PREMATURE

OVARIAN INSUFFICIENCY

ESHRE Guidelines,

2015

Aboubakr Elnashar

Benha university,

Egypt ABOUBAKR ELNASHAR

CONTENTS

1.DEFINITION

2.PREVALENCE

3.CAUSES

4.DIAGNOSIS

5.MANAGEMENT OF SEQUALAE

5

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1. DEFINITION

Terminology:

“Premature ovarian insufficiency” should be used to more effectively reflect its heterogeneous nature.19b

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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

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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.

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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.

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Relatives of women with POI

Relatives of women with the fragile-X premutation

should be offered genetic counseling.

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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.

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3. CAUSES

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Aetiology of premature ovarian failure cases managed at the West London Menopause and PMS 387 Centre, London, UK (Maclaran and Panay, 2011 ).

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4. DIAGNOSIS

Symptoms

strogen deficiency

below the age of 40 ys.

with oligomenorrhea or amenorrhea

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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.

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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

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

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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}.

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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.

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Routine screening for diabetes

insufficient evidence

Infection screening

No indication

Unexplained or idiopathic POI.

In a significant number of women with POI

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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

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1. REDUCED LIFE EXPECTANCY

{CVD}.

Advise to reduce CVD risk factors

not smoking

Regular exercise

Maintaining a healthy weight.

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2. SMALL CHANCE OF SPONTANEOUS

PREGNANCY.

Women with POI should be advised to use

contraception if they wish to avoid pregnancy.

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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.

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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.

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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.

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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

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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.

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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.

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4. REDUCED BMD

Particularly in the early years after onset.

An increased risk of fracture later in life

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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.

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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.

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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.

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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.

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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

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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.

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Cardiovascular risk factors to be screened in women

with POI or Turner Syndrome (Bondy and Turner Syndrome Study Group, 2007; Turtle, et al., 2013).

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6. PSYCHOLOGICAL WELLBEING / QUALITY OF

LIFE

Psychological support

Psychological and lifestyle interventions

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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.

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8. GENITO-URINARY SYMPTOMS

Treatment

Local estrogens

effective

may be given in addition to systemic HRT.

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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.

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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.

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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}

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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

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Monitoring

Clinical review annually

Routine monitoring tests

Not required

±if specific symptoms or concerns.

Turner Syndrome:

HRT throughout the normal reproductive lifespan

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Contraindications

Breast cancer survivors. BRCA gene mutation or

after breast cancer

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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.

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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

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Androgen

supported by limited data

long-term health effects are not clear yet.

evaluated after 3-6 months

should be limited to 24 months.

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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.

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Estrogen substitution therapy in adolescence (Bondy and Turner Syndrome Study Group, 2007)

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263 lectures

1. My scientific

page on face

book: 3622

members

2. Slide share: 1259

followers

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