Irene Souter

Changing profiles in spinal cord injuries and risk factors influencing recovery after penetrating injuries.

OBJECTIVE The changing profiles of spinal cord injuries in South Africa are addressed in this study. DESIGN A retrospective analysis of 551 patients with spinal cord injury. MATERIALS AND METHODS The cause of injury was motor vehicle crashes in 30%, stab wounds in 26%, gunshot wounds in 35%, and miscellaneous causes 9%. MEASUREMENTS AND MAIN RESULTS There was a significant shift from stab wounds towards bullet wounds over the last five years. Bullet spinal cord injuries increased from 30 cases in 1988 to 55 cases in 1992, while stab spinal cord injuries decreased from 39 cases in 1988 to 20 cases in 1992. The incidence of spinal cord injuries following a motor vehicle crash showed a declining tendency after a transient increase (28 cases in 1988, 40 in 1990, 31 in 1992). Moreover, the problem of severe septic complications has been investigated and various risk factors for sepsis that might impair the rehabilitation process have been examined. The risk of developing septic complications was higher in gunshot spine injuries (21 cases out of 193) than in knife injuries (5 cases out of 143). The presence of a retained bullet did not seem to increase the chances for sepsis. In seven patients the sepsis was the direct consequence of the retained bullet while in 14 patients sepsis developed with no bullet in situ. Furthermore, the site of the injury (cervical, thoracic, lumbar spine) did not correlate with the abovementioned risks. CONCLUSIONS Gunshots carry a heavier prognosis. Only 32% of our gunshot cases underwent a significant recovery as opposed to 61% of stab cases and 44% of the motor vehicle crash victims.

Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles.

OBJECTIVE To determine the fecundity of overweight and obese infertile women treated with gonadotropins and undergoing intrauterine insemination (IUI). DESIGN Retrospective study. SETTING Academic infertility clinic. PATIENT(S) Four hundred seventy-seven women undergoing 1,189 ovulation induction (OI)/IUI cycles stratified by body mass index (BMI). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) BMI groups were compared regarding the following: gonadotropin dose, duration of treatment, peak E(2), number of follicles (total, large, and medium size), E(2)/follicle, endometrial thickness, spontaneous abortion, and clinical and multiple pregnancy rates. RESULT(S) There was a significant trend toward higher medication requirements and lower E(2) levels with increasing BMI. BMI was inversely associated with [1] the E(2) level per produced preovulatory follicle and [2] the number of medium-size follicles. Furthermore, BMI was inversely associated with the number of medium, large, and total follicles divided by total FSH dose, suggesting that women with a higher BMI develop a lower number of medium and/or large follicles at a given total FSH dose. BMI was positively associated with endometrial thickness, and endometrial thickness was positively associated with pregnancy. Mean number of cycles required to conceive, clinical pregnancy, and spontaneous abortion rates did not differ significantly among the different BMI categories. CONCLUSION(S) Obese women require higher doses of medication and produce fewer follicles for a given dose, but once medication and response are adjusted to overcome the weight effect, the success of the treatment cycle is comparable to that of normal weight women.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004–2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were –0.19 (–0.29, –0.08) and –0.19 (–0.28, –0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. Citation: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831–839; http://dx.doi.org/10.1289/ehp.1509760

The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments.

In this prospective cohort of women undergoing infertility treatments, we measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used regression models to evaluate the association of BPA with antral follicle count (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume (OV). BPA, detected in >80% of women, had a geometric mean (±GSD) of 1.6±2.0, 1.7±2.1, and 1.5±1.8μg/L for the women contributing to the AFC (n=154), day-3 FSH (n=120), and OV (n=114) analyses, respectively. There was an average decrease in AFC of 12% (95% CI: -23%, -0.6%), 22% (95% CI: -31%, -11%), and 17% (95% CI: -27%, -6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st quartile, respectively (p-trend: <0.001). No association of SG-BPA with FSH or OV was observed. Among women from an infertility clinic, higher urinary BPA concentrations were associated with lower AFC, raising concern for possible accelerated follicle loss and reproductive aging.

Pharmacokinetics of testosterone after percutaneous gel or buccal administration

OBJECTIVE To determine the pharmacokinetics of testosterone following its administration using transdermal gel or buccal lozenges. DESIGN Pilot study. SETTING University-based hospital. PATIENT(S) Ten bilaterally oophorectomized women. INTERVENTION(S) Daily micronized testosterone gel (1 mg) and testosterone propionate lozenge (1 mg). MAIN OUTCOME MEASURE(S) Total testosterone, androstenedione, dihydrotestosterone, 3alpha-androstanediol glucuronide, and sex hormone-binding globulin were measured in serum by specific radioimmunoassays; free testosterone levels were also calculated. RESULT(S) Before treatment, serum testosterone levels in the groups using the lozenge and gel were 16 +/- 4.0 and 20 +/- 6.0 ng/dL, respectively. Mean maximum testosterone levels obtained with the lozenge occurred 1 hour after administration on days 1 (692 +/- 236 ng/dL) and 14 (836 +/- 309 ng/dL) of treatment and fell precipitously thereafter. In contrast, testosterone levels obtained with the gel showed a prolonged rise reaching maximal levels of 97 +/- 78 and 100 +/- 60 ng/dL after 18 hours. The serum level patterns of free testosterone, dihydrotestosterone, and 3alpha-androstanediol glucuronide were similar to the corresponding total testosterone levels. CONCLUSION(S) Administration of testosterone lozenge by buccal absorption produced a rapid and brief elevation of testosterone levels, with levels reaching upper limits of the male range. In contrast, transdermal testosterone gel absorption resulted in a prolonged elevation of testosterone levels, which were in the hyperandrogenic female range but resembled steady state pharmacokinetics.

Early closure of colostomies in trauma patients—A prospective randomized trial

BACKGROUND Most traumatic colon injuries can be repaired primarily, but a colostomy may still be required for severe colonic or rectal injury. The current trend is to reverse the colostomy early, rather than to wait the traditional 3 months before closure. METHODS Forty-nine patients with colostomies after abdominal trauma were entered into the study. All patients had undergone a contrast enema in the second postoperative week to assess distal colon healing. Patients were excluded from early closure for nonhealing of the bowel injury, unresolving wound sepsis, or an unstable condition. We then compared the outcome of the remaining 38 (77.6%) patients allocated to either an early or a late colostomy group in a controlled, prospective, randomized trial. RESULTS We found no significant difference in morbidity between the two groups, with an overall complication rate of 26.3%. Technically the early closure of colostomies was far easier than late closure and required significantly less operating time (p = 0.036) and with less intraoperative blood loss (p = 0.020). The closure of end colostomies was more time consuming, both early (p < 0.001) and late (p < 0.001) and caused more bleeding (p < 0.001 and p < 0.001, respectively). Total hospitalization was marginally shorter overall for early closure, but late closure of end colostomies resulted in prolonged hospitalization (p = 0.023). CONCLUSIONS The early closure of colostomies and the use of loop colostomies whenever possible are recommended as both safe and beneficial for patients with colonic injury after trauma. Contraindications for early closure include nonhealing distal bowel, persistent wound sepsis, or persistent postoperative instability.

Urinary paraben concentrations and ovarian aging among women from a fertility center.

Background: Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure. Objective: We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts. Methods: Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures. Results: Of the women enrolled in 2004–2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0–46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were –5.0% (–23.7, 18.4) and –16.3% (–30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (–0.26, 2.57) and 1.02 IU/L (–0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume. Conclusions: PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies. Citation: Smith KW, Souter I, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, Hauser R. 2013. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect 121:1299–1305; http://dx.doi.org/10.1289/ehp.1205350

Urinary phthalate metabolites and ovarian reserve among women seeking infertility care

STUDY QUESTION Are urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting? SUMMARY ANSWER Higher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care. WHAT IS KNOWN ALREADY Experimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown. STUDY DESIGN, SIZE, DURATION We examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study. PARTICIPANTS/MATERIALS, SETTING, METHODS We quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking. MAIN RESULTS AND THE ROLE OF CHANCE We observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated. LIMITATIONS, REASONS FOR CAUTION We demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals. WIDER IMPLICATIONS OF THE FINDINGS Environmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development. STUDY FUNDING/COMPETING INTERESTS Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.

Neurofibromatosis type 1 and pregnancy complications: a population-based study

OBJECTIVE The objective of the study was to determine whether vascular and other complications are more common in pregnant women with neurofibromatosis type 1 (NF1). STUDY DESIGN We performed a population-based retrospective cohort study using the US Nationwide Inpatient Sample, 1988-2009, defining a cohort of pregnancy-related hospitalizations with an associated diagnosis of NF1 and comparing it with the control group not associated with NF1. Multivariable logistic regression was used to adjust for suspected confounders. RESULTS Among 19 million pregnancy-related admissions between 1988 and 2009, we identified 1553 associated with NF1 (prevalence 0.008%). A diagnosis of NF1 in delivering mothers was associated with gestational hypertension (adjusted odds ratio [AOR], 1.6, 95% confidence interval [CI], 1.2-2.0), preeclampsia (AOR, 2.8, 95% CI, 2.3-3.4), intrauterine growth restriction (AOR, 4.6, 95% CI, 3.7-5.6), cerebrovascular disease (OR, 8.1, 95% CI, 2.6-25.4), preterm labor (AOR, 1.6, 95% CI, 1.4-1.9), and cesarean delivery (AOR, 2.0, 95% CI, 1.8-2.3). Women with NF1 were not significantly more likely to have deep venous thrombosis/pulmonary embolism, acute cardiac events, or stillbirth or to die during their hospitalizations compared with the general obstetric population. CONCLUSION NF1 was associated with increased maternal morbidity in pregnancy (including hypertensive and cerebrovascular complications) but not increased maternal mortality. Obstetricians should be aware of the potential for increased antenatal and peripartum complications among women with NF1.

Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility

Hyperprolactinemia is rare among asymptomatic patients with infertility. Its prevalence and the mean PRL levels did not differ with [1] the infertility diagnosis, [2] the presence or absence of menstrual irregularities, or [3] the severity of menstrual dysregulation. Abnormal magnetic resonance imaging findings, though, are not uncommon among women with hyperprolactinemia despite the lack of symptoms and the mild PRL elevations.