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.

Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.

PURPOSE: We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. METHODS: This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. RESULTS: Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2 years vs. 36.5 years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3 kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3 IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). CONCLUSION: Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.

Should there be an "AI" in TEAM? Embryologists selection of high implantation potential embryos improves with the aid of an artificial intelligence algorithm.

PURPOSE: A deep learning artificial intelligence (AI) algorithm has been demonstrated to outperform embryologists in identifying euploid embryos destined to implant with an accuracy of 75.3% (1). Our aim was to evaluate the performance of highly trained embryologists in selecting top quality day 5 euploid blastocysts with and without the aid of a deep learning algorithm. MATERIALS AND METHODS: A non-overlapping series of 200 sets of day 5 euploid embryo images with known implantation outcomes was distributed to 17 highly trained embryologists. One embryo in each set was known to have implanted and one failed implantation. They were asked to select which embryo to transfer from each set. The same 200 sets of embryos, with indication of which embryo in each set had been identified by the algorithm as more likely to implant was then distributed. Chi-squared, t-test, and receiver operating curves were performed to compare the embryologist performeance with and without AI. RESULTS: Fourteen embryologists completed both assessments. Embryologists provided with AI results selected successfully implanted embryos in 73.6% of cases compared to 65.5% for those selected using visual assessments alone (p < 0.001). All embryologists improved in their ability to select embryos with the aid of the AI algorithm with a mean percent improvement of 11.1% (range 1.4% to 15.5%). There were no differences in degree of improvement by embryologist level of experience (junior, intermediate, senior). CONCLUSIONS: The incorporation of an AI framework for blastocyst selection enhanced the performance of trained embryologists in identifying PGT-A euploid embryos destined to implant.

The impact of male factor infertility on early and late morphokinetic parameters: a retrospective analysis of 4126 time-lapse monitored embryos.

STUDY QUESTION: Is there an effect of male factor infertility (MFI) on either early or late morphokinetic parameters obtained during embryonic culture to blastocyst stage in a time-lapse imaging (TLI) incubator? SUMMARY ANSWER: Neither mild nor severe MFI had an impact on overall time to blastocyst or duration of individual cleavage stages in the total embryo population. WHAT IS KNOWN ALREADY: Prior studies have suggested that paternal DNA and sperm quality affect embryo morphokinetic parameters, but the impact of MFI is not fully understood. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, at a major academic fertility centre, included 536 couples (women, ≤44 years of age) undergoing IVF between September 2013 and September 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 4126 embryos cultured to the blastocyst stage in a TLI-monitored incubator were retrospectively reviewed. Embryos derived from the sperm of men with MFI were compared with those derived from patients with other infertility diagnoses. Generalized fixed and random effects models, t-test and χ2 were used as appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: Couples with MFI had a higher rate of ICSI utilization and fewer usable embryos on average, and the men were older compared with couples with other diagnoses. Additionally, the women in MFI couples were younger and had higher antral follicle counts (AFCs) and higher anti-Müllerian hormone (AMH) levels compared with the other women undergoing IVF. When controlling for maternal and paternal ages, AMH and fertilization method (conventional IVF versus ICSI), neither mild nor severe MFI affected duration of individual cleavage stages or overall time to the blastocyst stage, when all or only usable embryos were examined (coefficient 0.44 hours in all embryos, P = 0.57; coefficient 0.39 hours in usable embryos, P = 0.60). Whether the sperm was surgically extracted similarly had no significant effect on embryo morphokinetic parameters. When the fertilization method was assessed independently, ICSI lengthened the overall time to blastocyst stage by 1.66 hours (P = 0.03) on average, primarily due to an increase in duration of the time from 5-cell embryo stage to early blastulation (P5SB). LIMITATIONS, REASONS FOR CAUTION: This large cohort study avoided embryo selection bias due to random assignment of embryos to the TLI incubators. However, our findings may not be generalizable to groups under-represented in our clinic population. Future studies should also evaluate the impact of male hormonal status and detailed sperm morphology, such as head versus flagellum defects, on embryo morphokinetic development. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that the fertilization method rather than MFI per se impacts time to early blastulation. The clinical implications of this effect on embryo development warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S): There were no sources of funding for this study. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The effect of day 2 versus day 3 embryo transfer on early pregnancy outcomes in women with a low yield of fertilized oocytes.

PURPOSE: To evaluate the differences in implantation and pregnancy rates when embryo transfer occurs on D2 versus D3 in women with a low yield of fertilized oocytes. METHODS: A total of 156 IVF/ICSI cycles from 141 women at an academic fertility center were analyzed in a retrospective fashion. Women with a low number of fertilized oocytes (≤ 2 two pronuclei (2PN) stage zygotes) who had their fresh embryo transfer on D2 or D3 were included in the study. Positive pregnancy test per IVF cycle (PPT), clinical pregnancy rate (CPR), spontaneous abortion rate (SABR), and implantation rate (IMPR) were the main outcome measures assessed. Mann-Whitney U test and χ2 test were used as appropriate. A generalized linear mixed effect model adjusted for relevant covariates was conducted. P < 0.05 was considered significant. RESULTS: Patients having their embryo transfer on D2, when compared to those who had a D3 embryo transfer, experienced similar PPT [30.8 vs. 28.2%, respectively; adjusted OR (95%CI): 0.49 (0.16, 1.52)], CPR [26.9 vs. 25.6%, respectively; adjusted OR (95%CI): 0.44 (0.12, 1.67)], and IMPR [17.3 vs. 16.7%, respectively; adjusted ß (95%CI) - 5.6% (- 15.0, 3.9)]. CONCLUSION: Our findings suggest that transferring embryos on D2 versus D3 in women with a limited number of 2PN stage zygotes does not affect early pregnancy outcomes. These results indicate that there can be some flexibility in scheduling the day of transfer at the convenience of both the patient and the center.

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.

Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment.

INTRODUCTION: Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners. METHODS: This analysis included male-female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners' cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models. RESULTS: Two-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P=0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P=0.01 and P=0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P=0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes. CONCLUSION: Selected phthalates were associated with decreased odds of implantation and live birth.

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.

Fetal death after trauma in pregnancy.

Trauma in pregnancy places the mother and fetus at risk. The objective of this study is to identify risk factors independently associated with acute termination of pregnancy and/or fetal mortality after trauma. The medical and trauma registry records of 80 injured pregnant patients were reviewed. Data were collected and then analyzed by univariate and multivariate analysis. Three patients died (3.7%), 23 had the pregnancy acutely terminated (30%), and 14 suffered fetal death (17.5%). The only independent risk factors for fetal mortality were an Injury Severity Score (ISS) > or =9 and a nonviable pregnancy (<23 weeks). The combination of both risk factors increased the likelihood of fetal mortality by fivefold over that of patients without either risk factor. Maternal hemodynamic parameters did not predict fetal loss. Two patients lost their fetuses despite insignificant trauma (ISS = 1) and normal hemodynamic parameters, whereas eight delivered normal babies despite major trauma (ISS > or = 16). Hemodynamic stability on admission does not predict fetal mortality. Although the presence of moderate to severe injuries (ISS > or = 9) increases the likelihood of fetal mortality, this complication may occur even with insignificant trauma. Close maternal and fetal monitoring is justified, regardless of maternal hemodynamic presentation or severity of injury.

The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study.

OBJECTIVE: The study compared the efficacy of methylprednisolone with that of promethazine for the treatment of hyperemesis gravidarum. STUDY DESIGN: Patients with a normal-appearing intrauterine pregnancy of < or = 16 weeks' gestation with hyperemesis gravidarum (persistent vomiting and large ketonuria despite outpatient therapy) were admitted to the hospital for continuous intravenous hydration and offered participation in the study. Patients meeting study criteria were randomly assigned to receive (from identical-appearing dispensers packaged in advance with a 2-week supply) oral methylprednisolone, 16 mg 3 times daily, or oral promethazine, 25 mg 3 times daily. After 3 days the methylprednisolone was tapered completely during the course of 2 weeks whereas the promethazine was continued without change for 2 weeks. For patients who continued to vomit after 2 days the study medication was discontinued. Patients receiving study medication at discharge continued to take the remainder of the assigned medication from the packaged pill dispensers. Patients were followed up weekly. The study outcomes, as established in advance, were (1) improvement of symptoms within 2 days of starting therapy and (2) readmission for hyperemesis within 2 weeks of starting the study. RESULTS: Forty patients were enrolled in the course of 11 months (20 per group). There were no significant differences between the groups with respect to maternal age, gravidity, parity, gestational age at entry, number of previous admissions, or > 5% body weight loss. Three patients in the methylprednisolone group and 2 in the promethazine group failed to stop vomiting within 2 days. One patient from the promethazine group was unavailable for follow-up. No patient from the methylprednisolone group but 5 of the 17 patients receiving promethazine were readmitted for hyperemesis within 2 weeks of discharge (P = .0001). There were no adverse effects noted for either drug. CONCLUSION: A short course of methylprednisolone is more effective than promethazine for the treatment of hyperemesis.

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.

Decision making in multifetal pregnancy reduction for triplets.

The objective of this article is to examine the literature that forms the basis for counseling couples with higher order multiple gestation with regard to multifetal pregnancy reduction and present the data on expectant management of multiple gestations and multiple gestations managed with multifetal pregnancy reduction. The data sources for this article are computer-assisted search of the literature. Eighty-three articles, mainly published after 1989, and reporting on the natural history, management, and outcome of multifetal pregnancies, were reviewed. We analyze and present the data on expectant management of multiple gestations and multiple gestations managed with reduction to twins and then use the hypothetical patient-oriented questions listed below to organize the data. There is a general consensus that reducing triplets to twins results in significant secondary benefits: lower cost and fewer days in hospital and a decrease in a variety of moderate morbidities associated with prolonged hospitalizations and preterm delivery for mother and baby. However, it is not clear that couples are more likely to take home a healthy baby, if they undergo multifetal pregnancy reduction.

The McRoberts' maneuver for the alleviation of shoulder dystocia: how successful is it?

OBJECTIVE: Our purpose was to determine the rate of success of the McRoberts' maneuver as the initial treatment for shoulder dystocia and to compare the rate of maternal and neonatal morbidity with those cases of shoulder dystocia requiring additional obstetric maneuvers. A secondary goal was to assess those factors associated with successful McRoberts' maneuvers. STUDY DESIGN: A retrospective review of shoulder dystocia cases occurring between 1991 and 1994 was performed. The identified cases were divided into two groups on the basis of the maneuvers used to relieve the shoulder dystocia. The first group comprised cases in which the McRoberts' maneuver was used as the sole treatment and the second group consisted of cases in which additional maneuvers were subsequently used. Exclusion criteria included lack of documentation concerning the maneuvers used or cases in which the McRoberts' maneuver was not the initial technique used. The two groups were compared with respect to various antepartum, intrapartum, and neonatal characteristics. RESULTS: During the study period we identified 250 cases of shoulder dystocia among 44,072 vaginal deliveries, for an incidence of 0.57%. Of these, 236 cases (94%) fulfilled entry criteria. The McRoberts' position alone successfully alleviated the shoulder dystocia in 98 cases (42%). In the group of cases where the McRoberts' maneuver was the sole maneuver used, there were significantly lower mean birth weights (p = 0.008), shorter durations of the active phase of labor (p = 0.009), and shorter second stages (p < 0.0001). In the group of cases that required additional maneuvers to relieve the shoulder dystocia, there was a trend toward an increased incidence of postpartum hemorrhage and brachial plexus injury (p = 0.07). CONCLUSIONS: These data suggest that the McRoberts' maneuver is associated with a significant degree of success in relieving shoulder dystocia and may be associated with decreased morbidity compared with other maneuvers. On the basis of these findings, we recommend the McRoberts' maneuver as the initial technique for disimpaction of the anterior shoulder.

Penetrating injuries of the abdominal inferior vena cava.

This is a retrospective study of 74 patients with penetrating injuries of the abdominal inferior vena cava; the cause of injury was gunshot in 91% and stabbing in 9%. Of the patients, 77% underwent lateral venorrhaphy, 5% underwent infrarenal ligation of the inferior vena cava (IVC), and 18% died perioperatively before any caval repair could be carried out. There was an overall perioperative mortality of 39%. Persistent shock, the site of the venous injury, particularly in the retrohepatic position, and the number of associated vascular injuries were directly related to mortality. Irrespective of the improvements in resuscitation and the various operative methods available, penetrating trauma of the abdominal IVC remains a life-threatening injury.

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.

Penetrating ureteral injuries: the impact of associated injuries on management.

The ideal management for penetrating ureteral trauma is primary repair, but the effect of other abdominal injuries might preclude this. We attempted to determine what factors could be used to predict a poor outcome of a ureteral anastomosis, so that the initial management can be modified appropriately. The case notes of 41 patients treated for penetrating ureteral trauma were studied retrospectively. Any factors that could influence postoperative complications and outcome were statistically analyzed in order to determine which could be used pre- or intraoperatively to indicate a poor prognosis for the ureteral anastomosis. The presence of shock on admission (P = 0.013), intraoperative bleeding (P = 0.006), colonic injury and specifically injury requiring colectomy (P = 0.006) were associated with a high complication and mortality rate. Patients presenting with penetrating ureteral trauma who are severely shocked and have complicated intraoperative hemostasis and patients who require colectomy should not have a primary ureteral anastomosis, but rather initial ureteral exteriorization or even nephrectomy.

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.