SLE and infertility: Aboubakr Elnashar

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Transcript of SLE and infertility: Aboubakr Elnashar

  • SLE and infertility Aboubakr Elnashar Benha university Hospital, Egypt
  • Contents 1. Introduction 2. Causes of infertility in SLE 3.How to promote and safeguard fertility Conclusion
  • 1. Introduction Multisystem autoimmune disease: joints, kidneys, serous surfaces and vessel walls (Madhok and Wu 2007). Course highly variable, exacerbation and remission periods
  • 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).
  • 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).
  • 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
  • 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}
  • 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}
  • 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}.
  • 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).
  • 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}.
  • MMF Mycophenolate mofetil (Cellcept) Alternative for CYC in the induction and maintenance therapy for lupus nephritis Favoured {not cause POF}, although it is teratogenic
  • b. NSAIDs: : Risk of infertility {LUF syndrome} controversial. Women having problems conceiving should be advised to stop NSAIDs [Ostensen et al, 2006].
  • c. CSs Menstrual irregularities {high-dose CSs}
  • d. MTX Teratogenicity {doses used in SLE} Induce abortion {higher doses} Infertility after MTX: rare
  • 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
  • 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
  • 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].
  • b. Oocyte storage. Cryopreservation of gametes before gonadotoxic tt
  • 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
  • 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
  • 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)
  • 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)
  • 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.
  • 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.
  • Thank you Aboubakr Elnashar