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Effects of anti-TNF-mAb treatment on pregnancy in baboons with induced endometriosis

2007; Elsevier BV; Volume: 89; Issue: 5 Linguagem: Inglês

10.1016/j.fertnstert.2007.05.062

1556-5653

Henrik Falconer, Jason M. Mwenda, Daniel Chai, Xioa-yu R. Song, Freddy Cornillie, Agneta Bergqvist, Gabriel Fried, Thomas D’Hooghe,

Gynecological conditions and treatments

ObjectiveHormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFα, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons.DesignProspective, placebo-controlled fertility trial.SettingAnimal research and laboratory facility.Animal(s)Sixteen adult female baboons with induced endometriosis.Intervention(s)All animals received a single IV dose of the anti-TNFα monoclonal antibody c5N (n = 9) or placebo (n = 7) at four different time points. The animals were then exposed to timed mating up to nine completed cycles or until pregnancy was achieved.Main Outcome Measure(s)Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR).Result(s)Inhibition of TNFα did not result in a significant improvement in PR (100% c5N vs. 86% placebo), CFR (18% c5N vs. 30% placebo), median TTP (5 cycles c5N vs. 2 cycles placebo), or CPR (100% c5N vs. 80% placebo). The duration of the menstrual cycle was unchanged in both groups before and after the study. Two nonpregnant baboons in the c5N-group died during the study.Conclusion(s)Medical inhibition of TNFα allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFα blockers in baboons with moderate to severe endometriosis are needed to further test the potential of these agents in the prevention or treatment of endometriosis-associated subfertility. Hormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFα, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons. Prospective, placebo-controlled fertility trial. Animal research and laboratory facility. Sixteen adult female baboons with induced endometriosis. All animals received a single IV dose of the anti-TNFα monoclonal antibody c5N (n = 9) or placebo (n = 7) at four different time points. The animals were then exposed to timed mating up to nine completed cycles or until pregnancy was achieved. Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR). Inhibition of TNFα did not result in a significant improvement in PR (100% c5N vs. 86% placebo), CFR (18% c5N vs. 30% placebo), median TTP (5 cycles c5N vs. 2 cycles placebo), or CPR (100% c5N vs. 80% placebo). The duration of the menstrual cycle was unchanged in both groups before and after the study. Two nonpregnant baboons in the c5N-group died during the study. Medical inhibition of TNFα allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFα blockers in baboons with moderate to severe endometriosis are needed to further test the potential of these agents in the prevention or treatment of endometriosis-associated subfertility.