This document provides guidelines for the diagnosis and management of premature ovarian insufficiency (POI). It defines POI as depletion of follicular activity before age 40, characterized by menstrual disturbances, raised gonadotropins, and low estrogen. The prevalence is approximately 1% in the general population. Causes include genetic factors, autoimmune disorders, infections, chemotherapy and radiation. Management focuses on hormone replacement therapy (HRT) to reduce long-term health risks, fertility options, and treatment of symptoms like reduced bone mineral density and increased cardiovascular risk.

1. PREMATURE
OVARIAN
INSUFFICIENCY
ESHRE Guidelines,
2015
Aboubakr Elnashar
Benha university,
Egypt
ABOUBAKR ELNASHAR

2. CONTENTS
1.DEFINITION
2.PREVALENCE
3.CAUSES
4.DIAGNOSIS
5.MANAGEMENT OF SEQUALAE
5
ABOUBAKR ELNASHAR

3. 1. DEFINITION
Terminology:
“Premature ovarian insufficiency” should be used
to more effectively reflect its heterogeneous nature.19b
ABOUBAKR ELNASHAR

4. Define
Clinical syndrome
Depletion of follicular activity before the age of 40.
Characterized by:
1. Menstrual disturbance
amenorrhea or
oligomenorrhea
2. Raised gonadotropins
3. Low E2
ABOUBAKR ELNASHAR

5. 2. PREVALENCE
In the general population
1%.
Ethnicity may affect the prevalence.
To reduce the incidence
{long-term health consequences }
• gynaecological surgical practice
• lifestyle – smoking
• modified tt for malignant and chronic diseases.
ABOUBAKR ELNASHAR

6. Cigarette smoking and POI
No causal relation
There is a relation to early menopause.
: women who are prone to POI should be advised
to stop smoking.
ABOUBAKR ELNASHAR

7. Relatives of women with POI
Relatives of women with the fragile-X premutation
should be offered genetic counseling.
ABOUBAKR ELNASHAR

8. Relatives of women with non-iatrogenic POI
•No proven predictive test to identify women that
will develop POI
•No established POI preventing measures
•Potential benefit of fertility preservation: unclear
•Potential risk of earlier menopause should be
taken into account when planning a family.
ABOUBAKR ELNASHAR

9. 3. CAUSES
ABOUBAKR ELNASHAR

10. ABOUBAKR ELNASHAR

11. ABOUBAKR ELNASHAR

12. ABOUBAKR ELNASHAR

13. Aetiology of premature ovarian failure cases managed at theWest London Menopause
and PMS 387 Centre, London, UK (Maclaran and Panay, 2011 ).
ABOUBAKR ELNASHAR

14. 4. DIAGNOSIS
Symptoms
strogen deficiency
below the age of 40 ys.
with oligomenorrhea or amenorrhea
ABOUBAKR ELNASHAR

15.  Investigations for diagnosis
1. Cycle irregularly for at least
4 months +
Oligo/amenorrhea:
2. An elevated FSH level
> 25 IU/l on 2 occasions > 4
weeks apart.
ABOUBAKR ELNASHAR

16. Investigations for causes
1. Chromosomal analysis should be performed in
all.
{Gonadectomy should be recommended for all
women with detectable Y chromosomal
material}.
 Fragile-X premutation testing is indicated.
The implications of the fragile-X premutation
should be discussed before the test is
performed. Permission from the patient to perform the test
 Autosomal genetic testing is not indicated,
unless there is evidence suggesting a specific
mutation (e.g. BPES).
ABOUBAKR ELNASHAR

17. Fragile-X testing is indicated in all women with POI,
{1. establish the causation of POI
2. it has major implications for herself and her family}.
1. Family members ±carriers: developing POI and
a risk of having (grand)children with fragile-X
syndrome.
2. Patient: risk of fragile-X-associated
tremor/ataxia syndrome (FXTAS), a late onset
neurological problem
ABOUBAKR ELNASHAR

18. 2. Screening for 21OH-Ab (or alternatively
adrenocortical antibodies (ACA))
{if +ve: an endocrinologist for testing of adrenal
function and to rule out Addison’s disease}.
ABOUBAKR ELNASHAR

19. 3. Screening for thyroid (TPO-Ab) antibodies.
{if positive: TSH should be measured /y}.
If 21OH-Ab/ACA and TPO-Ab are negative:
No indication for re-testing later in life, unless signs
or symptoms of these endocrine diseases develop.
ABOUBAKR ELNASHAR

20. Routine screening for diabetes
insufficient evidence
Infection screening
No indication
Unexplained or idiopathic POI.
In a significant number of women with POI
ABOUBAKR ELNASHAR

21. ABOUBAKR ELNASHAR

22. ABOUBAKR ELNASHAR

23. 5. MANAGEMENT OF SEQUELAE
1. REDUCED LIFE EXPECTANCY
2. SMALL CHANCE OF SPONTANEOUS PREGNANCY.
3. OBSTETRIC RISKS
4. REDUCED BMD
5. INCREASED RISK OF CVD
6. PSYCHOLOGICAL WELLBEING / QUALITY OF LIFE
7. SEXUAL DYSFUNCTION
8. GENITO-URINARY SYMPTOMS
9. DETRIMENTAL EFFECT ON NEUROLOGICAL
FUNCTION
10. VASOMOTOR SYMPTOMS
ABOUBAKR ELNASHAR

24. 1. REDUCED LIFE EXPECTANCY
{CVD}.
Advise to reduce CVD risk factors
not smoking
Regular exercise
Maintaining a healthy weight.
ABOUBAKR ELNASHAR

25. 2. SMALL CHANCE OF SPONTANEOUS
PREGNANCY.
Women with POI should be advised to use
contraception if they wish to avoid pregnancy.
ABOUBAKR ELNASHAR

26. Fertility interventions
No interventions that have been reliably shown to
increase ovarian activity and natural conception
rates.
Oocyte donation is an established option for
fertility.
oocyte donation from sisters has a higher rate of
cycle cancellation.
In women with established POI, the opportunity for
fertility preservation is missed.
ABOUBAKR ELNASHAR

27. 3. OBSTETRIC RISKS
 idiopathic POI or most forms of chemotherapy:
No higher obstetric or neonatal risk than in the
general population.
 Radiation to the uterus:
high risk of obstetric complications: should be
managed in an appropriate obstetric unit.
 Turner Syndrome
very high risk of obstetric complications: should be
managed in an appropriate obstetric unit with
cardiologist.
ABOUBAKR ELNASHAR

28.  Oocyte donation pregnancies
high risk: should be managed in an appropriate
obstetric unit.
Antenatal aneuploidy screening should be based
on the age of the oocyte donor.
A cardiologist should be involved in care of
pregnant women who have received anthracyclines
and/or cardiac irradiation.
ABOUBAKR ELNASHAR

29. Assessment for fitness for pregnancy
Women presenting for oocyte donation who are
suspected of having POI should be fully
investigated prior to oocyte donation
thyroid and adrenal function as well as
karyotype.
Pregnancy in some women can be of such high
risk that clinicians may consider oocyte donation to
be life threatening and therefore inappropriate
ABOUBAKR ELNASHAR

30. Women previously exposed to anthracyclines,
high dose cyclophosphamide or mediastinal
irradiation
ECG prior to pregnancy.
Those who are identified to have impaired
cardiac function or structural abnormalities should
be referred to a cardiologist.
ABOUBAKR ELNASHAR

31. Women with Turner Syndrome
cardiologist with a specialist interest in adult
congenital heart diseas
 general medical and endocrine examination.
Women with POI
blood pressure
renal function
thyroid function assessed prior to pregnancy.
ABOUBAKR ELNASHAR

32. 4. REDUCED BMD
Particularly in the early years after onset.
An increased risk of fracture later in life
ABOUBAKR ELNASHAR

33. Bone protection and improvement
1. Healthy lifestyle:
weight-bearing exercise
avoidance of smoking
maintenance of normal body weight
2. A balanced diet will contain the recommended
intake of calcium and vitamin D.
3. Dietary supplementation
in women with inadequate vitamin D status and/or
calcium intake, and may be of value in women
with low BMD.
ABOUBAKR ELNASHAR

34. 4. Estrogen replacement
{maintain bone health: prevent osteoporosis: reduce
the risk of fracture}.
5. Other pharmacological tts
Bisphosphonates, should only be considered with
advice from an osteoporosis specialist.
Particular caution applies to women desiring
pregnancy.
ABOUBAKR ELNASHAR

35. Monitoring bone in women with POI
Measurement of BMD at initial diagnosis
DEXA should be performed where there are additional risk factors but
may not be of value in all women with a new diagnosis of POI where
estrogen replacement is initiated early.
Repeated measurement of BMD
If BMD is normal and adequate systemic estrogen replacement is
commenced, the value of repeated DEXA scan is low.
ABOUBAKR ELNASHAR

36. If a diagnosis of osteoporosis is made and
estrogen replacement or other therapy initiated,
BMD measurement should be repeated after 5
years.
A decrease in BMD should prompt review of
estrogen replacement therapy and of other potential
factors. Review by a specialist in osteoporosis may
be appropriate.
ABOUBAKR ELNASHAR

37. 5. INCREASED RISK OF CVD
Behavioural change to decrease risk:
stopping smoking
regular weight-bearing exercise
healthy weight
Turner Syndrome:
cardiologist with expertise in congenital heart
disease
ABOUBAKR ELNASHAR

38. Is estrogen replacement cardio-protective?
HRT
with early initiation is strongly recommended in
POI to control future risk of CVD
should be continued at least until the estimated
normal age of menopause.
ABOUBAKR ELNASHAR

39. Cardiovascular risk factors to be screened in women
with POI or Turner Syndrome
(Bondy and Turner Syndrome Study Group, 2007; Turtle, et al., 2013).
ABOUBAKR ELNASHAR

40. 6. PSYCHOLOGICAL WELLBEING / QUALITY OF
LIFE
Psychological support
Psychological and lifestyle interventions
ABOUBAKR ELNASHAR

41. 7. SEXUAL DYSFUNCTION
Routinely inquire about sexual function
Management of sexual dysfunction
Estrogen replacement:
normalising sexual function.
Local estrogen:
to treat dyspareunia.
Testosterone:
some women with POI and sexual dysfunction
but long-term efficacy and safety are unknown.
Lubricants:
vaginal discomfort
dyspareunia for women not using HRT.

ABOUBAKR ELNASHAR

42. 8. GENITO-URINARY SYMPTOMS
 Treatment
 Local estrogens
effective
may be given in addition to systemic HRT.
ABOUBAKR ELNASHAR

43. 9. DETRIMENTAL EFFECT ON NEUROLOGICAL
FUNCTION
on cognition should be discussed when planning hysterectomy and/or
oophorectomy under the age of 50 years, especially for prophylactic reasons.
Management
Estrogen replacement:
reduce the possible risk of cognitive impairment
For at least up to the age of natural menopause.
ABOUBAKR ELNASHAR

44. 10. VASOMOTOR SYMPTOMS
lifestyle measures
Exercise
cessation of smoking
maintaining a healthy weight to reduce possible
risks for cognitive impairment
HRT
for the tt of VMS.
ABOUBAKR ELNASHAR

45. ABOUBAKR ELNASHAR

46. Risks of HRT
No increase risk of breast cancer before the age of
natural menopause.
An intact uterus:
progestogen in combination with estrogen therapy
{endometrial protection}
ABOUBAKR ELNASHAR

47. HRT
17-β estradiol
preferred to EE or conjugated equine estrogens.
Synthetic progestogens
preferred, until safety data on the ability of
micronized progestogens to adequately protect the
endometrium from the mitogenic effects of estrogen.
Route:
According to patient preference
ABOUBAKR ELNASHAR

48. Monitoring
Clinical review annually
Routine monitoring tests
Not required
±if specific symptoms or concerns.
Turner Syndrome:
HRT throughout the normal reproductive lifespan
ABOUBAKR ELNASHAR

49. Contraindications
Breast cancer survivors. BRCA gene mutation or
after breast cancer
ABOUBAKR ELNASHAR

50. Not contraindication
1. women carrying BRCA1/2 mutations but without
personal history of breast cancer after
prophylactic BSO.
2. Surgically induced menopause because of
endometriosis:
E/P or tibolone
at least up to the age of natural menopause
3. Post-menopausal women after hysterectomy and
with a history of endometriosis:
Avoid unopposed E.
However, the theoretical benefit of avoiding disease reactivation and
malignant transformation of residual disease should be balanced against
the increased systemic risks associated with combined E/P or tibolone.
ABOUBAKR ELNASHAR

51. 4. Migraine:
changing dose, route of administration or regimen
if migraine worsens during HRT.
5. Hypertension
transdermal E2 is the preferred method of delivery
6. History of prior VTE
haematologist prior to commencing HRT.
Transdermal E2 is the preferred route
7. Obesity or overweight:
Transdermal E2 is the preferred method
8. Fibroids
ABOUBAKR ELNASHAR

52. Androgen
supported by limited data
long-term health effects are not clear yet.
evaluated after 3-6 months
should be limited to 24 months.
ABOUBAKR ELNASHAR

53. Induction of Puberty:
17β-estradiol
starting with low dose at the age of 12 with a
gradual increase over 2 to 3 years.
In cases of late diagnosis and for those girls in whom growth is not a
concern, a modified regimen of E2 can be considered.
Transdermal E2
: more physiological estrogen levels: preferred.
COC:
contra-indicated for puberty induction.
Cyclical progestogens
Start after at least 2 years of estrogen or when
breakthrough bleeding occurs.
ABOUBAKR ELNASHAR

54. Estrogen substitution therapy in adolescence
(Bondy and Turner Syndrome Study Group, 2007)
ABOUBAKR ELNASHAR

55. 263 lectures
1. My scientific
page on face
book: 3622
members
2. Slide share: 1259
followers
ABOUBAKR ELNASHAR