Women diag­nosed with breast can­cer and desir­ing preser­va­tion of fer­til­ity via egg or embryo freez­ing require spe­cial con­sid­er­a­tion because a. its the most com­mon can­cer in women and b. its estro­gen sen­si­tive. Estro­gen increases five to ten folds dur­ing con­ven­tional ovar­ian stim­u­la­tion. Lim­it­ing estro­gen expo­sure dur­ing stim­u­la­tion appears to be an impor­tant safety con­sid­er­a­tion. Briefly, breast can­cer is treated using surgery fol­lowed 4 weeks later by chemother­apy, radi­a­tion and other treat­ments (hor­monal treat­ment e.g. tamox­ifen, anti­bod­ies e.g. trestazumab..)

Ovar­ian stim­u­la­tion in the 3–4 week gap between surgery and chemotherapy

To mit­i­gate the rise in estro­gen dur­ing stim­u­la­tion, I par­tic­i­pated in design­ing a spe­cial method for ovar­ian stim­u­la­tion and study its safety. A newer class of med­ica­tion (aro­matase inho­bitors) became avail­able (and approved by The US Food & Drug Admin­stra­tion). One mem­ber of this group (letro­zole) is added to con­ven­tional med­ica­tion used for ovar­ian stim­u­la­tion. Letro­zole decreases the activ­ity of the enzyme that makes estro­gen. Estro­gen dur­ing stim­u­la­tion remain within a low level, com­pa­ra­ble to women’s nat­ural cycles.

When this pro­to­col was tested (by com­par­ing two groups of women; one under­went ovar­ian stim­u­la­tion and the other group declined and pro­ceeded directly to can­cer treat­ment), there was no dif­fer­ence in sur­vival or recur­rence between the group that under­went ovar­ian stim­u­la­tion and those that declined fer­til­ity preservation.

COS; con­trolled ovar­ian stim­u­la­tion, NED; no evi­dence of disease

Lets Take a Closer Look!

• Both embryo and egg freez­ing require ovar­ian stim­u­la­tion and about 2–3 weeks to accom­plish that
• An aver­age woman in this study was fol­lowed for about two years. So long term out­comes are not known yet
• After surgery, a woman is given 4 weeks or so for the inci­sion to heal. Stud­ies have shown that a delay of up to 84 days (12 weeks) between surgery and chemother­apy does not affect the outcome
• In expert hands, that pro­to­col yielded an aver­age of 10 embryos or oocytes per patient
• Embryos never get exposed to letro­zole as they are frozen and not trans­ferred in the same cycle
• Some physi­cians use con­ven­tional pro­to­cols for stim­u­la­tion with no mod­i­fi­ca­tion argu­ing that estro­gen expo­sure in brief (10 to 14 days). It seems pru­dent though to reduce estro­gen expo­sure dur­ing stimulation.

Call to action: Since pub­lished work indi­cates that stim­u­la­tion of the ovary to freeze eggs or embryos is unlikely to increase breast can­cer recur­rence, patients and physi­cians should engage in a can­did dis­cus­sions of risks and ben­e­fits of ovar­ian stim­u­la­tion for fer­til­ity preser­va­tion rather than dis­miss­ing it alto­gether on safety grounds in the absence of a clear evidence.