Anti-Müllerian Hormone and Ovarian Morphology in Women With Isolated Hypogonadotropic Hypogonadism/Kallmann Syndrome: Effects of Recombinant Human FSH

J Clin Endocrinol Metab. 2017 Apr 1;102(4):1102-1111. doi: 10.1210/jc.2016-3799.

Abstract

Context: Isolated hypogonadotropic hypogonadism (IHH), characterized by gonadotropin deficiency and absent puberty, is very rare in women. IHH prevents pubertal ovarian stimulation, but anti-Müllerian hormone (AMH) and antral follicle count (AFC) have not been studied.

Objectives: (1) To compare, in IHH vs controls, AMH, ovarian volume (OV), and AFC. (2) To compare, in IHH, ovarian responses to recombinant human follicle-stimulating hormone (rhFSH) and rhFSH plus recombinant human luteinizing hormone (rhLH).

Subjects: Sixty-eight IHH women; 51 matched healthy women.

Methods: Serum LH, FSH, sex steroids, inhibin B (InhB), AMH, and OV and AFC (sonography) were compared. Ovarian response during rhFSH administration was assessed in 12 IHH women with low AMH levels and low AFC and compared with hormonal changes observed in six additional IHH women receiving rhFSH plus rhLH.

Results: InhB was lower in IHH than in controls. AMH levels were also significantly lower in the patients, but two-thirds had normal values. Mean OV and total, larger, and smaller AFCs were lower in IHH than in controls. Ovarian stimulation by rhFSH led to a significant increase in serum estradiol and InhB levels and in the number of larger antral follicles. AMH and smaller AFC increased early during rhFSH stimulation but then declined despite continued stimulation. rhFSH plus rhLH stimulation led to a significantly higher increase in estradiol levels but to similar changes in circulating InhB and AMH than with rhFSH alone.

Conclusions: IHH women have both low AMH levels and low AFC. However, their decrease can be reversed by follicle-stimulating hormone. Serum AMH and AFC should not serve as prognostic markers of fertility in this population.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood*
  • Case-Control Studies
  • Female
  • Follicle Stimulating Hormone, Human / pharmacology*
  • Follicle Stimulating Hormone, Human / therapeutic use
  • Hormone Replacement Therapy
  • Humans
  • Hypogonadism* / blood
  • Hypogonadism* / drug therapy
  • Hypogonadism* / pathology
  • Kallmann Syndrome* / blood
  • Kallmann Syndrome* / drug therapy
  • Kallmann Syndrome* / pathology
  • Luteinizing Hormone / pharmacology
  • Luteinizing Hormone / therapeutic use
  • Organ Size / drug effects
  • Ovary / drug effects*
  • Ovary / pathology*
  • Ovulation Induction / methods
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Young Adult

Substances

  • Follicle Stimulating Hormone, Human
  • Recombinant Proteins
  • Anti-Mullerian Hormone
  • Luteinizing Hormone