Objective Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. MethodsWe performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses.Results Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence.Conclusion This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.

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Many of the sex-differentiated functions of the liver of adult male rats depend upon the occurrence of neonatal androgen imprinting, a brief surge of androgen early in life. We investigated whether androgen imprinting is necessary for the development and maintenance of levels of a microsomal enzyme, estrogen-2-hydroxylase (E-20Hase), and a male-specific cytosolic estrogen binder (MEB) which are higher in adult male than in adult female rats. Cimetidine, a weakly antiandrogenic H2 blocker, was administered to pregnant and lactating rats from day 12 of gestation through weaning on day 21. Livers of male progeny, 120-150 days of age, were assayed for E-2OHase and MEB activity; a maternal dose equivalent to 2.5 times the usual human dose inhibited MEB activity in the levels of the offspring by 40% but had no effect on E-2OHase. However, a higher dose (5 times the human dose) was effective in reducing the E-2OHase activity by 50%. Rats whose mothers had received either no drug or an equivalent dose of ranitidine, another H2 blocker without antiandrogenic activity, were used as controls. The groups were not different in hepatic cytosolic androgen receptor content, body weight, or serum testosterone. In other studies, the requirement of neonatal androgen imprinting for full expression of adult levels of MEB and E-2OHase was determined. Female rats, which have low levels of E-2OHase and undetectable levels of MEB, were given androgen on day 1, on day 60 after ovariectomy, or at both times. Levels of E-2OHase equivalent to those in adult males were induced in females receiving both androgen treatments, whereas either treatment alone induced E-2OHase to the level of that in males castrated at adulthood or neonatally, which is about 50% that in normal male controls. In addition, MEB levels were induced in females to 85% of that in normal males by both androgen treatments and to 50% by administration of androgen to adult females or to adult males castrated neonatally. Administration of androgen to females during the neonatal period only did not induce MEB. We conclude that both MEB and E-2OHase require androgen imprinting for full expression in adult male rats.

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embryos that were obtained, the blastocyst retrieval rate, the good-quality blastocyst retrieval rate, the pregnancy rate, the clinical pregnancy rate, and live birth rate.RESULTS: The mean age was 40.4 AE 0.9 years. The mean AFC, the number of follicular flushings, the oocytes retrieved, and the number of embryos that were obtained were significantly lower for the endometrioma-containing ovaries than for the contralateral intact ovaries (Table ). No significant differences were found with respect to the rate of blastocyst retrieval, the rate of good-quality blastocyst retrieval. The total pregnancy rate, the clinical pregnancy rate, or the live birth rate were not significantly different.CONCLUSIONS: Small endometriomas with average age 40 reduce ovarian reserves but do not significantly affect pregnancy rates. The decision to transfer an embryo from an endometrioma-contaiong ovary or from a contralateral intact ovary may also not influence the pregnancy rate.Comparing IVF/ICSI outcome in endometyrioma and in the contralateral intact ovary