Relationship Between Ankylosing Spondylitis, Fertility, and Pregnancy
Ankylosing spondylitis (AS) is a systemic rheumatic disease characterized primarily by arthritis of the spine and the sacroiliac joints, although other joints may become involved.11358 Additionally, it can cause inflammation of the eyes, lungs, and heart valves.11358 In advanced disease, chronic inflammation can cause the soft tissue around the spine to become ossified, leaving portions of the spine fused and immobile.11358 Ankylosing spondylitis occurs more commonly in males than in females with a ratio of approximately 2:1 and frequently occurs in adults of reproductive age.11358 Further, because AS is a disease that affects the pelvic joints, disease progression may affect the ability of a female to become pregnant, her pregnancy, and subsequent delivery. This section will discuss the impact of AS on pregnancy and the influence of pregnancy on the course of disease. In contrast to what has been observed in females with rheumatoid arthritis (RA), studies have shown that many females with AS generally do not experience symptom alleviation during pregnancy.11358, 11359 In addition, during the postpartum period, many report disease worsening, which may persist for a period of time.11359
Ankylosing Spondylitis and Fertility
It is generally accepted that fertility is not affected by AS. However, the impact of AS on male and female fertility has been incompletely characterized, with much of the research and literature focusing on the effect of pregnancy on the course of disease.
To address this gap in the research, 1 study evaluated fertility and reproductive performance in females with AS who had previous pregnancies.11376 Through a clinical questionnaire, 939 females with AS were asked questions about their disease and prior pregnancies. A total of 649 females older than age 40, who were presumed by the researchers to have completed their reproductive years, were asked to complete a second portion of the survey. These 649 females reported a total of 1586 pregnancies: 2.4 pregnancies (on average) per female, of which 1.4 pregnancies (on average) occurred during periods of active disease. Of these pregnancies, 15.1% ended in spontaneous abortions and 1.7% resulted in stillbirths. The authors stated that these reported rates were similar to those published previously for females with AS and were similar to that of the general, healthy population.
Few studies have addressed the question of AS
and any potential impact on male fertility. One study evaluated androgenic
status, sexual function, and fertility in 33 males with AS (age range
22-55 years; median 37 years), 31 males with RA (age range 19-60 years;
median 55 years), and 95 healthy male volunteers.11377 Blood
samples were collected on 1 occasion, and the serum extracts were
interrogated for the presence of luteinizing hormone (LH), follicle-stimulating
hormone (FSH), and testosterone. In serum of normal controls, LH and
FSH levels increased with age. After controlling for age-related changes,
patients with RA had significantly lower serum testosterone levels
(
Ankylosing Spondylitis and Pregnancy
Few studies have addressed the effect of pregnancy on AS or the effect of AS on pregnancy outcome. The influence of pregnancy, delivery, and the postpartum period on the course of AS is of concern to many females with the disease. In many rheumatic diseases, pregnancy has been shown to modify the course of disease. Often, females with RA who become pregnant report lessening of RA symptoms during their pregnancies.4831 In contrast, patients with AS who become pregnant generally do not report any change in underlying disease status11378, 11379 or report a worsening of disease status during pregnancy.11380 In addition, many females report disease flares during the postpartum period that are not necessarily related to disease status at conception.11359, 11381 One study suggests a role for regulatory T cells in the persistence of AS activity during pregnancy.11913 The results of a longitudinal, prospective study of 15 AS patients (10 pregnant; 5 nonpregnant) and 18 age-matched healthy females (14 pregnant; 4 nonpregnant) showed an increased frequency of CD4+CD25high regulatory T cells during the third trimester, compared with that seen at 8 weeks postpartum in both the healthy and AS populations. However, as opposed to the gestational regulatory T cells of healthy controls, those isolated from AS patients failed to establish an effective anti-inflammatory cytokine response. These data contrast research in patients with RA, which demonstrated that regulatory T cells of RA patients provide a more robust suppression of pro-inflammatory cytokines that may play a role in the amelioration of RA during pregnancy.11914
The effect of pregnancy on AS and the influence of AS on pregnancy, the fetus, and the newborn was evaluated in a retrospective study of female patients with confirmed AS.11381 The results suggest that the course of AS is largely unaffected by pregnancy. Of the 121 females diagnosed with AS, 78 had children during the course of disease. Of these, 50 fulfilled the New York criteria for AS and were included in the study. The 50 AS patients had borne 120 children; of these, 87 were delivered during the course of disease. Remission of disease was reported in 18 pregnancies in 12 patients, while exacerbation of disease was recorded in 21 pregnancies in 11 patients. Thirty-two patients experienced unaltered disease activity throughout the course of 48 pregnancies. During the 6 month period following delivery, exacerbation of AS was reported in 39 cases, while disease improvement and unaltered disease were reported in 4 and 44 cases, respectively. These data demonstrate that the majority of females (82%) had normal pregnancies which resulted in full-term delivery of live, healthy children. Three children had congenital abnormalities, including Down’s syndrome, clubfoot, and congenital hip displacement; however, this rate is consistent with the rate in the healthy, non-AS population.
The influence of pregnancy on the course of AS
was further evaluated in a large population of females.11376 In collaboration with the Ankylosing Spondylitis International
Federation, a questionnaire, including information on their AS and
details on past pregnancies, was completed by 939 females with AS.
Twenty-one percent of the participants reported that disease onset
was temporally related to a pregnancy, either occurring during pregnancy
or in the 6 months immediately following delivery. Six hundred forty-nine
of all responders were age 40 or older and were presumed to have completed
their reproductive years. These females had a total of 1586 pregnancies
of which 1340 occurred during active disease. Disease activity was
unchanged in 35.3% of pregnancies, while disease symptoms were aggravated
or improved in 39.9% and 24.8% of pregnancies, respectively. A postpartum
disease flare was experienced by 57% of patients and was significantly
correlated with reporting active disease at conception
Many females with AS experience aggravation of disease during pregnancy while some note that the disease is unaltered by pregnancy. However, many females with AS report postpartum disease flares. In this study, 65% of AS patients reported problems caring for an infant or a toddler, while 30% reported needing help to care for their children. In general, females who reported postpartum flare more often reported a need for child care assistance.11376
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| 11377. | Gordon D, Beastall GH, Thomson JA, et al. Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis. Q J Med. 1986;60(231):671-679. |
| 11378. | Hart FD, Bell AC, Organe GS. Pregnancy in ankylosing spondylitis: a report of 2 cases. Ann Rheum Dis. 1951;10(1):54-60. |
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| 11380. | Steinberg CL. Ankylosing spondylitis and pregnancy. Ann Rheum Dis. 1948;7(4):209-215. |
| 11381. | Ostensen M, Romberg O, Husby G. Ankylosing spondylitis and motherhood. Arthritis Rheum. 1982;25(2):140-143. |
| 11913. | Forger F,Villiger PM, Ostensen M.. Pregnancy in patients with ankylosing spondylitis: do regulatory T cells play a role? Arthritis Rheum. 2009;61(2):279-283. |
| 11914. | Förger F, Marcoli N, Gadola S, Möller B, Villiger PM, Østensen M. Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67(7):984-990. |
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