Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy.
Unit of Rheumatology, Ospedale Maggiore, Bologna, Italy.
Autoimmun Rev. 2022 Apr;21(4):103038. doi: 10.1016/j.autrev.2022.103038. Epub 2022 Jan 4.
Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function.
This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE.
This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Studies selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool.
Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.28, 95%-CI [0.14; 0.55]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF.
The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.
人们认为系统性红斑狼疮（SLE）女性的生育能力不受影响，然而，疾病相关因素、慢性疾病的心理社会影响以及药物暴露可能会损害性腺功能。
本系统文献综述（SLR）旨在探讨与生育能力相关的临床、激素、血清学和治疗因素，以评估生育年龄的 SLE 女性的生育结局。
本 SLR 遵循系统评价和荟萃分析的首选报告项目（PRISMA）声明进行。检索 Pubmed、EMBASE、Scopus 和 Cochrane Library 中所有可用的英文文献（1972 年至 2021 年 4 月 30 日）。两名独立审查员对研究进行筛选和数据收集。使用标准化模板提取所有数据。使用 NIH 偏倚风险工具评估纳入研究的偏倚风险。
在评估的 789 篇摘要中，我们纳入了本综述中的 46 项研究，其中 1 项 SLR、16 项横断面研究、18 项队列研究、10 项观察性研究和 1 项病例系列研究，共涉及 4704 名患者（平均年龄 31.5±3.7 岁，疾病持续时间 83.27±38.3 个月）。研究中采用的卵巢早衰（POF）定义在考虑闭经的月数和闭经发病年龄方面存在差异。与 POF 发生相关的临床因素为治疗开始时年龄较大，以及 SLE 疾病发病时年龄较大。环磷酰胺（CYC）暴露及其累积剂量影响 SLE 女性的性腺功能，导致闭经和 POF，19 项研究报告了这一点。与 CYC 相比，霉酚酸酯、硫唑嘌呤、钙调神经磷酸酶抑制剂和类固醇与 POF 的风险较低。与未接受 GnRH-a 的患者相比，同时接受 CYC 和 GnRH-a 治疗的患者 POF 发生率较低（风险比 0.28，95%CI [0.14;0.55]）。11 项研究评估了损伤累积和疾病活动对卵巢储备的影响，但证据相互矛盾。最后，18 项研究调查了激素和血清学因素的暴露情况，其中抗苗勒管激素和黄体生成素抗体均与 POF 无关。
与生育年龄的 SLE 女性生育能力相关的管理因素的最强证据仍然是 CYC 的治疗，以及其累积剂量。激素和血清学因素似乎不会影响生育结局，但它们可能被用作特定疾病药物治疗时生育能力的替代指标。
