we presented uh data and suggestion on how to manage a patient who wants to be pregnant who or who is pregnant and is affected by CML um we now know after 10 years of experience and 20 years of experience with Ty in kyes Inhibitors that a normal life is possible and normal life include family and we know that a family desire can be accomplished in a CML both for male and female patients concerning pregnancy and conception we know that it's possible and there are two different scenarios that we need to keep into consideration one is the male part for the conception and the other one is the female part since tkis are embryo toxic and teratogenic but not genotoxic we assumed that there were no problems in male patient to uh conceive and uh and have a safe pregnancy in their female partner actually now this has been confirmed by more than 500 cases reported and also FDA has released um uh communicate that being in the safer part when you have more than 25 exposure risk being aimin that is the newer drug uh 250 and the tkis 500 they release the possibility to not um proceed with contraception but that a pregnant C is safer in male patient taking therapy so not no need to stop therapy but still working on collecting cases to be sure about that for female patients it's completely different because being the the drug embryotoxic and teratogenic you must be very careful many cases have been reported in the past with problems at Birth of the babies exposed to tkis especially during the um the the organogenesis organogenesis takes place between the fifth and the 12th week of pregnancy so this is the window in which you have not to deal with tkis [Music] um they pass poorly the placenta so um many cases have been published so far of patients treated after the placental formation meaning the 16th 20th week of pregnancy with no problem with those two drugs the other drugs does be toxic all the time and it passes the placenta and the newer drugs we don't have any information so we just assume is not um is not safe to deal with if you need to treat the patient at the beginning of pregnancy interfering is something that you can consider because it's safe uh it acts not through a cytotoxic um mechanism of action but it acts through at the protein level and managing the control of the immune system and micro environment so even at the beginning of the pregnancy or preconceptionally you can use this drug in at the end for suggestion for patients who wants to be pregnant or got pregnant while on treatment with u CML stop tki at first pregnancy test among the third fourth weeks of U um of pregnancy is not suggested to stop before that because you're risking to lose your uh TFR in the moment that you cannot assume any tki um male patient can conceive with no problem interference can be used at any stage and keep an eye of the importance of fertile preservation and also medically assisted reproduction techniques for those patients