Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure.
OBJECTIVE
To document in the endometrium the correlation among the interleukin (IL)-12, -15, and -18 mRNA and the correlation between cytokine levels, vascular status, and endometrial natural killer (NK) cell count in the context of recurrent implantation failure.


METHODS
A pilot study.


METHODS
Department of Reproductive Immunology.


METHODS
Women who failed to become pregnant after repeated IVF-embryo transfer and fertile control subjects.


METHODS
Ultrasonic evaluation and endometrial biopsy in luteal phase.


METHODS
Uterine artery Doppler, count of uterine CD56 bright cells/field, and quantification by real-time polymerase chain reaction (PCR) to monitor IL-12 family (IL-12p40, IL-12p35, EBI3, IL-23), the IL-18 system (IL-18, IL-18R, IL18BP), and the IL-15 mRNA ratio.


RESULTS
The uterine artery Doppler and the CD56 bright cell counts were significantly different in fertile and infertile patients. The mean uterine artery pulsatility index correlated significantly negatively with the IL-18/actin ratio suggesting a defect of the cytokine-dependent vascular remodeling pathway. The number of uterine CD56 bright cells was significantly correlated with the IL-15/actin and IL-18/IL-18BP ratios. Thus, IL-18 and IL-15 seems to be involved in the local recruitment and the activation of uterine natural killer (uNK) cells. IL-18 was itself correlated with IL-15 and IL-12, suggesting a local control of uNK cells activation.


CONCLUSIONS
The assessment of the tripod IL-12/-15/-18 shows distinct immune-related mechanisms that are involved in the broader context of inadequate uterine receptivity.
Lédée-Bataille
Nathalie
N
Institut National de Santé et Recherche Médicale (INSERM) U131, Equipe cytokines et relation materno-foetale, et Service de Gynécologie Obstétrique, Hôpital Antoine Béclère (AP-HP), Clamart, France. Ledeenathalie@aol.com
Bonnet-Chea
Karen
K
Hosny
Ghada
G
Dubanchet
Sylvie
S
Frydman
René
R
Chaouat
Gérard
G
D000328:Adult; D004624:Embryo Transfer; D004717:Endometrium / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D008183:Luteal Phase / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000502:physiology; D010865:Pilot Projects; D011247:Pregnancy; D011256:Pregnancy Outcome; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017211:Treatment Failure; D014599:Uterus / Q000502:physiology*
C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D019409:Interleukin-15; D020382:Interleukin-18; D007378:Interleukins; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12