Biomarkers of pregnancy loss

The method according to any one of the preceding claims, wherein a decreasing level of the marker gene for decidual cells, as compared with a reference sample or level, and/or

• an increasing level of the marker gene for decidual senescent cells, as compared with a reference sample or level,
• indicates that the individual is at risk of pregnancy loss or embryo implantation failure.

The method according to any one of the preceding claims, further comprising

• (a) detecting and/or quantifying the level of uterine natural killer (uNK) cells or the level of at least one marker gene for uNK cells in the biological sample, optionally wherein a decreasing level of uNK cells or level of the at least one marker gene for uNK cells, as compared with a reference sample or level, indicates that the individual is at risk of pregnancy loss or embryo implantation failure;
• and/or
• (b) a step of determining one or more risk indicia selected from the group consisting of maternal body mass index, maternal age and number of previous pregnancy losses or embryo implantation failures.

A method of monitoring or evaluating the effect of a treatment to reduce the risk of pregnancy loss or embryo implantation failure in an individual, wherein the method comprises detecting and/or quantifying the amount of at least one marker gene for decidual cells and at least one marker gene for decidual senescent cells in a biological sample obtained from the individual, and thereby monitoring or evaluating the effect of the treatment, wherein the at least one marker gene for decidual cells comprises PLA2G2A.

The method according to any one of the preceding claims, wherein

• (a) the risk of pregnancy loss is risk of euploid pregnancy loss, or wherein the risk of embryo implantation failure is not due to chromosomal abnormalities in an embryo;
• and/or
• (b) the risk of pregnancy loss is risk of recurrent pregnancy loss.

A method of diagnosing a reproductive disorder in an individual, wherein the method comprises detecting and/or quantifying the amount of at least one marker gene for decidual cells and at least one marker gene for decidual senescent cells in a biological sample obtained from the individual, thereby diagnosing the disorder, wherein the at least one marker for decidual cells comprises PLA2G2A.

The method according to any one of the preceding claims, wherein

• (a) the biological sample is an endometrial biopsy sample;
• and/or
• (b) the biological sample is taken during the luteal phase of the menstrual cycle, optionally wherein the biological sample is taken during the mid-luteal phase of the menstrual cycle.

The method according to any one of the preceding claims, wherein the individual

• (a) suffers or has suffered from infertility or embryo implantation failure following in vitro fertilisation treatment;
• and/or
• (b) has already suffered from at least one previous pregnancy loss or embryo implantation failure, or is suffering from recurrent pregnancy loss.

The method according to any one of the preceding claims, wherein

• (a) the method further comprises detecting and/or quantifying genes that allow identification of the day in the menstrual cycle, optionally wherein the genes that allow identification of the timing of the day in the menstrual cycle comprise, consist of, or consist essentially of, Glutathione Peroxidase 3 (GPX3) and Solute Carrier Family 15 Member 2 (SLC15A2);
• and/or
• (b) the marker genes are detected and/or quantified using ELISA, Western blotting, immunohistochemistry, immunoassays, enzymatic assays or sequencing methods, optionally wherein the sequencing methods include qPCR, Taqman-PCR, multiplex Taqman-PCR, Nanostring, targeted sequencing or digital PCR, optionally wherein the digital PCR is digital droplet PCR (ddPCR).

A method of selecting patients for treatment to reduce risk of embryo implantation failure or pregnancy loss, wherein the method comprises detecting and/or quantifying the amount of at least one marker gene for decidual cells and at least one marker gene for decidual senescent cells in a biological sample obtained from an individual, and selecting the patients for treatment to reduce the risk of pregnancy loss or embryo implantation failure based on the level of the marker genes, wherein the at least one marker for decidual cells comprises PLA2G2A

A test kit suitable for use in a method of any one of the preceding claims, wherein the test kit comprises means for detecting or quantifying at least one marker gene for decidual cells and at least one marker gene for decidual senescent cells at a nucleic acid or protein level, and optionally means for detecting and/or quantifying the level of UNK cells or the level of at least one marker gene for uNK cells in the individual, wherein the at least one marker gene for decidual cells comprises PLA2G2A.