3. 1. Introduction
Multisystem autoimmune disease: joints, kidneys,
serous surfaces and vessel walls
(Madhok and Wu 2007).
Course
highly variable, exacerbation and remission periods
4. 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).
5. 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).
6. 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
7. 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}
8. 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}
9. 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}.
10. 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).
11. 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}.
12. MMF Mycophenolate mofetil (Cellcept)
Alternative
for CYC in the induction and maintenance
therapy for lupus nephritis
Favoured
{not cause POF}, although it is teratogenic
13. b. NSAIDs:
: Risk of infertility
{LUF syndrome}
controversial.
Women having problems conceiving should be
advised to stop NSAIDs
[Ostensen et al, 2006].
16. 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
17. 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
18. 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].
20. 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
21. 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
22. 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)
23. APA, Hx of thrombosisAPA, 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)
24. 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.
25. 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.
