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Objective To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility. Design Telephone survey, administered between March 2019 and February 2020. Setting Large urban university-affiliated fertility center. Patient(s) Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT). Intervention(s) None. Main Outcomes Measure(s) Number of live births, methods of conception, adoption, and satisfaction regarding family size. Result(s) Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT. Conclusion(s) The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment.

Objective:Dietary quality (DQ), as assessed by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), and conception and pregnancy outcomes were evaluated.Design:In this prospective cohort study on couples planning their first pregnancy. Cox proportional hazards regression assessed the relationship between AHEI-P score and clinical pregnancy, live birth and pregnancy loss.Setting:Participants were recruited from the Northeast region of the USA.Participants: Healthy, nulliparous couples (females, n 132; males, n 131; one male did not enrol).Results:There were eighty clinical pregnancies, of which sixty-nine resulted in live births and eleven were pregnancy losses. Mean (sd) female AHEI-P was 71·0 (13·7). Of those who achieved pregnancy, those in the highest tertile of AHEI-P had the greatest proportion of clinical pregnancies; however, this association was not statistically significant (P = 0·41). When the time it took to conceive was considered, females with the highest AHEI-P scores were 20 % and 14 % more likely to achieve clinical pregnancy (model 1: hazard ratio (HR) = 1·20; 95 % CI 0·66, 2·17) and live birth (model 1: HR = 1·14; 95 % CI 0·59, 2·20), respectively. Likelihood of achieving clinical pregnancy and live birth increased when the fully adjusted model, including male AHEI-P score, was examined (clinical pregnancy model 4: HR = 1·55; 95 % CI 0·71, 3·39; live birth model 4: HR = 1·36; 95 % CI 0·59, 3·13).Conclusions:The present study is the first to examine AHEI-P score and achievement of clinical pregnancy. DQ was not significantly related to pregnancy outcomes, even after adjustments for covariates.

Background Diet is a modifiable lifestyle factor linked with fertility in a growing number of studies. Objective The objective of this study was to evaluate the association between dietary energy density (ED), a summary measure of diet quality that estimates the amount of energy per unit food (kcal/g) consumed, and conception and pregnancy outcomes. Methods A prospective cohort study of couples planning their first pregnancy was conducted in the Northeast region of the USA. Dietary data were collected prior to conception via 3 unannounced interviewer-administered 24-h dietary recalls. Multivariable-adjusted logistic regression (ORs and Cox proportional hazards models [RR] and 95% CIs) were estimated for continuous and categorical (tertile [T]) variables of dietary ED. Results The majority of women (n = 80; 61%) achieved clinical pregnancy. Median time to conception of a clincal pregnancy(TTC) for those who conceived was 4.64 mo with an IQR of 4.37 mo. ED modeled as a continuous variable was not associated with clinical pregnancy, live birth, or TTC after controlling for race, physical activity, and male partner's ED. When ED was categorized to consider nonlinear associations, 60%, 73%, and 50% of the participants in the tertiles (from lowest ED to highest) achieved clinical pregnancy. In multivariable logistic analyses with the middle group as the referent (ED = 1.37–1.60), membership in the highest ED group (ED >1.60) was associated with lower odds of clinical pregnancy (OR = 0.30; 95% CI: 0.11, 0.81, P = 0.02). In Cox proportional hazards analyses, membership in the highest ED group was associated with significantly longer TTC compared with the middle category (HR = 0.41; 95% CI: 0.21,0.82, P = 0.01). Conclusions These results suggest that high dietary ED is associated with reduced fertility. This study evaluated associations between dietary energy density and the probability of conceiving clinical pregnancy, having a live birth, and the time to conception among couples planning pregnancy.

To compare the occurrence of superficial surgical site infections in obese women using prophylactic negative pressure therapy with standard dressings after cesarean delivery.We conducted a randomized controlled, nonblinded, two-center study of prophylactic negative pressure therapy compared with standard surgical dressings placed at the time of primary closure at cesarean delivery in obese women with body mass indexes (BMI) of 35 or higher (ie, class II and III obesity). Our primary outcome was occurrence of a superficial surgical site infection. We assumed a superficial surgical site infection occurrence rate of 20% and intended to recruit 400 women. However, after low enrollment of 166 women over 24 months, an interim analysis for futility was conducted and the decision was made to halt the study.Women were recruited between January 5, 2015, and January 7, 2017, from two sites. The mean BMI on admission was 44.9 (±8) for the prophylactic negative wound therapy group and 43.4 (±7) for the standard dressing group. There were no differences in the occurrence of observed superficial surgical site infections between women using prophylactic negative pressure wound therapy (12/80 [15%]) compared with women who received the standard dressing (8/81 [10%], P=.35, relative risk 1.52, 95% CI 0.66-3.52). There were no differences in the occurrence of composite wound complications between women using prophylactic negative pressure wound therapy (25/80 [31%]) compared with women who received the standard dressing (24/81 [30%], P=.87).In this randomized controlled trial that did not achieve full anticipated enrollment, we did not observe a decrease in superficial surgical site infections after cesarean delivery in obese women with the use of prophylactic negative pressure wound therapy.ClinicalTrials.gov, NCT02390401.

Antioxidants play a vital role in reproductive health and fertility. The local cellular environment influences oocyte development, ovulation, successful fertilization, and maintenance of early pregnancy. An offset of reactive oxygen species (ROS)-induced cellular oxidative stress can adversely affect function of reproductive organs and fertility. ROS and antioxidants have emerged as ubiquitous participants in normal human reproductive processes. Imbalance in the oxidant/antioxidant relationship has been implicated in numerous reproductive disorders and complications, including endometriosis, polycystic ovarian syndrome, oocyte aging, dysmenorrhea and premenstrual syndrome, spontaneous abortion, and infertility. Studies have examined dietary antioxidant supplementation in hopes to prevent and treat reproductive pathologies. Dietary antioxidants, including isoflavones, antioxidant vitamins, and trace elements, which are cofactors of key antioxidant enzymes, have been targeted as nutritional antioxidants for prevention and/or treatment of unexplained infertility and recurrent spontaneous abortions. However, there is a vast knowledge deficit to fill, and targeted studies are needed to elucidate the role of ROS in normal reproductive physiology and fertility, as well as in treatment of reproductive pathologies. This chapter reviews the role played by antioxidants in female reproductive health and fertility and antioxidant interventions for the prevention and treatment of reproductive pathology in association with oxidative stress.

To determine whether increased antioxidant intake in women is associated with shorter time to pregnancy (TTP) among a cohort of couples being treated for unexplained infertility.Secondary data analysis of a randomized controlled trial.Academic medical center associated with a private infertility center.Females with unexplained infertility.None.The time it took to establish a pregnancy that led to a live birth.Mean nutrient intake exceeded the estimated average requirement (EAR) for vitamins C and E. No differences in mean intake of any of the antioxidants were noted between women who delivered a live-born infant during the study period vs. those who did not. In multivariable models, intake of β-carotene from dietary supplements was associated with shorter TTP among women with body mass index (BMI) ≥25 kg/m(2) (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.09-1.53) and women35 y (HR 1.19, 95% CI 1.01-1.41). Intake of vitamin C from dietary supplements was associated with shorter TTP among women with BMI25 kg/m(2) (HR 1.09, 95% CI 1.03-1.15) and women35 y (HR 1.10, 95% CI 1.02-1.18). Intake of vitamin E from dietary supplements among women ≥35 y also was associated with shorter TTP (HR 1.07, 95% CI 1.01-1.13).Shorter TTP was observed among women with BMI25 kg/m(2) with increasing vitamin C, women with BMI ≥25 kg/m(2) with increasing β-carotene, women35 y with increasing β-carotene and vitamin C, and women ≥35 y with increasing vitamin E.NCT00260091.

Objective To evaluate the role of vitamin D intake and serum levels on conception of clinical pregnancy and live birth. Design Prospective cohort study. Setting Academic medical centers. Patient(s) Healthy, nulliparous women, age 18–39 years, and their male partners. Intervention(s) None. Main Outcome Measure(s) Clinical pregnancy and live birth were compared between those who did or did not meet the vitamin D estimated average requirement (EAR) intake (10 μg/d) and with serum 25-hydroxyvitamin D (25(OH)D) considered at risk for inadequacy or deficiency ( Result(s) Among 132 women, 37.1% did not meet the vitamin D EAR and 13.9% had serum levels at risk for inadequacy or deficiency. Clinical pregnancies were significantly higher among women who met the vitamin D EAR (67.5% vs. 49.0%) and with sufficient serum 25(OH)D (64.3% vs. 38.9%) compared with those who did not. Live births were higher among those who met the vitamin D EAR (59.0% vs. 40.0%). The adjusted odds ratio (AOR) of conceiving a clinical pregnancy was significantly higher among those who met the EAR (AOR = 2.26; 95% confidence interval [CI], 1.05–4.86) and had sufficient serum 25(OH)D (AOR = 3.37; 95% CI, 1.06–10.70). The associations were not significant after controlling for selected nutrients and dietary quality. Conclusion(s) Women with vitamin D intake below EAR and serum 25(OH)D levels at risk for inadequacy or deficiency may be less likely to conceive and might benefit from increased vitamin D intake to achieve adequacy. Clinical Trial Registration Number NCT00642590.

Gonadotropin therapy has been a cornerstone of infertility therapy for half a century. From the very beginning, its use has been associated with a high rate of multiple births, particularly high order multiples, and ovarian hyperstimulation syndrome. Initially, success rates seemed acceptable when used for superovulation (SO)/IUI therapy. However, as data from RCTs have emerged, reported outcomes suggest that we question the use of injectible gonadotropins. This manuscript examines the studies that have challenged gonadotropin use for SO/IUI and other research that supports reduced doses of gonadotropins for IVF. We examine the challenges for its continued use for SO/IUI and for moving to lower doses worldwide for IVF. We propose a future that views gonadotropins as a relic of the twentieth century.

Objective To determine the optimal number of day 3 embryos to transfer in women ≥38 years by conducting an evidence-based evaluation. Design Retrospective analysis of 2000–2004 national SART data. Setting National writing group. Patient(s) A total of 36,103 day 3 embryo transfers in women ≥38 years undergoing their first assisted reproductive technology cycle. Intervention(s) None. Main Outcome Measure(s) Logistic regression was used to model the probability of pregnancy, delivery, and multiple births (twin or high order) based on age- and cycle-specific parameters. Result(s) Pregnancy rates, delivery rates, and multiple rates increased up to transfer of three embryos in 38-year-olds and four in 39-year-olds; beyond this number, only multiple rates increased. In women ≥40 years, delivery rates and multiple rates climbed steadily with increasing numbers transferred. Multivariate analysis confirmed the statistically significant effect of age, number of oocytes retrieved, and embryo cryopreservation on delivery and multiple rates. Maximum FSH level was not an independent predictor by multivariate analysis. Use of intracytoplasmic sperm injection was associated with lowered delivery rate. Conclusion(s) No more than three or four embryos should be transferred in 38- and 39-year-olds, respectively, whereas up to five embryos could be transferred in ≥40-year-olds. Numbers of embryos to transfer should be adjusted according to number of oocytes retrieved and availability of excess embryos for cryopreservation.

Objective To evaluate preoperative abdominal leak point pressures (ALPP) with pre- and postoperative Incontinence Severity Index (ISI) scores. Methods A review of women who underwent a midurethral sling procedure between August 2004 and April 2006 was conducted. Eligible women completed preoperative urodynamic testing with ALPP determination and subjective incontinence severity assessment using the ISI before and 6 weeks after surgery. The ISI and ALPP relationship was analyzed using a Spearman rank correlation (Rho). Results Ninety-nine women met the inclusion criteria. Mean ALPP was 77.7 (25-172 cm H2O). Mean improvement in ISI following surgery was 4 (-8 to 12). ALPP correlated with preoperative ISI (Spearman Rho -0.28, P=0.01), preoperative leakage frequency (ISI question 1) (Spearman Rho -0.32, P=0.001), and the ISI change 6 weeks postoperatively (ISI-delta) (Spearman Rho -0.23, P=0.002). Conclusion ALPP is associated with subjective incontinence severity. Women with the lowest ALPP improved most following a midurethral sling procedure.

Background Reproductive failure is a significant public health concern. Although relatively little is known about factors affecting fertility and early pregnancy loss, a growing body of literature suggests that environmental and lifestyle factors play an important role. There is sufficient evidence to hypothesize that diet, particularly its constituent antioxidants, and oxidative stress (OS) may influence the timing and maintenance of a viable pregnancy. We hypothesize that conditions leading to OS in the female affect time-to-pregnancy and early pregnancy loss. Methods We review the epidemiology of female infertility related to antioxidant defenses and oxidation and examine potential sources of OS from the ovarian germ cell through the stages of human pregnancy and pregnancy complications related to infertility. Articles were identified through a search of the PubMed database. Results Female OS is a likely mediator of conception and threshold levels for OS exist, dependent on anatomic location and stage of preconception. Conclusions Prospective pregnancy studies with dietary assessment and collection of biological samples prior to conception with endpoints of time-to-pregnancy and early pregnancy loss are needed.

Article-at-a-Glance Background No nationally accepted set of quality indicators exists in obstetrics. A set of 10 outcome measures and three quality improvement tools was developed as part of a study evaluating the effects of teamwork on obstetric care in 15 institutions and > 28,000 patients. Each outcome was assigned a severity weighting score. Measures Three new obstetrical quality improvement outcome tools were developed. The Adverse Outcome Index (AOI) is the percent of deliveries with one or more adverse events. The average AOI during the pre-implementation data collection period of the teamwork study was 9.2% (range, 5.9%–16.6%). The Weighted Adverse Outcome Score (WAOS) describes the adverse event score per delivery. It is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries. The average WAOS for the pre-implementation period was 3 points (range, 1.0–6.0). The Severity Index (SI) describes the severity of the outcomes. It is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. The average SI for the pre-implementation period was 31 points (range, 16–49). Discussion The outcome measures and the AOI, WAOS, and SI can be used to benchmark ongoing care within and among organizations. These tools may be useful nationally for determining quality obstetric care.

Objective Women who are carrying a trisomy 13 fetus are more prone to develop preeclampsia. Excess circulating soluble fms-like tyrosine kinase-1 has been implicated recently in the pathogenesis of preeclampsia. Since the fms-like tyrosine kinase-1/soluble fms-like tyrosine kinase-1 gene is located on chromosome 13q12, we hypothesized that the extra copy of this gene in trisomy 13 may lead to excess circulating soluble fms-like tyrosine kinase-1, reduced free placental growth factor level, and increased soluble fms-like tyrosine kinase-1/placental growth factor ratio. This may then contribute to the increased risk of preeclampsia that has been observed in these patients. Our objective was to characterize the maternal circulating angiogenic proteins in trisomy 13 pregnancies. Study design Maternal serum samples of trisomy 13, 18, 21 and normal karyotype pregnancies were obtained from first and second trimester screening programs. We chose 17 cases of trisomy 13 that were matched for maternal age, freezer storage time, and parity with 85 normal karyotype control samples. Additionally, 20 cases of trisomy 18 and 17 cases of trisomy 21 were included. Cases and control samples were assayed for levels of soluble fms-like tyrosine kinase-1 and placental growth factor by enzyme-linked immunosorbent assay in a blinded fashion. Because of the skewed distributions of soluble fms-like tyrosine kinase-1 and placental growth factor, nonparametric analytic techniques were used, and the results are reported as median and ranges. Results In early pregnancy trisomy 13 cases and control samples, the median circulating soluble fms-like tyrosine kinase-1/placental growth factor ratios were 17.0 (range, 1.2-61.3) and 6.7 (range, 0.8-62.9), respectively (P = .003). The median soluble fms-like tyrosine kinase-1/placental growth factor ratios in trisomy 18 and 21 were 4.8 (range, 0.9-53.9) and 5.1 (range, 1.0-18.1), which were not significantly different than the control samples. Furthermore, the differences between trisomy 13 and control samples were more pronounced in the second trimester specimens than in the specimens from the first trimester. Conclusion These data suggest that alterations in circulating angiogenic factors may be involved intimately in the pathogenesis of preeclampsia in trisomy 13. A larger clinical study that measures these factors longitudinally and correlates them with pregnancy outcomes is needed to further establish the link between trisomy 13, altered angiogenic factors, and preeclampsia.

Objective To describe live birth rates and predictors of success in 1-year age increments for women ≥40 years when initiating assisted reproductive technologies (ART). Design Retrospective database analysis. Setting A large university-affiliated infertility center. Patient(s) One thousand two hundred sixty-three women undergoing 2,705 ART cycles at age 40 or above. Intervention(s) Couples undergoing ART. Main Outcome Measure(s) Pregnancy and live birth rates per cycle start were determined based on 1-year increments in women aged ≥40. Predictors of success, including number of embryos transferred, number of fetal heartbeats, availability of embryos for cryopreservation, and cycle day 3 FSH levels, were analyzed. Result(s) The overall live birth rate per cycle start was 9.7%. Cumulative live birth rates in women ranged from 28.4% if starting ART at age 40 to 0 by age 46. The overall spontaneous abortion rate was 32.6% (range, 23.9%–66.7%). Higher pregnancy rates were predicted by the greater number of embryos available for transfer, by the availability of excess embryos for cryopreservation, and by the presence of two fetal heartbeats on ultrasound. The outcome of the first IVF cycle did not predict the outcome of subsequent cycles. Conclusion(s) Assisted reproductive technology has a reasonable chance for success (>5%) up until the end of the forty-third year. Twins on initial ultrasound, large numbers of embryos available for transfer, and the presence of excess embryos for cryopreservation predict higher live birth rates.

Background . A randomized trial was conducted to test the effectiveness of a videotape for increasing mammography screening among a multiethnic sample of older women. Methods . A multiethnic sample of Caucasian, African-American, and Hispanic women between the ages of 50 and 70 was recruited from Resident Lists compiled by the State of Massachusetts. After completing a baseline questionnaire, women were randomized to receive either a videotape or pamphlet about mammography and recontacted at 2 and 12 months after baseline to assess attitudes, beliefs, and mammography screening. A total of 581 women completed questionnaires at all three time points. Results . At baseline, approximately 75% of women reported having a mammogram in the past year and 90% reported having one in the past 2 years. Rates did not differ between groups. At the 12-month follow-up, mammography rates, adjusted for baseline screening, were 80.4% in the video and 74.8% in the pamphlet group. Logistic regression analysis of mammography at 12 months (within past year vs. >1 year ago) controlling for baseline mammogram produced an odds ratio of 1.48 for the video group that was not significantly different from unity (95% CI = 0.95–2.28). Conclusions . The videotape had a small effect on increasing mammography screening. Although the effect was smaller than more intensive interventions, the video is a convenient, low cost, and easily implemented method to increase mammography screening.

Objectives. We compared complication rates after surgical abortions performed by physician assistants with rates after abortions performed by physicians. Methods. A 2-year prospective cohort study of women undergoing surgically induced abortion was conducted. Ninety-one percent of eligible women (1363) were enrolled. Results. Total complication rates were 22.0 per 1000 procedures (95% confidence interval [CI] = 11.9, 39.2) performed by physician assistants and 23.3 per 1000 procedures (95% CI = 14.5, 36.8) performed by physicians (P = .88). The most common complication that occurred during physician assistant–performed procedures was incomplete abortion; during physician-performed procedures the most common complication was infection not requiring hospitalization. A history of pelvic inflammatory disease was associated with an increased risk of total complications (odds ratio = 2.1; 95% CI = 1.1, 4.1). Conclusions. Surgical abortion services provided by experienced physician assistants were comparable in safety and efficacy to those provided by physicians.

Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks.

Summary objective We evaluated menopausal symptoms, menstrual cycle bleeding characteristics and reproductive hormones for their associations with thyroid stimulating hormone (TSH) concentrations in women at the mid-life from five ethnic groups. methods This report is from the baseline evaluation of the Study of Women's Health Across the Nation (SWAN), a community-based multiethnic study of the natural history of the menopausal transition. Enrollees were 42–52 years old (pre- and early perimenopausal) African American, Caucasian, Chinese, Hispanic and Japanese women (n = 3242). Enrollees were interviewed about self-reported diagnosed hypo- and hyperthyroidism or thyroid treatment, menopausal symptoms and menstrual cycle bleeding characteristics. Serum was assayed for TSH, oestradiol, testosterone, FSH and SHBG. results There were 6·2% of women with TSH > 5·0 mIU/ml and 3·2% with TSH 5·0 mIU/ml (P

Background: The associations between homocysteine, B vitamin status, and pregnancy outcomes have not been examined prospectively. Objective: We assessed the associations of preconception homocysteine and B vitamin status with preterm birth and birth of lowbirth-weight (LBW) and small-for-gestational-age (SGA) infants in Chinese women. Design: This was a case-control study of women aged 21‐34 y. Preterm cases (n = 29) delivered living infants at < 37 wk gestation; term controls (n = 405) delivered infants at ≥ 37 wk. LBW cases (n = 33) had infants weighing < 2500 g; normal-birth-weight controls (n = 390) had infants weighing ≥ 2500 g. SGA cases (n = 65) had infants below the 10th percentile of weight-forgestational-age; appropriate-for-gestational-age controls (n = 358) had infants above this cutoff. Nonfasting plasma concentrations of homocysteine, folate, and vitamins B-6 and B-12 were measured before conception. Results: Elevated homocysteine (≥ 12.4 � mol/L) was associated with a nearly 4-fold higher risk of preterm birth (OR: 3.6; 95% CI: 1.3, 10.0; P < 0.05). The risk of preterm birth was 60% lower among women with vitamin B-12 ≥ 258 pmol/L than among vitamin B-12‐deficient women (OR: 0.4; 95% CI: 0.2, 0.9; P < 0.05) and was 50% lower among women with vitamin B-6 ≥ 30 nmol/L than among vitamin B-6‐deficient women (OR: 0.5; 95% CI: 0.2, 1.2; NS). Folate status was not associated with preterm birth, and homocysteine and B vitamin status were not associated with LBW or SGA status. Conclusions: Elevated homocysteine and suboptimal vitamin B-12 and B-6 status may increase the risk of preterm birth. These results need to be confirmed in larger prospective studies. Am J Clin Nutr 2002;76:1385‐91.

OBJECTIVE: To assess the association between preconception homocysteine and B vitamin status and risk of clinical spontaneous abortion in women from Anqing, China. METHODS: All women were aged 21–34 years, had never smoked, and were primigravid. Patients ( n = 49) were women with a clinically recognized pregnancy who experienced a fetal death before 100 days’ gestation. Controls ( n = 409) were women who maintained a pregnancy that ended in a live birth. Homocysteine, folate, and vitamins B 6 and B 12 concentrations were measured in plasma obtained before conception. RESULTS: Mean vitamin B 6 concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L, P = .04). In addition, the risk of spontaneous abortion tended to increase with decreasing plasma vitamin B 6 and folate concentration ( P for trend = .06 and .07, respectively), although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of spontaneous abortion was four-fold higher among women with suboptimal plasma concentrations of both folate and vitamin B 6 (folate less than or equal to 8.4 nmol/L and vitamin B 6 less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1, 95% confidence interval 1.2, 14.4). Homocysteine and vitamin B 12 status were not associated with spontaneous abortion risk. CONCLUSION: Suboptimal preconception folate and vitamin B 6 status, especially when they occur together, may increase the risk of clinical spontaneous abortion. Additional prospective studies are needed to confirm these findings and to determine whether antenatal B vitamin supplementation reduces spontaneous abortion risk.

BACKGROUND: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented ‘no conception,’ a ‘continuing conception’ or a ‘conception lost.’ METHODS: Urine samples were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. RESULTS: Pairwise agreement among the assessors for any of the three options ranged from 78–89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. CONCLUSION: The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with20 ml Thorotrast and approached 50%.

Abortion is one of the most common surgical procedures performed on women in the US and its safety has been demonstrated. Little research has focused however on womens reports and ratings of the service. This study explored the association of demographic factors medical outcomes and client ratings of service dimensions with global satisfaction. For this cross-sectional study permission to access clinic medical records was obtained. Surveys were distributed after the procedure with instructions to return by mail. Study subjects were 797 women who underwent an outpatient surgical abortion at one of two New England health centers in 1996 and 1997. Demographic data pregnancy history and information on the procedure were collected from medical records. Survey items measured reports of access medical outcomes and satisfaction ratings with service domains. Women with positive ratings of staff sensitivity and of the counseling process and information received and those who had the procedure at a younger gestational age were less likely to report that care would be better. Although very few women reported a medical complication this was associated with agreement that care could have been better as was reporting agreement that the wait between the preexamination visit and the procedure was too long. Satisfaction with abortion services is high. Education and counseling play very important roles. Survey items could routinely be used to monitor services. (authors)

Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era.Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods.Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[ x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant.Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

To examine the relation between family history of breast cancer in a mother or sister and a man's risk of fatal prostate cancer, we analyzed data from a prospective mortality study of adult men in the United States. During 12 years of follow-up, there were 3,141 deaths from prostate cancer in a cohort of 480,802 men who were cancer-free at study entry in 1982. Results from Cox proportional hazards models, adjusted for other risk factors, showed a modest increased risk of fatal prostate cancer associated with a family history of breast cancer (in the absence of a family history of prostate cancer) [rate ratio (RR) = 1.16; 95% confidence interval (CI) = 1.01-1.33]. The association was stronger among men younger than 65 years of age whose relatives were diagnosed with breast cancer before age 50 years (RR = 1.65; 95% CI = 0.88-3.10) and among Jewish men (RR = 1.73; 95% CI = 1.00-2.97). The increased risks observed in these subgroups may reflect genetic alterations underlying familial clustering of prostate and breast cancer.

Conclusions regarding estimates of infertility may reflect study bias based on the definition of infertility used. Careful consideration of how the infertile population is defined, as well its use in subgroup analysis that may not be generalizable to the population of infertile women as a whole, is needed.

In this introductory chapter to the second edition of Women & Health we discuss what we mean by women’s health and our perspective on where the women’s health movement is today. We then present an overall picture of the state of women’s health using major health indicators as a guide and review some of the more prevalent diseases affecting women. In the final section we recommend where, in our view, research investigations and advances in clinical medicine are most needed now. The book chapters that follow this one explore the most pressing of these topics in more detail and are intended to stimulate new ideas about research worth pursuing and the methodological challenges that must be addressed as women’s health and health care enter a new era.

There is increasing evidence that nutrition and other lifestyle factors are important in the etiology of reproductive failure. Diet and its constituent antioxidants as well as oxidative stress in females may be influential in the timing and continuation of viable pregnancies. This chapter reviews oxidative stress with particular reference to folliculogenesis and oogenesis. The evidence suggests that there are threshold levels for oxidative stress that may depend on anatomic site and stage of preconception. Oxidative stress, may influence oogenesis, folliculogenesis and the establishment of a viable early pregnancy. Reactive oxygen species are continuously formed in cells of the reproductive tract, secondary to biochemical reactions, such as those within the mitochondrial respiratory chain, and also as a result of external factors.

Several studies have examined the association between body mass index and infertility. We compared body mass index in 597 women diagnosed with ovulatory infertility at seven infertility clinics in the United States and Canada with 1,695 primiparous controls who recently gave birth. The obese women (body mass index > or = 27) had a relative risk of ovulatory infertility of 3.1 [95% confidence interval (CI) = 2.2-4.4], compared with women of lower body weight (body mass index 20-24.9). We found a small effect in women with a body mass index of 25-26.9 or less than 17 [relative risk (RR) = 1.2, 95% CI = 0.8-1.9; and RR = 1.6, 95% CI = 0.7-3.9, respectively). We conclude that the risk of ovulatory infertility is highest in obese women but is also slightly increased in moderately overweight and underweight women.

Data from an international case-control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast-cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic-regression-adjusted odds ratio (OR) was 1.21, the 95% confidence interval (CI), 0.94 to 1.55. The OR was significantly elevated during the 15-year period following the latest multiple birth (1.76; CI, 1.12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast-cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast-cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long-term reduction of breast-cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary-gland cells.

We studied the history of sexually transmitted diseases in 283 nulliparous women diagnosed with infertility due to tubal adhesions or occlusion and 3,833 women admitted for delivery at seven collaborating hospitals. The adjusted risks of tubal infertility associated with the history of each sexually transmitted disease were estimated by the odds ratios obtained by multiple logistic regression. Women who reported prior infection with gonorrhea were at a significantly increased risk of tubal infertility (relative odds = 2.4, 95% confidence interval 1.3-4.4). In addition, the risk of tubal infertility was almost twice as high in women who recalled previous trichomoniasis compared with women with no such infection (relative odds = 1.9, 95% confidence interval 1.3-2.8). Furthermore, there was a trend of increasing risk with an increasing number of episodes of gonorrhea or trichomoniasis.

To review the role of oxidative stress in the context of female fertility.Oxidative stress is associated with decreased female fertility in animal and in-vitro models, but no studies to date have directly assessed the relationship in women. Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia), extremes of body weight, alcohol, tobacco, and caffeine intake. Intake of antioxidant nutrients, including use of multivitamins, impacts the generation of reactive oxygen species and may play a beneficial role in female fertility.Infertility is a significant public health problem and diagnosis and treatment are stressful, invasive, and costly. The role of oxidative stress in female fertility is an understudied and compelling area for investigation. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.

Objective To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21–39 years. Design Randomized controlled trial. Setting Academic medical center associated with a private infertility center. Patient(s) Couples with unexplained infertility. Intervention(s) Couples were randomized to receive either conventional treatment (n = 247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n = 256) that omitted the three cycles of FSH/IUI. Main Outcome Measure(s) The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby. Result(s) An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00–1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries. Conclusion(s) A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.

We evaluated the association between subfertility and low birth weight infants.Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes.Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980.Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year).The relative risk of low birth weight was estimated using the cumulative incidence risk ratio.After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4).In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth.

This article surveys the health of women from an international perspective and includes information and statistics on women's health in developed and, where available, developing nations. The World Health Organization has identified three barriers to progress in improving women's health: (1) inequities related to gender, (2) adolescents' exposure to risk, and (3) inequities related to poverty and poor access to health care. The influence of these barriers on reproductive health outcomes and chronic and infectious diseases is examined.