Uterine embryo implantation: the endometrium, seminal plasma

Infertility is an increasing health challenge affecting around 17.5% of the world's adult population. Despite the continuous improvement in the field of medically assisted reproduction, the implantation rate is still a limiting factor. Successful implantation requires a good-quality embryo and a receptive endometrium influenced by hormonal, genetic and immunological factors. This thesis aim was to study the endometrium, its immune profile and the effect of seminal plasma on endometrial receptivity. The thesis was based on five studies.

The first study was a literature review of menstruating animal species in which we provided an overview of possible animal models to study the human menstrual cycle and reproduction. We focused on the length of their menstrual cycle, ovulation, implantation, placentation, decidualization, endometrial characteristics and similarity with human menstrual cycle.

The second and third studies focused on the differences between using donor or partner sperm and the importance of seminal plasma in endometrial stimulation and implantation. The second study was a nationwide cohort study based on Danish health registries related to medically assisted reproduction (MAR) in women who used partner or donor sperm. Our results showed that most women using donor sperm have comparable or even better results than women using male partner sperm. The third study was a randomized, double-blinded, placebocontrolled trial where we investigated changes in the endometrial transcriptomic profile after vaginal application of seminal plasma. We found that seminal plasma stimulated the endometrium, upregulating gene pathways related to the immune response, cell proliferation, embryo development, oocyte maturation and angiogenesis.

The fourth and fifth studies focused on the immune system's role in implantation and pregnancy success. The fourth study was a literature review in which we investigated the chance of having a live-born child after assisted reproductive technology (ART) in women with chronic diseases, compared to other women in the general population receiving ART. Women with ulcerative colitis, Crohn's disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 had lower chances due to low implantation rate or early embryo development during ART. Women with hypothyroidism, diabetes mellitus type 1, and epilepsy had the same success rate as other women undergoing ART. The fifth study was a pilot case-control study investigating the endometrial cytokine profiles of women undergoing ART with or without autoimmune diseases. We found no significant difference between the groups, but women with different autoimmune diseases showed different cytokine patterns, which are worth further study.