On the basis of the data presented by experts in the field of fertility preservation in cancer patients during a workshop in Genova in April 2015, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation.

Recommendations:

  • Ovarian stimulating drugs with standard treatment protocols may be administered in subfertile/infertile women without increasing the risk of developing breast cancer (III, B). The long-term use of clomiphene outside the current limited indications (i.e. first-line therapy of WHO Group II anovulatory infertility) should be discouraged because of a possible increase in breast cancer risk (III, B).
  • Pregnancy in cancer survivors, after adequate treatment and follow up, should not be discouraged, including among patients with endocrine-sensitive breast cancer (III, A).
  • All patients with potential interest in keeping their fertility should be referred to fertility unit for adequate determination of risk of infertility, chances of future conception and how to proactively preserve it (V, A). However, some cancer patients will not require the help of a fertility clinic after cancer treatment (V, B). Since several patient- and treatment-related factors are associated with the risk of developing infertility, the oncofertility counseling should be tailored to the individual patient (V, A).
  • In men, sperm cryopreservation is an easily accessible and widely available option in more than 95 % of patients and should be encouraged for those who want to preserve fertility (III, A). On the contrary, from 2 % to 65 % of women undergo one of the available cryopreservation options: oncologists should discuss with them the fertility issues and secure proper counseling in appropriate centers prior to cancer treatment (IV, A).
  • Paucity of data is available on fatherhood after cancer. Although most of the published data are reassuring, some recent conflicting results suggest a potential increased risk of birth defects particularly among the children born closer to a paternal cancer diagnosis, and caution should be taken in counseling these patients (V, B for discussion with patients); data on children conceived after ART are too scarce to draw any conclusion although in the general population, available evidence for the outcomes of progeny after ART suggests safety of the techniques themselves (V, B for discussion with patients).
  • The current limited data suggest the safety of a COS in cancer patients (III, B). “Random-start protocols” can be employed to avoid delays in anticancer treatment initiation (III, B). LHRHa ovulation triggering should be adopted in patients at moderate-high risk for OHSS (I, A). Letrozole (or tamoxifen) should be incorporated in the protocol for COS in cancer patients with hormone-responsive tumors (III, B).
  • Embryo and oocyte cryopreservation are standard options for fertility preservation (III, B). Vitrification showed a better performance than slow freezing (II, B). During oncofertility counseling, patients should be aware that data on the success of these strategies derive from infertile women in general and that a different ovarian response to stimulation might be expected in cancer patients (IV, B).
  • The best candidates for ovarian tissue cryopreservation are prepubertal girls (III, A). The technique may also be proposed to patients scheduled for treatments with a high risk of premature ovarian insufficiency who cannot delay anticancer treatments or who have already received chemotherapy, or with contraindications to COS (III, B). Patients with cancer with a high risk of malignant contamination to the ovaries (e.g. aggressive hematologic malignancies) should not be considered eligible for ovarian tissue auto-transplantation (V, B).
  • In order to optimize the procedure in terms of both patient management and cost-effectiveness, the harvesting of the tissue can be performed locally but subsequent sample freezing and storage centralized (III, B). A well-organized network between fertility units is required (III, B).
  • Ovarian suppression with the use of LHRHa during chemotherapy should be considered a reliable strategy to preserve ovarian function and fertility, at least in breast cancer patients, given the availability of new data suggesting both the safety and the efficacy of the procedure have become available (I, A)*. (*CYA, HAA, GBLS and WHW disagree with this statement, considering the strategy still experimental).

Several registries and prospective studies are ongoing to evaluate feasibility, safety and efficacy of fertility preserving strategies in cancer patients and encouraging patient participation in these studies is crucial to acquire more robust conclusions.

Citation
Lambertini et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Medicine (2016) 14:1 DOI 10.1186/s12916-015-0545-7

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