A low plasma level of mannose binding lectin (p-MBL) is associated with unexplained recurrent pregnancy loss (RPL), but it is not investigated if it is associated with unexplained reproductive failure in general, including recurrent implantation failure (RIF) after assisted reproductive technology (ART) (including IVF, ICSI and FET), recurrent pregnancy loss (RPL) after spontaneous conception, and RPL after ART.

The prevalence of a low p-MBL level is higher in patients with unexplained RPL than in the background population, while a high level is significantly less frequent in RPL patients (Nørgaard-Pedersen et al., submitted).

Approximately 50% of RPL patients have none of the evidence-based risk factors associated with RPL. Unexplained RPL is more complicated since finding the cause is essential for offering the optimal intervention to improve the patient's chances of a child.

Other conditions characterized by reproductive failure are infertility and recurrent implantation failure (RIF). The underlying mechanisms and the physiologic stage in early pregnancy being complicated and impeding normal pregnancy may probably differ between these pathologic conditions, since theoretically RIF would involve complicated embryo apposition, adhesion and invasion and clinical/visualized pregnancy losses would involve complicated stages later in the implantation process and fetal development. However, these conditions are suggested to have partly overlapping causes since most of the evidence-based risk factor recur; including parental chromosomal abnormalities, and maternal endocrine disorders, acquired thrombophilia, anatomic abnormalities in the uterine cavity, and endometrial and ovarian diseases. In addition, adverse immune responses against the embryo have been suggested as a cause of reproductive failure. If RPL is associated with a low p-MBL level, RIF may be so too.

The investigators aim to explore the p-MBL level in patients suffering from reproductive failure.

If low p-MBL level is associated with all the investigated subgroups of patients suffering from reproductive failure, this would strengthen our theory that MBL is involved in the pathophysiology characterized by reproductive failure in the very early stages of pregnancy and should therefore take part in the exploration of all patients with reproductive failure.

Inclusion Criteria:

fulfil one of the following:

• 3 consecutive pregnancy losses after spontaneous conception
• 3 consecutive pregnancy losses after assisted reproductive technology treatment (ART) including IVF, ICSI and FET
• 3 failed embryo transfers characterized by no achieved pregnancy (after 3 cycles with minimum 1 embryo transfer of a good-quality embryo in each cycle.)

Exclusion Criteria:

• Age <18 or >45 years
• AMH <4.0 pmol/l unless donor egg in previous cycles
• Significant uterine malformation
• Known endometrial pathologies including intrauterine endometriosis, adenomyosis, hyperplasia or polyps
• Known chromosomal abnormalities
• Pregnancy >9 weeks of gestation at the time collecting the blood sample

Danish female population. The centers cover mainly the western region of Denmark, but patients from all over Denmark can be treated at each center.

The Aagaard Klinik is a private IVF clinic and therefore their patients pay for their ART treatments. Patients contact the clinic themself when they need medical support because of reproductive failure.

The RPL center at AaUH (public hospital) is available without costs for the patient. Patients are referred from their practitioner or fertility clinic or gynecologist when they have experienced 3 or more pregnancy losses (including biochemical and clinical pregnancies).

Data obtained through this study may be provided to qualified researchers with academic interest in RPL after approval by the researchers. Data will be coded with no personal identifiers included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party. Please contact the primary researcher. The researchers maintain the right to reject the request. Data requests can be submitted starting 12 months after article publication.

Data requests can be submitted starting 12 months after article publication and up to 36months only on request.

Only on request.