Optimizing the "Time to pregnancy" in women with multiple sclerosis: the OPTIMUS Delphi survey

Background: The debate on how to manage women affected by multiplesclerosis (MS) during reproductive age is still open, as is the issue of fertility in suchpatients. Main issue regard the identification of the optimal window for pregnancyand how to deal with medical therapy before and during conception. The aim ofthis Delphi consensus was to collect the opinions of a multidisciplinary group,involving reproductive medicine specialists and neurologists with experience inthe management of multiple sclerosis women with reproductive desire.Methods: Four experts plus scientific coordinators developed a questionnairedistributed online to 10 neurologists and later discussed the responses andamended a list of statements. The statements were then distributed via an onlinesurvey to 23 neurologists (comprising the first 10), who voted on their level ofagreement/disagreement with each statement. Consensus was achieved ifagreement or disagreement with a statement exceeded 66%.Results: Twenty-one statements reached consensus after two rounds of voting,leading to the following main recommendations: (1) Fertility evaluation shouldbe suggested to wMS, in case of the need to shorten time to pregnancy and beforetreatment switch in women on DMTs contraindicated in pregnancy, particularly incase of highly active disease and age  >  35  years. (2) ART should not be discouragedin wMS, but the use of DMTs until pregnancy confirmation should be suggested;ART may be considered in order to reduce time to pregnancy in MS women witha reduced ovarian reserve and/or age  >  35  years, but in case of an expected poorART prognosis and the need for more than one ART cycle, a switch to a highefficacy DMD before ART should be offered. (3) Oocyte cryopreservation maybe considered in women with reduced ovarian reserve, with unpredictable timeto complete diagnostic workup and achieve disease control; a risk/cost–benefitanalysis must be performed in women >35  years, considering the diminishedovarian reserve.Conclusion: This consensus will help MS neurologists to support family planningin wMS, respecting MS therapeutic needs while also taking into account the safetyand impact of advancing age on fertility.