Iron intake in relation to ovarian reserve among women seeking infertility treatment.

STUDY QUESTION: Is there an association between iron intake and ovarian reserve among women seeking fertility care? SUMMARY ANSWER: Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care. WHAT IS KNOWN ALREADY: Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects. STUDY DESIGN, SIZE, DURATION: This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007-2019) enrolled in the Environment and Reproductive Health (EARTH) Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation. MAIN RESULTS AND THE ROLE OF CHANCE: Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45-64 mg/day of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (P, linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P, linear trend = 0.02). LIMITATIONS, REASONS FOR CAUTION: Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron. WIDER IMPLICATIONS OF THE FINDINGS: Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose-response relation of this association across the entire distribution of ovarian reserve and the risk-benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C., M.M., L.M.-A., E.O.-P., S.W., I.S., and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences. TRIAL REGISTRATION NUMBER: N/A.

Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction.

STUDY QUESTION: Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes? SUMMARY ANSWER: Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART. WHAT IS KNOWN ALREADY: Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART. STUDY DESIGN SIZE, AND DURATION: This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth. MAIN RESULTS AND ROLE OF CHANCE: The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes. LIMITATIONS REASONS FOR CAUTION: The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up. WIDER IMPLICATIONS OF THE FINDINGS: Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART. STUDY FUNDING/COMPETING INTERESTS: NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.

The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.

STUDY QUESTION: Is pre-treatment alcohol and caffeine intake associated with infertility treatment outcomes among women undergoing ART? SUMMARY ANSWER: Low to moderate alcohol and caffeine intakes in the year prior to infertility treatment were not related to ART outcomes. WHAT IS KNOWN ALREADY: Alcohol and caffeine intake have been found to be associated with infertility in some studies. Nevertheless, data on their relation with outcomes of infertility treatments are scarce and inconsistent. STUDY DESIGN, SIZE, DURATION: We included 300 women (493 ART cycles) from the Environment and Reproductive Health Study, an ongoing cohort study (2006-2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: Pre-treatment intakes of alcohol and caffeine were assessed retrospectively using a validated food frequency questionnaire. Intermediate and clinical endpoints of ART were abstracted from electronic medical records. Generalized linear mixed models with random intercepts to account for multiple ART cycles per woman were used to evaluate the association with ART outcomes adjusting for age, BMI, smoking status, infertility diagnosis, protocol type, race, dietary patterns, and calories, vitamin B12 and folate intake. MAIN RESULTS AND THE ROLE OF CHANCE: Median (range) pre-treatment alcohol and caffeine intakes were 5.6 (0.0-85.8) g/day and 124.9 (0.3-642.2) mg/day, respectively. The adjusted percentage of initiated cycles resulting in live birth (95% CI) for women in increasing categories of pre-treatment alcohol intake was 34% (20, 52%) for non-consumers, 46% (36, 57%) for 0.1-6 g/day, 41% (29, 53%) for 6.1-12 g/day, 42% (31, 55%) for 12.1-24 g/day, and 41% (22, 63%) for >24 g/day (P, trend = 0.87). The adjusted percentage of cycles resulting in live birth (95% CI) for women in increasing categories of caffeine intake was 46% (36-57%) for <50 mg/day, 44% (29, 60%) for 50.1-100 mg/day, 42% (31, 53%) for 100.1-200 mg/day, 40% (28, 53%) for 200.1-300 mg/day and 40% (21, 63%) for >300 mg/day (P, trend = 0.34). When specific types of alcoholic and caffeinated beverages were evaluated, no relations with ART treatment outcomes were observed. LIMITATIONS, REASONS FOR CAUTION: Residual confounding by other diet and lifestyle factors cannot be ruled out owing to the observational nature of this study. It is also unclear how generalizable these results are to women who are conceiving without the assistance of ART. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide reassurance that low to moderate intakes of alcohol (e.g. ≤12 g/day) and caffeine (e.g. <200 mg/day) in the year prior to infertility treatment initiation do not have an adverse effect on intermediate or clinical outcomes of ART. STUDY FUNDING/COMPETING INTEREST(S): The authors are supported by National Institutes of Health (NIH) grants ES022955, R01ES009718, R01ES000002, P30DK46200 and L50-HD085359. No conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT00011713.

The association of protein intake (amount and type) with ovarian antral follicle counts among infertile women: results from the EARTH prospective study cohort.

OBJECTIVE: To evaluate the association between protein intake (amount and type) and antral follicle count (AFC). DESIGN: Prospective cohort. SETTING: Academic fertility centre. POPULATION: Two hundred and sixty-five women undergoing fertility treatments at an academic fertility centre and participating in an ongoing study on environment and reproductive health. METHODS: We measured AFC in ultrasonographic evaluation among women undergoing infertility treatments. Women completed a previously validated semi-quantitative food frequency questionnaire. We used Poisson regression to evaluate the relation between protein intake and AFC while adjusting for age, body mass index, race, smoking status, and total energy intake. MAIN OUTCOME MEASURES: Antral follicle count. RESULTS: Among 265 women (mean age: 35.0 ± 3.9 years, 85% Caucasian), total protein intake (% energy) was unrelated to AFC. When protein from different food sources was considered separately, we found a negative association between dairy protein intake and AFC. The mean AFC was 14.4% (3.9-23.7%) lower for women in the highest quintile of dairy protein intake than for women in the bottom quintile after adjusting for potential confounders (P-trend = 0.04). This association was stronger among women who had never smoked (P-trend = 0.002) but was not observed among previous smokers (P-trend = 0.36). There were no associations between protein intake from either non-dairy animal or vegetable sources and AFC. CONCLUSION: Higher dairy protein intake (≥5.24% of energy) was associated with lower antral follicle counts among women presenting for infertility treatment. These findings should be further investigated in prospective studies also designed to clarify the biology underlying the observed associations. TWEETABLE ABSTRACT: Higher dairy protein intake was associated with lower antral follicle counts in an infertile population.

Dairy intake in relation to in vitro fertilization outcomes among women from a fertility clinic.

STUDY QUESTION: Is dairy food consumption associated with live birth among women undergoing infertility treatment? SUMMARY ANSWER: There was a positive association between total dairy food consumption and live birth among women ≥35 years of age. WHAT IS KNOWN ALREADY: Dairy food intake has been previously related to infertility risk and measures of fertility potential but its relation to infertility treatment outcomes are unknown. STUDY DESIGN, SIZE, DURATION: Our study population comprised a total of 232 women undergoing 353 in vitro fertilization (IVF) treatment cycles between February 2007 and May 2013, from the Environment and Reproductive Health study, an ongoing prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed before assisted reproductive technology (ART) treatment using a validated food frequency questionnaire. Study outcomes included ovarian stimulation outcomes (endometrial thickness, estradiol levels and oocyte yield), fertilization rates, embryo quality measures and clinical outcomes (implantation, clinical pregnancy and live birth rates). We used generalized linear mixed models with random intercepts to account for multiple ART cycles per woman while simultaneously adjusting for age, caloric intake, BMI, race, smoking status, infertility diagnosis, protocol type, alcohol intake and dietary patterns. MAIN RESULTS AND THE ROLE OF CHANCE: The age- and calorie-adjusted difference in live birth between women in the highest (>3.0 servings/day) and lowest (<1.34 servings/day) quartile of dairy intake was 21% (P = 0.02). However, after adjusting for additional covariates, this association was observed only among women ≥35 years (P, interaction = 0.04). The multivariable-adjusted live birth (95% CI) in increasing quartiles of total dairy intake was 23% (11, 42%), 39% (24, 56%), 29% (17, 47%) and 55% (39, 69%) (P, trend = 0.02) among women ≥35 years old, and ranged from 46 to 54% among women <35 years old (P, trend = 0.69). There was no association between dairy intake and any of the intermediate outcomes. LIMITATIONS, REASONS FOR CAUTION: The lack of a known biological mechanism linking dairy intake to infertility treatment outcomes calls for caution when interpreting these results and for additional work to corroborate or refute them. WIDER IMPLICATIONS OF THE FINDINGS: Dairy intake does not appear to harm IVF outcomes and, if anything, is associated with higher chances of live birth. STUDY FUNDING/COMPETING INTERESTS: This work was supported by NIH grants R01-ES009718 and R01ES000002 from NIEHS, P30 DK046200 from NIDDK and T32HD060454 from NICHD. M.C.A. was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. She is currently employed at the Nestlé Research Center, Switzerland and completed this work while at the Harvard School of Public Health. The other authors declare no conflicts of interest.

Relaparotomies for abdominal sepsis--why, when, how? A collective review.

Despite numerous reports in the recent literature, the indications for relaparotomies for abdominal sepsis are still not clear cut. In particular there is no consensus concerning the decision or the optimal time to reoperate. There is more benefit than hazard in a low threshold for surgically exploring the critically ill patient, especially the one who cannot easily be assessed clinically. Exclusive reliance on radiological confirmation of ongoing sepsis might delay diagnosis and treatment. Relaparotomy at regular intervals (preferably every 24-48 hours) should be done until complete eradication of sepsis is achieved.

Primary repair for colonic gunshot wounds.

BACKGROUND: Penetrating injuries of the colon have been managed traditionally by diverting colostomy. Recently, a trend towards primary repair has been observed, particularly for knife injuries. The purpose of this study is to evaluate the safety of primary repair for colonic gunshot wounds in the presence of certain clinical risk factors. METHODS: A retrospective analysis of 223 patients with colonic bullet injuries in a period of 3 years (1990-93) was performed. RESULTS: Of 223 patients with colonic trauma, 168 were primarily repaired (group A) and 55 underwent a colostomy (group B). Intra-abdominal septic complications occurred in 5.9% of group A patients and 10.9% of group B patients (P > 0.05, NS). These patients were, furthermore, stratified according to well-known risk factors for the development of complications, namely, site of injury, presence of shock on admission, degree of faecal contamination and number of associated injuries. We were unable to find any statistically significant differences in intra-abdominal septic complication rates between patients treated with primary repair and patients treated with colostomy. CONCLUSIONS: Primary repair seems to be a safe therapeutic option for gunshot wounds of the colon. Even in the presence of the above-mentioned risk factors, colostomy may be avoided in most cases as primary repair does not appear to be associated with higher complication rates.

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.

Outcome of a strict policy on emergency department thoracotomies.

OBJECTIVE: To audit emergency department thoracotomies from January 1981 to May 1993. DESIGN: Retrospective analysis of case records. SETTING: A large (3000-bed) tertiary care academic hospital; the department of general surgery (including trauma) consists of 360 beds. PATIENTS: All patients who underwent a thoracotomy in the emergency department during the above period. INTERVENTION: An emergency department thoracotomy was performed on trauma patients with recordable vital signs and rapid deterioration and on patients with uncontrollable bleeding or profound hypotension not responsive to resuscitation. The procedure was performed either on the resuscitation trolley in the emergency department or in the adjacent operating room. MAIN OUTCOME MEASURES: Survival and subsequent neurological function after thoracotomy. RESULTS: There were 312 stab injuries, 358 gunshot injuries, and 176 blunt injuries. Survival occurred in 26 stab-wound cases (8.3%), in 16 gunshot cases (4.4%), and in one blunt injury case (0.6%). There was one patient with neurological impairment in each of the three injury groups. Those with penetrating chest injuries had the best survival rate (20%), and the survival rate for penetrating abdominal trauma was 6.8%. CONCLUSIONS: Emergency department thoracotomies have a definite role in the management of trauma patients. The best results are obtained in patients with penetrating chest injuries.

Selective surgical management in penetrating neck injuries.

OBJECTIVE: To evaluate selective operative management in penetrating neck trauma. DESIGN: A chart review. SETTING: A university-affiliated hospital in Johannesburg, South Africa. PATIENTS: All adults admitted to the hospital between January 1988 and June 1993 with a penetrating neck wound. Excluded were patients in whom there was no suspicion of an occult injury that might need further investigation. There were 755 patients in the study. INTERVENTIONS: Immediate surgical exploration (group A, 613 patients) and observation with constant monitoring (group B, 142 patients). MAIN OUTCOME MEASURES: Unnecessary explorations in group A and missed significant injuries in group B. RESULTS: In group A there was a 3% incidence of unnecessary explorations, and 4.2% of the patients died. In group B there was a 9.1% incidence of missed injuries, and 2.8% of the patients died as a result of the delayed diagnosis. Overall the death rate was 4%. CONCLUSION: Selective operative intervention for penetrating neck trauma results in fewer negative explorations and a death rate comparable to those of series that support mandatory neck exploration.

Penetrating trauma to the heart: a relatively innocent injury.

BACKGROUND: The purpose of this study was to examine the mortality rate of penetrating cardiac trauma in a large urban hospital. METHODS: This was a retrospective study over a period of 5 years and 5 months of all patients admitted alive with a stab or a gunshot cardiac injury. RESULTS: There were 310 patients with a stab wound and 63 with a gunshot wound. The overall mortality rate was 19%. The mortality rates for the stab and the gunshot groups were 13% and 50.7%, respectively. In the 296 patients with a cardiac stab wound confined to a single chamber and with no other associated extracardiac injury the mortality rate was 8.5%. CONCLUSIONS: An isolated cardiac stab wound is a relatively innocent injury in a patient at a hospital accustomed to managing penetrating trauma expeditiously.

Penetrating injuries of the subclavian vessels.

A study was made of 76 patients with subclavian vessel injury. The mechanism of trauma was stabbing in 40 patients (53 per cent) and gunshot in 36 (47 per cent). There were marked differences between the two groups in clinical presentation, operative management and outcome. The group with gunshot injury was characterized by a more immediate threat to life, and a greater need for a median sternotomy and use of interposition grafts. The mortality rate in patients with gunshot wounds was more than twice that in the group with stab injury.

Pyloric exclusion in severe penetrating injuries of the duodenum.

This study comprises 74 patients with penetrating injuries of the duodenum. Sixty-three of these had sustained gunshot wounds, many of which were high velocity. The change in the incidence and the severity of the gunshot injuries within the last few years resulted in changes in the operative management of the duodenal wound with gradually improving results. When pyloric exclusion was added to the operative management of grade III duodenal injuries, the postoperative leakage rate was 12%. When only primary repair was done, the leakage rate was 43%. We suggest that pyloric exclusion be added to the treatment of most severe grade II and all grade III gunshot duodenal injuries. The adequacy of primary repair and pyloric exclusion in grade IV injuries requires further study.