Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's)

Objective Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study, we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX). Methods Patients in the Wegener's Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women ages <50 years, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti‐Müllerian hormone (AMH) and follicle‐stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as an AMH level of <1.0 ng/ml. Results Of 42 women in this analysis (mean age 35 years), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6 of 8 who received CYC during the trial developed diminished ovarian reserve, compared to 0 of 4 who did not receive CYC ( P < 0.05). Changes in AMH correlated inversely with cumulative CYC dose ( P < 0.01), with a 0.74 ng/ml decline in AMH level for each 10 gm of CYC. Conclusion Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88079/1/20605_ftp.pd

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/1/art41191.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/2/art41191_am.pd

Aspirin for Prevention of Preeclampsia in Lupus Pregnancy

Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy

Aspirin for Prevention of Preeclampsia in Lupus Pregnancy

Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A 2 /prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A 2 /prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy

Breastfeeding in women with rheumatic diseases

Objective Many rheumatologists and women with rheumatic disease worry that the disease or treatment will prevent breast feeding. International guidelines establish, however, that most antirheumatic medications are compatible with breast feeding. We sought to identify the frequency and predictors of desire to and actually breast feeding in women with rheumatic diseases.Methods Pregnant women with rheumatic disease were enrolled prospectively. Demographics and breastfeeding intention were collected at study entry, while actual breastfeeding decision was recorded postpartum. Maternal diagnosis, demographics and medication use was collected throughout the study. Predictors of breast feeding and intention were identified using stepwise logistic regression.Results A total of 265 pregnancies were included in the study, 88 with SLE, 33 with undifferentiated connective tissue disease, 100 with arthritis and 44 with other rare rheumatic diagnoses. Of these, 79% intended to breastfeed, 84% of women ever breast fed and 65% were still breast feeding at an average of 7.6 weeks postpartum. Medication concern was the most commonly cited reason not to breastfeed though only 5% of women were taking or planning to start a non-lactation compatible medication at their postpartum visit. In multivariate analysis, women with a college degree were more likely and women with SLE were less likely to intend to breastfeed. Actual breast feeding was most strongly predicted by the woman’s intention to breastfeed, but also increased with maternal age, decreased if the baby was born preterm and decreased the further the postpartum appointment occurred from delivery.Conclusion This study demonstrates that the majority of women with rheumatic disease want to and can breastfeed successfully. Additionally, very few women required a medication that was not compatible with breast feeding to control their rheumatic disease in the postpartum period. Despite this, an important minority of patients did not continue breast feeding due to their personal concerns about the risks of antirheumatic medications to their infant

Family planning and pregnancy issues for women with systemic inflammatory diseases:patient and physician perspectives

OBJECTIVES: To identify family planning and pregnancy (FPP) issues for female patients of childbearing age living with a chronic inflammatory disease and to assess whether current clinical practice routinely provides adequate support to alleviate these concerns. SETTING: Multinational survey and an analysis of online patient activity. PARTICIPANTS: Premenopausal women (aged 20–45 years; N=969) were surveyed in the USA, the UK, Germany, France, Italy and Spain. Rheumatologists were surveyed in Germany (N=50), France (N=50), Italy (N=50) and the USA (N=100), and gastroenterologists were also surveyed in the USA (N=100). PRIMARY AND SECONDARY OUTCOME MEASURES: Two online surveys were undertaken to identify FPP issues for physicians and patients. The surveys examined the frequency of dialogue on these topics between physicians and patients, alongside assessment of patient satisfaction regarding these conversations. Online analysis identified key themes for patient discussion outside their doctors’ office/clinic/surgery. RESULTS: 32–56% of physicians spontaneously reported having talked about FPP with their female patients of childbearing age. When prompted, the majority of rheumatologists (74–92%) and gastroenterologists (74%) reported having discussed conception/pregnancy with female patients; however, less than half reported consulting their patient's treating general practitioner/gynaecologist about these topics. The majority of patients reported their FPP-related concerns are not adequately addressed/settled during their medical appointments. Furthermore, only 30–40% of patients considered advice/information to be consistent across multiple healthcare professionals. Key online FPP-related patient discussions included disease state, adverse effects, treatment, switch behaviour and wash-out requirements. CONCLUSIONS: Female patients who live with chronic inflammatory disease have important FPP concerns. The majority of patients, however, do not feel that their FPP concerns are adequately addressed in current clinical practice and report that they receive inconsistent advice from the various healthcare professionals who manage different aspects of their care. There is a clear need for provision of up-to-date and consistent information/support to female patients