Successful Live Birth Following Natural Cycle Oocyte Retrieval in a Woman with Primary Infertility and Atypical Primary Ovarian Insufficiency with a DNAH1 Gene Deletion Mutation.

Background

Dynein, axonemal, heavy chain 1 (DNAH1) gene mutations have been found to be related to primary ciliary dyskinesia (PCD) and the DNAH1 gene is associated with abnormal flagellar morphology in spermatozoa. Infertility is a common condition in women presenting with primary ovarian insufficiency (POI) characterized by hypergonadotropic hypogonadism. The purpose of this study was to explore the clinical significance of genetic diagnostics in several Chinese primary infertile women with atypical POI.

Methods

Four atypical POI patients and 100 healthy subjects were recruited, genetic pathogenicityc factors were investigated by whole exome sequencing (WES).

Results

WES revealed a homozygous deletion mutation in the DNAH1 gene (NM_015512.5; c.11726_11727delCT, p.Pro3909Argfs*33) in one of the four POI patients. The 31-year-old affected woman presented with a normal menstrual cycle and elevated plasma levels of FSH, around the postmenopausal range, but had a normal antral follicle count and normal anti-Müllerian hormone levels. The patient, after two failed ovulation cycles, became pregnant in the third IVF cycle and delivered a healthy girl at term.

Conclusions

The homozygous deletion mutation in the DNAH1 gene suggested that the patient might have a cilia movement disorder of the fallopian tubes, which is a known infertility factor. Moreover, the significantly elevated plasma level of FSH in this patient is likely one of the most important factors leading to her decreased fertility.