Does Spondyloarthritis Affect Female Fertility?
Spondyloarthritis has not been shown to impact fertility in women. A large study that assessed data from 939 questionnaires completed by women with ankylosing spondylitis (AS) in the United States, Canada, and 11 European countries found that these women have similar fertility rates to those observed in healthy women in Western countries.1 Nevertheless, data suggest women with spondyloarthritis might have decreased fecundity.2 The reasons for this are likely multifactorial, including physical and psychological factors.2 Inflammation or stiffness of the sacroiliac joints, lumbar spine, or hips can make sex painful or uncomfortable. Spondyloarthritis can also cause fatigue and anxiety or depression, hampering interest in sex. Therefore, these factors need to be taken into consideration during fertility discussions.
Does Spondyloarthritis Affect Male Fertility?
Spondyloarthritis and its treatments do not appear to negatively impact male fertility, at least not permanently. A longitudinal assessment of sperm quality in 23 male patients with active AS treated with anti-tumor necrosis factors (TNFs) found these patients to have similar sperm quality to healthy controls at baseline and as long as 1 year after treatment.3 Agents taken included adalimumab, etanercept, and infliximab. However, the impact of longer term biologic use (>1 year) on male fertility has not been well established. Secondary infertility following 3 years of adalimumab treatment for AS has been reported.4 The patient had an unusually low sperm count and decreased sperm motility, both of which recovered enough after 6 months of treatment discontinuation to enable his sperm to be frozen. These findings indicate that infertility could be a reversible AE of anti-TNF treatment, and that treatment-related infertility should be ruled out in any male patients reporting reproductive challenges.
How Does Pregnancy Impact Spondyloarthritis Disease Course?
Studies have reported AS symptoms to remain unaltered during pregnancy, but a 64-week prospective study that used validated disease-activity assessment instruments found patients with AS to have higher disease activity scores during pregnancy.5 AS disease activity peaked in the second trimester and then lessened in the third trimester. Additionally, compared with their RA counterparts, the women with AS had continuously higher pain scores. These findings indicate that better assessment instruments are needed to more effectively monitor AS patients during pregnancy.5 Another study reported worse scores for bodily pain (P <.001) and physical functioning (P =.007-.001) in pregnant women with AS compared with healthy controls, both during pregnancy and in the postpartum period.6 AS patients also had lower health perception (P <.05). Their mental and emotional health appeared to remain stable, but this could be because all patients were in stable relationships and free of psychosocial stress. Photo credit: Credit: Airelle-Joubert/Science Source
Do Disease-Modifying Antirheumatic Drugs Need to Be Discontinued During Pregnancy?
Many drugs can be safely continued during conception and pregnancy, but the risk of any drug therapy on the child must always be carefully weighed against the risks of untreated disease on mother and child.7 Treatment decisions should be based on collaboration with and agreement between the internist/rheumatologist, obstetrician, patient, and other healthcare providers, as needed.7 Although NSAIDs are often a frontline treatment for spondyloarthritis, the latest EULAR guidelines suggest their use should be restricted during pregnancy.7 In contrast, use of TNF inhibitors during the first part of pregnancy can be considered, with etanercept and certolizumab potentially being used throughout the pregnancy due to their low rate of transplacental passage.7 In a small French study, infliximab and adalimumab also appeared to be safe, with no congenital malformations detected in any of the babies born to mothers who took these agents throughout their pregnancy.8
Can Traditional DMARDs Be Safely Used During Pregnancy?
Sulfasalazine and methotrexate, whether used alone or in combination with other agents, are the most commonly used traditional DMARDs to treat spondyloarthritis.7 Whereas sulfasalazine appears to be compatible with pregnancy, methotrexate is teratogenic and should be discontinued by male and female patients well before conception.7 The general recommendation is that men and women wait 3 to 6 months after discontinuing methotrexate treatment before trying to conceive.9 Following conception, men may resume methotrexate treatment, whereas women should not resume this treatment until after they have given birth and/or completed breastfeeding. The prescribing information for all spondyloarthritis treatments should be carefully reviewed before conception to ensure the safest treatment approach is used before, during, and after pregnancy, as even agents in the same medication class can have vastly different teratogenic potential.
What Adverse Events Have the “Safe” Spondyloarthritis Medications Shown in Pregnancy?
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to increase the risk of miscarriage when used in the first trimester.10 Prolonged use (>1 week) or use near conception increased this risk. When used later in pregnancy, NSAIDs have been reported to decrease amniotic fluid levels, resulting in oligohydramnios and inadequate pulmonary development. Adverse events (AEs) associated with TNF inhibitors have varied, but these agents are considered category B medications, indicating good safety.10 Some data suggest these agents increase the risk of VACTERL anomalies (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and limb defects), but this association remains unclear. Sulfasalazine has not been associated with congenital defects when used alone.10 When combined with corticosteroids, a case of congenital deafness and of cleft palate with microglossia has been reported, but sulfasalazine’s role remains unclear. Folate supplementation is recommended.10 Photo Credit: CDC/Dr James W. Hanson
Does Spondyloarthritis Affect Birth Outcomes?
There is some evidence that spondyloarthritis affects birth outcomes. A Swedish study found that women with AS had a higher rate of emergency and elective Cesarean sections compared with matched controls from the general population (16.5% and 9.8% vs 6.5% and 6.9% of such deliveries, respectively).11 Women with AS also had more preterm deliveries (9.0% vs 4.9%, respectively) and babies that were small for their gestational age (3.1% vs 1.5%, respectively). These associations remained even when adjusting for confounding variables, such as age, smoking habits, parity, and education level, and excluding women with comorbidities.
Do Spondyloarthritis Treatments Need to Be Discontinued While Breastfeeding?
Many spondyloarthritis treatments can be safely continued while breastfeeding. TNF inhibitors, including infliximab, adalimumab, etanercept, and certolizumab, have shown low transfer to breastmilk and are considered safe for use while breastfeeding.7 Nonselective COX inhibitors and sulfasalazine can also be continued while breastfeeding, provided the child does not have any contraindications to these treatments.7 However, because sulfasalazine can increase the risk of kernicterus in infants aged <2 years, caution is warranted.12 Methotrexate should not be used while breastfeeding.7 Additionally, any agent with no or limited safety data on breastfeeding should be avoided.7
Reproductive Counseling and Planning
Pregnancy is a major consideration in patients with spondyloarthritis, and family planning discussions should be undertaken in patients of reproductive age as early as possible to ensure optimal outcomes when starting or expanding a family is desired. Even before conception, alterations to the treatment regimen might be necessary in both male and female patients to avoid adverse effects (AEs), such as miscarriage or congenital malformations.1
Many patients develop spondyloarthritis just as they are reaching reproductive age, with the onset of symptoms often manifesting during their prime reproductive years (17-45 years).1 Unlike many patients with rheumatoid arthritis, those with spondyloarthritis generally do not experience relief of their symptoms during pregnancy and are more likely to require continued treatment with a safe agent.
- Østensen M, Ostensen H. Ankylosing spondylitis–the female aspect. J Rheumatol. 1998;25(1):120-124.
- Bazzani C, Andreoli L, Agosti M, Nalli C, Tincani A. Antirheumatic drugs and reproduction in women and men with chronic arthritis. RMD Open. 2015;1(Suppl 1):e000048.
- Micu MC, Micu R, Surd S, Gîrlovanu M, Bolboacă SD, Østensen M. TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment. Rheumatology (Oxford). 2014;53(7):1250-1255.
- Wildi LM, Haraoui B. Reversible male infertility under treatment with an anti-TNFα agent: a case report. Ann Rheum Dis. 2012;71(3):473-474.
- Østensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis. 2004;63(10):1212-1217.
- Förger F, Østensen M, Schumacher A, Villiger PM. Impact of pregnancy on health-related quality of life evaluated prospectively in pregnant women with rheumatic diseases by the SF-36 health survey. Ann Rheum Dis. 2005;64(10):1494-1499.
- Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75(5):795-810.
- Berthelot JM, De Bandt M, Goupille P, et al; CRI (Club Rhumatismes et Inflammation). Exposition to anti-TNF drugs during pregnancy: outcome of 15 cases and review of the literature. Joint Bone Spine. 2009;76(1):28-34.
- Hackmon R, Sakaguchi S, Koren G. Effect of methotrexate treatment of ectopic pregnancy on subsequent pregnancy. Canadian Family Physician. 2011;57(1):37-39.
- Krause ML, Amin S, Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014;6(5):169-184.
- Jakobsson GL, Stephansson O, Askling J, Jacobsson LT. Pregnancy outcomes in patients with ankylosing spondylitis: a nationwide register study. Ann Rheum Dis. 2016;75(10):1838-1842.
- American College of Rheumatology. Sulfasalazine (Azulfidine): Fast Facts. www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Sulfasalazine-Azulfidine. Updated March 2015. Accessed October 20, 2016.