What’s the relationship between MS and pregnancy?

Q&A with Dr Jeanette Lechner Scott

Wondering how MS impacts pregnancy and fertility? Senior staff specialist in the Department of Neurology and Conjoint Professor at the University of Newcastle Dr Jeanette Lechner-Scott discusses the impact of family planning, hormonal changes and pregnancy on MS.

MS and Pregnancy

What does pregnancy do to the risk of developing MS?
Pregnancy delays the onset of MS and there’s an earlier diagnosis of MS if you haven’t had a baby, but having more than one baby does not seem to further delay the onset of MS.[i]

Is there an optimal time to become pregnant?
The best time to fall pregnant is when your MS is stable. However, it’s all very well to plan a pregnancy but we should be aware that the majority of pregnancies just happen. Maybe when you’re a person with a chronic condition, you think about it a bit more and are more careful when you’re on treatment to use precautions, but 51 percent of Australian women have at least one unplanned pregnancy.

What are the common fertility issues in women with MS?
Some symptoms of MS can reduce the chance of falling pregnant. Sexual dysfunction, which is quite common in 30 to 70 percent of women with MS, contributes to less frequent sexual intercourse. This includes reduced libido, difficulties reaching an orgasm, sensory disturbance, and bladder and bowel problems.

Hormonal abnormalities also play an important role, including higher follicle stimulating hormone which regulates the functions of the ovaries (lack or insufficiency can cause infertility or subfertility); lower anti Mullerian hormone, which is a hormone that’s associated with ovarian reserve; higher prolactin levels, which interfere with the normal production of other hormones such as estrogen and progesterone, causing a change or a stop to ovulation.

There are comorbidities that also don’t help fertility including depression and endometriosis, which are more common in women with MS and are major causes of infertility.

In addition, disease modifying therapies (DMTs) and symptomatic treatment might impact fertility as well.

What is the effect of pregnancy on the immune system?
There are complex immune system changes that happen when you fall pregnant; the uterine natural killer cells increase to help implantation of the egg. Unfortunately, this does not necessarily correlate with the peripheral blood natural killer cells but it’s an interesting concept because we know that the increasing number of natural killer cells (which is an effect that some of our disease modifying therapies have), is associated with a more stable disease. Pregnancy usually results in a reduction of disease activity, but the exact mechanism of how this occurs is not yet known.

In addition, you need more immune cells in the placenta for implantation because you do not want bacteria or viruses getting into your womb at the same time as your baby is implanting and growing. So we usually see an increase in GM-CSF and an increase in neutrophils in women that fall pregnant as well as an increase in particular regulatory T cells. This results in a change from TH1 to TH2, which is known to have a positive effect on MS disease activity. In the third trimester just before you have the baby, your immune system is stimulated again. You make sure that you’re prepared for the passage out of the womb with increased immune function and this might result in increased relapses postpartum.

What’s the relapse rate during pregnancy?
22 percent of women still have relapses during pregnancy and 14 percent postpartum. The 2014 MS Base Data[ii] confirmed that in the first trimester, the relapse rate goes down and the third trimester has the lowest relapse rate, then it rebounds to the pre-pregnancy time postpartum. The best way to prevent postpartum relapses is to have your disease under control with effective DMTs 2 years prior.

Some treatments such as Natalizumab and Fingolimod are known to cause rebound phenomenon, so stopping them might counteract the protective effect of pregnancy and lead to increased relapses during pregnancy. Sometimes, it might be better to continue treatments like Natalizumab for some weeks into the pregnancy.

So what treatment to choose?
Whilst the safety of some DMTs like Glatiramer Acetate and Beta-Interferon during pregnancy are well established, this is not the case with all DMTs. Pregnancy planning should be part of DMT decision-making and it’s essential to have a conversation with your neurologist as there are a variety of DMTs and it all depends on your particular situation and needs.

If pregnancy in itself is a protective factor, why is estrogen not given to all women with MS?
We know in animal models there’s a positive effect of estrogen on MS. Estrogen downregulates TNF alpha, and upregulates regulatory T cells, reducing the immune activity for patients with MS overall. There have been small studies conducted which demonstrated a clear improvement in relapsing remitting MS with estrogens but not in secondary progressive MS, and side effects have stopped larger trials.

For family planning advice relating to your particular situation, speak with your neurologist.

For information about treatment options and referrals for appropriate services in your area, call our MS Connect team on 1800 042 138 or email msconnect@ms.org.au.

[i] JAMA Neurol. doi:10.1001/jamaneurol.2020.3324
[ii] https://www.msbase.org/

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