Background: Fertility is thought to be not reduced in women affected by systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease as well as medication exposure might impair gonadal function.

Objectives: The aim of this systematic review was to explore clinical, hormonal, serological, instrumental and management factors associated with fertility outcomes in women of childbearing age with SLE.

Methods: This systematic review was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English, published from 1972 to 15th August 2020 in Pubmed, EMBASE, Scopus and Cochrane Library. Study selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. Risk of bias of the included studies was assessed by using the NIH risk-of-bias tool [1].

Results: Of 788 abstracts, we included in the review 45 studies of which 1 systematic literature reviews, 16 cross-sectional studies, 15 cohort studies, 12 observational studies and 1 case-series study, with a total of 4656 patients. The mean age was 33.5 ± 5.4 years, while the mean disease duration was 97.4 ± 65.2 months. Figure 1 illustrates the quality of the included studies. Definitions of fertility/premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered. Most studies did not use a hormonally based definition of fertility. Clinical factors associated with the development of POF were older age at the time 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 ovarian failure, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids seem to be associated with a lower risk of ovarian failure compared to CYC. 3 studies demonstrated that POF was more frequent in patients treated with CYC not receiving gonadotropin-releasing hormone analogues (GnRH) in comparison to those co-treated with GnRH. 11 studies evaluated the impact of damage and disease activity on ovarian reserve in patients with SLE with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors able to influence fertility outcomes; among others nor Anti-Müllerian Hormone, neither anti-corpus luteum antibodies were associated with POF.

Conclusion: The role of disease activity on fertility in SLE patients is contradictory. Regarding management factors associated with fertility in SLE women of childbearing age, the strongest evidence is about the treatment with CYC and its cumulative dose. Hormonal and serological factors did not impact on fertility outcome but might be used as a surrogate of fertility, especially after treatment with disease-specific drugs.

REFERENCES:

[1]Study Quality Assessment Tools NIH. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools .

[2]Andreoli L. et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017; 76: 476–485.

Disclosure of Interests: None declared