The proliferative phase underpins endometrial development: Altered cytokine profiles in uterine lavage fluid of women with idiopathic infertility

- Glandular epithelium area is unaltered in the infertile proliferative endometrium.
- CCL11, TGFα, IFNγ and IL-1α are significantly elevated in younger infertile women.
- Endometrial gland functionality is altered in younger infertile women.

Endometrial gland development occurs during the proliferative phase of a woman's menstrual cycle, laying the foundation for the subsequent receptive, secretory phase when pregnancy is established. Idiopathic infertility has been rarely investigated with respect to the proliferative phase endometrium. We investigated whether gland development and/or altered secretion of cytokines during the proliferative phase is associated with infertility. Area of the glandular epithelium (GE) was measured in proliferative phase endometrial tissue collected from fertile (n = 18) and infertile (n = 14) women. Cytokines were measured in proliferative phase uterine lavage of fertile (n = 15) and infertile (n = 15) women. Immunohistochemistry determined cellular localisation of transforming growth factor alpha (TGFα) and interferon gamma (IFNγ) in proliferative phase endometrial tissue. For statistical analysis the cohort was divided into women <35 years and ⩾35 years. There were no significant differences in GE area of infertile and fertile women. C-C motif chemokine 11 (P = 0.048), TGFα (P = 0.049), IFNγ (P = 0.033) and interleukin-1 alpha (P = 0.047) were significantly elevated in uterine lavage from infertile women <35 years compared to fertile but not in women ⩾35 years. TGFα and IFNγ localised predominantly to GE in both the fertile and infertile endometrium. The potential impact of this altered proliferative phase environment on subsequent receptivity is discussed.