SLE and infertility: Aboubakr Elnashar

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SLE and infertility Aboubakr Elnashar Benha university Hospital, Egypt [email protected]

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Transcript of SLE and infertility: Aboubakr Elnashar

Page 1: SLE and infertility: Aboubakr Elnashar

SLE and infertility

Aboubakr Elnashar

Benha university Hospital, Egypt [email protected]

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Contents 1. Introduction

2. Causes of infertility in SLE

3.How to promote and safeguard

fertility

Conclusion

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1. Introduction Multisystem autoimmune disease: joints, kidneys,

serous surfaces and vessel walls (Madhok and Wu 2007).

Course

highly variable, exacerbation and remission periods

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Incidence:

1 in 2000 adult women

Tripled in the last 40 ys {improved detection of

mild disease}

Female-to-male ratio: 9:1

Peak onset: during childbearing age (Madhok and Wu 2007).

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Role of female hormones

unquestionable in the etiology

{1. 90% of those affected are women}.

2. Menopausal with SLE: EP RT: significantly

increased the incidence of lupus flares (Geva et al. 2004; Buyon et al. 2005).

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SLE & infertility

Fertility rate: comparable to that of the general

population,

This viewpoint is challenged (Hickman and Gordon, 2011)

1. SLE: 1% of infertile patients, which is more than

expected for a disease with incidence 1 in 2000

adult women

2. Decrease PR once SLE is diagnosed

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2. Causes of infertility Disease activity

Cytotoxic tt.

1. Ageing

•Delay planning conception 6-month after flare

2. Primary ovarian failure.

{Autoimmune causes or

drug induced}

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3. Menstrual disturbances

Common

Menorrhagia

{1. Anti-coagulation therapy given to those with

thrombotic complications

2. Thrombocytopenia: rare}.

Amenorrhea

{1. CYC causing ovarian failure

2. Disease itself: anti-corpus luteum antibodies}

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4. Cervico-vaginal inflammation and other

infections

{1. SLE

2. immunosuppressive tt]

5. Lupus nephritis.

30-75% of patients with SLE.

±deteriorate: CRF: infertility

{hypothalamicpituitary dysfunction}.

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6. Secondary APS.

30%

Miscarriage, stillbirths and PTL, venous and

arterial thrombotic events.

Recent studies failed to find a correlation between

the presence of such antibodies and infertility or

affecting the outcome of ART (Bellver and Pellicer 2009; Cervera and Balasch 2008; Mackillop et al. 2007).

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7. Treatment-related causes of infertility

a. CYC-induced POF

{deplete oocytes}.

Depend on:

1. Cumulative dose of CYC

2. Age (highest after 31 y)

Daily oral CYC:

amenorrhea within a year: permanent ov failure in

70%

Plans to conceive:

should be delayed, until at least 3 months after the

last dose {avoid teratogenicity}.

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MMF Mycophenolate mofetil (Cellcept)

Alternative

for CYC in the induction and maintenance

therapy for lupus nephritis

Favoured

{not cause POF}, although it is teratogenic

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b. NSAIDs:

: Risk of infertility

{LUF syndrome}

controversial.

Women having problems conceiving should be

advised to stop NSAIDs [Ostensen et al, 2006].

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c. CSs

Menstrual irregularities

{high-dose CSs}

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d. MTX

Teratogenicity {doses used in SLE}

Induce abortion {higher doses}

Infertility after MTX: rare

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8. Psycho-social aspects

1. SLE itself:

depression, fatigue and loss of libido/sexual

function

2. Drugs:

diminish libido (CSs)

reduction in the frequency of intercourse

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3. How to promote and safeguard

fertility 1. CYC

Lowest effective dose

Shortest duration

Gonadal protection if risk of therapy-induced POF.

use a different disease-modifying and steroid-sparing

therapy e.g. Mycophenolate mofetil MMF (Cellcept)

Fertility is more likely to be preserved if

Age ≤ 30 ys

IV pulse course of CYC lasts ≤ 6 months

Cumulative dose ≤ 7 g

No changes in the menstrual cycle during tt

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2. Prevention of POF

a. GnRha: leuprolide.

protective against POF when administered

10-14 d before each CYC pulse.

Leuprolide: reduction in E and P levels.

significantly reduce the risk of POF from 30 to 5% [Somers et al,2005].

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b. Oocyte storage.

Cryopreservation of gametes before gonadotoxic tt

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3. IVF.

Ovarian stimulation using GnRHa:

1. increase levels of oestrogens: increase the risk

of thrombosis

Thrombosis often occurs in the context of overt

OHSS

2. Flare

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Avoid ART

{high risk of complications for mother and fetus during

pregnancy & puerperium}

1. SLE manifested in acute flares

2. Badly controlled arterial hypertension, pulmonary

hypertension

3. Advanced renal disease

4. Severe heart disease and major previous

thrombotic events

Before ART:

1. Disease has been silent for at least 6 months

2. BP

3. Urine analysis

4. RFT

5. Pulmonary hypertension to be ruled out

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During ART:

1. Ovarian stimulation

Aggressive should be avoided

low effective Gnt dose

Mild ovarian stimulation {avoid high E2}.

Anti-oestrogens (CC or aromatase inhibitors)

Avoidance of OHSS & multiple pregnancy

2. OR:

If Heparin: to be stopped 12-24 h prior to OR & restarted

6-12 after

3. ET:

Single

4. Luteal phase support:

Natural P through a non-oral route

{avoid OHSS and first passage effect in liver} (Huong et al. 2002; Askanase and Buyon 2002; Bellver , 2012)

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APA, Hx of thrombosis APA, No Hx of

thrombosis

SLE, No APA

1. Warfarin is switched to

heparin therapeutic dose

before ov stim.

2. Heparin to be stopped 12-24

h prior to OR & restarted 6-

12 after

3. Heparin to be continued till

day of preg test & if pregnant

to continue during

pregnancy

4. Aspirin low dose to be added

, but to be interrupted 5-7 d

before OT

1.Heparin:

prophylactic dose

from day of ET

2. Aspirin:

unproven

1. Anti coagulation is not

recommended

2. Anti-inflammatory(

Corticosteroids or

immunosuppressant) to

be introduced or

increased

5. Prophylactic therapy

Anticoagulant: for thrombosis

Corticosteroids or immunosuppressant: for lupus

activity) during and after ovarian stimulation (Huong et al, 2002)

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Conclusion Although many authors state that the prevalence

of infertility in SLE patients is no greater than the

average population rate, there is a significant risk

of SLE and its treatment causing infertility.

CYC can cause menstrual irregularity,

amenorrhea, and infertility by inducing ovarian

failure

The disease itself can reduce fertility through

autoimmune mechanisms, hormonal disturbances

or renal failure.

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For optimal management of SLE in reproductive

age group:

we should consider how to reduce the risk from

all of these factors predisposing to infertility.

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Thank you Aboubakr Elnashar