SAT-279 Can Preimplantation Genetic Diagnosis Be Used for Monogenic Endocrine Diseases?

Abstract

Abstract Background: Preimplantation genetic diagnosis (PGD) is currently used for over 400 monogenic diseases. Some endocrine conditions that occur due to monogenic defects are either life threatening or can cause severe morbidities; thus, PGD may be an option to avoid the occurrence of such diseases. But a high cost and limited availability of licensed IVF centers can be a barrier for many patients who might otherwise benefit from PGD. Objective: To review the literature for endocrine monogenic disorders that have been prevented with PGD. Methods: An initial search in PubMed/Medline search was done to identify monogenic endocrine conditions using MeSH term “preimplantation diagnosis” and other searches using “preimplantation genetic diagnosis (PGD)”, plus “endocrine” or “monogenic” anywhere in the title or abstract. Studies were eligible for consideration if they included use of PGD for any known monogenic endocrine disease. Studies were omitted if the disease was non-endocrine or PGD was not used for embryo selection. Eleven articles (1999-2018) reported 15 cases using PGD for monogenic endocrine diseases. These were Congenital adrenal hyperplasia (n=2), X-linked adrenoleukodystrophy (n=2), Congenital lipoid adrenal hyperplasia (n=1), Persistent hyperinsulinemic hypoglycemia of infancy (n=4), Pseudohypoparathyroidism type 1a (n=1), Hypoparathyroidism-retardation-dysmorphism syndrome (n=2) and Multiple endocrine neoplasia types 1 (n=1) and 2a (n=2). Techniques used for PGD included PCR, whole genome amplification, FISH and more recently next generation sequencing. Clinical and outcome data of these cases were reviewed with respect to number of PGD cycles, successful pregnancy rates, live births and their genetic status. Results: Fifteen couples underwent 32 PGD cycles (ranging from 1-9 per couple), of which 17 cycles resulted in a pregnancy. Seven couples underwent a single PGD cycle. Four of these 7 couples had successful pregnancies each resulting in live births (all singletons), 1 couple was unable to achieve pregnancy, 1 chose to terminate the pregnancy as the karyotype detected a Turner fetus (45XO) and outcome data was not reported in one. The remaining 8 couples underwent multiple PGD cycles (2-9 per couple) and all had successful pregnancies in at least one cycle, resulting in 16 livebirths (6 singletons and 5 twins). Amongst the total live births (n=20), 60% were genetically unaffected for the tested monogenic disorder and 40% were carriers of the autosomal recessive gene mutation for which PGD was performed. Conclusion: Preimplantation genetic diagnosis may be a potential tool for preventing the inheritance of severe monogenic endocrine diseases in future generations. The current use of PGD in endocrine disorders is rare, but provides a promising option on a case by case basis provided the optimal resources are available.