Diagnostic laparoscopy in infertile women with normal hysterosalpingograms

Abstract:
OBJECTIVE: To assess the value of laparoscopy in infertile women with normal hysterosalpingograms, with and without risk factors suggesting pelvic disease.

STUDY DESIGN: We retrospectively reviewed 1,022 consecutive charts from a tertiary infertility practice. In 265 women, laparoscopies were performed after normal hysterosalpingograms.

RESULTS: Laparoscopies were normal in 136 (51%) women, whereas 129 (49%) had one or more abnormal laparoscopic findings, including minimal or mild endometriosis (n = 85), moderate or severe endometriosis (n = 11), adnexal adhesions (n = 27), subserosal myomas (n = 17), ovarian neoplasms (n = 5), distal phimosis (n = 1) and salpingitis isthmica nodosa (n = 1). Only 7% of cases had findings that might require standard operative laparoscopy or laparotomy, although not all were causally related to infertility. A history of dysmenorrhea or dyspareunia increased the likelihood of detecting endometriosis from 41% to 64% and 69%, respectively. The presence of both symptoms increased the likelihood to 83%.

CONCLUSION: In the presence of a normal hysterosalpingogram, laparoscopy identified other pelvic disease in about half of patients. Because most abnormalities were mild, this knowledge can be used to plan a micro-laparoscopic approach for many women, reserving traditional or operative laparoscopy for women with an abnormal hysterosalpingogram or extensive disease following micro-laparoscopy. Alternately, knowledge of the nature and severity of the expected laparoscopic findings might lead to bypassing laparoscopy in favor of assisted reproduction when the perceived benefit of surgical intervention is small.


Induced abortion and subsequent pregnancy duration

Abstract:
OBJECTIVE: To examine whether induced abortion influences subsequent pregnancy duration.

METHODS: Women who had their first pregnancies during 1980, 1981, and 1982 were identified in three Danish national registries. A total of 15,727 women whose pregnancies were terminated by first-trimester induced abortions were compared with 46,026 whose pregnancies were not terminated by induced abortions. All subsequent pregnancies until 1994 were identified by register linkage.

RESULTS: Preterm and post-term singleton live births were more frequent in women with one, two, or more previous induced abortions. After adjusting for potential confounders and stratifying by gravidity, the odds ratios of preterm singleton live births in women with one, two, or more previous induced abortions were 1.89 (95% confidence interval [CI] 1.70, 2.11), 2.66 (95% CI 2.09, 3.37), and 2.03 (95% CI 1.29, 3.19), respectively. Odds ratios of post-term singleton live births in women with one, two, or more previous induced abortions were 1.34 (95% CI 1.24, 1.44), 1.50 (95% CI 1.26, 1.78), and 1.58 (95% CI 1.09, 2.28), respectively.

CONCLUSION: The study showed an increase in preterm and post-term pregnancies after induced abortions. The risk of post-term delivery was high regardless of the interpregnancy interval, whereas increased risk of preterm delivery was seen mainly when interpregnancy intervals were longer than 12 months.


Live-birth rates and multiple-birth risk using in vitro fertilization

Gary Jeng

National Center for Chronic Disease Prevention and Health Promotion

Abstract:
CONTEXT: To maximize birth rates, physicians who perform in vitro fertilization (IVF) often transfer multiple embryos, but this increases the multiple-birth risk. Live-birth and multiple-birth rates may vary by patient age and embryo quality. One marker for embryo quality is cryopreservation of extra embryos (if embryos are set aside for cryopreservation, higher quality embryos may have been available for transfer).

OBJECTIVE: To examine associations between the number of embryos transferred during IVF and live-birth and multiple-birth rates stratified by maternal age and whether extra embryos were available (ie, extra embryos cryopreserved).

DESIGN AND SETTING: Retrospective cohort of 300 US clinics reporting IVF transfer procedures to the Centers for Disease Control and Prevention in 1996.

SUBJECTS: A total of 35554 IVF transfer procedures.

MAIN OUTCOME MEASURES: Live-birth and multiple-birth rates (percentage of live births that were multiple).

RESULTS: A total number of 9873 live births were reported (multiple births from 1 pregnancy were counted as 1 live birth). The number of embryos needed to achieve maximum live- birth rates varied by age and whether extra embryos were cryopreserved. Among women 20 to 29 years and 30 to 34 years of age, maximum live-birth rates (43 % and 36%, respectively) were achieved when 2 embryos were transferred and extra embryos were cryopreserved. Among women 35 years of age and older, live-birth rates were lower overall and regardless of whether embryos were cryopreserved, live-birth rates increased if more than 2 embryos were transferred. Multiple-birth rates varied by age and the number of embryos transferred, but not by whether embryos were cryopreserved. With 2 embryos transferred, multiple-birth rates were 22.7%, 19.7%, 11.6%, and 10.8% for women aged 20 to 29, 30 to 34, 35 to 39, and 40 to 44 years, respectively. Multiple-birth rates increased as high as 45.7% for women aged 20 to 29 years and 39.8% for women aged 30 to 34 years if 3 embryos were transferred. Among women aged 35 to 39 years, the multiple-birth rate was 29.4% if 3 embryos were transferred. Among women 40 to 44 years of age, the multiple-birth rate was less than 25% even if 5 embryos were transferred.

CONCLUSIONS: Based on these data, the risk of multiple births from IVF varies by maternal age and number of embryos transferred. Embryo quality was not related to multiple birth risk but was associated with increased live-birth rates when fewer embryos were transferred.


The cost of infertility evaluation and therapy: findings of a self-insured university healthcare plan

Abstract:
OBJECTIVE: To assess the total costs of infertility coverage, determine the proportion of healthcare costs related to infertility, compare infertility costs to those of other diseases, and calculate a per member per month cost of an infertility benefit.

DESIGN: Historical prospective analysis.

SETTING: A university-based, self-insured, fee-for-service healthcare plan.

PATIENT(S): Healthcare policy members from January 1993 through December 1995.

INTERVENTION(S): General and infertility-specific healthcare that included diagnostic tests for infertility, induction of ovulation, artificial insemination, donor gametes, in vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, microsurgical epididymal sperm aspiration, embryo cryopreservation, and frozen embryo transfer.

MAIN OUTCOME MEASURE(S): Healthcare costs, as calculated from the International Classification of Diseases, Volume 9 codes.

RESULT(S): Total healthcare and infertility-specific costs of the university healthcare plan over a 3-year period were $86,445,642 and $680,921, respectively. Therefore, infertility accounted for 0.79% of the total university healthcare costs. The mean total and infertility-specific per member per month healthcare costs were $86.15 and $0.67, respectively.

CONCLUSION(S): These data reveal that infertility costs account for only a small fraction of the total healthcare costs and can be attained at a nominal monthly fee.


Prevalence of polycystic ovary syndrome in women seeking treatment from community electrologists. Alabama Professional Electrology Association Study Group

Abstract:
OBJECTIVE: To determine the prevalence of the polycystic ovary syndrome (PCOS) among women seeking electrology, clients presenting to nine electrology centers completed a questionnaire.

STUDY DESIGN: Women with potential risk factors were referred to the University of Alabama at Birmingham. They underwent a detailed history and physical examination, including hirsutism scoring by a modified Ferriman-Gallwey (F-G) method. Serum was assayed for total testosterone, sex hormone binding globulin and dehydroepiandrosterone sulfate.

RESULTS: Three hundred fifteen (40%) of 779 patients had potential risk factors for hyperandrogenism and were referred. Eighty-two (26%) completed their evaluation. Six were excluded secondary to prepubertal or menopausal status. Of the remaining 76 patients, 20% had F-G scores of 7 or 8, 13% had scores of 9 or 10, and 21% had scores > 10. Forty-nine (64%) patients reported irregular menstrual cycles. Sixty-four patients were not receiving hormonal therapy: 25 reported regular menstrual cycles, and 39 reported irregular cycles. Seventeen (68%) of the 25 had at least one abnormal androgen value, while 33 (85%) of the 39 women had at least one abnormal value (nonsignificant difference). Overall, PCOS was evident in 39 of the 76 women, or 12% of the 315 patients who were referred for further evaluation.

CONCLUSION: Thirty-nine of the 315 referred patients (12%) fulfilled the diagnostic criteria for PCOS. However, they were not receiving medical care for this condition. In addition, this percentage is a conservative estimate in that 74% of the referred patients did not pursue a medical evaluation. Therefore, efforts to educate both electrologists and their clients of the possibility of underlying endocrine disorders and subsequent metabolic morbidity should be undertaken.


The effect of reproductive history on future pregnancy outcomes

P Doyle

London School of Hygiene & Tropical Medicine

Abstract: The aim of this study was to examine the separate and joint effects of previous pregnancy history, year of pregnancy outcome, maternal age, height, smoking and fertility on risk of fetal death. Data were available from a study of female radiographers. Analyses were carried out on 3053 women with a total of 6993 pregnancies. Women reporting problems with conception or previous fetal losses had an increased risk of a pregnancy ending in a fetal death. In particular, women with primary or secondary infertility had an approximately fourfold increase in risk compared with women who reported no difficulties [odds ratio (OR): 3.92; 95% confidence interval (CI): (3.02, 5.07)]. This relationship was independent of pregnancy order and pregnancy history and was more marked in older maternal ages. The effect of pregnancy history was cumulative and possibly multiplicative in effect, with a threefold increase in the risk of losing a third pregnancy following two previous losses [OR: 3.19; 95% CI: (1.60, 6.35)]. There were no consistent patterns of risk associated with year of pregnancy outcome, maternal age, height or smoking status. These results suggest that previous pregnancy outcomes and problems with conception may be the strongest determinants of fetal loss in subsequent pregnancies.


Tocolytics for preterm labor: a systematic review

K Gyetvai

Coalition for Research in Women's Health

Abstract:
OBJECTIVE: To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor.

DATA SOURCES: We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate."

METHODS OF STUDY SELECTION: We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria.

TABULATION, INTEGRATION, AND

RESULTS: Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment.

CONCLUSION: Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.


Correlation between endometriosis and pelvic pain

Abstract:
STUDY OBJECTIVE: To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis.

DESIGN: Prospective, observational study (Canadian Task Force classification II-2).

SETTING: University Hospital.

PATIENTS: Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis.

INTERVENTION: Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated.

MEASUREMENTS AND

MAIN RESULTS: Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

The Journal of the American Association of Gynecologic Laparoscopists


Physicians' knowledge and practices regarding natural family planning

Abstract:
OBJECTIVE: To assess physicians' knowledge and practices of modern methods of natural family planning.

METHODS: A questionnaire was mailed to 840 physicians selected randomly from Missouri state licensing records for obstetrics-gynecology, family practice, general practice, and general internal medicine.

RESULTS: The response rate was 65%. A total of 375 physicians (69% of respondents) saw women for reproductive issues. About half (46%) of physicians reported that they mentioned natural family planning to at least some women when discussing family planning issues. Observing vaginal discharge of cervical mucus was discussed by 40% of physicians in the context of avoiding pregnancy and by 36% of physicians in the context of helping a couple achieve pregnancy. Twenty-two percent of physicians estimated the best possible effectiveness of natural family planning to avoid pregnancy to be greater than 90%, and 35% estimated the actual effectiveness to avoid pregnancy to be greater than 70%. (The threshold rates of 90% best possible effectiveness and 70% actual effectiveness were chosen to be somewhat less than those reported in medical literature.) Physicians who gave higher estimates of effectiveness of natural family planning and physicians who were aware of an instructor in their community were more likely to provide women with relevant information about natural family planning.

CONCLUSION: Most physicians, especially those unaware of availability of instructors in their areas, underestimate the effectiveness of natural family planning and do not give information about modern methods to women.


Physiciansʼ Knowledge and Practices Regarding Natural Family Planning

Abstract: In Brief Objective To assess physicians' knowledge and practices of modern methods of natural family planning. Methods A questionnaire was mailed to 840 physicians selected randomly from Missouri state licensing records for obstetrics-gynecology, family practice, general practice, and general internal medicine. Results The response rate was 65%. A total of 375 physicians (69% of respondents) saw women for reproductive issues. About half (46%) of physicians reported that they mentioned natural family planning to at least some women when discussing family planning issues. Observing vaginal discharge of cervical mucus was discussed by 40% of physicians in the context of avoiding pregnancy and by 36% of physicians in the context of helping a couple achieve pregnancy. Twenty-two percent of physicians estimated the best possible effectiveness of natural family planning to avoid pregnancy to be greater than 90%, and 35% estimated the actual effectiveness to avoid pregnancy to be greater than 70%. (The threshold rates of 90% best possible effectiveness and 70% actual effectiveness were chosen to be somewhat less than those reported in medical literature.) Physicians who gave higher estimates of effectiveness of natural family planning and physicians who were aware of an instructor in their community were more likely to provide women with relevant information about natural family planning. Conclusion Most physicians, especially those unaware of availability of instructors in their areas, underestimate the effectiveness of natural family planning and do not give information about modern methods to women Most physicians underestimate the effectiveness of natural family planning, and half do not include it among family planning options discussed with their patients.


What is the best strategy for presenting ART results? A controversial comment

Abstract: Doctors love conventions. They have them in exotic places and they frequently use them to defend what would otherwise be inexplicable calculations. Thus 38 weeks of true gestation is, of course, 40 weeks of amenorrhoea, which may also be viewed as 38–40 weeks of pregnancy if timing is based on a “conventional” menstrual cycle. Even if this leaves the outside world to wonder, the clinicians understand. Many of the proponents of such ambiguity have moved away from obstetrics into reproductive medicine but have carried with …

Journal of Assisted Reproduction and Genetics


Endometriosis ascites: a case report

Endometriosis ascites: a case report

Abstract: This is a case presentation of an usual nature, a 43-year-old Hispanic female, multigravida presenting with physical findings of massive ascites. In most instances, the presence of massive ascites is associated with malignancies, tuberculosis or perforated visous. In this case, the diagnosis of extensive endometriosis with ascites is reported as a very rare complication of the disease.

JSLS : Journal of the Society of Laparoendoscopic Surgeons


Antibiotic use in pregnancy and drug-resistant infant sepsis

Abstract:
OBJECTIVE: We sought to evaluate the effect of antepartum and intrapartum antibiotic use on antimicrobial-resistant neonatal sepsis.

STUDY DESIGN: We analyzed perinatal outcomes for 8474 pregnancies (8593 live births) delivered at 6 hospitals. Data were collected regarding maternal antibiotic use and perinatal course, neonatal cultures, and outcomes. The diagnosis of confirmed neonatal sepsis required at least one positive blood or cerebrospinal fluid culture. Neonatal cultures were evaluated on the basis of the occurrence and timing of maternal antibiotic exposure.

RESULTS: There were 96 neonates with confirmed sepsis (11.2/1000 live births). Sepsis was 19.3-fold more common after preterm birth (57 vs 3. 1/1000; P <.001), with 76% of septic infants being delivered preterm. Forty-five percent of pathogens were ampicillin resistant. Ampicillin resistance increased with preterm birth (50% vs 26%; P =. 04), antepartum antibiotics (57% vs 34%; P =.03), intrapartum antibiotics (55% vs 28%; P <.01), and any prenatal antibiotic exposure (52% vs 22%; P =.01). Infection with an organism resistant to at least one maternal antibiotic was more common with intrapartum antibiotic exposure than with antepartum exposure only (57% vs 17%; P =.01). Regarding early-onset sepsis (n = 55), ampicillin resistance was more common with intrapartum antibiotics (50% vs 16%; P <.01), and resistance to at least one maternally administered antibiotic was more frequent with intrapartum exposure (56.7% vs 0%; P <.01).

CONCLUSIONS: Maternal antibiotic treatment is associated with neonatal sepsis by organisms resistant to ampicillin and to maternally administered antibiotics.

American Journal of Obstetrics and Gynecology


Phantom endometriosis of the sciatic nerve

Luigi Fedele

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Abstract:
OBJECTIVE: To assess the efficacy and diagnostic value of GnRH agonist (GnRH-a) therapy in cases of hidden sciatic nerve endometriosis.

DESIGN: Case report.

SETTING: Academic tertiary referral center for endometriosis treatment.

PATIENT(S): Three patients with cyclic, catamenial sciatica associated with pelvic endometriosis who had electromyographic evidence of sciatic nerve damage but negative computed tomography and magnetic resonance imaging findings.

INTERVENTION(S): Monthly administration of the GnRH-a leuprolide acetate plus daily transdermal E2 (25 microg).

MAIN OUTCOME MEASURE(S): Relief of pain symptoms and improvement in motor function.

RESULT(S): All three patients had clear decreases in pain and partial amelioration of claudication.

CONCLUSION(S): Endometriosis of the sciatic nerve may be hard to diagnose with the use of current imaging techniques but may be proved by clinical response to GnRH analogue treatment and may be more frequent than previously thought.


Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity?

Abstract:
OBJECTIVES: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes.

STUDY DESIGN: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation.

RESULTS: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2).

CONCLUSIONS: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.


A critical woman-centred review of Is Menstruation Obsolete? By Coutinho and Segal

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Is Menstruation Obsolete? argues that regular monthly bleeding is not the “natural” state of women, and that it actually places them at risk of several medical conditions of varying severity. The authors maintain that while menstruation may be culturally significant, it is not medically meaningful. Moreover, they propose that suppressing menstruation has remarkable health advantages. Because of cultural changes, shorter durations of breast feeding, and birth control, the reproductive patterns of modern women no longer resemble that of their Stone age ancestors. Women have moved from the age of incessant reproduction to the age of incessant menstruation. Consequently, they often suffer from clinical disorders related to menstruation: anemia, endometriosis, and PMS, just to name a few. The authors encourage readers to recognize what has gone previously unnoticed that this monthly discomfort is simply not obligatory. They present compelling evidence that the suppression of menstruation is a viable option for women today, and that it can be easily attained through the use of birth control pills. In fact, they reveal that contraceptive manufacturers, knowing that many women equate menstruation with femininity and that without monthly bleeding would fear that they were pregnant, engineered pill dosage regimens to ensure the continuation of their cycles. Indeed, throughout history societies have assigned menstruation powerful meaning, and Is Menstruation Obsolete? presents a fascinating history of how menstruation inspired doctors to try therapeutic bleeding for a variety of ailments, and how this therapy remained dominant in Western medicine until the early 20th century. Is Menstruation Obsolete? offers women a fresh view of menstruation, providing them with the information they need to make progressive choices about their health. This is a message whose time has come.


Effect of prenatal care on infant mortality rates according to birth-death certificate files

Abstract: Infant mortality has decreased nationwide; however, our national rates still log behind those of other industrialized countries, especially the rates for minority groups. This study evaluates the effect of prenatal care and risk factors on infant mortality rates in Chicago. Using linked infant birth and death certificates of Chicago residents for 1989-1995, a total of 5838 deaths occurring during the first year of life were identified. Birth certificate variables, especially prenatal care, were reviewed. Variables were compared by stratified analysis. Pearson chi 2 analysis and odd ratios (ORs) were computed. Infant mortality rate (IMR) in Chicago decreased from 17 in 1989 to 12.6 in 1995 (P < .0001). Some factors increased IMR several fold: prematurity (OR 17.43), no prenatal care (OR 4.07), inadequate weight gain (OR 2.95), African-American ethnicity (OR 2.55), and inadequate prenatal care (OR 2.03). Compared with no care, prenatal care was associated with lower IMR; however, early care was associated with higher IMR and ORs than later care. These results demonstrate prenatal care is associated with lower IMR; however, compared with late prenatal care, early care does not improve IMR. Further studies should evaluate whether improving the quality of care improves IMRs.

Journal of the National Medical Association


Is adolescent pregnancy associated with adverse perinatal outcome?

Abstract:
BACKGROUND: The number of teenage pregnancies has increased throughout the world and these pregnancies are reported in association with a higher rate of maternal and fetal complications.

AIM OF THE STUDY: To evaluate the social surroundings; the results of ante-, intrapartum surveillance and perinatal outcome in adolescent pregnancies where mothers were below the age of 18.

METHODS: Between 1st January, 1991 and 31st December, 1996 there were 13,131 births at our department. During this period, 209 newborns were born of 207 adolescent mothers. We compared the data of adolescent mothers with the data of all mothers who delivered in Hungary during the study period.

RESULTS: 39 (18.6%) from 209 newborns were delivered before 37th week of gestation, and 34 (16.3%) newborns showed signs of intrauterine growth retardation (IUGR). The rate of primiparous adolescent mothers was 72.0%, 131 (63.3%) were primigravidae, and 136 (65.7%) received adequate prenatal care. Maternal complications (pregnancy induced hypertension, threatened preterm delivery, gestational diabetes and pre-eclampsia) and adverse perinatal outcome (higher rate of IUGR and perinatal mortality) were found more frequently in adolescent pregnancies.

CONCLUSIONS: As young maternal age is associated with an increased risk of unfavourable fetal outcome, teenage mothers need improved prenatal care and increased observation during labour. In addition, improvement of the social environment of adolescents and the prevention of teenage pregnancies should be recommended.


Cardiovascular pharmacology of hormone replacement therapy

Abstract: The incidence of cardiovascular disease in women is negligible before natural or surgically-induced menopause, and increases after menopause. Epidemiological data suggest that estrogen replacement therapy reduces the occurrence of coronary artery, and possibly cerebrovascular, disease by 25 to 50% in treated women compared with non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls. Early reports suggested that up to 60% of the protective effect of estrogens on coronary artery disease was attributable to favourable changes in plasma lipids. Reanalysis of the data indicated that the lipid changes probably account for approximately 25% of the cardioprotective effect of estrogens and that other effects are, therefore, likely to be important. The influence of estrogens on carbohydrate metabolism, atheroma formation and cardiovascular haemodynamics may also play an integral role in the overall beneficial effect of the hormones. Animal and human studies have shown that the administration of estrogens leads to a restoration of endothelial function, an increase in cardiac output, an increase in arterial flow velocity, a decrease in vascular resistance, and a decrease in systolic and diastolic blood pressure. Recent studies on hormone replacement regimens have shown that estrogens may favourably affect fibrinolysis and reduce plasma fibrinogen to premenopausal levels. Despite these effects of estrogens the recent Heart and Estrogen/Progestin Replacement Study (HERS) failed to show a cardioprotective effect of hormone replacement therapy (HRT) in elderly women with coronary artery disease. However, the HERS study has several limitations and stands alone against the large body of evidence that suggest that HRT may reduce cardiovascular mortality and morbidity.


Pregnancy probabilities during use of the Creighton Model Fertility Care System

Abstract:
OBJECTIVE: To evaluate pregnancy probabilities during use of the Creighton Model Fertility Care System (CrMS).

DESIGN: Couples who began use of the CrMS were entered into this observational cohort study. Follow-up included detailed reviews of use of the CrMS. Pregnancy probabilities were calculated with both net and gross life-table analysis through 18 months.

SETTING: A natural family planning service delivery program based at an urban hospital in Houston, Tex.

SUBJECTS: A group of 701 couples who received instruction in the CrMS were entered into the study. Most couples (93%) were engaged or married. Most women were white (83%), between the ages of 20 and 34 years (88%), and college graduates (58%).

MAIN OUTCOME MEASURE: Pregnancies were classified based on a detailed evaluation involving the pregnant woman (usually with her partner).

RESULTS: At 12 months, the following net pregnancy probabilities were found per 100 couples: method-related pregnancies, 0.14; pregnancies caused by user and/or teacher error, 2.72; pregnancies caused by achieving-related behavior (genital contact during a time known to be fertile), 12.84; unresolved pregnancies, 1.43; and total pregnancies, 17.12. Pregnancy probabilities were similar when stratified by the following reproductive categories: uncomplicated regular cycles, long cycles, discontinuing oral contraceptives, breastfeeding, and other.

CONCLUSIONS: Pregnancy probabilities of the CrMS compare favorably with those of other methods of family planning. Most pregnancies result from genital contact during a known fertile time. Women need not have regular cycles to use the CrMS successfully.


Women's satisfaction with birth control: a population survey of physical and  psychological effects of oral contraceptives, intrauterine devices, condoms,  natural family planning, and sterilization among 1466 women

B J Oddens

International Health Foundation, Geneva, Switzerland. info@ihf.nl

Abstract: User satisfaction and the physical and psychological effects of five commonly used contraceptive methods were investigated in a population survey among 1466 West German women. The focus was on effects attributed by current and past users to these methods, rather than objectively assessed effects, to shed further light on personal experiences that are highly relevant to the user but often remain unknown to prescribers and unreported in the medical literature. Within the overall sample, 1303 women were surveyed concerning their current or past use of oral contraceptives (OC), 996 regarding condoms, 342 with respect to intrauterine devices (IUD), 428 in regard to natural family planning (NFP), and 139 in relation to sterilization (respondents completed questions about each method used). It emerged that satisfaction was greatest with sterilization (92% of users), followed by OC (68% of ever users), IUD (59%), NFP (43%), and condoms (30%). Almost one in three NFP users had experienced an unwanted pregnancy during use of this method, as compared with one in 20 OC and condom users. The majority of users reported no mood changes during use of the methods studied. The percentages reporting negative mood changes (various items were scored) were up to 16% among OC users, 23% among condom users, and 30% among NFP users. The latter observations suggested that subjective side effects of a contraceptive agent on mood generally reflected, at least in part, the user's sense of confidence in the method concerned (notably, with regard to efficacy and safety). Oral contraceptives, IUD, and sterilization had a broadly positive impact on sex life, whereas that of condoms was often negative. Whereas OC users often reported less heavy and painful menstruation (in up to 56% of cases), IUD were associated with heavier, prolonged, and more painful menstruation (in up to 65% of cases), as also was sterilization, although to a lesser extent (in up to 32% of cases). Overall, the study findings indicated that OC and sterilization had less negative impact on physical and psychological functioning than the other methods studied, in contrast to what the general public often believes.


The influence of donated gametes on the incidence of hypertensive disorders of pregnancy

Abstract: Pregnancies achieved from oocyte, sperm or embryo donation are unique, since they have resulted from donor gametes that are immunologically foreign to the mother. Thus, studying the obstetric outcome of such pregnancies may shed some light on the pathophysiology of preeclampsia, particularly in women conceiving with donated embryos, since the entire fetal genome is allogenic in these pregnancies. In this retrospective cohort study, a total of 144 women were studied. Of these, 72 were infertility patients who had conceived as a result of sperm, ovum or embryo donation and the other 72 women were age- and parity-matched control patients who became pregnant with their own gametes, either spontaneously, or following intrauterine insemination with their partner's spermatozoa. Study patients were divided into three groups depending on the origin of the donated gametes. Group 1 consisted of pregnancies achieved by intrauterine insemination with washed donor spermatozoa (n = 33). Group 2 included women who conceived using donated oocytes (n = 27) and group 3 consisted of women who conceived as a result of embryo donation (n = 12). The incidence of pregnancy-induced hypertension in the donated gametes study group was 12.5% (9/72) compared with 2.8% (2/72) in the control group. In addition, pre-eclampsia was diagnosed in 18.1% (13/72) of the donated gametes study group compared to 1.4% (1/72) in the age- and parity-matched controls. The increased incidence of gestational hypertension in pregnancies resulting from donated gametes gives evidence for a maternal genetic component, with an equally strong fetal influence, in the complicated aetiology of gestational hypertension, and pre-eclampsia in particular.


Are all contraceptive failures unintended pregnancies? Evidence from the 1995 National Survey of Family Growth

James Trussell

Princeton University; Office of Population research; Wallaca Hall Princeton New Jersey USA NJ 08544

Abstract:
Context: The incidence of unintended pregnancy has long been used as a primary indicator of the state of reproductive health. However, the definition--and therefore the measurement--of this indicator has been elusive.

Methods: Data from the 1995 National Survey of Family Growth (NSFG) were used to compare levels of unintended pregnancy among contraceptive users based on two definitions--the standard definition based on women's reports of contraceptive failure, and the NSFG definition based on pregnancy timing (wanted then, wanted later, or not wanted then or in the future). An attitudinal scale was used to examine women's feelings about their unintended pregnancy.

Results: Of pregnancies classified as contraceptive failures under the standard definition, only 68% were unintended pregnancies--94% of those ending in abortion and 60% of those ending in birth. Just 59% of women with a contraceptive failure classified as an unintended pregnancy reported feeling unhappy or very unhappy about their pregnancy, while 90% of those with a failure classified as an intended pregnancy reported being happy or very happy.

Conclusions: Measures of wantedness based on women's feelings about their pregnancy may correlate more closely with important pregnancy outcomes than do traditional measures of intendedness. This study examines the alternative implications of the measurements of unintended pregnancy during contraceptive failure in the US. The data from the 1995 National Survey of Family Growth (NSFG) were used to compare levels of unintended pregnancy among contraceptive users based on two definitions: the standard definition based on women's report of contraceptive failure; and the NSFG definition based on pregnancy timing. An attitudinal scale was used to examine women's feeling about their unintended pregnancy. The results of the analysis revealed 68% were unintended pregnancies under the classification of standard definition, while 59% of women with contraceptive failure classified under NSFG definition and reported feeling unhappy or very unhappy about their pregnancy. About 90% of those with contraceptive failure classified as an intended pregnancy reported feeling happy or very happy. Although these results were consistent with one another, it is still unclear why these women feeling happy about their unintended pregnancy are practicing contraception.


Ovulatory and Metabolic Effects of D-chiro-inositol in the Polycystic Ovary Syndrome

John E Nestler

Virginia Commonwealth University Medical Center

Daniela Jakubowicz

Hospital Clínico Universitario de Caracas


Ovarian cancer and infertility: a genetic link?

Abstract: A genetic mechanism may be responsible for the increased incidence of ovarian cancer in some infertile women (ie, those who failed to conceive despite treatment).


Ovarian endometriosis: a marker for more extensive pelvic and intestinal disease

Abstract:
OBJECTIVE: To describe a computerized pelvic mapping system for pelvic and intestinal endometriosis and preliminary insights gained from it with respect to the effects of ovarian disease.

DESIGN: Contemporaneous computerized tabulation of pelvic and intestinal sites of biopsy-proved endometriosis.

SETTING: Tertiary referral center for the surgical treatment of endometriosis.

PATIENT(S): One thousand nine hundred seventy-nine patients with endometriosis, 547 of whom had intestinal endometriosis. Patients with endometriosis with previous hysterectomy (n = 194) with or without castration were excluded from this total, leaving 1,785 patients for this study.

INTERVENTION(S): Computer tabulation of sites of biopsy-proved pelvic and intestinal endometriosis.

MAIN OUTCOME MEASURE(S): Extent of pelvic and intestinal endometriosis as reflected by number of pelvic or intestinal areas involved. Results were stratified by the presence or absence of ovarian endometriosis and by status of previous therapy.

RESULT(S): Compared with patients without ovarian endometriosis, patients with ovarian endometriosis have more pelvic and intestinal areas involved by endometriosis. Patients with ovarian endometriosis and intestinal endometriosis are more likely to require full-thickness or segmental bowel resections for complete removal of intestinal disease. These findings persisted when adjusted for previous therapies or presence of superficial versus deep ovarian disease. Only 1.06% of patients had ovarian disease exclusively.

CONCLUSION(S): Superficial or deep ovarian endometriosis is a marker for the presence of more extensive pelvic and intestinal disease. Surgeons diagnosing and treating only ovarian endometriosis may be underdiagnosing and undertreating their patients.


Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss

S Longo

Consejo Nacional de Investigaciones Cientificas y Tecnicas

Abstract:
OBJECTIVE: To determine effectiveness of transdermal progesterone cream for controlling vasomotor symptoms and preventing postmenopausal bone loss.

METHODS: We randomly assigned 102 healthy women within 5 years of menopause to transdermal progesterone cream or placebo. Study subjects and investigators were masked until data analysis was completed. An initial evaluation included complete history, physical examination, bone mineral density determination, and serum studies (TSH, FSH, lipid profile, and chemistry profile). Subjects were instructed to apply a quarter teaspoon of cream (containing 20 mg progesterone or placebo) to the skin daily. Each woman received daily multivitamins and 1200 mg of calcium and were seen every 4 months for review of symptoms. Bone scans and serum chemistries were repeated after 1 year.

RESULTS: Thirty of the 43 (69%) in the treatment group and 26 of the 47 (55%) in the placebo group complained initially of vasomotor symptoms. Improvement or resolution of vasomotor symptoms, as determined by review of weekly symptom diaries, was noted in 25 of 30 (83%) treatment subjects and five of 26 (19%) placebo subjects (P < .001). However, the number of women who showed gain in bone mineral density exceeding 1.2% did not differ (alpha = .05, power of 80%).

CONCLUSION: Although we found no protective effect on bone density after 1 year, we did see a significant improvement in vasomotor symptoms in the treated group.


Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism

Abstract:
OBJECTIVE: To compare the effectiveness of finasteride and flutamide in the treatment of idiopathic hirsutism.

DESIGN: Randomized study.

SETTING: Department of Gynecological Endocrinology, University of Brescia, Italy.

PATIENT(S): Forty-six women with idiopathic hirsutism were selected.

INTERVENTION(S): Patients were assigned randomly to receive 5 mg of finasteride once daily or 250 mg of flutamide twice daily for 12 consecutive months.

MAIN OUTCOME MEASURE(S): Hirsutism was evaluated at 6 and 12 months of therapy by measuring the Ferriman-Gallwey score and the terminal-hair diameters (microm) taken from different body areas. Blood samples were taken and side effects were monitored during the treatment.

RESULT(S): Both finasteride and flutamide induced a statistically significant decrease in hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 20.5% at 6 months and by 34.2% at 12 months, and hair diameter by 18.9%-23.6% at 6 months and by 29.6%-37.9% at 12 months. Flutamide reduced the Ferriman-Gallwey score by 26.6% at 6 months and by 50.9% at 12 months, and hair diameter by 22.3%-28.2% at 6 months and by 47.7%-56.5% at 12 months. Flutamide did not induce hormonal variations, whereas finasteride increased T levels by 60% and decreased 3alpha-androstanediol glucuronide by 69.5% at 12 months.

CONCLUSION(S): Both drugs were effective in the treatment of idiopathic hirsutism, but flutamide was more effective than finasteride.


Intratubal pressure before and after transcervical catheterization of the fallopian tubes

Abstract:
OBJECTIVE: To assess the intratubal pressure (ITP) and patency status of the fallopian tubes before and after transcervical catheterization of the fallopian tubes (TCFT).

DESIGN: Prospective procedural assessment.

SETTING: Pope Paul VI Institute for the Study of Human Reproduction.

PATIENT(S): Two hundred thirty-four women with either primary or secondary infertility.

INTERVENTION(S): Patients underwent selective hysterosalpingography and, in some cases, TCFT with measurement of the ITP before and after the procedure.

MAIN OUTCOME MEASURE(S): The ITP before and after TCFT.

RESULT(S): The mean (+/-SD) ITP in freely patent tubes was 0.53 +/- 0.06 atm, that in partially obstructed tubes was 1.23 +/- 0.52 atm, and that in completely obstructed tubes was 2.79 +/- 1.40 atm. After TCFT, the mean (+/-SD) ITP in partially obstructed tubes decreased to 0.64 +/- 0.31 atm and that in completely obstructed tubes decreased to 1.86 +/- 1.35 atm. The ITP was normalized in 76% of partially obstructed tubes and in 29.5% of completely obstructed tubes. In all cases of complete obstruction in which surgical correction was attempted, organic pathology was identified.

CONCLUSION(S): The procedure described is a safe and easy means of obtaining reliable and significant information on the status of the proximal fallopian tube.


How old is endometriosis? Late 17th- and 18th-century European descriptions of the disease

Abstract:
DESIGN OF THE PROJECT: This study is the result of a detailed examination of numerous historical documents as well as several contemporary works describing endometriosis. The historic texts are housed in the National Library of Medicine in Bethesda, Maryland, and had not been unearthed previously. Those primary sources date from 1690 to 1797 and repeatedly describe the organic damage and constitutional symptoms currently identified with endometriosis. The biologic research for this study was done during 1997 and 1998 in the Pathology Department of the Canton-Potsdam Hospital located in Potsdam, New York.

CONCLUSION(S): Endometriosis was described in European history approximately 300 years ago.


Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome

Abstract:
OBJECTIVES: To test the association between cytokine levels in the amniotic fluid and (i) the vascular invasion phase of intrauterine infection, (ii) the occurrence of periventricular leukomalacia; to assess the correlation between C-reactive protein levels, a recognised biological marker of inflammation in maternal serum and cytokine levels in the amniotic fluid.

DESIGN: Prospective clinical study.

SETTING: Fetal medicine unit and neonatal intensive care unit, Antoine Beclere Hospital, Clamart, France.

SAMPLE: Thirty-one pregnancies complicated by chorioamnionitis leading to birth before 32 weeks of gestation.

METHODS: Interleukin 1-beta, Interleukin 6 and TNF-alpha prospectively measured in the amniotic fluid. Histological examination of the placenta. Ultrasound examination and magnetic resonance imaging of the brains of the newborn infants performed within the first week of life.

MAIN OUTCOME MEASURES: The occurrence of periventricular leukomalacia was assessed by transfontanellar ultrasound and magnetic resonance imaging.

RESULTS: There was a significant positive correlation between the occurrence of histological chorioamnionitis, vascular extension of infection of the membranes, maternal inflammatory syndrome and neonatal sepsis. A strong association was found between maternal serum C-reactive protein concentrations and cytokine levels in the amniotic fluid. Interleukin-1beta was the best predictor of vascular extension of chorioamnionitis, and TNF-alpha was the best predictor of the development of severe early neonatal infection. There was no association between the amniotic fluid levels of cytokines and the development of periventricular leukomalacia.

CONCLUSIONS: These data suggest that IL-1beta, IL-6 and TNF-alpha are produced in relation to intrauterine inflammation and infection, but cannot be directly implicated in the development of fetal cerebral white matter lesions.

British Journal of Obstetrics and Gynaecology


[Polycystic ovary syndrome--only relevant in reproductive medicine?]

S C Heim

Abteilung für gynäkologische Endokrinologie und Reproduktionsmedizin, Universitäts-Frauenklinik, Basel.

Abstract: The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.

Therapeutische Umschau. Revue Therapeutique


Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients

Abstract: The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.


Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection

Abstract:
OBJECTIVE: To determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor.

METHODS: We performed amniocenteses in 44 women between 22 and 35 weeks' gestation who presented to our center with preterm labor and clinical suspicion of intra-amniotic infection. Each sample was analyzed by glucose measurement, Gram stain, and culture for aerobes, anaerobes, and mycoplasmas. We tested the AF for matrix metalloproteinase-9 using gelatin zymography and a commercial enzyme-linked immunosorbent assay (ELISA) system. We calculated accuracy and confidence intervals (CIs) for AF matrix metalloproteinase-9, glucose, and Gram stain for diagnosing intra-amniotic infection, using culture as the criterion standard.

RESULTS: All patients who had matrix metalloproteinase-9 detectable by ELISA also demonstrated matrix metalloproteinase-9 by zymography. Six cases of intra-amniotic infection were confirmed by culture (prevalence 14%). The performance statistics of AF matrix metalloproteinase-9 for diagnosing intra-amniotic infection were: sensitivity 83% (95% CI 53, 99), specificity 95% (95% CI 88, 99), positive predictive value 71% (95% CI 37, 99), and negative predictive value 97% (95% CI 92, 99). Two women had false-positive results; one had gram-negative rods on the AF Gram stain and developed clinical signs and symptoms of chorioamnionitis several hours after amniocentesis and the other had a purulent vaginal discharge and an AF glucose level less than 15 mg/dL. Both delivered within 24 hours of amniocentesis.

CONCLUSION: Measuring matrix metalloproteinase-9 in the AF appeared to be reliable for diagnosing intra-amniotic infection. An elevated matrix metalloproteinase-9 concentration in the AF at a preterm gestational age may portend imminent delivery regardless of microbiologic confirmation of intra-amniotic infection.


Change in cervical length after prophylactic cerclage

Abstract:
OBJECTIVE: To determine changes in length of incompetent cervices after cerclage, using transvaginal ultrasound.

METHODS: Patients were enrolled in a prospective, observational study under an Institutional Review Board-approved protocol. McDonald or Shirodkar sutures were placed according to physician preference. Pre- and postcerclage cervical lengths were measured within 72 hours of the procedure. At each examination, the first measurement was discarded, and a mean of the subsequent three measurements was calculated.

RESULTS: Twenty-one Shirodkar and ten McDonald operations were done. The mean (+/- standard deviation) precerclage cervical length was 2.7+/-0.9 cm and the postcerclage cervical length was 3.6+/-0.9 cm (P<.001, paired t test).

CONCLUSION: Prophylactic cerclage results in measurable increases in cervical length, which might contribute to the success of the procedure. Further study is needed to determine whether the degree of cervical lengthening after cerclage predicts term delivery.


Running and ovulation positively change cancellous bone in premenopausal women

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Purpose: Exercise is understood to exert positive effects on bone. However cancellous bone has not been shown to increase with exercise. Previous results of our 1-yr observational prospective study in ovulatory women related 20% of the change in cancellous spinal bone mineral density (BMD), measured by quantitative computed tomography (QCT), to luteal phase length (the time from ovulation to menstruation, LL).

Methods: The 66 women who documented exercise daily included normally active women (N = 23) and those who ran consistently or were increasing running in preparation for a marathon (N = 43). Exercise did not affect BMD change in the women as a whole. We re-evaluated those data to determine whether exercise-related effects on spinal cancellous BMD change in regularly cycling premenopausal women were related to ovulatory characteristics. The potential relationship of exercise to BMD change was reanalyzed by stratifying women into tertiles according to average LL documented by quantitative basal temperature analysis.

Results: Repeated-measures ANOVA indicated independent positive effects of both luteal length (P = 0.001) and activity (P = 0.041). The 11 runners with LL > 10.9 d had a nonsignificant 0.5% increase in lumbar BMD while the 15 who averaged short LL (<9.9 d) experienced a significant 3.6% loss. In the runners as a group, however, kilometers run per week was negatively related to BMD change throughout (r = -0.347, P = 0.024).

Conclusions: These data are the first to indicate that, in women with regular cycles, luteal length and exercise independently and positively affect change in spinal cancellous BMD.

Medicine and Science in Sports and Exercise


Amniotic fluid concentrations of adrenomedullin in preterm labor

Abstract:
OBJECTIVE: To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor.

METHODS: We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women.

RESULTS: Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL).

CONCLUSION: Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.


The differential risk of oral contraceptives: the impact of full exposure  history

Abstract: Previous discussions have indicated that the small increases of risk of venous thromboembolism (VTE) associated with newer combined oral contraceptives (third generation, containing desogestrel and gestodene) may be attributed to bias due to cohort effects. In a case-control analysis, this may produce an overestimate of risk of newer preparations. In 10 centres in Germany and the UK, the Transnational Study analysed data from 502 women aged 16-44 years with VTE, and from 1864 controls matched for 5-year age group and region. Information on lifetime exposure history from all subjects was added to the dataset used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17 622 continuous exposure episodes comprising 47 914 person-years of observation, the adjusted hazard ratio (equivalent to odds ratio, OR) of VTE for the comparison of current users of third-generation versus current users of second-generation (primarily levonorgestrel compounds) combined oral contraceptives was 0.8 (0.5 to 1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1 to 2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the Transnational Study data show no evidence for an increased risk of VTE with thirdcompared with second-generation combined oral contraceptives.


Venous thromboembolic disease and combined oral contraceptives: A re-analysis of  the MediPlus database

Geraldine Leydon

London School of Hygiene & Tropical Medicine

Abstract: In October 1995 the Committee on Safety of Medicines advised UK doctors and pharmacists that oral contraceptives containing desogestrel and gestodene were associated with double the risk of venous thromboembolic events (VTE) compared to pills containing other progestogens. In 1997 data was analysed from the MediPlus database of UK general practitioner records, which reported odds ratios for desogestrel and gestodene lower than that for levonorgestrel. Here the results of a more stringent nested case control analysis on the MediPlus database are reported. The study was larger and cases were verified. A crude incidence of idiopathic VTE was found amongst users of combined oral contraceptives of 4.6 per 10 000 exposed women years. Using levonorgestrel 150 microg + ethinyloestradiol 30 microg as reference, non-significant odds ratios of 1.1 (0.5-2.6) for desogestrel 150 microg + ethinyloestradiol 30 microg and 1.1 (0.5-2.4) for gestodene 75 microg + ethinyloestradiol 30 microg were found. The results of this study show no significant difference in risk between different formulations of combined oral contraceptive.


The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks

Abstract: Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.

Endocrinology and Metabolism Clinics of North America


Uses of progesterone in clinical practice

Michelle P Warren

Columbia University Irving Medical Center

Abstract: Progesterone is the natural progestagen produced by the corpus luteum during the luteal phase. It is absorbed when administered orally, but is greater than 90% metabolized during the first hepatic pass. This greatly limits the efficacy of once-daily administration and also results in unphysiologically high levels of progesterone metabolites, particularly those reduced at the 5-a position. These metabolites can cause dizziness and drowsiness to the point of preventing the operation of a motor vehicle. Synthetic progestins, such as medroxyprogesterone acetate and norethindrone acetate (NETA), have been specifically designed to resist enzymatic degradation and remain active after oral administration. However, these compounds exert undesirable effects on the liver and often cause severe psychological side effects. The permeability of the skin does not allow for administration of progesterone in the quantities normally produced by the corpus luteum, i.e., up to 25 mg/day during the mid-luteal phase. To avoid this problem, synthetic progestins such as NETA have been administered transdermally. These compounds, though, just like synthetic estrogens administered non-orally, retain undesirable hepatic effects even when administered transdermally. Transvaginal administration of progesterone is a practical non-oral route available for administering progesterone. Early experience was gained with vaginal suppositories, which lack manufacturing controls. Recently, a new progesterone gel formulation has been designed for vaginal use. The clinical acceptability of this product has been enhanced by the bioadhesive characteristics of its polycarbophil-based gel, which conveys controlled and sustained-released properties. Investigations have shown that because of local direct vagina-to-uterus transport, which results in a preferential uterine uptake of progesterone, this formulation given in conjunction with physiological amounts of estradiol produces endometrial changes similar to those seen in the luteal phase, despite plasma progesterone levels that remain subphysiologic. Studies in infertility show that vaginal progesterone in this form allows secretory transformation of the endometrium and the development of pregnancy despite providing low systemic progesterone concentrations. Fewer side effects occur when used for hormone replacement than typically encountered with progestins and oral progesterone. Uses in patients with infertility and hypoestrogenism and secondary amenorrhea are reviewed.

International Journal of Fertility and Women's Medicine


Pregnancy rates after in-vitro fertilization in cases of tubal infertility with  and without hydrosalpinx: a meta-analysis of published comparative studies

Abstract: This meta-analysis was intended to evaluate differences in pregnancy rates after in-vitro fertilization (IVF) in tubal fertility with and without hydrosalpinx. It examined nine published retrospective comparative series and five series published as abstracts for which additional information was obtained. In all, these studies involved 5592 patients (1004 with hydrosalpinx and 4588 with tubal infertility without hydrosalpinx). The main outcome measures were rates of pregnancy, implantation, live delivery, and early pregnancy loss. Pregnancy rates were significantly lower in the presence of hydrosalpinx: 31.2% for the tubal sterility group without hydrosalpinx and 19.7% for the group with hydrosalpinx (odds ratio: 0.64; 95% confidence interval: 0.56, 0.74). Similarly, the implantation rate and the delivery rate per transfer in the hydrosalpinx group were only slightly more than half those of the non-hydrosalpinx group (implantation: 8.5 and 13.7%, respectively; delivery: 13.4 and 23.4%). The incidence of early pregnancy loss was also higher in the hydrosalpinx group (43.7%) than in the control group (31.1%). This meta-analysis makes it clear that hydrosalpinx present during IVF-embryo transfer has negative consequences on the rates of pregnancy, implantation, live delivery, and early pregnancy loss. It would be premature, nonetheless, to conclude that routine salpingectomy should be performed on all patients with hydrosalpinx.


Metaanalysis of the safety and efficacy of an adhesion barrier (Interceed TC7) in laparotomy

Abstract:
OBJECTIVE: To evaluate the safety and efficacy of an oxidized, regenerated, cellulose adhesion barrier (Interceed TC7) in the reduction of pelvic adhesions.

STUDY DESIGN: Clinical studies published or completed by December 31, 1994, evaluating the barrier used at laparotomy were considered for a metaanalysis.

RESULTS: Of 10 studies (n = 560) identified, data from 7 (n = 389) met the inclusion criteria for determining the reduction in the incidence of adhesions and 5 (n = 311) for determining the reduction in adhesion extent (raw surface area after adhesiolysis). There was a 24.2 +/- 3.3% difference in the incidence of adhesions (P < .001) between barrier-treated and untreated sites. Adhesion-free outcomes were 1.5-2.5 times more likely at barrier-treated sites than at sites with good surgical technique alone (odds ratio = 2.89; 95% confidence interval = 2.15-3.90). Barrier treatment resulted in a greater reduction (1.1 +/- 0.4 cm2) in adhesion extent (raw surface area) than good surgical technique alone (P < .001). Four adverse events were recorded; they were typical of those seen after surgery. No event was considered to be definitely related to the use of the barrier.

CONCLUSION: The barrier significantly reduced the incidence and extent of adhesions as compared with no treatment, confirming the conclusion from individual studies that it is safe and effective in pelvic laparotomy surgery.


Pathophysiology and management of proximal tubal blockage

A E Holden

The University of Texas Health Science Center at San Antonio

Abstract:
OBJECTIVE: To review the physiology, pathology, and treatment of proximal tubal disease.

DATA IDENTIFICATION: Relevant reports on the pathophysiology of proximal tubal disease were reviewed. All studies in English of microsurgery and macrosurgery, and of radiographic and hysteroscopic cannulation in women with proximal tubal blockage were identified through MEDLINE searches.

STUDY SELECTION: All studies of therapy for proximal blockage that included pregnancy rates were considered. Series of sterilization reversals, series of unilateral or combined procedures, and series in which the location of tubal blockage was not given were excluded from the data analyses.

DATA ANALYSIS: Raw data were assessed for homogeneity, then standardized and pooled. Total and ongoing pregnancy rates after microsurgery and macrosurgery, as well as radiographic and hysteroscopic transcervical cannulation, were compared by the chi2 test. Relative risks for total and ongoing pregnancies were calculated for all treatment methods.

RESULT(S): This meta-analysis suggests that, overall, microsurgical anastomosis results in higher total and ongoing pregnancy rates than macrosurgery or radiographic tubal cannulation. However, pregnancy rates in selected series of transcervical tubal cannulation are similar to those reported for microsurgery.

CONCLUSION(S): Ongoing intrauterine pregnancy rates near 50% can be achieved in patients with proximal blockage of the fallopian tube. Selective salpingography and transcervical cannulation under fluoroscopic guidance are effective at establishing patency in appropriately selected patients and are less invasive and costly than the surgical alternatives.


Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study

Abstract:
OBJECTIVE: To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers.

DESIGN: Long-term, historic-prospective study.

SETTING: Fertility clinic in a university hospital.

PATIENT(S): Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files.

INTERVENTION(S): Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed.

MAIN OUTCOME MEASURE(S): Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment.

RESULT(S): Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors.

CONCLUSION(S): An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.


Oral-contraceptive use and risk of hip fracture: a case-control study

Abstract:
Background: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. Method: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded.

Findings: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30.

Interpretation: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.


Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome

Daniela Jakubowicz

Hospital Clínico Universitario de Caracas

John E Nestler

Virginia Commonwealth University Medical Center

Abstract:
BACKGROUND: Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity.

METHODS: We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation.

RESULTS: In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001).

CONCLUSIONS: D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.


Pitfalls in ultrasonic cervical length measurement for predicting preterm birth

Nicole P. Yost

The University of Texas Southwestern Medical Center

Abstract:
OBJECTIVE: To describe the anatomic and technical difficulties encountered with transvaginal ultrasound imaging of the cervix in a consecutive series of women at risk for preterm delivery.

METHODS: Three groups of women had cervical ultrasound examinations: those with histories of preterm birth, those with incompetent cervices, and those admitted for preterm labor that did not progress. Standardized ultrasound examinations of the cervix involved measuring the length of the endocervical canal, funneling length, and internal os dilation with and without fundal pressure.

RESULTS: Sixty consecutive women had transvaginal ultrasound examinations for assessment of the cervix. Forty-six had histories of preterm birth, five had incompetent cervices, and nine had arrested preterm labor. Six types of problems arose, which can be divided into anatomic or technical considerations, with an overall frequency of 27% (95% confidence interval 16%, 40%). Anatomic pitfalls that hampered identification of the internal os included an undeveloped lower uterine segment (n = 5), a focal myometrial contraction (n = 1), rapid and spontaneous cervical change (n = 1), and an endocervical polyp (n = 1). Technical pitfalls included incorrect interpretation of internal os dilation because of vaginal probe orientation (n = 7) and artificial lengthening of the endocervical canal because of distortion of the cervix by the transducer (n = 1).

CONCLUSION: We caution those who perform cervical length examinations to be wary of falsely reassuring findings due to potential anatomic and technical pitfalls.


Endometriosis: a clinically malignant disease

A Henkel

Department of Gynecology, Centre of Gynecology and Obstetrics, University Essen, Germany.

Abstract: According to the literature this is the first patient with the primary diagnosis of an endometriosis (EMT) based on the cardinal symptom of an uremia in combination with a colorectal ileus. Operative removal of EMT was possible after hormonal suppression with Dienogest.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study

Abstract:
OBJECTIVE: To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist.

DESIGN: Randomized prospective clinical trial.

SETTING: University-based IVF center.

PATIENT(S): Women <40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation.

INTERVENTION(S): Patients were randomized to receive either oral micronized progesterone (200 mg three times daily) or IM progesterone (50 mg daily).

MAIN OUTCOME MEASURE(S): Progesterone levels at standardized days 21 and 28, and pregnancy and embryo implantation rates.

RESULT(S): Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group. Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group. The clinical pregnancy rates were 57.9% and 45.8% for the IM and oral groups, respectively. The implantation rate per embryo was significantly higher in the IM group (40.9%) than in the oral group (18.1%).

CONCLUSION(S): When used according to our protocols, oral progesterone and IM progesterone result in comparable levels of circulating progesterone. However, oral progesterone results in a reduced implantation rate per embryo.


Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs

Abstract:
OBJECTIVE: To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates.

DESIGN: Prospective, randomized, double-blind trial.

SETTING: Academic center.

PATIENT(S): Twenty-three patients with unexplained infertility.

INTERVENTION(S): Twenty-three patients with unexplained infertility underwent 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group), or placebo on days 1-5 and CC on days 5-9 (control group).

MAIN OUTCOME MEASURE(S): The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates.

RESULT(S): Gonadotropins and E2 levels, as well as uterine artery pulsatility index, were significantly higher in the study group on day 5. In addition, in the study group, a longer time interval existed between finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1.1-72.4).

CONCLUSION(S): Clomiphene citrate commenced on day 1 of the menstrual cycle, rather than day 5, results in more rapid follicular growth, a longer CC-free period before IUI, and higher pregnancy rates. Although methodologically sound, our results should be taken with some degree of caution because they are based on a relatively small number of patients.


Etiologic Factors in Women with a History of Recurrent Pregnancy Loss

William H Kutteh

University of Tennessee Health Science Center


Human assisted conception: a cautionary tale. Lessons from domestic animals

Abstract: A variety of embryo-based technologies used in farm animal reproduction, including embryo culture, nuclear transfer, embryo-somatic cell co-culture and asynchronous embryo transfer can lead to the production of large offspring; the so-called large calf/lamb syndrome. In some cases, abnormalities in the fetus and newborn are apparent. The nature of these associations is explored with emphasis on the biological differences between in-vivo- and in-vitro-produced embryos. A unifying framework and research programme aimed at explaining anomalies in early embryo development is then proposed in terms of the response of somatic cells and embryos to cellular stress. The review concludes with a caution against developments in assisted conception technologies, in man and domestic animals, being determined too much by the needs of commerce at the expense of research on the molecular, biochemical and physiological basis of early mammalian development.


Menstrual cycle pattern and fertility: a prospective follow-up study of pregnancy and early embryonal loss in 295 couples who were planning their first pregnancy

Abstract:
OBJECTIVE: To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss.

DESIGN: Prospective follow-up study.

SETTING: Healthy couples recruited throughout Denmark.

PATIENT(S): Two hundred ninety-five couples who were planning their first pregnancy were followed up from the discontinuation of birth control until a pregnancy was recognized within six menstrual cycles. Early embryonal losses were detected by changes in urinary hCG levels.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The probability of pregnancy occurring within one menstrual cycle (fecundity).

RESULT(S): In women who had a cycle length that differed by >10 days from the usual cycle length, fecundity was approximately 25% that of women who had no variation (odds ratio 0.25, 95% confidence interval 0.09-0.68). When the combined effect of cycle variation and cycle length was assessed, cycle variation was a persistent strong predictor of fecundity.

CONCLUSION(S): The mechanisms of the present findings probably are female functional disturbances in ovulation, conception, implantation, or sustained pregnancy, linked with variable menstrual cycle length. Thus, identification of medical and environmental causes of abnormal menstrual cycle patterns may provide clues to the causes of infertility. Moreover, the menstrual cycle pattern also should be taken into consideration in the clinical decision-making process.


Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility

Abstract:
OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility.

DESIGN: Prospective, randomized clinical study.

SETTING: University-affiliated infertility clinic.

PATIENT(S): Couples with newly diagnosed infertility and no prior treatment.

INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility.

MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy.

RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same.

CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.


Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

Abstract: This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.


The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone

Abstract: The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. In this study, we have compared the chemistry of the major catechol metabolite of equilin (4-hydroxyequilin), which is found in several estrogen replacement formulations, to the equilenin catechol (4-hydroxyequilenin). Unlike endogenous catechol estrogens, both equilin and equilenin were primarily converted by rat liver microsomes to 4-hydroxylated rather than 2-hydroxylated o-quinone GSH conjugates. With equilin, a small amount of 2-hydroxyequilin GSH quinoids were detected (4-hydroxyequilin:2-hydroxyequilin ratio of 6:1); however, no peaks corresponding to 2-hydroxyequilenin were observed in incubations with equilenin. These data suggest that unsaturation in the B ring alters the regiochemistry of P450-catalyzed hydroxylation from primarily 2-hydroxylation for endogenous estrogens to 4-hydroxylation for equine estrogens. 4-Hydroxyequilenin-o-quinone reacts with GSH to give two mono-GSH conjugates and one di-adduct. The behavior of 4-hydroxyequilin was found to be more complex than 4-hydroxyequilenin as conjugates resulting from 4-hydroxyequilenin were detected in addition to the 4-hydroxyequilin-GSH adducts. The mechanism of decomposition of 4-hydroxyequilin likely involves isomerization to a quinone methide which readily aromatizes to 4-hydroxyequilenin followed by autoxidation to 4-hydroxyequilenin-o-quinone. Similar results were obtained with 2-hydroxyequilin, although, in contrast to 4-hydroxyequilenin, 2-hydroxyequilenin does not autoxidize and the reaction stops at the catechol. Since 4-hydroxyequilin is converted to 4-hydroxyequilenin and 4-hydroxyequilenin-o-quinone, similar effects were observed for this equine catechol, including consumption of NAD(P)H likely by the 4-hydroxyequilenin-o-quinone, depletion of molecular oxygen by 4-hydroxyequilenin or its semiquinone radical, and alkylation of deoxynucleosides and DNA by 4-hydroxyequilenin quinoids. Finally, preliminary studies conducted with the human breast tumor cell line MCF-7 demonstrated that the cytotoxic effects of the catechol estrogens from estrone, equilin, and 2-hydroxyequilenin were similar, whereas 4-hydroxyequilenin was a much more potent cytotoxin ( approximately 30-fold). These results suggest that the catechol metabolites of equine estrogens have the ability to cause alkylation/redox damage in vivo primarily through formation of 4-hydroxyequilenin quinoids.


The prevalence of polycystic ovaries in healthy women

Juha Tapanainen

Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland

Abstract:
BACKGROUND: To study the prevalence of polycystic ovaries (PCO) in women of reproductive age.

METHODS: A total of 189 healthy volunteers aged 20-45 years were examined. The subjects were divided into two groups according to age: < or =35 and > or =36 years. Transvaginal ultrasonography was performed and blood samples were collected on cycle day 1-6.

RESULTS: The prevalence of PCO in the entire study population was 14.2% (27/189). In the age group of < or =35 years the prevalence was 21.6% (19/88) and in the age group of > or =36 years 7.8% (8/101). Compared to women with normal ovaries, those with PCO had significantly higher serum testosterone (T) concentrations. Women with PCO tended to have lower serum FSH concentrations and higher LH/FSH ratios than controls. Women with PCO had significantly more irregular cycles (44% vs. 19%, p=0.001) and problems in conceiving (25.9% vs. 9.2%, p=0.01) than women with normal ovaries.

CONCLUSIONS: The findings demonstrate that the prevalence of PCO in healthy women varies with age, being more common among women aged < or =35 years than in those aged > or =36 years. Although the hormonal parameters and clinical findings among women with PCO mimicked those of PCOS, it remains unclear if these women will later develop full-blown syndrome.

Acta Obstetricia Et Gynecologica Scandinavica


The effect of therapeutic McDonald cerclage on cervical length as assessed by transvaginal ultrasonography

Abstract:
OBJECTIVE: Our goal was to study the effect of therapeutic McDonald cerclage on cervical length with the use of transvaginal ultrasonography.

STUDY DESIGN: Cervical length was measured serially in singleton pregnancies in which there were doubts regarding cervical competence. When shortening of the cervix was substantial before 27 weeks' gestation a McDonald cerclage was applied. Wilcoxon signed rank test was used, and 1-tailed P <.05 was considered significant.

RESULTS: In the 34 pregnancies studied, the mean cervical length measured at a mean gestational age of 14 weeks had decreased significantly (P <.0001) from 42 mm (95% confidence interval 38-47) to 21 mm (95% confidence interval 19-23) at a mean gestational age of 20 weeks 5 days, when a cerclage was applied. After the cerclage the mean cervical length increased significantly (P <.0001) to 34 mm (95% confidence interval 30-38) at a mean gestational age of 22 weeks 1 day (95% confidence interval 21 weeks 1 day-23 weeks 2 days).

CONCLUSIONS: Therapeutic McDonald cerclage results in a longer cervical length as measured by transvaginal ultrasonography.

American Journal of Obstetrics and Gynecology


Do hyperandrogenic women with normal menses have polycystic ovary syndrome?

Abstract:
OBJECTIVE: To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses.

DESIGN: Prospective observational study.

SETTING: Academic practice in reproductive endocrinology.

PATIENT(S): Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses.

INTERVENTION(S): Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17-hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E2, 17-OHP, insulin, and androgen levels.

MAIN OUTCOME MEASURE(S): Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate.

RESULT(S): Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS.

CONCLUSION(S): The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS.


Relationship between endometriosis and ovarian cancer

Abstract:
PURPOSE: To investigate the occurrence of ovarian cancer (OC) arising in ovarian endometriosis (OE) diagnosed in our laboratory, and the relation of the disease to patient age.

METHODS: Histopathological reports were reviewed in cases of endometriosis and ovarian cancer diagnosed between 1982 and 1989 and in 1997. The occurrence of OE and OC was studied in relation to patient age.

RESULTS: Of the 796 OE cases, 36 (4.5%) ovarian cancers were found in the eight-year period, and of the 216 OC cases 36 (16.7%) were associated with OE; 12 patients (1.7%) were under 50 years old and 24 (22.9%) were over 50. In 1997 there were 168 cases of OE, and 4 cases were associated with OC. Of the 60 OC cases 4 cases arose in endometriosis. Two patients were over 50 and two under 50.

CONCLUSION: In our report the occurrence of OC arising in OE was most influenced by patient age, the extent of sampling and the consistency of histologic reports about the presence of endometriosis in ovarian adenocarcinoma.

European Journal of Gynaecological Oncology