Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles

Abstract

Though various advantages associated with the use of letrozole as an ovulation inducing drug are documented, there is inadequate information regarding its effect on endometrial receptivity. Expression of endometrial receptivity markers including α_vβ₃ integrin, L-selectin, LIF, and pinopods during the implantation window in infertile women stimulated with letrozole or clomiphene citrate (CC), and spontaneous cycles is investigated. A total of 36 women were included in the study out of which 16 women were diagnosed with primary unexplained infertility and the other 20 women with severe oligoasthenozoospermic/azoospermic male partners. Both groups were sub-divided into three groups; women stimulated with letrozole, or with CC, and the third group was allowed to ovulate spontaneously (natural cycles). Women having natural cycles and not given any drug were considered as controls. Once ovulation was confirmed by ultrasonography, endometrial samples were collected on the seventh day post-ovulation and analyzed. In women with unexplained infertility treated with letrozole and CC, epithelial and stromal expression of α_vβ₃ integrin, L-selectin, leukemia inhibitory factor (LIF), and pinopod formation was found to be significantly higher as compared to controls. Expression of these receptivity markers was found to be comparable amongst the letrozole, CC, and control groups in women with severe oligoasthenozoospermic/azoospermic male partners. Cell cycle analysis showed similar cell cycle phase fractions on comparing the CC and the letrozole groups. Stimulation with letrozole and CC appears to enhance endometrial receptivity in women with unexplained infertility. However, letrozole and CC did not have any significant effect on the endometrial receptivity markers of women with severe oligoasthenozoospermic/azoospermic male partners.

• Clomiphene citrate
• endometrial receptivity
• integrin
• letrozole
• leukemia inhibitory factor
• L-selectin

Acknowledgments

The authors thank Mr. Debnath Das for preparing tissue sections for immunohistochemistry studies. The authors also thank Mr. Suvankar Das and Mr. Asim Mahata for assisting in the Medical Biotechnology laboratory. Two of the authors, Dr. Ashalatha Ganesh and Mr. Soumen Das sincerely acknowledge the Council of Scientific and Industrial Research (CSIR) for providing financial support (CSIR file no.s 9/81(675)/08 – EMR - I, dated 25-03-08 and 9/81(674)/08 – EMR - I, dated 26-03-08).

Author contributions

All authors have significantly contributed to the preparation and review of the manuscript, and were involved in the study. Conceived and designed the experiments: AG, BNC; Performed the experiments: SD, NC, AG; Analyzed the data: AG, KC, NC; Contributed reagents/materials/analysis tools: KC, BNC; Wrote the manuscript: AG, KC.