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• W2074413595 abstract "The failure of antibiotic prophylaxis to reduce preterm birth in women at risk and the increased rate of preterm birth in singleton pregnancy after ART may have a common explanation: persistent bacterial endotoxin in the endometrium, reported by Kamiyama et al. as an explanation for reduced fertility. The failure of antibiotic prophylaxis to reduce preterm birth in women at risk and the increased rate of preterm birth in singleton pregnancy after ART may have a common explanation: persistent bacterial endotoxin in the endometrium, reported by Kamiyama et al. as an explanation for reduced fertility. The study by Kamiyama et al. (1Kamiyama S. Teruya Y. Nohara M. Kanazawa K. Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer.Fertil Steril. 2004; 82 (–92): 788Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar) in this issue of Fertility and Sterility has importance beyond its proximate implications for fertility care. Although gestational age at delivery is not supplied for the six successful pregnancies, the report suggests that two enigmatic observations in the recent prematurity literature may have a common cause. The increased rate of preterm and low birth weight infants in singleton pregnancies after IVF (2Jackson R.A. Gibson K.A. Wu Y.W. Crough M.S. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis.Obstet Gynecol. 2004; 103: 551-563Crossref PubMed Scopus (904) Google Scholar, 3Schieve L.A. Meikle S.F. Ferre C. Peterson H.B. Jeng G. Wilcox L.S. Low and very low birth weight in infants conceived with use of assisted reproductive technology.N Engl J Med. 2002; 346: 731-737Crossref PubMed Scopus (834) Google Scholar) and the mixed but generally disappointing results of trials of antibiotic prophylaxis to reduce the rate of preterm birth in women with genital tract infection (4Andrews W.W. Sibai B.M. Thom E.A. Dudley D. Ernest J.M. McNellis D et al.Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women.Obstet Gynecol. 2003; 101: 847-855Crossref PubMed Scopus (90) Google Scholar, 5Carey J.C. Klebanoff M.A. Hauth J.C. Hillier S.L. Thom E.A. Ernest J.M et al.Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis.N Engl J Med. 2000; 342: 534-540Crossref PubMed Scopus (531) Google Scholar, 6Kekki M. Kurki T. Pelkonen J. Kurkinen-Raty M. Cacciatore B. Paavonen J. Vaginal clindamycin in preventing preterm birth and peripartal infections o asymptomatic women with bacterial vaginosis: a randomized controlled trial.Obstet Gynecol. 2001; 97: 643-648Crossref PubMed Google Scholar, 7Klebanoff M.A. Carey J.C. Hauth J.C. Hillier S.L. Nugent R.P. Thom E.A et al.Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.N Engl J Med. 2001; 345: 487-493Crossref PubMed Scopus (346) Google Scholar, 8Lamont R.F. Duncan S.L. Mandal D. Bassett P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora.Obstet Gynecol. 2003; 101: 516-522Crossref PubMed Scopus (140) Google Scholar, 9McDonald H. Brocklehurst P. Parsons J. Vigneswaran R. Antibiotics for treating bacterial vaginosis in pregnancy.Cochrane Database Syst Rev. 2003; 2: CD000262PubMed Google Scholar, 10Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P. Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: Wiley & Sons.Google Scholar) may also be sequelae of persistent bacterial endotoxin in the endometrium. The increased incidence of preterm and low birth weight infants after ART has most often been attributed to the greater frequency of multiple gestations. However, an increase in singleton preterm births after IVF-ET is now well documented (1Kamiyama S. Teruya Y. Nohara M. Kanazawa K. Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer.Fertil Steril. 2004; 82 (–92): 788Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar). The etiology of the increased risk is not readily apparent. Proposed explanations have included abnormal placental implantation and intrauterine bleeding related to intrauterine instrumentation or embryo resorption, increased iatrogenic preterm birth, preterm cervical ripening caused by elevated relaxin levels secondary to superovulation, and factors related to the cause of the often-unexplained infertility. The finding by Kamiyama et al. (1Kamiyama S. Teruya Y. Nohara M. Kanazawa K. Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer.Fertil Steril. 2004; 82 (–92): 788Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar) of increased bacterial endotoxin in endometrial fluid and its effect on the success of IVF-ET supports the last of these hypotheses. The reduction in fertility in women with high levels of endotoxin is presumably the result of chronic intrauterine inflammation, a condition that is increasingly seen as the pathway by which most early preterm births occur (11Goldenberg R.L. Hauth J.C. Andrews W.W. Intrauterine infection and preterm delivery.N Engl J Med. 2000; 342: 1500-1507Crossref PubMed Scopus (1928) Google Scholar). In the obstetrical patient, inflammation is most often the consequence of genital tract infection. Although preterm birth has been linked clearly to intrauterine infection (12Hillier S.L. Martius J. Krohn M. Kiviat N. Holmes K.K. Eschenbach D.A. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity.N Engl J Med. 1988; 319: 972-978Crossref PubMed Scopus (844) Google Scholar, 13Watts D.H. Krohn M.A. Hillier S.L. Eschenbach D.A. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor.Obstet Gynecol. 1992; 79: 351-357Crossref PubMed Scopus (370) Google Scholar), eradication of common organisms recovered from the upper and lower genital tract in women who deliver preterm has not been accompanied by a decline in preterm births, even when appropriate prophylactic medications were administered in the second trimester. In an attempt to select women with evidence of upper as well as lower tract infection and inflammation, Andrews et al. (4Andrews W.W. Sibai B.M. Thom E.A. Dudley D. Ernest J.M. McNellis D et al.Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women.Obstet Gynecol. 2003; 101: 847-855Crossref PubMed Scopus (90) Google Scholar) treated women with a positive test for fetal fibronectin in cervicovaginal fluid with both metronidazole and erythromycin or placebo in a randomized blinded trial. There was no difference in the rate of preterm birth according to treatment arm, and the rate of spontaneous preterm delivery was actually increased among women with a prior preterm birth who received the antibiotics. To test the benefit of eradication of chronic intrauterine colonization of microorganisms before conception, a subsequent trial enrolled women with a preterm birth to receive placebo or metronidazole plus azithromycin every 4 months until a subsequent pregnancy occurred (14Andrews W.W. Goldenberg R.L. Hauth J.C. Cliver S. Interconceptional antibiotics to prevent spontaneous preterm birth: a randomized trial.Am J Obstet Gynecol. 2003; 189 ([abstract 5]): S57Abstract Full Text Full Text PDF Google Scholar). Again, there was no reduction in pregnancy loss or preterm birth in women who received antibiotic prophylaxis. These and other studies have directed the attention of obstetrical researchers toward host factors and in particular to variations in inflammatory response caused by maternal and fetal genetic polymorphisms (15Roberts A.K. Monzon-Bordonaba F. Van Deerlin P.G. Holder J. Macones G.A. Morgan M.A et al.Association of polymorphism within the promoter of the tumor necrosis factor-alpha gene with increased risk of preterm premature rupture of the fetal membranes.Am J Obstet Gynecol. 1999; 180: 1297-1302Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 16Hao K. Wang X. Niu T. Xu X. Li A. Chang W et al.A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods.Hum Mol Genet. 2004; 13: 683-691Crossref PubMed Scopus (76) Google Scholar). Kamiyama et al. (1Kamiyama S. Teruya Y. Nohara M. Kanazawa K. Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer.Fertil Steril. 2004; 82 (–92): 788Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar) suggest that the persistence of bacterial endotoxin in endometrium might be the result of chronic adnexal infection. Their hypothesis should prompt a re-evaluation of studies of antibiotic prophylaxis to prevent prematurity and of the relationship between IVF-ET and preterm and low birth weight delivery in singleton pregnancies." @default.
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• W2074413595 title "Endometrial endotoxin, assisted reproductive technology, and preterm birth" @default.
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