Sparaco Maddalena, Carbone Luigi, Landi Doriana, Ingrasciotta Ylenia, Di Girolamo Raffaella, Vitturi Giacomo, Marfia Girolama Alessandra, Alviggi Carlo, Bonavita Simona
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 2, 80138, Naples, Italy.
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, Federico II University of Naples, Naples, Italy.
CNS Drugs. 2023 Oct;37(10):849-866. doi: 10.1007/s40263-023-01036-1. Epub 2023 Sep 7.
Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure.
多发性硬化症(MS)主要影响育龄女性。MS的各个方面都可能影响生育能力,如性功能障碍、内分泌改变、自身免疫失衡以及疾病修正治疗(DMTs)。随着时间的推移,寻求不孕不育管理和辅助生殖技术(ART)的MS女性(wMS)比例在增加。在本综述中,我们报告了有关wMS中ART的数据并探讨了安全问题。我们还讨论了在规划不孕不育治疗方案时应考虑的临床方面,并提供最新建议以指导神经科医生管理接受ART的wMS,目标是降低该手术后疾病激活的风险。根据大多数研究,ART后复发率和磁共振成像活动会增加。因此,为降低复发风险,应在疾病稳定的wMS中考虑ART。在wMS中,尤其是疾病活动度高的患者,应尽早讨论生育问题作为DMT的选择,并且在某些特定情况下可能会提出生育力保存策略,以确保疾病得到控制且妊娠安全。对于正在服用与妊娠兼容的DMT且疾病稳定的患者,在ART前不应中断治疗。如果正在进行的治疗在妊娠中禁忌,则应切换为兼容的治疗方法。在wMS开始生育治疗之前,评估血清维生素D水平、甲状腺功能及其抗体血清水平;开始补充叶酸;并确保戒烟戒酒、充足睡眠和食品卫生是合理的。应进行解脲脲原体、人型支原体和沙眼衣原体的宫颈阴道拭子检查,以及病毒性肝炎、HIV、梅毒和巨细胞病毒的血清学检查。在特定指征下可使用类固醇。尽管现有数据并未明确显示与特定ART方案相关的明确复发风险增加,但使用促性腺激素释放激素(GnRH)拮抗剂进行卵巢刺激似乎相当安全。合理建议进行密切的临床和影像学监测,特别是在激素刺激后以及妊娠失败的情况下。