Recurrent pregnancy losses (RPL) are characterized by the occurrence of more than one spontaneous pregnancy loss. It is caused by different known factors, but about half of the cases remain without an explanation. Efforts are being done in the scientific community to solve this cases. In this study, the investigators aim to investigate genetic factors that might predispose to RPL, as well as the influence of the uterine microbiota (microorganisms that normally live in the uterus of women).

Recurrent pregnancy losses (RPL) are adverse reproductive outcomes characterized by the occurrence of more than one spontaneous pregnancy loss. It is estimated that RPL occurs in 1 to 5% of couples in reproductive period and is caused by different known factors. Despite this, around half of the cases remain without a defined etiology. In this context, efforts are being done in the scientific community to elucidate idiopathic cases. Among them, robust genomic investigations, such as exome sequencing, stand out for maximizing the chances of identifying causative gene variants rather than a gene-specific approach. Another front of study to understand the factors that modulate complex etiology conditions such RPL is the characterization of the microbiota of different anatomical sites. Each human anatomical site presents a distinct microbiota selected through a long co-evolutionary process and its individual and pathological variability can lead to functional repercussions. Therefore, the aim of this study is to investigate factors predisposing to recurrent pregnancy loss through a genomic evaluation and characterization of the uterine microbiota of patients affected by RPL. To achieve this, two approaches will be conducted: a genomic approach, where the exome of women with RPL will be analyzed and compared with population genomic databases; and a etagenomic approach, where the characterization of the uterine microbiota of women with RPL will be performed and compared with that of fertile women. Using the data produced in this study, the investigators hope to be able to understand more broadly how the genome influences the predisposition to RPL and how changes in certain marker genes can lead to an increased risk for the occurrence of this reproductive condition. Furthermore, based on analyzes of the uterine microbiota, the investigators hope to be able to understand how the variability of microorganisms present in this organ acts during pregnancy, especially in cases of RPL. The results of the investigations proposed in this project will help to understand the predisposing factors to RPL and may lead to the development of new investigative approaches, such as the design of genetic panels and analyzes of the uterine microbiota, which may have an impact on the clinical management of the condition in the future.

Inclusion Criteria:

• RPL group: history of at least two spontaneous pregnancy losses, regardless of whether they have living children, and whose etiology for the pregnancy losses was not determined by the care team's protocols;
• Control group: at least two full-term pregnancies and no history of difficulty getting pregnant, pregnancy loss or other infertility factors.

Exclusion Criteria:

• RPL group: less than two spontaneous pregnancy losses and those with a known cause for repeated pregnancy losses;
• Control group: N/A

Women who seek the Gynecology and Obstetrics Service of the Hospital de Clínicas de Porto Alegre (HCPA) for care and investigation of causes of infertility or for exams not related to this condition will be included in the study.