1. SLE and infertility
Aboubakr Elnashar
Benha university Hospital, Egypt
elnashar53@hotmail.com

2. Contents
1. Introduction
2. Causes of infertility in SLE
3.How to promote and safeguard
fertility
Conclusion

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].

14. c. CSs
Menstrual irregularities
{high-dose CSs}

15. d. MTX
Teratogenicity {doses used in SLE}
Induce abortion {higher doses}
Infertility after MTX: rare

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].

19. b. Oocyte storage.
Cryopreservation of gametes before gonadotoxic tt

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.

26. Thank you
Aboubakr Elnashar