AUTHOR=Carbone Luigi , Landi Doriana , Di Girolamo Raffaella , Anserini Paola , Centonze Diego , Marfia Girolama Alessandra , Alviggi Carlo ,  the Interdisciplinary Group for Fertility in Multiple Sclerosis (IGFMS) , Alviggi Carlo , Di Girolamo Raffaella , Carbone Luigi , Lanzillo Roberta , Landi Doriana ,  Marfia Girolama Alessandra , Anserini Paola , Centonze Diego , Annovazzi Pietro , Bonavita Simona , Borriello Giovanna , Cavalla Paola , Cerqua Raffaella , Clerico Marinella , Cocco Eleonora , Cordioli Cinzia , D’Amico Emanuele , De Luca Giovanna , Di Filippo Massimiliano , Fantozzi Roberta , Ferraro Diana , Iaffaldano Pietro , Inglese Matilde , Perini Paola , Portaccio Emilio , Ragonese Paolo , Clerici Valentina Torri , Tortorella Carla , Valentino Paola 

TITLE=Optimizing the “Time to pregnancy” in women with multiple sclerosis: the OPTIMUS Delphi survey

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1255496

DOI=10.3389/fneur.2023.1255496

ISSN=1664-2295

ABSTRACT=Background: The debate on how to manage women affected by Multiple Sclerosis (MS) during reproductive age is still opened, like the issue of fertility in such patients. Main arguments regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. The aim of this Delphi consensus was to collect opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of Multiple Sclerosis women with reproductive desire. 
Methods: Four experts plus Scientific Coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. The statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. Consensus was achieved if agreement or disagreement with a statement exceeded 66%. 
Results: Twenty-one statements reached consensus after 2 rounds of voting, leading to the following main recommendations: 1) Fertility evaluation should be suggested to wMS, in case of need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age >35 years. 2) ART should not be discouraged in wMS, but use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age >35 years, but in case of expected poor ART prognosis and need of more than one ART cycle, a switch to a high-efficacy DMD before ART should be offered. 3) Oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost benefit analysis must be performed in women >35 years considering the diminished ovarian reserve.
Conclusions: This consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs but also taking into account the safety and impact of advancing age on fertility.