Fertility, Pregnancy and Childbirth in Patients with Multiple Sclerosis: Impact of Disease-Modifying Drugs

Abstract

In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

The Effects of Multiple Sclerosis and Disease Modifying Therapy on Pregnancy

“…Endocrinological studies have shown differences in the levels of sex hormones and the gonadotropins that regulate their production between women with MS compared to women of the general population [9]. Significantly higher levels of folliclestimulating hormone (FSH) and luteinizing hormone (LH) have been recorded, as well as significantly lower levels of estrogen in the early follicular phase of the menstrual cycle [10,11].…”

“…Fingolimod Fingolimod (trade name Gilenya®) acts to reduce the number of lymphocytes present in the central nervous system by preventing their release from lymph nodes. Rat experiments have shown no effect on female fertility upon administration of fingolimod, but they exerted teratogenic effects, the most common being congenital heart defects [9]. The rate of spontaneous abortion in women using fingolimod is higher than that of the general population [25].…”

“…Although there are no studies of the effects of natalizumab on the fertility of humans, trials in guinea pigs have shown that high doses of natalizumab decrease fertility in females [26]. Reduced fetal survival and significant hematological effects have been seen in animal studies, as well as in children whose mothers took natalizumab in the third trimester of pregnancy [9,27]. Additionally, it has been well established that natalizumab is excreted into breast milk, and is therefore not recommended during lactation [23,27].…”

“…The use of mitoxantrone in women has been linked to amenorrhea and a reduced ovarian reserve in multiple studies [9,28]. Furthermore, mitoxantrone has been associated with fetal growth retardation in rats, and has an increased rate of premature delivery in rabbits [9].…”

“…The use of mitoxantrone in women has been linked to amenorrhea and a reduced ovarian reserve in multiple studies [9,28]. Furthermore, mitoxantrone has been associated with fetal growth retardation in rats, and has an increased rate of premature delivery in rabbits [9]. Although clinical trials have not been conducted in humans due to the overwhelming contraindications in animal studies, case studies have been reported where women have used mitoxantrone while pregnant.…”