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1. In the name of God
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2. premature ovarian
failure(POF)?
Supervisor : Dr . Bahmanpour
Presenting by : Eisa . Moradiyan
2Department of anatomical sciences

3. What is the premature ovarian
failure(POF)?
(POF)
↓
characterized by
↓
premature depletion of ovarian follicles before the age
of 40 years, representing one major cause of female
infertility
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4. Anatomy
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5. (POF)
• (FSH) > 20 to 40 mIU/mL < 40 years
• 1% to 3% of women experience POF
• primary amenorrhea
• secondary amenorrhea
• POF may become pregnant spontaneously albeit
the likelihood is low
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6. (POF)
• The incidence is lower in younger women.
• variety of mechanisms and highly heterogeneous
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7. 7

8. • I Genetic aberrations (X chromosome or
autosome)
• II Autoimmune ovarian damage
• III Environmental factors
• IV Iatrogenic (surgical, radio or chemotherapy)
• V Metabolic changes (galactosaemia …)
• VI Defect in structure/effects of gonadotrophins
• VII Idiopathic

9. Cause of POF
• Genetic aberrations (in some Cases):
45,X or Turner syndrome
Fragile X syndrome
Deletions of the short or long arm of the X chromosome
Fetuses Trisomy 13 and 18 ovarian dysgenesis
Numerous autosomal genes mutation(ovarian
development) 9

10. Cause of POF
(APS type 1 and 2)
Perrault syndrome(POF and neurosensory deafness)
Ataxia telangiectasia(ATM gene)
Type I blepharophimosis, ptosis, epicanthus inversus
syndrome can present with POF(FOXL2 mutations)
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11. Cause of POF
 Perturbations of somatic genes (FSHR, LHR)
 It is estimated that the cause of 90% of the primary POF
cases still remains unknown
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12. Turner syndrome
• abnormalities is 45,X
• affects 1 in 2500 female
• spontaneous abortion (75%)
• short stature
• cardiovascular anomalies (coarctation of the aorta
and aortic valvular abnormalities)
• webbed neck
• lymphedema
• Ovarian dysgenesis
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13. Turner syndrome
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14. Deletions of the short or long arm of
the X chromosome
• variable phenotype
• Proximal deletions of Xq21(primary amenorrhea)
• Xp another phenotype
• critical region : at Xq13.3-Xq27
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15. Deletions of the short or long arm of
the X chromosome
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16. Fragile X syndrome
• located on chromosome Xq27.3
• Premutation, <200 CGG repeats
• Gene FMRI
• between 3% and 12% depending on the family
history.
• approximately 20% of the fragile X carriers
develop POF.
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17. Fragile X syndrome
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18. Trisomy 13 and 18
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19. Mutation Numerous autosomal
genes(ovarian development)
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BMP-15 and GDF-9.31

20. 20

21. Autoimmune polyendocrine
syndrome (APS) type 1 and 2
• (APS) type 1: AIRE Genes
• adrenal insufficiency
• hypoparathyroidism
• Hypothyroidism
• type 1 diabetes mellitus
• ovarian failure
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22. Perrault syndrome
• Both males and females
• Sensorineural hearing loss
• Ovarian dysgenesis
• Mutation TWNK, CLPP, HSD17B4, and LARS2
genes
• External genitalia are normal
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23. Perrault syndrome
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24. Ataxia telangiectasia
• Defective DNA repair mechanisms
• ATM gene
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25. Blepharophimosis–ptosis–epicanthus
inversus
syndrome(BPES)
• Mutation FOXL2 genes (eyelids and ovaries)
• Eyelid malformations
• POF
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26. Blepharophimosis–ptosis–epicanthus
inversus
syndrome (BPES)
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27. Iatrogenic
• Chemotherapy
• Irradiation
• Infections such as mumps oophoritis
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28. Chemotherapy
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29. Chemotherapy
Treatment by CYC
Ovarian
atrophy
Reduce
number of
follicles
growing
Increased
ovarian
fibrosis
Reduce
number of
primordial
follicles
29Xiu- yinchenal et al, 2016

30. Irradiation
• Patient’s age
• The x-ray dose
• Younger women (less likely to have POF)
• Gonadotropins levels rise after irradiation
.
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31. Risk Factors
• Age : The risk of ovarian failure rises sharply
between age 35 and age 40
• Family history : Having a family history of
premature ovarian failure increases your risk of
developing this disorder.
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32. Symptoms
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Irregular or
skipped periods
Hot flashes
Decreased
sexual desire
Vaginal
dryness
Night sweats

33. 33
POF
osteoporosis
osteoarthritis
cardiovascular
disease
neurodegenerative
diseases

34. Diagnostic workup of POF
• Follicle-stimulating hormone (FSH) test.
• Estradiol test.
• Prolactin test
• Karyotype
• FMR1 gene testing.
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35. History
1. Last spontaneous menstrual cycle
2. Prior pelvic surgeries, irradiation, or
chemotherapy
3. Symptoms of adrenal insufficiency:
Skin hyperpigmentation
Salt craving
Abdominal pain
5. mental retardation,autoimmune disorders
6. Symptoms of estrogen deprivation
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36. Managment
• Hormone replacement therapy (HRT)Estrogens
Estrogens→ orally or transdermally
Progestins → 10-14 days each month, to prevent
endometrial hyperplasia
Androgens → methyl testosterone → 1.25-2.5
mg/d
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37. Restoration fertility
• Steroids ≠ autoimmune POF→ osteonecrosis
• Gonadotropin therapy → risk of exacerbating
autoimmune POF
• ART
Oocyte donation
Embryo adoption
 Surrogacy
 Ovarian cryopreservation
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38. Life style modification
• Diet
– Elemental Calcium : 1200-1500 mg day.
– Adequate intake of vitamin D.
• Activity
– exercises for 30 at least 3 days per week improve
muscle strength and maintain bone mass
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39. • 1. Bilgin EM, Kovanci E. Genetics of premature ovarian failure. Current Opinion in
Obstetrics and Gynecology. 2015;27(3):167-74.
• 2. Zhao H, Chen ZJ, Qin Y, Shi Y, Wang S, Choi Y, et al. Transcription factor FIGLA is
mutated in patients with premature ovarian failure. Am J Hum Genet. 2008;82(6):1342-8.
• 3. Chapman C, Cree L, Shelling AN. The genetics of premature ovarian failure: current
perspectives. International journal of women's health. 2015;7:799.
• 4. Del Mastro L, Ceppi M, Poggio F, Bighin C, Peccatori F, Demeestere I, et al.
Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced
premature ovarian failure in cancer women: systematic review and meta-analysis of
randomized trials. Cancer treatment reviews. 2014;40(5):675-83.
• 5. Jankowska K. Premature ovarian failure. Przegla̜ d Menopauzalny= Menopause Review.
2017;16(2):51.
• 6. Kovanci E, Schutt AK. Premature ovarian failure: clinical presentation and treatment.
Obstet Gynecol Clin North Am. 2015;42(1):153-61.
• 7. Lai D, Wang F ,Yao X, Zhang Q, Wu X, Xiang C. Human endometrial mesenchymal
stem cells restore ovarian function through improving the renewal of germline stem cells in a
mouse model of premature ovarian failure. Journal of translational medicine. 2015;13(1):155.
• 8. Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian
failure. Journal of molecular endocrinology. 2010;45(5):257-79.
• 9. Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency.
Clinical genetics. 2017 ;91)2:)183-98.
• 10. Yang JJ, Cho LY, Lim YJ, Ko K-P, Lee K-S, Kim H, et al. Estrogen receptor-1 genetic
polymorphisms for the risk of premature ovarian failure and early menopause. Journal of
Women's Health. 2010;19(2):297-304.
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41. Life is short.
cut out negativity,
forget gossip,
forgive who hurt you .
Spend your days with peopele
who are always there
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