Women and men diag­nosed with chronic myeloid leukemia  should con­sider fer­til­ity issues and safety of preg­nancy while under treat­ment. Chronic myeloid leukemia (CML) is formed of malig­nant cells from the bone mar­row. It may later spread to the blood stream or other organs. It may also progress to a fast grow­ing stage-acute leukemia. It is diag­nosed in 2000 women and 2800 men yearly in The US, mostly dur­ing their adult years. Most indi­vid­u­als diag­nosed with CML carry an abnor­mal chro­mo­so­mal arrange­ment called Philadel­phia chro­mo­some. Many patients do not have any symp­toms. CML is sus­pected from blood counts and con­firmed by exam­in­ing blood smears and bone mar­row examination.

Newer drugs like ima­tinib, dasa­tinib and nilo­tinib have changed the treat­ment of CML dra­mat­i­cally. More than 90% of patients that received these med­ica­tions sur­vived for 5 years or more. These belong to a group of med­ica­tions called tyro­sine kinase inhibitors (TKIs). These med­ica­tion slow the prop­a­ga­tion of lym­phoma cells. Their side effects are less than stan­dard chemother­apy. Response to treat­ment is assessed using blood counts, the pres­ence of Philadel­phia chro­mo­some and mol­e­c­u­lar genet­ics tests for a spe­cific gene. Some indi­vid­u­als require stem cell trans­plan­ta­tion. Trans­plan­ta­tion requires treat­ment with high dose chemother­apy and total body irra­di­a­tion, both are asso­ci­ated with very high risk for ovar­ian failure.

Effects of TKIs on fer­til­ity. Ani­mal stud­ies indi­cate that expo­sure to TKIs dur­ing adult life was not asso­ci­ated with impaired fer­til­ity in males and females. Expo­sure before puberty lead to reduced sperm pro­duc­tion in males. There has been few case reports of low sperm count and early ovar­ian fail­ure after expo­sure to ima­tinib in humans. This was not reported in large stud­ies. Because of the pos­si­ble effects of ima­tinib on fer­til­ity and because all indi­vid­u­als treated for CML are at risk for pro­gres­sive dis­ease requir­ing stem cell trans­plan­ta­tion, men and women diag­nosed with CML should con­sider fer­til­ity preser­va­tion. Men should con­sider sperm freez­ing. Women should con­sider embryo cry­op­reser­va­tion (if they have a part­ner) or egg freez­ing.

Effects of leukemia on preg­nancy. In gen­eral preg­nancy itself does not  appear to affect the prog­no­sis for leukemia There is no evi­dence that  brief expo­sure to ima­tinib in early preg­nancy is asso­ci­ated with adverse out­comes  or abnor­mal­i­ties in the babies. There are no exten­sive data, how­ever on the effects of ima­tinib and data on the effects of newer TKIs dasa­tinib and nilo­tinib are very sparse. Women are usu­ally advised to use a birth con­trol  method while on these med­ica­tions. In one study two of  16 babies had minor abnor­mal­i­ties (hypospa­dias in one baby and rota­tion of small intes­tine in one baby) that were sur­gi­cally repaired. Women who were in remis­sion and chose to stop ima­tinib dur­ing preg­nancy, had 40 to 50% chance of show­ing evi­dence of prop­a­ga­tion of the leukemia cells. The major­ity of them though achieved remis­sion again after re-starting treatment.

Chil­dren born to men who are actively tak­ing ima­tinib at the time of con­cep­tion appear healthy and cur­rent advice is not to dis­con­tinue treat­ment. This is based on out­comes of 60 preg­nan­cies  reported world­wide in female part­ners of imatinib-treated men. In con­trast the data relat­ing to chil­dren born to women exposed to ima­tinib dur­ing preg­nancy are less encour­ag­ing. Although num­bers are small-12 con­gen­i­tal anom­alies were found among 125 pregnancies-there has been a  clus­ter of rare con­gen­i­tal mal­for­ma­tions such that ima­tinib can­not be safely rec­om­mended, par­tic­u­larly dur­ing the period of organ for­ma­tion in the baby-first 8 to 12 weeks.

Women inter­ested in get­ting preg­nant while on ima­tinib and other TKIs should co-ordinate their spe­cific care between oncol­o­gists and repro­duc­tive endocri­nol­o­gist so that they attempt preg­nancy while in remis­sion for ide­ally 1–2 years and in the same time min­i­mize the period of time while off treat­ment. Alter­na­tive treat­ments than TKIs can be used dur­ing preg­nancy. After deliv­ery, TKIs are restarted and breast-feeding is dis­cour­aged as the med­i­cine is excreted in milk. Read more at http://nycivf.org