A case of a pregnant woman with luteal insufficiency and a mutation in thebeta-subunit of luteinizing hormone

We report a case of a pregnant woman with luteal insufficiency and infertil ity associated with a variant luteinizing hormone (LH) beta -subunit and no rmal follicle-stimulating hormone (FSH) concentration. A 29-year-old woman presented to our hospital with infertility. Given the presence of low mid-l uteal serum progesterone concentration and out-of-phase endometrial biopsy, luteal insufficiency was suspected. Several forms of treatment (clomiphene citrate therapy and human menopausal gonadotrophin therapy) were administe red, but did not improve the patient's luteal insufficiency. However, admin istration of hCG during the luteal phase could distinctly improve the lutea l insufficiency. She became pregnant after luteal support with progesterone . Sequence analysis of the patient's LH beta -subunit gene indicated hetero zygosity for the point mutations Trp(8) to Arg(8) and Ile1(5) to Thr1(5) in the coding sequence. LH hypersecretion resembling that seen in polycystic ovary syndrome was observed. Serum concentrations of variant LH showed a mo re rapid increase in response to gonadotrophin-releasing hormone and reache d a higher apparent value than did those of normal LH. Therefore, abnormal bioactivity and mistimed secretion of variant LH at mid-cycle may have a de leterious effect on the completion of oocyte maturation, ovulation, and sub sequent corpus luteum function.