Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.

1. PRESENTS
Genetics of Ovarian Failure
By: Maire Peters
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2. Age at natural menopause
• Menopause is the cessation of reproductive
function of the human ovaries.
• The median age at menopause
– in Europe from 50.1 to 52.8 years,
– in North America from 50.5 to 51.4 years,
– in Latin America from 43.8 to 53 years,
– in Asia from 42.1 to 49.5 years.
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3. Premature menopause
• Premature ovarian failure/primary ovarian
insufficiency (POF/POI) is a cause of female
infertility due to the loss of normal ovarian
function in women before the age of 40 years.
• POI affects approximately 1 in 10,000 women by
age 20; 1 in 1,000 women by age 30; 1 in 100
women by age 40.
• Early menopause (EM) is defined as menopause
occurring at 40-45 years of age. EM occurs in 510% of women.
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4. Mechanisms leading to POI
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Persani L et al. J Mol Endocrinol 2010;45:257-279

5. Causes of POI
≈ 25%
FOXL2
FSHR
≈ 10%
POI
≈5%
≈ 20%
≈ 65%
Figure adapted from Shelling 2010
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6. X chromosome defects
X chromosome defects
Frequency of POI
Frequency in POI
Turner’s syndrome
100%
4-5%
Normal
FMR1 premutation
13-26%
15% (familial)
3% (sporadic)
7-54 CGG repeats
Translocations, deletions 55-200 CGG repeats
80-100%
Premutation
BMP15 variants
0-10%
Full mutation
Unknown
1.5%
more than 200 repeats
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7. Autosomal defects
Autosomal defects
Frequency in POI
Complex diseases: galactosemia (GALT),
BPES (FOXL2), mitochondrial (POLG),
ovarian leukodystrophy (EIF2B)
Rare
FSH/LH resistance (FSHR and LHR)
<1%
INHA variants
unknown
GDF9 variants
≈1%
NOBOX, FIGLA
unknown
Each single gene is responsible for less than 1-6% of POI.
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8. Genes involved in POI pathogenesis
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Persani L et al. J Mol Endocrinol 2010;45:257-279

9. GWASs in POI
Ethnicity
Sample size
(cases/controls)
Replication
Region
SNP
Reference
Korean
24/24
98/218
-
-
Pyun et al.,
2012
Chinese
391/895
400/800
8q22.3
8 SNPs
Qin et al.,
2012
European
99/235
60/90
-
-
Knauff et al.,
2009
GWAS – Genome-wide association study
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10. Genes associated with
age at natural menopause
Function
Genes
Related genes
DNA repair
EXO1, HELQ, UIMC1,
TLK1, POLG, PRIM1
FAM175A, FANCI
Immune function
NLRP11, BAT2
IL11
X-chromosome
inactivation
ASH2L
EIF4EBP1
Hormonal regulation
-
FSHB
Known binding partner
for FMR1
TDRD3
Various functions
RHBDL2, FNDC4,
MCM8, SYCP2L,
TMEM150B
EIF2B4
These 17 variants explain 2.5–4.1% of the population variation in
menopausal age (Stolk et al., 2012).
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11. Genetics of early menopause
• EM has a substantial genetic component.
• A woman whose mother had an EM has a 6-fold
increased risk of having EM.
• Large GWAS with sample size of 3,500 cases
(women with menopause before 45 years of age)
and 13,500 controls (Perry et al., 2013).
• For all 17 variants associated with age at natural
menopause, the allele that was associated with
younger menopause age was also associated with
increased risk of EM and POI (Perry et al., 2013).
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12. Genetics of early menopause
• Combining the effect of the 17 variants shows
a larger effect on EM risk than smoking.
• It is hypothesized that EM and POI represent
the tail of the menopause distribution, with
individuals carrying more age at menopauselowering variants having increased risk of EM
and POI (Perry et al., 2013).
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13. Future perspectives
The discovery of additional genetic
components involved in the determination of
menopause age should make it possible to
predict the onset of menopause, enabling
women to make informed reproductive
choices.
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14. Thank you for your attention
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