Gestational carrier BMI and reproductive, fetal and neonatal outcomes: are the risks the same with increasing obesity?

OBJECTIVE: Data suggest that female obesity impairs uterine receptivity and increases the risk of fetal and neonatal mortality. We analyzed the reproductive outcomes of gestational carriers (GCs) undergoing donated oocytes and assisted reproductive technology according to body mass index (BMI). DESIGN: A retrospective analysis of 163 GCs undergoing 226 in vitro fertilization (IVF) and embryo transfer cycles. METHODS: GCs undergoing in vitro fertilization and embryo transfer cycles were analyzed and divided according to their BMI (healthy weight: 20-24.9 kg m(-2) (n=77 in 114 cycles); overweight: 25-29.9 kg m(-)(2) (n=55 in 71 cycles); and obese: 30-35 kg m(-)(2) (n=31 in 41 cycles)). All GCs underwent a complete medical evaluation and were cleared for pregnancy before being selected. Overweight and obese GCs also underwent a metabolic screening, including an oral glucose tolerance test and lipid profile. The main outcomes measured were clinical pregnancy and live birth rates, antenatal and neonatal outcomes. RESULTS: Clinical pregnancy and live birth rates were similar despite increasing BMI. There were no statistically significant differences in the implantation rates, clinical pregnancy rates or live birth rates per embryo transfer among patients in the three BMI groups. In the healthy weight, overweight and obese GCs, the clinical pregnancy rates per GC were 72%, 84% and 79%, and per embryo transfer rates were 52%, 49% and 56%, respectively; P=NS. The live birth rates per GC were 70%, 84% and 75%, and per embryo transfer rates were 50%, 49% and 53%, respectively; P=NS. Twin rates were similar between the groups (35%, 31% and 29%, respectively; P=NS). There were no differences in gestational diabetes, preterm admissions or cesarean section rates. Neonatal intensive care unit admissions were similar (11%, 13% and 12%, respectively; P=NS), and no maternal, neonatal or infant mortality occurred. CONCLUSIONS: These data show that increasing obesity does not impair the reproductive outcome in GC cycles. Larger sample size is indicated to verify these findings. Furthermore, this study suggests that the standard metabolic screening used for GCs may lead to selection of healthier patients compared with women of comparable BMI who conceive outside of a fertility clinic setting, indicating the metabolic profile, rather than BMI, may better explain differences in pregnancy outcomes.

Whole-body protein turnover response to short-term high-protein diets during weight loss: a randomized controlled trial.

To determine whole-body protein turnover responses to high-protein diets during weight loss, 39 adults (age, 21±1 years; VO2peak, 48±1 ml kg(-1) min(-1); body mass index, 25±1 kg m(2)) were randomized to diets providing protein at the recommend dietary allowance (RDA), 2 × -RDA or 3 × -RDA. A 10-day weight maintenance period preceded a 21-day, 40% energy deficit. Postabsorptive (FASTED) and postprandial (FED) whole-body protein turnover was determined during weight maintenance (day 10) and energy deficit (day 31) using [1-(13)C]leucine. FASTED flux, synthesis and breakdown were lower (P<0.05) for energy deficit than weight maintenance. Protein flux and synthesis were higher (P<0.05) for FED than FASTED. Feeding attenuated (P<0.05) breakdown during weight maintenance but not energy deficit. Oxidation increased (P<0.05) between dietary protein levels and feeding stimulated oxidation, although oxidative responses to feeding were higher (P<0.05) for energy deficit than weight maintenance. FASTED net balance decreased between dietary protein levels, but in the FED state, net balance was lower for 3 × -RDA as compared with RDA and 2 × -RDA (diet-by-state, P<0.05). Consuming dietary protein at levels above the RDA, particularly 3 × -RDA, during short-term weight loss increases protein oxidation with concomitant reductions in net protein balance.

Breath carbon stable isotope ratios identify changes in energy balance and substrate utilization in humans.

Rapid detection of shifts in substrate utilization and energy balance would provide a compelling biofeedback tool for individuals attempting weight loss. As a proof of concept, we tested whether the natural abundance of exhaled carbon stable isotope ratios (breath δ(13)C) reflects shifts between negative and positive energy balance. Volunteers (n=5) consumed a 40% energy-restricted diet for 6 days followed by 50% excess on day 7. Breath was sampled immediately before and 1 h and 2 h after breakfast, lunch and dinner. Exhaled breath δ(13)C values were measured by cavity ring-down spectroscopy. Using repeated measures analysis of variance (ANOVA) followed by Dunnett's contrasts, pre-breakfast breath values on days 2-6 were compared with day 1, and postprandial day 7 time points were compared with pre-breakfast day 7. Energy restriction diminished pre-breakfast breath δ(13)C by day 3 (P<0.05). On day 7, increased energy intake was first detected immediately before dinner (-23.8±0.6 vs -21.9±0.7‰, P=0.002 (means±s.d.)), and breath δ(13)C remained elevated at least 2 h post dinner. In conclusion, when shifting between negative and positive energy balance, breath δ(13)C showed anticipated isotopic changes. Although additional research is needed to determine specificity and repeatability, this method may provide a biomarker for marked increases in caloric intake.

Effect of clothing weight on body weight.

BACKGROUND: In clinical settings, it is common to measure weight of clothed patients and estimate a correction for the weight of clothing, but we can find no papers in the medical literature regarding the variability in clothing weight of adults with weather, season and gender. METHODS: Fifty adults (35 women) were weighed four times during a 12-month period with and without clothing. Clothing weights were determined and regressed against minimum, maximum and average daily outdoor temperature. RESULTS: The average clothing weight (±s.d.) throughout the year was significantly greater in men than in women (1.2±0.3 vs 0.8±0.3 kg, P<0.0001). The average within-person minimum and the average within-person maximum clothing weights across the year were 0.9±0.2 and 1.5±0.4 kg for men, and 0.5±0.2 and 1.1±0.4 kg for women, respectively. The within-person s.d. in clothing weight was 0.3 kg for both men and women. Over the 55 °C range in the lowest to the highest outdoor temperatures, the regressions predicted a maximal change in clothing weight of only 0.4 kg in women and 0.6 kg in men. CONCLUSION: The clothing weight of men is significantly greater than that of women, but there is little variability throughout the year. Therefore, a clothing adjustment of approximately 0.8 kg for women and 1.2 kg for men is appropriate regardless of outdoor temperature.

Safety profile of conjugated linoleic acid in a 12-month trial in obese humans.

Conjugated linoleic acid (CLA) is marketed in numerous commercially available dietary supplements, but few studies have looked at the long-term safety of this product. The current study evaluated the safety of one CLA product (Clarinol) over a one-year period in obese humans who were generally healthy. This was a randomized, double-blind study consisting of three phases in which subjects were given 6 g/day of CLA or placebo. Phase 1 was a low calorie diet (13 kcal/kg desirable weight) for 12 weeks or until 10-20% of initial body weight was lost. In phase 2, from weeks 12 to 28, subjects were re-fed a diet providing 25-30 kcal/kg of desirable body weight. Phase 3 was open label, with subjects from both groups taking CLA from weeks 28 to 52. At biweekly visits, subjects completed a questionnaire evaluating side effects and adverse events. Blood was taken for assay of liver function, glucose, insulin, serum lipids, blood counts, and general chemistry. Overall, body composition did not differ between groups. Laboratory tests showed no adverse effects of CLA. Adverse events and side effects were less in the CLA group compared to placebo. We conclude that CLA as Clarinol is safe for use in obese humans for at least one year.

Increased vegetable and fruit consumption during weight loss effort correlates with increased weight and fat loss.

BACKGROUND: Individuals who focused on calorie counting lost more weight than those who focused on increasing vegetable and fruit (V&F) intake in a weight loss program. We now present serum carotenoid data (biomarkers of V&F intake) from both groups and test whether these biomarkers correlate with changes in weight and body fat. DESIGN: Sixty obese volunteers were randomized to one of the following weight loss programs: 500 kcal per day reduction (Reduction) or a focus on consuming eight vegetables per day and 2-3 fruits per day (HiVeg). Volunteers in the Reduction group were 36.8±10.3 years with a body mass index of 33.5; 83% were white, 17% chose not to report race; 70% were not Hispanic or Latino, 13% were Hispanic or Latino and 17% chose not to report ethnicity. Volunteers in the HiVeg group were 30.4±6.6 years with a body mass index of 33.2: 74% white, 11% Asian, 5% black or African American, 5% multiracial and 5% chose not to report race; 89% were not Hispanic or Latino, 5% were Hispanic or Latino and 5% chose not to report ethnicity. Subjects were taught basic nutrition principles, received breakfast and lunch 5 days per week for 3 months, meals 2 days per week during month 4, then regular phone calls to month 12. RESULTS: Total serum carotenoid concentrations increased from baseline to 3 months and remained elevated at 12 months, but there was no difference between groups. Changes in weight, fat and % fat correlated negatively with serum carotenoid concentrations. CONCLUSION: Increased serum carotenoids (a biomarker for V&F intake) correlated with improved weight and fat loss indicating that increased V&F consumption is an appropriate strategy for weight loss. However, in light of the fact that the Reduction group lost more weight, the consumption of increased V&F for the purpose of weight loss should happen within the context of reducing total caloric intake.

Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.

BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.

Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome.

INTRODUCTION: Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI). OBJECTIVE: To determine whether PA females have altered body fat distribution. DESIGN: Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation. RESULTS: There were no differences in age, weight, BMI or somatometrics. LPA females had approximately 20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P< or =0.05). LPA females also had approximately 40% more CT-determined non-visceral abdominal fat than EPA or control females (P< or =0.05). The volume of visceral fat was similar among the three groups. EPA (R (2)=0.94, P< or =0.01) and LPA (R (2)=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R (2)=0.98, P< or =0.001). There was a positive relationship between basal insulin and total body (R (2)=0.95, P< or =0.007), total abdominal (R (2)=0.81, P< or =0.04) and visceral (R (2)=0.82, P< or =0.03) fat quantities in EPA, but not control females. CONCLUSIONS: Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.

Conjugated linoleic acid: implications for human health.

Conjugated linoleic acid (CLA) is being sold as a panacea that has the capability of reducing or eliminating cancer, preventing heart disease, improving immune function, and altering body composition to treat obesity or build lean body mass. Unfortunately, there has been very little published human research on CLA. This review will examine the literature on CLA and discuss the animal research on which the above claims are made. The limited human studies will be presented with an evaluation of the potential uses of CLA for human health and disease.

CLA reduces antigen-induced histamine and PGE(2) release from sensitized guinea pig tracheae.

Conjugated linoleic acid (CLA) has been shown to enhance immune reactions such as lymphocyte blastogenesis and delayed-type hypersensitivity. We investigated the role of CLA in type I (immediate) hypersensitivity, using a guinea pig tracheal superfusion model for measuring antigen-induced airway smooth muscle contraction and inflammatory mediator release. Female Hartley guinea pigs were fed a diet supplemented with 0.25 g corn oil or linoleic acid/100 g of diet (control) or 0.25 g CLA/100 g of diet for at least 1 wk before and during active sensitization to ovalbumin antigen. Tracheae from sensitized guinea pigs were suspended in air-filled water-jacketed (37 degrees C) tissue chambers in a superfusion apparatus. Tracheae were superfused with buffer containing antigen, and tissue contraction was recorded. Superfusate was collected at 90-s intervals for evaluation of histamine and PGE(2) release. CLA did not affect antigen-induced tracheal contractions when expressed as gram contraction per gram tissue. CLA significantly reduced antigen-induced histamine and PGE(2) release. CLA appears to decrease release of some inflammatory mediators during type I hypersensitivity reactions.