Pregnancy after Endometriosis: Maternal and Neonatal Outcomes according to the Location of the Disease.

Objective: To systematically evaluate pregnancy and labor course, obstetrical complications, and maternal and neonatal outcomes in women with endometriosis, stratifying according to the specific location of the disease. Study Design: We retrospectively analyzed our prospectively maintained obstetrical database from January 2011 to August 2014 to identify all women with a previous histological diagnosis of endometriosis who delivered at our institution (cases). We divided the cases according to the specific location of the disease (deep infiltrating endometriosis, ovarian endometriosis, and peritoneal endometriosis). As controls, we identified all unaffected women who delivered in the year 2013. To avoid the confounding effect of parity, we limited our analysis to nulliparous women. Results: A total of 118 nulliparous women with endometriosis and 1,690 nulliparous controls were identified. Women with endometriosis were significantly older, had a lower body mass index, and had a higher incidence of assisted reproductive technology. The duration of pregnancy was significantly shorter among women with endometriosis. A higher incidence of placenta previa (3.4 vs. 0.5%; p = 0.006), hypertension (11 vs. 5.9%; p = 0.04), cesarean section (41.5 vs. 24.2%; p < 0.0001), and vacuum delivery (10.1 vs. 2.9%; p = 0.006) was found in women with endometriosis. Neonatal outcomes were similar between groups. The incidence of placenta previa in patients with deep endometriosis was 11.7 versus 0.5% among controls (p < 0.0001), whereas in women with ovarian and peritoneal endometriosis, it was similar to the controls. Conclusion: Women with endometriosis have a higher incidence of vacuum delivery, cesarean section, and placenta previa compared with unaffected women. The higher risk of placenta previa is attributable exclusively to women with deep endometriosis. Neonatal outcomes are unaffected by the presence of the disease

Structures of DNA duplexes containing O-6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing pyrimidine transition mutations

N-nitrosation of glycine and its derivatives generates potent alkylating agents that can lead to the formation of O6-carboxymethylguanine (O6-CMG) in DNA. O6-CMG has been identified in DNA derived from human colon tissue, and its occurrence has been linked to diets high in red and processed meats. By analogy to O6-methylguanine, O6-CMG is expected to be highly mutagenic, inducing G to A mutations during DNA replication that can increase the risk of gastrointestinal and other cancers. Two crystal structures of DNA dodecamers d(CGCG[O6-CMG]ATTCGCG) and d(CGC[O6-CMG]A ATTCGCG) in complex with Hoechst33258 reveal that each can form a self-complementary duplex to retain the B-form conformation. Electron density maps clearly show that O6-CMG forms a Watson– Crick–type pair with thymine similar to the canonical A:T pair, and it forms a reversed wobble pair with cytosine. In situ structural modeling suggests that a DNA polymerase can accept the Watson–Crick–type pair of O6-CMG with thymine, but might also accept the reversed wobble pair of O6-CMG with cytosine. Thus, O6-CMG would permit the mis-incorporation of dTTP during DNA replication. Alternatively, the triphosphate that would be formed by carboxymethylation of the nucleotide triphosphate pool d[O6-CMG]TP might compete with dATP incorporation opposite thymine in a DNA template