Maternal exposure to busulfan reduces the cell number in the somatosensory cortex associated with delayed somatic and reflex maturation in neonatal rats.

Busulfan is a bifunctional alkylating agent used for myeloablative conditioning and in the treatment of chronic myeloid leukemia due to its ability to cause DNA damage. However, in rodent experiments, busulfan presented a potential teratogenic and cytotoxic effect. Studies have evaluated the effects of busulfan on fetuses after administration in pregnancy or directly on pups during the lactation period. There are no studies on the effects of busulfan administration during pregnancy on offspring development after birth. We investigated the effects of busulfan on somatic and reflex development and encephalic morphology in young rats after exposure in pregnancy. The pregnant rats were exposed to busulfan (10 mg/kg, intraperitoneal) during the early developmental stage (days 12-14 of the gestational period). After birth, we evaluated the somatic growth, maturation of physical features and reflex-ontogeny during the lactation period. We also assessed the effects of busulfan on encephalic weight and cortical morphometry at 28 days of postnatal life. As a result, busulfan-induced pathological changes included: microcephaly, evaluated by the reduction of cranial axes, delay in reflex maturation and physical features, as well as a decrease in the morphometric parameters of somatosensory and motor cortex. Thus, these results suggest that the administration of a DNA alkylating agent, such as busulfan, during the gestational period can cause damage to the central nervous system in the pups throughout their postnatal development.

Sexual dysfunction in infertile women: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the prevalence of sexual dysfunction and Female Sexual Function Index (FSFI) score in women with infertility. STUDY DESIGN: A systematic search of the literature was conducted using PubMed, EMBASE, IBECS, and LILACS. The search was limited to articles published from January 2000 to September 2016, without language restriction. Data were analyzed using Stata 12.0. Random effects meta-analyses in weighted mean difference (WMD) were performed for six comparative studies (infertility versus fertility). Heterogeneity was estimated using I2. Moreover, to explore the heterogeneity sources among the studies, meta-regression analyses were also performed. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation guidelines, and risk of bias, with a graphic funnel. RESULTS: Meta-analysis was performed in 11 of 13 comparative studies. The result indicated a significant association between an increase in sexual dysfunction and infertility in women (WMD=-0.16, 95% confidence interval=-0.254 to -0.084, p<0.001), and high heterogeneity between studies was noted (I2=98.6%, p<0.000). Meta-regression analysis did not indicate heterogeneity (I2=0.00%). We also performed a meta-analysis of individual FSFI domains in 10 studies. Infertile women had problems with lubrication, orgasm, and satisfaction. Meta-regression analysis also showed that heterogeneity had no influence on the final results of all the analyses. CONCLUSIONS: Infertility was associated with an increase in female sexual dysfunction. The most affected areas of sexual function were lubrication, orgasm, and satisfaction.