Development of Mycobacterium tuberculosis post in vitro fertilization and embryo transfer: A case series derived from a multi-omics analysis and literature review.

The extensive progress in assisted reproductive technology has facilitated successful pregnancies through in vitro fertilization and embryo transfer (IVF-ET) for patients facing infertility. Pregnancy induces substantial endocrine and immune alterations that may diminish immune function, consequently heightening vulnerability to Mycobacterium tuberculosis (M.tb) infection or reactivation. Hematogenous disseminated pulmonary tuberculosis (TB), tuberculous meningitis, and potential congenital TB are serious complications that may arise after IVF-ET, posing significant risks to both maternal and fetal health. The clinical manifestations of TB during pregnancy frequently coincide with non-typical pregnancy symptoms, and the nonspecific characteristics of early-stage presentations render prompt diagnosis especially difficult. The existing literature on this subject is sparse, primarily consisting of isolated case studies involving individual participants, thereby yielding insufficient data and inadequate representations to comprehensively clarify this clinical emergency. This paper presents a case series of patients with normal immune function who developed hematogenous disseminated TB, including placental and central nervous system involvement, subsequent to IVF-ET. We showcased the multi-omic findings, including metagenomic sequencing and histopathological analyses, from patients with twin and singleton pregnancies and presented an extensive literature review. Additionally, we used metagenomic next-generation sequencing (mNGS) to detect pathogenic microorganisms in blood, bronchoalveolar lavage fluid (BALF), and cerebrospinal fluid (CSF) samples. Rare histopathological findings of placental TB were also documented, providing direct pathological evidence relevant to congenital TB. These findings expand the limited clinical evidence on TB following IVF-ET and underscore the importance of heightened clinical vigilance and multimodal diagnostic strategies in this high-risk population.