Page 38 - Fertility in Women with Rheumatoid Arthritis Vruchtbaarheid van vrouwen met reumatoïde artritis

Chapter 2
Since DAS28 did not increase during a 1-year follow-up in the preconception period, it is not likely that increasing disease activity over time explains an even longer TTP in these women.
The second factor is the use of NSAIDs. NSAIDs may interfere with ovulation, implantation and placentation through inhibition of prostaglandin synthesis.10,24,25 Selective COX-2 inhibitors seem to inhibit ovulation more potently than traditional non-selective NSAIDs. However, this nding is only based upon case reports or small case series.24
Finally, the use of prednisone prolongs the TTP. Although prednisone has been considered not to have any effect on fertility when used for the treatment of chronic inflammatory diseases,26,27 our results show that in daily dosages >7.5 mg it does indeed signi cantly lengthen the TTP. A possible explanation for this may be the transient suppression of the hypothalamic-pituitary-ovarian axis by glucocorticoids. Glucocorticoids in therapeutic dosages have been shown to decrease luteinising hormone pulse frequency from the pituitary gland.28,29 Another possibility is a direct effect of prednisone on ovarian function or on the endometrium.30-32
Use of MTX in the past did not have a negative effect on the TTP. This is in contrast to animal studies, where MTX has been shown to cause a reduction in the number of primordial follicles (i.e. ovarian reserve) and a subsequent loss of ovarian function.33 We have previously shown that short term MTX use in early RA does not affect ovarian reserve.34 As the women in the current study had been using MTX for several years, our results suggest that long-term use of MTX also does not have a negative effect on ovarian function and fertility.
Even in the era of biologicals, our results are still relevant due to safety concerns regarding biologicals during pregnancy, and because not all women have access to them. Therefore, prednisone and NSAIDs are still important anti-rheumatic drugs during pregnancy and the preconception period.
It has been reported that women with inflammatory joint disease are more often nulliparous when diagnosed in early adulthood than when diagnosed in childhood or at a later age.9 However, introducing age at diagnosis into our analysis has no signi cant effect on TTP (data not shown).
A reduced frequency of intercourse may also play a role in explaining the observed fertility problems. If a patient has chronic pain (eg, in the hip or knee joints), intercourse frequency is expected to be lower, thereby diminishing the chance of conception in a
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