Fertility in Women With Rheumatoid Arthritis
Fertility in Women With Rheumatoid Arthritis
Objectives Many female rheumatoid arthritis (RA) patients attempting to conceive have a time to pregnancy (TTP) of >12 months. During this period RA often cannot be treated optimally. We sought to identify clinical factors associated with prolonged TTP in female RA patients.
Methods In a nationwide prospective cohort study on pregnancy in RA patients (PARA study), women were included preconceptionally or during the first trimester. Cox regression analysis was used to study the association of disease characteristics and medication use with TTP.
Results TTP exceeded 12 months in 42% of 245 patients. Longer TTP was related to age, nulliparity, disease activity (DAS28), and preconception use of non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. These variables were independently associated with TTP, with HRs for occurrence of pregnancy of 0.96 (95% CI 0.92 to 1.00) per year of age, 0.52 (0.38 to 0.70) for nulliparity, 0.81 (0.71 to 0.93) per point increase in DAS28, 0.66 (0.46 to 0.94) for NSAIDs and 0.61 (0.45 to 0.83) for prednisone use. The impact of prednisone use was dose dependent, with significantly longer TTP when daily dose was >7.5 mg. Smoking, disease duration, rheumatoid factor, anti-citrullinated protein antibodies, past methotrexate use, and preconception sulfasalazine use did not prolong TTP.
Conclusions TTP in RA is longer if patients are older or nulliparous, have higher disease activity, use NSAIDs or use prednisone >7.5 mg daily. Preconception treatment strategies should aim at maximum suppression of disease activity, taking account of possible negative effects of NSAIDs use and higher prednisone doses.
Conceiving a child is a major life event and most adults try to have a child during their reproductive life span. In women with inflammatory rheumatic disease, however, it seems to be more difficult to achieve parenthood.
Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age. Nearly one-third of female RA patients diagnosed before the completion of child-bearing experience fertility problems. They have a prolonged time to pregnancy (TTP), the time between the start of actively trying to conceive and actually becoming pregnant. Pregnant RA patients are more likely to have had fertility treatment than pregnant controls. Women with RA have fewer children than women without RA, and more often fail to conceive at all. Hence fertility as well as fecundity seems to be compromised in women with RA.
Subfertility in RA has been studied only in retrospective studies or comparisons of registries. None of these studies have extensively examined the causes underlying the higher subfertility in RA, which may include disease activity, anti-rheumatic medication and immunological factors.
To identify clinical factors associated with a higher rate of subfertility in women with RA, we studied the TTP in consecutive RA patients who participated in a large prospective cohort study in the Netherlands on Pregnancy-induced Amelioration of Rheumatoid Arthritis (the PARA study).
Abstract and Introduction
Abstract
Objectives Many female rheumatoid arthritis (RA) patients attempting to conceive have a time to pregnancy (TTP) of >12 months. During this period RA often cannot be treated optimally. We sought to identify clinical factors associated with prolonged TTP in female RA patients.
Methods In a nationwide prospective cohort study on pregnancy in RA patients (PARA study), women were included preconceptionally or during the first trimester. Cox regression analysis was used to study the association of disease characteristics and medication use with TTP.
Results TTP exceeded 12 months in 42% of 245 patients. Longer TTP was related to age, nulliparity, disease activity (DAS28), and preconception use of non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. These variables were independently associated with TTP, with HRs for occurrence of pregnancy of 0.96 (95% CI 0.92 to 1.00) per year of age, 0.52 (0.38 to 0.70) for nulliparity, 0.81 (0.71 to 0.93) per point increase in DAS28, 0.66 (0.46 to 0.94) for NSAIDs and 0.61 (0.45 to 0.83) for prednisone use. The impact of prednisone use was dose dependent, with significantly longer TTP when daily dose was >7.5 mg. Smoking, disease duration, rheumatoid factor, anti-citrullinated protein antibodies, past methotrexate use, and preconception sulfasalazine use did not prolong TTP.
Conclusions TTP in RA is longer if patients are older or nulliparous, have higher disease activity, use NSAIDs or use prednisone >7.5 mg daily. Preconception treatment strategies should aim at maximum suppression of disease activity, taking account of possible negative effects of NSAIDs use and higher prednisone doses.
Introduction
Conceiving a child is a major life event and most adults try to have a child during their reproductive life span. In women with inflammatory rheumatic disease, however, it seems to be more difficult to achieve parenthood.
Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age. Nearly one-third of female RA patients diagnosed before the completion of child-bearing experience fertility problems. They have a prolonged time to pregnancy (TTP), the time between the start of actively trying to conceive and actually becoming pregnant. Pregnant RA patients are more likely to have had fertility treatment than pregnant controls. Women with RA have fewer children than women without RA, and more often fail to conceive at all. Hence fertility as well as fecundity seems to be compromised in women with RA.
Subfertility in RA has been studied only in retrospective studies or comparisons of registries. None of these studies have extensively examined the causes underlying the higher subfertility in RA, which may include disease activity, anti-rheumatic medication and immunological factors.
To identify clinical factors associated with a higher rate of subfertility in women with RA, we studied the TTP in consecutive RA patients who participated in a large prospective cohort study in the Netherlands on Pregnancy-induced Amelioration of Rheumatoid Arthritis (the PARA study).
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