Abstracts of the 24th Annual Congress of the SBRA, 2020 (Virtual Meeting).

Abstract

Objective:Osteogenesis Imperfecta (OI) is a disease characterized by fragile bones and a decrease in bone mass. There are approximately nineteen types of OI differing from each other by morbidity, mortality and causative mutation. The OI Type IV occurs in most cases of deleterious variant in heterozygosis (autosomal dominant) in the COL1A1 or COL1A2 genes. Those genes are responsible for the production of procollagen chains that are part of type I collagen molecule. Patients with OI type IV have a high risk (50%) of transmitting the pathogenic variant to their offspring being recommendable genetic counseling to discuss family planning alternatives. The use of assisted human reproduction techniques followed by analysis of Pre-implantation Genetic Test for Monogenic Diseases (PGT-M) in embryos has proven to be an effective alternative to reduce the risk of recurrence. Objective: Family planning with In Vitro Fertilization (IVF) cycles and cumulation of frozen embryos followed by PGT-M as an alternative to reduce the risk of transmission of the pathogenic variant that causes OI Type IV.Methods:The case reported a couple in which the male patient has a diagnosis of OI Type IV caused by a deleterious variant in COL1A2. Informative study was conducted with the carrier and his wife before the IVF cycle and the PGT-M. The previous test was designed to find the informative polymorphic Short Tandem Repeats (STR) markers linked to mutations or genomic regions. For the IVF treatment three cycles were made with the same stimulation protocol. It was used clomiphene citrate, gonadotropin, antagonist GnRh and trigger with agonist GnRh. In the first cycle, six embryos were produced and frozen on the third day of development (D3). In the following cycle three embryos had vitrified in the same development day. In the third cycle six embryos were developed and after they reached cleavage state (D3), all other embryos, from the previous cycles, were thawed, survived the technique and developed until the blastocyst stage. From the total fifteen embryos in the cleavage stage, nine evolved to the blastocyst stage. The PGT-M was performed at all blastocysts followed by embryo cryopreservation. Regarding the genetic analysis of embryo cells, for those samples that the deleterious variant in COL1A2 was not found, the research advanced with Pre-implantation Genetic Test for Aneuploidy (PGT-A). The antagonist protocol used for the endometrial preparation in the embryo thaw cycle, from the third day of menstrual flow progressive doses of estradiol were used until the appropriate thickness and pattern was reached. It was administered 10.000 UI of urinary HCG subcutaneous. After 48 hours, 75 mg of intramuscular progesterone was started. On the sixth day of administration, the euploid embryo without the mutation searched was thawed and transferred to the uterine cavity.Results:In this cohort of nine embryos, there were five embryos with COL1A2 mutation present. From the four embryos without the mutation, three of them were aneuploids. One embryo did not present the haplotype with the mutation in COL1A2 and was euploid. This embryo was thawed and followed by transfer and resulted in an unaffected live birth. Conclusion:This article evidences an IVF cycle with a multidisciplinary approach with genetic counseling, serial ovarian stimulation, cumulative IVF cycles with embryo freezing, PGT-M, PGT-A and cycle of thawing can be a viable treatment to reduce recurrence risk of autosomal-dominant disease (50%).