Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer.

STUDY QUESTION: Is supraphysiologic estradiol (E2) an independent predictor of low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET) cycles? SUMMARY ANSWER: Our results suggest that E2 > 2500 pg/ml is an independent predictor for LBW in full-term singletons born to normal responder patients undergoing fresh IVF-ET cycles. WHAT IS KNOWN ALREADY: The pathogenesis of LBW in IVF singletons remains unknown. However, recent studies have suggested that the hyperestrogenic milieu generated during ovarian stimulation may create a sub-optimal peri-implantation environment, leading to placental dysfunction, and therefore, LBW. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of normal responder patients, <40 years old, undergoing fresh IVF-ET cycles resulting in live singleton births between January 2005 and June 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 6419 patients had live births after fresh IVF-ET during the study period, of which 2348 (36.6%) patients were excluded due to multiple gestation, vanishing twins or incomplete records. Perinatal outcomes recorded for all patients included birth weight, gestational age (GA) at delivery, mode of delivery and gender. Term birth, preterm birth (PTB) and LBW incidence proportions were plotted against E2 level on the day of trigger. The term LBW incidence proportion (i.e. singletons born at GA ≥ 37 weeks with birth weight <2500 g) was considered the primary outcome of interest. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4071 patients with live singleton births were included. The median age, BMI, E2 level and birth weight for the study cohort was 36 (33-39) years, 22.3 (20.4-25.0) kg/m2, 1554 (1112.7-2179) pg/ml and 3289 (2920-3628) g, respectively. The incidence proportion of LBW rose from 6.4% (E2 2001-2500 pg/ml) to 20.7% (E2 3501-4000 pg/ml), without a corresponding rise in the incidence proportion of PTB. The odds of term LBW with E2 > 2500 pg/ml were 6.1-7.9 times higher compared to the referent E2 group. Multivariable logistic regression analysis revealed that E2 was an independent predictor for term LBW, even after adjusting for age, BMI, race, parity, infertility diagnosis, duration of ovarian stimulation, gonadotropin dosage and method of insemination (adjusted odds ratio 10.8, 95% CI 9.2-12.5). Receiver operating characteristic analysis generated an AUC estimate of 0.85 for E2 level as a predictor of LBW. LIMITATIONS REASONS FOR CAUTION: The current study did not include analyses of hypertensive disorders of pregnancy or placental abnormalities. Furthermore, all patients were normal responders and of normal BMI, possibly limiting the overall generalizability of the study. Finally, as with any retrospective study, prospective data are required to validate the role of E2 in predicting LBW. WIDER IMPLICATIONS OF THE FINDINGS: Our results emphasize the importance of minimizing the supraphysiologic elevations of E2 levels during ovarian stimulation in fresh IVF-ET cycles. This, in turn, can optimize the early peri-implantation environment and mitigate adverse perinatal outcomes such as LBW. STUDY FUNDING/COMPETING INTEREST(S): Dr Paul J. Christos was partially supported by the following grant: Clinical and Translational Science Center at Weill Cornell Medical College (UL1-TR000457-06). TRIAL REGISTRATION NUMBER: N/A.

Evaluation of skeletal muscle regeneration in experimental model after malnutrition / Avaliação da regeneração do músculo esquelético em modelo experimental após desnutrição

Abstract The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-β1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.

Resumo O objetivo do presente estudo foi analisar a regeneração muscular após criolesão no músculo tibial anterior de ratos jovens desnutridos e recuperados. Foram utilizados 40 ratos da linhagem Wistar, divididos em 2 grupos: ratos nutridos receberam dieta normoproteica (14% de caseína) por 90 dias; e ratos desnutridos e recuperado submetidos a duas fases nutricionais pós-desmame, correspondendo a 45 dias de desnutrição com dieta hipoproteica (6% caseína), seguida por 45 dias de dieta normoproteica (14% caseína). Ao completar a fase de recuperação, todos os animais foram submetidos à criolesão no músculo tibial anterior direito e a eutanasia ocorreu 7, 14 e 21 dias após a lesão. A quantidade de tecido conjuntivo e a área de inflamação 14 dias pós-lesão foi maior no grupo desnutrido, recuperado e lesado (MRI – malnourished, recovered and injured group) (p < 0,05). A área de secção transversa (AST) das fibras regeneradas do grupo MRI foi menor (p < 0,05). O conteúdo das proteínas MyoD e Miogenina foi maior no grupo nutridos e lesados. A citocina TGF-β1 não apresentou diferença entre os grupos. O protocolo proposto foi eficaz para demonstrar alterações no processo de regeneração do músculo tibial anterior de ratos jovens, atrasando o reparo muscular mesmo após a recuperação nutricional.

Evaluation of skeletal muscle regeneration in experimental model after malnutrition.

The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-ß1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.