Clinical trial NCT01411644: Pheno- & Genotyping POF (WHO III)
Official title: Phenotyping and Genotyping of Women Presenting With Ovarian Dysfunction Associated With a Hypergonadotropic Hypo-estrogenic Hormonal Status (WHO III) and Their First and Second Degree Relatives
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Premature Ovarian Failure (POF)
Incipient Ovarian Failure
Poor Response After Ovarian Hyperstimulation
Early Menopause
Hypergonadotropic Amenorrhea
Keywords: POF
IOF
Poor response
early menopause
Primary amenorrhea
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: Medical Center Alkmaar
name: University Medical Center Groningen
name: Leiden University Medical Center
name: Medisch Spectrum Twente
name: Isala
name: Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.
name: Amphia Hospital
name: Deventer Ziekenhuis
name: Catharina Ziekenhuis Eindhoven
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Academisch Ziekenhuis Maastricht
name: Amsterdam UMC, location VUmc
First posted: 2011-08-08
Enrollment: 650
Sex: FEMALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with WHO III status who attend the outpatient clinic of participating hospitals.

Brief summary: This study focuses on the phenotyping and genotyping of women with hypergonadotropic ovarian dysfunction (WHO III status).

Detailed description: First goal of the study is to phenotype patiens with hypergonadotropic ovarian dysfunction (WHO III) adequately. This group includes women with premature ovarian failure (POF), incipient ovarian failure (IOF), poor response after ovarian hyperstimulation, early menopause and hypergonadotropic primary amenorrhea. The standardized phenotyping consists of a questionnaire focusing on reproductive, medical, and family history; ultrasonography to assess ovarian reserve and/or antral follicle count and obtaining an extra blood sampling during routine endocrine screening for genotyping.

Phenotyping of patients presenting with ovarian dysfunction is of crucial importance when genotyping will be performed. The goal of this genotyping will be the identification of genetic factors associated with the (premature) depletion of the stock of ovarian follicles. It will be performed for isolated WHO III patients in an association (case-control) study for known candidate genes. In familial WHO III cases, genome wide linkage analysis will be performed.

Eligibility criteria: Inclusion Criteria:

* POF; defined as secondary amenorrhea before 40 years of age and basal FSH \> 40 IU/L
* Incipient ovarian failure; defined as normo-ovulatory cycles, raised basal FSH \> 12 IU/L
* Poor response patients; defined as less than 4 oocytes retrieved or cancellation in case of absent follicle growth after ovarian hyperstimulation with 300 IU gonadotropins or cancellation in case of absent follicle growth
* Women with early menopause (between 40-45 years)
* Hypergonadotropic primary amenorrhea

Exclusion Criteria:

* Primary amenorrhea with early development disorders causing absence of ovaries and Swyer syndrome (XY)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Bart CJ Fauser, MD PhD
role: STUDY_DIRECTOR
References:
citation: Knauff EA, Franke L, van Es MA, van den Berg LH, van der Schouw YT, Laven JS, Lambalk CB, Hoek A, Goverde AJ, Christin-Maitre S, Hsueh AJ, Wijmenga C, Fauser BC; Dutch POF Consortium. Genome-wide association study in premature ovarian failure patients suggests ADAMTS19 as a possible candidate gene. Hum Reprod. 2009 Sep;24(9):2372-8. doi: 10.1093/humrep/dep197. Epub 2009 Jun 9.
citation: Knauff EA, Westerveld HE, Goverde AJ, Eijkemans MJ, Valkenburg O, van Santbrink EJ, Fauser BC, van der Schouw YT. Lipid profile of women with premature ovarian failure. Menopause. 2008 Sep-Oct;15(5):919-23. doi: 10.1097/gme.0b013e31816b4509.
citation: Knauff EA, Eijkemans MJ, Lambalk CB, ten Kate-Booij MJ, Hoek A, Beerendonk CC, Laven JS, Goverde AJ, Broekmans FJ, Themmen AP, de Jong FH, Fauser BC; Dutch Premature Ovarian Failure Consortium. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab. 2009 Mar;94(3):786-92. doi: 10.1210/jc.2008-1818. Epub 2008 Dec 9.
citation: Janse F, Knauff EA, Niermeijer MF, Eijkemans MJ, Laven JS, Lambalk CB, Fauser BC, Goverde AJ; Dutch Premature Ovarian Failure Consortium. Similar phenotype characteristics comparing familial and sporadic premature ovarian failure. Menopause. 2010 Jul;17(4):758-65. doi: 10.1097/gme.0b013e3181cf8521.
citation: Knauff EA, Blauw HM, Pearson PL, Kok K, Wijmenga C, Veldink JH, van den Berg LH, Bouchard P, Fauser BC, Franke L; Dutch Primary Ovarian Insufficiency Consortium. Copy number variants on the X chromosome in women with primary ovarian insufficiency. Fertil Steril. 2011 Apr;95(5):1584-8.e1. doi: 10.1016/j.fertnstert.2011.01.018. Epub 2011 Feb 12.