Clin Exp Reprod Med.  2017 Mar;44(1):40-46. 10.5653/cerm.2017.44.1.40.

Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization

• Sills ES
• Obregon-Tito AJ
• Gao H
• McWilliams TK
• Gordon AT
• Adams CA
• Slim R

• KMID: 2408586
• DOI: http://doi.org/10.5653/cerm.2017.44.1.40

Abstract

OBJECTIVE
To describe in vitro development of human embryos derived from an individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect.
METHODS
A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, in vitro fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening. Findings in NLRP7 were recorded and embryo culture and biopsy data were tabulated as a function of parental origin for any identified ploidy error.
RESULTS
The patient was found to have a pathogenic variant in NLRP7 (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10 embryos were available after fertilization via intracytoplasmic sperm injection. Developmental arrest was noted for all 10 embryos after 144 hours in culture, thus no transfer was possible. These non-viable embryos were evaluated by karyomapping and all were diploid biparental; two were euploid and eight had various aneuploidies all of maternal origin.
CONCLUSION
This is the first report of early human embryo development from a patient with any NLRP7 mutation. The pathogenic variant identified here resulted in global developmental arrest at or before blastocyst stage. Standard IVF should therefore be discouraged for such patients, who instead need to consider oocyte (or embryo) donation with IVF as preferred clinical methods to treat infertility.

Keyword

Hydatidiform mole; In vitro fertilization; Preimplantation embryo development; Recurrent miscarriage; Reproductive genetics

MeSH Terms

Abortion, Habitual
Aneuploidy
Biopsy
Blastocyst
Diploidy
Embryonic Development*
Embryonic Structures*
Female
Fertilization
Fertilization in Vitro*
Genetic Testing
Gestational Trophoblastic Disease*
Humans
Hydatidiform Mole
In Vitro Techniques*
Infertility
Oocytes
Parents
Ploidies
Pregnancy
Sperm Injections, Intracytoplasmic