The document discusses premature ovarian insufficiency (POI), also known as premature ovarian failure. It provides information on: - The prevalence of POI is approximately 1% in the general population. - Common causes of POI include genetic factors like Turner syndrome, Fragile X syndrome, and other chromosomal abnormalities. - POI can be diagnosed based on menstrual irregularities, elevated follicle-stimulating hormone levels, and low estrogen levels. - Management of POI focuses on hormone replacement therapy, lifestyle changes, fertility preservation and treatment, and prevention of long-term health issues associated with low estrogen levels like osteoporosis.

1. FAILING OVARY
DR SHIPRA KUNWAR
MD,FICOG,FMAS,MRCOG(UK)
PROFESSOR
DEPARTMENT OF OBSTETRICS AND
GYNAECOLOGY
ERA’S LUCKNOW MEDICAL COLLEGE

2. Ovary

3. At birth around 1-2
million oocytes
6-7 million
at 5 months
Only 3
lac
OVARIAN FOLLICULAR DEVELOPMENT
500

4. DNA, proteins, and messenger RNA (mRNA)
NO FURTHER PRODUCTION OF
OOCYTE
This time is utilised for
Most oocytes are lost during fetal development, and the remaining
follicles are steadily “used up” throughout the intervining years until menopause
OVARIAN PHYSIOLOGY

5. Quantitative & Qualitative decline of follicle
pool

6.  showed that production of oocytes and corresponding
folliculogenesis can occur well into adult life.

7. The reservoir of germline stem cells responsible for this
oocyte development appears to reside in the bone
marrow.
Study in humans is awaited and the result of such study
may provide the clinical leverage in disorders.

8. POOR OVARIAN RESERVE
CLINICAL
1. Age
2. History of poor response or cancelled cycles
3. Menstrual cycle length
BIOCHEMICAL
AMH, inhibin B,FSH
PROVOCATIVE TESTS
CCCT
ULTRASOUND MARKERS
AFC,OVARIAN VOLUME

9. Premature ovarian insufficiency
• Aging is associated in decline of ovarian function,
however, if it occurs earlier than 40 years of age it
is premature ovarian insufficiency ( premature
ovarian failure )

10. STAGES OF PREMATURE OVARIAN INSUFFICIENCY
Occult Biochemical Overt

11. Ovarian Clinical
Situation
Menses
Gonadotropins Fertility
Occult
insufficiency
Normal Normal Reduced
Biochemical
insufficiency
Abnormal Elevated Reduced
Overt
insufficiency Abnormal/Abse
nt
Elevated Reduced/ABSENT

12. PREMATURE OVARIAN INSUFFICIENCY
Apart from menstrual problems and infertility, POI is
a serious endocrine disorder as it leads to a two fold
age specific increase in mortality due to
cardiovascular disease, stroke and osteoporosis.

13. Stud Coulam CB, et al. Obstet Gynecol. 1986.
• Cohort of 1858 women born between 1928 and 1932.
these women were followed for date and type of
menopause.
AGE No.OF WOMEN
15-29 YEARS 10/100 women year
30 - 39 76/100 women year
40- 44 881/100 women year
1 percent risk
before 40
years

14. The prevalance is 10-28 % in women presenting with primary
amenorrhea, whereas in secondary amenorrhea the
prevalance is 4-18%.

15. ETHINIC VARIATION IN INCIDENCE
1.4 % African – American and Hispanic
descent
1% Caucasian
0.5% Chinese
0.1% Japanese

16. 27 JUNE 2016

17. S No Causes
1 Idiopathic 88.2%
2 X chromosome abnormalities
Turner/Turnersyndrome-likekaryotype FMR-
1premutation(Xq27.3) Bone morphogenetic protein
Other Xchromosome abnormalities (deletion,
translocation, others
6.7%
3 Autosomal causes
FSH receptor mutation Blepharophimosis
ptosis epicanthus inversus syndrome
0.5%
4 XY Gonadal dysgenesis 1.6%
5 Iatrogenic
hysterectomy
Chemotherapy/radiotherapy
Uterine artery embolisation
2.1%

18. S No Causes
7 Infections ?
8 Cigarette smoking ?
9 Other Autoimmune diseases associated with POF are thyroid,
parathyroid, diabetes mellitus, hypophysitis, chronic candidiasis,
autoimmune haemolytic anaemia, SLE, Myasthenia Gravis and
Crohn’s disease.
0.8%

19. TURNERS SYNDROME(X0)

20. Not necessarily you would find exact phenotypic features
American Gymnast Missy Marlowe Dr. Catherine Ward Melver

21. Fragile X syndrome( X-LINKED DOMINANT)
Developmental problems including learning disabilities and cognitive
impairment.
 Males are more severely affected by this disorder than females.
 May also have anxiety and hyperactive behavior such as fidgeting or
impulsive actions/ attention deficit disorder (ADD), which includes an
impaired ability to maintain attention and difficulty focusing on specific
tasks.
Most males and about half of females with fragile X syndrome have
characteristic physical features that become more apparent with age.
These features include long and narrow face , large ears , a prominent jaw
and forehead , unusually flexible fingers ,flat feet and in males, enlarged
testicles

22. • INDUCED PREMATURE MENOPAUSE-
Gonadal toxicity due to chemotherapy,
especially with alkylating agents or with
radiotherapy, leads to amenorrhea
which is reversible if only
the mature follicles are destroyed
and irreversible when all the primordial follicles are destroyed.
Complete ovarian failure occurs with a dose of 20 Gy of radiation.
Surgical menopause is induced by oophorectomy.

23.  hysterectomy maybe associated with an early menopause due
to damage to ovarian blood vessels, it may also be due to
inflammation.
Uterine Artery embolization interferes
with ovarian blood supply.

24. Clinical Presentation
• Menstrual irregularity
• Primary ammenorhoea ( 20%)
• Secondary ammenorhoea
• Symptoms of oetrogen deficiency
• hypothyroidism
• Diabetes mellitus
• hypoparathyroidism
• Family history of POI
• Mental retardation

25. Diagnosis and evaluation:
Any young woman with less than 9 menstrual cycles per year or missing more
than three or more consecutive menstrual cycles should be evaluated.
FSH
>25 AMH
TSH PRL

26. USG
• confirm absence of follicles, low ovarian
volume and poor ovarian blood flow
Chromosomal
analysis
• Should be carried out in all patients who present with primary
amenorrhoea or early onset ovarian failure. Gonads must be
removed if a Y chromosome or its part is present, because the
risk of malignancy
Autoimmune
screening
• Anti-adrenal and anti-thyroid antibodies should be done in all
women who present with late onset ovarian failure

27. BMD
• Bone Mineral Density should also be assessed at
it leads to increased incidences of Osteoporosis.
OVARIAN
BIOPSY
• is not indicated

28. POI
amenorrhea
Elevated
gonadotrophin
levels
signs and
symptoms of
oestrogen
deficiency

29. MANAGEMENT
To reduce the
psychological
trauma on
their
emotional
health
To manage
the
consequent
infertility
To prevent
the long term
effects of
oestrogen
deficiency
arising from
ovarian
failure

30. Daily intake of 1000 mg of calcium and 800 IU of vitamin D
Avoiding smoking and alcohol
Reduction of caffeine intake
Regular weight bearing exercises
Maintaining an active Lifestyle

31. Fertility management:
The chances of spontaneous conception in
women with POI is 5-10% .
However, advances in assisted reproductive techniques (ART) are a boon to these
women who desire a pregnancy.
In patients with a minimal ovarian reserve, conventional ovulation induction with
exogenous gonadotrophins can be tried. Success rates can be improved by pre-
treatment with oestrogen, thus lowering FSH levels followed by ovulation
induction.
In women with a confirmed diagnosis of POF, oocyte donation remains the most
elective form of therapy

32. Oocyte donation:
Oocyte donation and embryo donation has provided hope
the only realistic strategy for women with POI to achieve
motherhood.
A retrospective analysis in 2009 demonstrated its success of oocyte
donation in women with POF and physiological menopause.
IVF with donor oocytes confers the highest chance of successful
pregnancy with a success rate of 40-50% per cycle.

33. Menopausal hormonal therapy:
 offered to all POI women
alleviate the symptoms due to oestrogen deficiency
and more importantly to prevent the development of osteoporosis and
cardiovascular diseases.
 In adolescents, replacement therapy is required to help induce
secondary sexual characteristics. Women with POI will typically
require high doses of oestrogen.
They do well with conjugated oestrogens in a dose of 0.625–1.25 mg
or
transdermal oestradiol 100 mcg a day or oral oestradiol in a dose of
1-2 mg per day.

34. This typically achieves circulating serum oestradiol levels of, approximately,
100 pg/mL, which is the average level found during a normal menstrual
cycle.
Progesterone supplementation is recommended as micronized
progesterone 100-200 mg or medroxy progesterone acetate 5-10 mg per
day for 12-14 days per cycle. Progesterone is added to oestrogen, at least
for 12 days every month in order to protect the endometrium against
development of endometrial hyperplasia.
 The transdermal route offers the advantage of avoiding the
first pass hepatic metabolism and subsequent effects on clotting factors and
triglycerides (PDF) Premature Ovarian Failure.

35. • GLOBAL CONSENSUS STATEMENT ON MENOPAUSAL
HORMONAL THERAPY FOR WOMEN WITH PREMATURE
MENOPAUSE:
 MHT is the most effective treatment for vasomotor symptoms associated
with menopause at any age.
 Systemic MHT is recommended at least until the average age of natural
menopause.
 Estrogen as a single systemic agent is appropriate in women after hysterectomy
but additional progestogen is required in the presence of uterus.
 MHT is elective and appropriate for the prevention of osteoporosis related
fractures and standard oestrogen therapy alone in women of age <60 years may
decrease the coronary heart disease.

36. Local low dose estrogen therapy is preferred for women
whose symptoms are limited to vaginal dryness or
dyspareunia.
The dose and duration of MHT should be consistent with
treatment goals and safety issues should be individualised.
Current safety data does not support the use of MHT on
breast cancer survivors

37. Strategies for fertility preservation in young cancer
patients:
• Embryo cryopreservation
• Oocyte cryopreservation
• Primordial follicle extraction with IVM
• GnRH analogue therapy during chemotherapy GnRH
agonists at least 7 days prior to chemotherapy and continuing every 28-30 days
throughout the chemotherapy duration leads to interruption of FSH secretion
• Ovarian tissue cryopreservation
• Ovarian tissue transplantation- lateral ovarian transposition
>1.5 cm above the iliac crest has been significantly associated with ovarian
preservation.

39. 1.The overall prevalence of POI is :
A) 1%
B) 2%
C) 3%
D) 4%
E) 5%

40. 1.The overall prevalence of POI is :
A) 1%
B) 2%
C) 3%
D) 4%
E) 5%
ANSWER :1%

41. 2.With regard to Turners Syndrome, which is true
A. Women always present with primary ammenorrhoea
B. Women have karyotype 47 XXX
C. Women are always infertile
D. The external genitalia are underdeveloped
E. Women should be investigated for cardiac anomalies

42. 2.With regard to Turners Syndrome, which is true
A. Women always present with primary ammenorrhoea
B. Women have karyotype 47 XXX
C. Women are always infertile
D. The external genitalia are underdeveloped
E. Women should be investigated cardiac anomalies
ANSWER :E

43. 3.With regard to Fragile X Syndrome which is correct:
A. It has autosomal dominant inheritance
B. It has autosomal recessive inheritance
C. It is X-linked recessive inheritance
D. It is X –linked dominant inheritance

44. 3.With regard to Fragile X Syndrome which is correct:
A. It has autosomal dominant inheritance
B. It has autosomal recessive inheritance
C. It is X-linked recessive inheritance
D. It is X –linked dominant inheritance
Ans D