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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 facts 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):

Additional information

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).

Women who become pregnant after the onset of MS may have a decreased risk of transitioning from relapsing-remitting to secondary-progressive MS as compared to women who do not become pregnant (Runmaker & Andersen, 1995).

One study (Ponsonby et al., 2012) 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. The authors postulate that if these associations are shown to be causal, they could help explain the increasing female to male ratio in MS (Alonso & Hernan, 2008) in a time when women are getting pregnant at a later age and having fewer children. No association was found between the number of offspring and the risk of a first demyelinating event in men.

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 generally advised to stop their medication one to two menstrual cycles prior to trying to conceive (Ferrero et al., 2004). Women of child-bearing potential who wish to take teriflunomide (pregnancy rating X) or mitoxantrone (pregnancy rating D) must be using effective birth control. 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. Women and men of child-bearing potential who wish to take mitoxantrone  (pregnancy rating D) must be using effective birth control and may wish to harvest and store eggs/sperm for future use.

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 approximately two weeks after delivery).

The impact of a father’s disease-modifying therapy regimen on spermatogenesis or fetal development has received less study. A man may want to consider stopping his injectable medication, fingolimod, or natalizumab during efforts to conceive.

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 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 (Coyle, 2016; Bove et al., 2014; Ferrero 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).  [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 affect the likelihood of relapse post partum (Vukusic & Confavreux, 2006).

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

In infants of mothers exposed to Ocrevus during pregnancy, do not administer live or live-attenuated vaccines to the infant before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Menstrual cycle

Self-report studies suggest that women commonly experience transient worsening of their neurologic symptoms during the premenstrual (Voskuhl R & Giesser B 2011. Gender and reproductive issues. In Giesser (ed.) Primer on Multiple Sclerosis, NY: Oxford University Press).

Two studies – with conflicting results – have looked at the relationship between hormone levels over the course of the menstrual cycle and gadolinium-enhancing lesion activity on MRI (Bansil et al., 1999; Pozzilli et al., 1999).

Menopause

In the only study to date of the impact of menopause on MS, 54% of post-menopausal women reported worsening of their neurologic symptoms (Studd, 1992)

There are no known neurologic contraindications for women with MS to use to HRT.

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