Читать книгу Assisted Reproduction Techniques - Группа авторов - Страница 85

Accurate preconception counseling is required in SLE patients to assess disease activity and drug compatibility with pregnancy. Pregnancies should be planned during periods of disease stability, and treatment needs to be adjusted to obtain the remission of the disease or modified to avoid its potential teratogenic effects. Well‐controlled disease at conception is associated with better maternal and fetal outcomes. However, the postponement of conception, recommended in SLE patients with active disease until a period of clinical remission or disease stability of at least 6 months, may result in a decrease in the ovarian reserve associated with age [9]. In the Case History, ovarian stimulation was initiated 12 months after the last lupus flare.

Drugs commonly used in infertility treatments are not contraindicated in patients with SLE. Controlled ovarian stimulation is generally safe for infertile women diagnosed with SLE and/or APS, especially in patients with a stable disease. In the presence of active SLE, poorly controlled arterial hypertension, heart or renal disease and major prior thrombotic events, infertility treatments should be discouraged due to the high risk of maternal and fetal complications during pregnancy [10].

In aPL‐positive women undergoing ovarian stimulation, an antithrombotic treatment according to the individual risk profile is highly recommended to prevent vascular thrombosis [11]:

 Women with aPL antibodies and a history of thrombosis: should receive therapeutic doses of low molecular weight heparin (LMWH) and low dose aspirin (LDA) from the beginning of COS;

 Women with aPL antibodies but no history of thrombosis: should receive prophylactic LMWH starting on the day of embryo transfer, in combination with LDA [9].

In all cases, LMWH should be stopped 12–24 hours before the procedure of egg retrieval and started again 6–12 hours later if no bleeding occurs. LDA should be discontinued 5–7 days before egg retrieval and resumed the following day. According to the 2017 European League Against Rheumatism (EULAR) recommendations, LDA should be stopped only 3 days before oocyte retrieval [9]. Heparin and aspirin are to be maintained until the day of the pregnancy test and should be continued in the case of pregnancy [11].

In women with only SLE and not APS, anticoagulation is not recommended, but the use of anti‐inflammatory therapy (corticosteroids, immunosuppressants) should be considered depending on the disease activity to prevent SLE flares, especially when gonadotropins are used and serum estradiol level rises [12].

Stimulation protocols should be adapted for each patient, balancing safety and risks. Patients with SLE, especially if with concomitant aPL positivity, are at higher risk of complications linked to hormonal stimulation. The estrogenic peak reached during the ovarian stimulation increases the risk of thrombosis, ovarian hyperstimulation syndrome (OHSS) and lupus flare. The incidence of thrombotic complications is low and is often linked to a lack of adequate prophylactic anticoagulant therapy. During ovarian stimulation the predominant estrogen involved is 17 beta estradiol, which is less procoagulant than a synthetic one, and estrogens are only temporarily elevated. The risk of thrombosis during infertility treatments is lower than that observed during pregnancy where estrogens are up by 10‐fold than those obtained with fertility medications. Even if the risk of OHSS is comparable to that observed in the general population of infertile patients (3–8%) [13], SLE patients are at higher risk for OHSS‐related complications. The rate of disease exacerbations after infertility treatments in patients with a well‐controlled or quiescent disease appears to be comparable with nonstimulated women with SLE [10]. In the Case History, thrombotic complications were prevented by the administration of anticoagulants (aspirin, heparin) during and after ovarian stimulation, while lupus activity was controlled with the use of corticosteroids.

The use of oral contraceptives for cycle programming should be discouraged because of the increased risk of thrombosis, particularly in women with positive aPL[14]. A milder hormonal stimulation, a GnRH antagonist protocol, a GnRH agonist for ovulation triggering, administration of lower doses of hCG, freeze‐all approach and a single embryo transfer are some of the strategies available to prevent OHSS syndrome[11].

Progestins can be administered in patients with SLE and/or APS for luteal phase support (LPS) and during pregnancy. Depending on the individual thromboembolic risk, anticoagulant therapy may be required during progestins administration (aPL positivity) [9]. Nonoral route administration of natural progesterone (P) should be preferred to synthetic oral drugs in terms of thrombotic risk prevention [11].