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Reproductive Issues

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Overview

Multiple sclerosis (MS) is diagnosed most commonly in young adulthood, when men and women are in the process of making important lifestyle, career, and family decisions. Reproductive issues are among those of greatest concern to those living with this unpredictable, chronic disease, and the concerns are emotional and social as well as medical. The following information can help inform conversations between MS patients and their healthcare providers (Coyle, 2016; Herbstritt et al., 2016; Thiel et al, 2016; Bove et al., 2014; Lu e t al., 2014; Lu et al., 2013).

MS and contraception

In general, decisions about contraception in women with MS should be made on gynecologic rather than neurologic grounds; all methods of contraception appear to be safe for women with MS from a neurologic standpoint. Some oral contraceptives may interfere with the effectiveness of other drugs used for symptom management and vice versa. Women with decreased upper extremity dexterity may have difficulty using barrier methods of contraception (Voskuhl R & Giesser B. Gender and reproductive issues. In Giesser (ed.) Primer on Multiple Sclerosis - 2nd ed., NY: Oxford University Press, 2016).

MS and conception

In general, MS does not impact fertility. A few very small studies of women who have received some types of fertility drugs have reported increases in exacerbations and inflammation. More information is needed in this area (Voskuhl R & Giesser B. Gender and reproductive issues. In Giesser (ed.) Primer on Multiple Sclerosis - 2nd ed., NY: Oxford University Press, 2016).

The impact of pregnancy on MS

Pregnancy is characterized by a down-regulation of cellular immune responses and the presence of potentially neuroprotective hormones, both of which protect the developing fetus. The combined anti-inflammatory and neuroprotective effects of pregnancy appear to have a positive impact on MS as well (Voskuhl R & Giesser B. Gender and reproductive issues. In Giesser (ed.) Primer on Multiple Sclerosis - 2nd ed., NY: Oxford University Press, 2016).

The risk of relapse drops over the nine months of pregnancy (with the risk being lowest in the third trimester), rises significantly in the three-six months postpartum, and then returns to the woman’s pre-pregnancy rate. The more active a woman’s disease is during pregnancy and the year prior, the higher her risk of postpartum relapse (Coyle, 2016; Bove et al., 2014; Vukusic et al., 2004; Confavreux et al., 1998).

One study indicated a robust, cumulative, and beneficial effect of pregnancy and childbirth on the risk of a first clinical demyelinating event (CDE) in women, including a permanent additive effect from each birth. Increased numbers of pregnancies and deliveries were associated with decreasing risk of a first clinical demyelinating event. No association was found between the number of offspring and the risk of a first demyelinating event in men (Ponsonby et al., 2012). A subsequent study of parity in reducing the risk of MS suggests that the effect is limited to pregnancies that have occurred within 5 years of onset of MS( Hedstrom et al., 2014).
 
One study which examined 188 pregnancies with early termination ( spontaneous and elective) found an increased rate of relapses and inflammatory lesions on MRI, with the effects being more pronounced in women with more active disease and more inflammatory lesions prior to conception(Landi et al. 2018).

Impact of MS on pregnancy

In general, MS does not impact miscarriage rates, congenital malformations or stillbirths. One recent review has reported an increase in pregnancy complications for women with MS compared to women without MS (Houtchens et al., 2018).

Disease management before, during and after

None of the disease-modifying therapies are approved for use during pregnancy or breastfeeding. The reviews by Coyle (2016), Bove et al. (2014) and Cree (2013) provide comprehensive information for clinicians who are counseling their patients about treatment options.

Women are advised to stop DMT for the appropriate period of time specific to that agent (Kaisey et al., 2018). Because of its relative safety, some practitioners permit use of glatiramer acetate up until the time of conception. Women of child-bearing potential who wish to take teriflunomide must be using effective birth control due to its teratogenic effects. Women on teriflunomide who wish to become pregnant, and men on teriflunomide who wish to father a child, must stop the medication, undergo the recommended procedure for eliminating the drug from the body as quickly as possible, and wait until a confirmed level of < 0.02 mg/L has been achieved. Without accelerated elimination, the drug can persist for up to two years (teriflunomide prescribing information).  
 
Recent studies have reported that stopping natalizumab and/or fingolimod prior to pregnancy is associated with increased risk of relapse during pregnancy, but this observation may be confounded by the possibility that women with more active disease, who are at increased risk for relapse anyway, would be more likely to use these particular medications (Alroughani, et al., 2018). Also stopping these agents has been reported to produce “rebound” disease activity ( Das et al., 2018) which may also be contributing to the increased relapses seen during pregnancy after stopping natalizumab or fingolimod. In contrast, rituximab used within 6 months of conception may confer protection during pregnancy and has not been associated with increased relapses during pregnancy or major safety signal (Das et al., 2018).

If a woman’s disease has been particularly active prior to and during pregnancy, the recommendation may be for her to resume her medication as soon as possible (within several weeks after delivery).

The impact of a father’s disease-modifying therapy regimen on spermatogenesis or fetal development has received less study. Data from several population-based clinical and health administrative databases in British Columbia, Canada found no association between paternal MS, disease duration at conception and level of disability with birth outcomes (Lu E et al., 2014).

Symptom and relapse management during pregnancy

Many of the medications used to manage MS symptoms are Category C drugs (e.g., baclofen for spasticity; fluoxetine for depression; solifenacin succinate for bladder management) and should not be used during pregnancy; other management strategies (e.g. rehabilitative) should be implemented (Coyle, 2016; Bove et al., 2014).

MS-related fatigue may augment the normal fatigue of pregnancy; bladder and bowel symptoms may increase, including a higher risk of urinary tract infections and increased constipation; balance problems may worsen with weight gain.

Relapses severe enough to warrant treatment can be safely managed with a short course of corticosteroids after the first trimester. Methylprednisolone is the preferred drug because it is metabolized before crossing the placenta (Coyle, 2016; Bove et al., 2014; Ferrero et al., 2004). IVIG is safe for use during pregnancy and may provide some benefit when administered post partum in preventing relapses in patients judged to be at high risk for relapse. (Coyle, 2016; Bove et al., 2014; Ferrero et al., 2004; Achiron et al. 2004).

Delivery and post partum

All forms of anesthesia are considered safe for women with MS; anesthesia management does not need to be altered. Epidural anesthesia does not affect the likelihood of post-partum relapse (Vukusic & Confavreux, 2006; Makris et al, 2014; Bornemann-Cimenti et al., 2017).  [This information should be discussed with the anesthesia team during the early weeks of pregnancy].

Compared to the general population, women with MS are at significantly-increased risk for depression, which means they may also be at greater risk of depression in the post-partum period.  Women and their doctors need to be alert to mood changes during pregnancy and the post-partum period, since these can affect self-care and care of the baby. Antidepressant medications should be used with caution during pregnancy (Patil et al., 2011).

Women who wish to breastfeed should be encouraged to do so unless it is judged critical that they resume their disease-modifying treatment as soon as possible after delivery. Breastfeeding does not appear to increase the likelihood of relapse post-partum (Vukusic & Confavreux, 2006). Some studies have suggested that exclusive breastfeeding may be associated with a decreased risk of post-partum relapse (Kaisey et al., 2018), although other studies have not confirmed this. Use of DMTs during breast feeding is not recommended, as it is either unknown if the agent passes into breast milk, or transmission is known e.g. beta interferon, natalizumab (Coyle, 2018).

Glucosorticoids are excreted in breast milk, which means that a woman may need to stop breastfeeding temporarily after receiving glucocorticoid treatment for a relapse.

Menstrual cycle

Self-report studies suggest that women commonly experience transient worsening of their neurologic symptoms during the premenstrual phase of their cycle (Voskuhl R & Giesser B 2016. Gender and reproductive issues. In Giesser (ed.) Primer on Multiple Sclerosis-2nd ed., NY: Oxford University Press).

Menopause

In one early study of the impact of menopause on MS, 54% of post-menopausal women reported worsening of their neurologic symptoms (Smith & Studd, 1992). Some (but not all) subsequent studies suggest a menopause associated worsening of MS symptoms ( Bove et al., 2014). Many symptoms of MS and menopause may overlap, e.g. fatigue, bladder dysfunction, cognitive difficulties, depression and sleep disorders, and should be addressed accordingly. There are no known neurologic contraindications for women with MS to use HRT.

Additional resources



This was reviewed by Barbara Giesser, MD, February 2019.
 

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