Patient awareness about family planning represents a major knowledge gap

For patients with MS, family planning is important. According to the definition of the WHO, family planning allows individuals and couples to anticipate and attain their desired number of children, and the spacing and timing of births. Family planning is achieved through use of contraceptive methods and treatment of involuntary infertility. “It is good to consider that”, Prof. Marie D’Hooghe (National MS Center, Belgium) said. “However, family planning is planning the future. How can we plan the future, if someone is diagnosed with MS?”

Reproductive decisions

When people are diagnosed with MS, it comes with a great deal of uncertainty, Prof. D’Hooghe emphasised. “They don’t know what is going to happen. They have to redefine their personal identity and modify their lifestyle (e.g. smoking and diet). Furthermore, they have to consider MS treatment and take into account factors such as way of administration, side effects, complications, and teratogenicity.

Family planning appears to be a major knowledge gap for patients. An online survey in Denmark (n=590) showed that 10% of men and women with MS indicated that there were unplanned pregnancies on DMTs. About half of these pregnancies were terminated and 18% ended in a spontaneous abortion. Only half of the surveyed patients felt well informed about the teratogenic risk of DMTs and family planning. However, 42% female and 74% male patients were not aware of potential teratogenic effects of their current DMTs [1].

MS has a clear impact on reproductive decisions, as there is an increased risk of nulliparity among MS patients, having no children (25.6%) compared with a reference population (19.9%). Furthermore, MS patients have on average fewer children: in females both before and after diagnosis, and in males only after diagnosis [2]. As much as 79% of MS patients indicated that following MS diagnosis there was no pregnancy or fathering pregnancy. It should be noted that this was due to MS-related reasons in only on third of patients; two thirds answered that their family was already complete [3]. The most frequent MS-related reason for not becoming pregnant was the presence of symptoms that might interfere with parenting (71.2%). Other reasons included burdening their partner (50.7%), financial issues (39.4%), worries about children inheriting MS (34.7%), and risks associated with exposure to medication (30%) [3].

Associated disease prognosis

Women of reproductive age have a higher incidence of relapsing-remitting MS, including mild forms (benign MS). They have more relapses, but less disability progression, namely a longer time from onset to EDSS score 6.0 when compared with men. “Women somehow appear to be protected against progression with respect to cognitive impairment, thalamic atrophy, and the occurrence of primary progressive MS during reproductive age”, Prof. D’Hooghe stated. “We really don’t know why this is the case.” There is also no indication that pregnancy has an adverse effect on long-term prognosis of MS, at least according to most studies. “Nevertheless, we know that there is an increased relapse risk in the postpartum period, especially when MS is very active before pregnancy. So, we should be very careful when stopping highly effective DMTs with potential rebound before and during pregnancy.”

Assisted reproductive therapies have also been introduced for MS patients. There appears to be an increased relapse risk following these hormonal treatments, at least when having led to pregnancy. There is no adverse effect of epidural analgesia. MS itself does not appear to have a major effect on reproductive outcomes, i.e. fertility, pregnancy outcomes (abortion, ectopic pregnancy, and delivery), and neonatal outcomes. “We cannot exclude minor effects, but there are no major effects”, Prof. D’Hooghe reassured. “However, DMTs may affect these outcomes due to gonadal/foetal toxicity, birth defects, rebound activity, and autoimmune thyroiditis”, she added, referring to the EMA recommendation about restricted use of fingolimod [4].

Successful pregnancy planning

The trends are that both pregnancy rates and number of annual live births in MS are increasing. However, it appears that women with MS become pregnant with a delay of 2-3 years compared to reference persons, indicating increased risk for the foetus and the mother. Furthermore, there is an increasing number of pregnancies conceived under DMTs. “This is really impressive”, according to Prof. D’Hooghe. “Data from MSBase shows an increase from 26% to 62% with respect to the number of pregnancies conceived under DMTs in recent times.”

Overall, it is important to manage MS with patient preference and reproductive decisions taken into consideration. Before starting, stopping, or switching DMT, it is very relevant to consider the risk of long-term MS disability, to actively ask for pregnancy plans and contraceptive use, to include the mother’s preferences and risk avoidance, and to discuss how contraceptive choice impacts DMT selection. “In case of a pregnancy planning, we should monitor whether disease activity is under control”, Prof. D’Hooghe advised. “We should consider treatment, if needed, with modestly effective DMTs, that are safe to continue taking through to conception. As previously mentioned, that could be injectables rather than orals or second-line therapy. We could also consider not starting with DMT.” Furthermore, Prof. D’Hooghe emphasised the need to restrict the use of highly teratogenic drugs. “These drugs need to be stopped in time, but then there is a risk of relapse. We also have to take into account that there is a variable period to become pregnant (6-24 months). Furthermore, we should restrict the use of highly effective drugs with risk of rebound disease activity 8-16 weeks after cessation, because pregnancy is not protecting against this rebound, so we really have a risk of relapse during pregnancy.”

On the other hand, it is important to avoid unplanned pregnancy under DMT, the motto is: safety first. “During treatment with all DMTs, patients need safe and effective contraception”, D’Hooghe mentioned. “We should be aware that gastrointestinal side effects may reduce effectivity or oral contraceptives. Intrauterine devices may be considered, because they have a long-term effect and are safe. Some highly teratogenic DMTs need double contraceptive method, at least temporarily.”

1. Rasmussen PV, et al. Mult Scler Relat Disord. 2018;24:129-134.
2. Moberg JY, et al. Mult Scler. 2019:1352458519851245.
3. Alwan S, al. Mult Scler. 2013;19:351-8.
4. https://www.ema.europa.eu/en/news/updated-restrictions-gilenya-multiple-sclerosis-medicine-not-be-used-pregnancy

Posted on 8 November, 201918 March, 2024