) of the intraovarian blood vessels and uterine artery decreased gradually during the follicular and luteal phase. The PI of the arcuate artery did not change significantly. The PI of the intraovarian blood vessels correlated with the number of follicles (> 15 mm; day of hCG). Serum E2 concentrations but not P demonstrated negative linear correlation with the PI of the intraovarian vessels and uterine artery. CONCLUSIONS: Induced cycles are associated with decreased impedance to blood flow in the utero-ovarian circulation. Intraovarian PI correlates negatively at each stage of the cycle with the eventual number of preovulatory follicles. Little or no changes are observed when the response to ovarian stimulation is poor.

Transvaginal embryo aspiration--a safe method for selective reduction in multiple pregnancies.

OBJECTIVE: To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN: Retrospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION: Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS: In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS: Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view.

Duplex sonography in the diagnosis of portal vein thrombosis.

Portal vein thrombosis was readily diagnosed by pulsed duplex Doppler sonography in five patients. The cases represent different stages in the development of the thrombotic event, from partial or complete occlusion by an echogenic intraluminal thrombus to cavernous transformation of the portal vein. The unique ability of duplex scanning to demonstrate abnormal vascular structures and flow pattern is emphasised. This method should be the technique of choice in the diagnosis of portal vein thrombosis.

The value of Doppler ultrasonography in prolonged pregnancies.

One hundred forty-two gravid women at term were followed prospectively by a non-stress test, estimation of amniotic fluid volume and Doppler velocimetry of the umbilical and uterine arteries. Adverse perinatal outcome was detected in 12 women (8.5%). Abnormal antepartum tests were detected in 26 women (17%). Seven women had an abnormally elevated resistance index (RI) in the umbilical artery; but only two had an abnormal outcome. Seven women had an abnormally elevated RI in the uterine artery, but only two had abnormal outcome. Three out of 11 women with oligohydramnion had abnormal perinatal outcome. Only one out of seven women with an abnormal non-stress test had abnormal perinatal outcome. In six women, more than one antepartum test was abnormal. The various surveillance methods demonstrated a low sensitivity (the highest was obtained by estimating amniotic fluid volume: 25%) and a low positive predictive value (the highest obtained by measuring the resistance index in either the umbilical or the uterine arteries: 28.6%). By considering any abnormal test as a positive test result for a given patient, a substantial improvement in sensitivity (66.7%) and positive predictive value (33.3%) are obtained. Doppler velocimetry adds very little in itself to the follow-up of patients with post-term gestations. However, when combined with additional antepartum tests, it may increase our ability to predict the compromised fetus in this condition.

Fetal heart rate patterns in pregnancies complicated by maternal diabetes.

OBJECTIVE: To compare the fetal heart rate (FHR) pattern between fetuses of well controlled diabetic and non diabetic mothers using a computerized analysis of FHR. STUDY DESIGN: Weekly fetal surveillance was performed in 99 fetuses of mothers with diabetes class A, 21 fetuses of mothers with diabetes class B-R, and 55 fetuses of non-diabetic women, starting at 30 weeks' gestation. All diabetic patients were well controlled. Fetal surveillance included a computerized analysis of the FHR, umbilical and uterine Doppler velocimetry, and a biophysical profile. Changes of FHR variation, frequency of FHR accelerations, and umbilical and uterine Doppler velocimetry were calculated using a regression analysis for each patient. The average slopes and the intercept at 30, 34, and 38 weeks' gestation of these variables were compared among the three groups. RESULTS: The slope of FHR variation and the frequency of accelerations had a lower rate of increase during the third trimester in fetuses of mothers with diabetes class A (0.84 +/- 0.25 ms/week and 0.06 +/- 0.02/20 min/week, respectively) compared with fetuses of non-diabetic mothers (1.34 +/- 0.55 ms/week and 0.5 +/- 0.1/20 min/week, respectively). In fetuses of mothers with diabetes class B-R, FHR variation did not change with gestation (-0.011 +/- 0.2 ms/week) with a small increase in the frequency of accelerations (0.02 +/- 0.004/20 min/week). While no differences were observed at 30 weeks' gestation, FHR variation and the frequency of accelerations were significantly reduced at 34 weeks' gestation in fetuses of mothers with diabetes class B-R compared with fetuses of non-diabetic mothers (P < 0.01). At 38 weeks' gestation, fetuses of mothers with diabetes class B-R and diabetes class A had both significantly reduced FHR variation as well as frequency of accelerations compared with fetuses of non-diabetic mothers (P < 0.01). The rate of decrease of the umbilical and uterine artery S/D ratios were similar among the three groups. CONCLUSIONS: The FHR pattern appears to be different in fetuses of well controlled diabetic mothers when related to fetuses of non-diabetic mothers. Disease specific standards should be considered for interpretation of FHR patterns in diabetic pregnancies.

Transvaginal imaging: applied physical principles and terms.

In this article the properties of ultrasound in tissues and the factors governing image quality are discussed. Particular emphasis is placed on the vaginal probe. The virtues of transvaginal scanning both in gynecology and obstetrics are well described in subsequent articles in this symposium. Only by understanding the properties of ultrasound can the capabilities and limitations of this technique be appreciated. A comprehensive knowledge of the basic physical principles is mandatory for the clinician as well the investigator to attain the highest quality results. The technical aspects of operating ultrasound instruments, e.g., machine controls, electronic image formation, scan converters and techniques for preprocessing and postprocessing, are not discussed.

The uterus: a new look with transvaginal sonography.

Targeted scanning of the uterus and its adjacent structures is made possible by high-resolution transvaginal sonography. A systematic approach is applied so that the normal anatomy and abnormal processes in the various uterine components can be visualized. By adopting this method we detected various pathologies in the cervix, endometrium, myometrium, and in the uterine vessels and ligaments. Cervical pathology included inflammatory processes, cysts, malignant lesions, and incompetence during pregnancy. By scanning the endometrium, a reflection of the hormonal status of the patient under both normal (e.g., the menstrual cycle) and abnormal conditions may be obtained. More sinister lesions, such as endometrial hyperplasia and carcinoma, can be suspected based on the sonographic appearance of the endometrium. In hydatiform mole, a typical sonographic picture directs the sonographer to the diagnosis. Uterine fibroids are the most common lesion of the corpus uteri, and are readily detected by transvaginal sonography, including any degenerative changes that may complicate this condition. Changes in uterine size, particularly when accompanied by profuse intracavitary fluid, should raise the suspicion of a malignant process. Intracavitary fluid may also be associated with inflammatory lesions (e.g., tuberculosis). Congenital uterine anomalies may be diagnosed and defined by this method. Uterine ligaments are best visualized in the presence of fluid in the pelvis. Intraligamentary masses can be also be detected and defined. Finally, the main vessels supplying the uterus can be visualized, both in pregnant and nonpregnant patients. Using a transvaginal image-directed Doppler system, flow velocity profiles can be obtained from these vessels and form the basis for defining abnormalities in uterine perfusion.

HELLP syndrome associated with factor V R506Q mutation.

The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on two patients with HELLP syndrome who were found to be heterozygous for factor V R506Q mutation, leading to activated protein C resistance. These findings suggest that the pathogenesis of HELLP syndrome is associated with a thrombotic process, and point to the potential benefit of anti-thrombotic therapy in this condition.

Intrauterine device and pelvic inflammatory disease.

Using a retrospective case control design on 101 women with a first episode of acute pelvic inflammatory disease (PID), it was found that 15% were wearing an intrauterine device, as compared to 7% out of a control group of 101 women matched for age, marital status, and interval since their last pregnancy termination. No statistically significant correlation between IUD usage and PID was demonstrated. A significant correlation (P less than 0.01) between previous induced abortion and subsequent PID was found. In the PID group, a significantly higher proportion of previous abdominal and pelvic operations (P less than 0.005) was found as compared to the control group, but the numbers were small. In the absence of a higher frequency of IUD wearers among PID patients as compared with matched controls, we do not believe that there is an increased risk of pelvic inflammatory disease.

PIP: A retrospective study of 101 women who were hospitalized with an initial attack of acute pelvic inflammatory disease (PID) at the Rambam Medical Center in Haifa, Israel, between 1969-1975, was conducted. A control group was chosen which matched the study group for age, marital status, and interval since last pregnancy. The women were not matched on origin or socioeconomic status. Results of the study do not indicate a higher risk of PID among IUD wearers. These results conflict with results from 4 other recent studies. This study showed significant associations between incidence of PID and previous induced abortion and previous abdominal and pelvic operations. The PID patients had an average of 2.37 pregnancies as compared to an average of only 1.61 pregnancies among the non-PID controls.