Page 16 - Fertility in Women with Rheumatoid Arthritis Vruchtbaarheid van vrouwen met reumatoïde artritis

Chapter 1
and in pregnancy. Often, NSAIDs were added for pain management.21 A minority of pregnant RA patients received biologic DMARDs.22,24 Over the past years, more data on the use of the biologic DMARDs has become available. Since TNF inhibitors appear to be safe before and during pregnancy, at least until the end of the second trimester25-28, their use among women with RA trying to conceive is increasing nowadays.20
Ovarian function and ovarian ageing
Female fertility decreases with increasing age. Generally, women above 30 years of age are considered to have gradually decreasing fertility over time, with an acceleration in declining fertility after the age of 37 years. On average female fertility is considered to come to an end around an age of 40 years.29 However, this varies considerably between women since there are women who lose their fertility as early as 30 years of age, or as late as 45 years of age. This decrease in fertility with increasing age is attributed to a decreasing ovarian function through the reduction in the number of ovarian primordial follicles over time and a concomitant decrease in oocyte quality.30,31 In the female foetus, mitosis of germ cells results in approximately 7,000,000 oocytes in the developing ovaries.32 Once they have entered meiosis, the number of oocytes ceases to increase.32 During early folliculogenesis, when somatic cells surround the oocytes to form primordial follicles, the majority of germ cells are eliminated. As a result, a number of 700,000 to 1,000,000 oocytes are present in the ovaries at birth.33,34 During childhood, the number of oocytes further decreases, and at menarche, the primordial follicle pool consists of approximately 400,000 oocytes.33
During the reproductive period, every menstrual cycle a number of around 800-1000 primordial follicles will grow and leave the primordial pool. Rising and subsequent decreasing levels of follicle stimulating hormone (FSH) will cause one follicle to become dominant, which can be fertilized after ovulation. The other follicles that left the primordial follicle pool will become atretic and are lost.27 This cyclic recruitment and subsequent follicle atresia cause a continuous decline of the primordial follicle pool. (Figure 1) When the primordial follicle pool is nearly exhausted and only contains approximately 1,000 follicles, no more cyclic follicle growth occurs and anovulation sets in. As a de nite hallmark a woman’s menstrual periods will stop and hence menopause occurs33. On average, menopause is reached at an age of 50-51 years, with a broad range spanning 20 years and ranging from 40-60 years.31 However, in populations not interfering with natural infertility the age at which the last child is born is on average around an age of 40-41 years. Hence, fertility and also fecundity
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