Effects of anti-TNF-mAb treatment on pregnancy in baboons with induced endometriosis.
OBJECTIVE
Hormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFalpha, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons.


METHODS
Prospective, placebo-controlled fertility trial.


METHODS
Animal research and laboratory facility.


METHODS
Sixteen adult female baboons with induced endometriosis.


METHODS
All animals received a single IV dose of the anti-TNFalpha 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.


METHODS
Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR).


RESULTS
Inhibition of TNFalpha 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.


CONCLUSIONS
Medical inhibition of TNFalpha allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFalpha 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.
Falconer
Henrik
H
Division for Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
Mwenda
Jason M
JM
Chai
Daniel C
DC
Song
Xioa-Yu R
XY
Cornillie
Freddy J
FJ
Bergqvist
Agneta
A
Fried
Gabriel
G
D'Hooghe
Thomas M
TM
D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004715:Endometriosis / Q000150:complications / Q000473:pathology*; D005260:Female; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008597:Menstrual Cycle / Q000187:drug effects; D010215:Papio; D010919:Placebos; D011247:Pregnancy; D018873:Pregnancy Rate; D011270:Pregnancy, Animal; D011446:Prospective Studies; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha