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


OBJECTIVE
(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).


METHODS
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.
Assistance Publique-Hôpitaux de Paris.|Department of Reproductive Endocrinology.|Medical Procreation Unit, Gynecology-Obstetrics Department, University of Paris XII, Créteil Hospital, 94000 Créteil, France.
Hélène
H
Bry-Gauillard
Assistance Publique-Hôpitaux de Paris.|Department of Reproductive Endocrinology.
Florence
F
Larrat-Ledoux
Assistance Publique-Hôpitaux de Paris.|Department of Gynecology-Obstetrics, and.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|Medical Procreation Unit, Gynecology-Obstetrics Department, University of Paris XII, Créteil Hospital, 94000 Créteil, France.
Jean-Marc
JM
Levaillant
Medical Procreation Unit, Gynecology-Obstetrics Department, University of Paris XII, Créteil Hospital, 94000 Créteil, France.
Nathalie
N
Massin
Assistance Publique-Hôpitaux de Paris.|Department of Reproductive Endocrinology.|Department of Hormonology and Molecular Genetics, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.
Luigi
L
Maione
Department of Reproductive Endocrinology.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|INSERM Unité 1185, 94276 Le Kremlin-Bicêtre, France.
Isabelle
I
Beau
University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|INSERM Unité 1185, 94276 Le Kremlin-Bicêtre, France.
Nadine
N
Binart
Assistance Publique-Hôpitaux de Paris.|Department of Reproductive Endocrinology.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|INSERM Unité 1185, 94276 Le Kremlin-Bicêtre, France.
Philippe
P
Chanson
Assistance Publique-Hôpitaux de Paris.|Department of Hormonology and Molecular Genetics, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|INSERM Unité 1185, 94276 Le Kremlin-Bicêtre, France.
Sylvie
S
Brailly-Tabard
Reproductive Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.|Clinical Research Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Janet E
JE
Hall
Assistance Publique-Hôpitaux de Paris.|Department of Reproductive Endocrinology.|University of Paris-Sud, Paris-Sud Medical School, 94276 Le Kremlin-Bicêtre, France.|INSERM Unité 1185, 94276 Le Kremlin-Bicêtre, France.
Jacques
J
Young
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000494:pharmacology* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D017436:Kallmann Syndrome / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D007986:Luteinizing Hormone / Q000494:pharmacology / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000473:pathology*; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone