Family and happiness will mean many different things to different patients. Some may choose advanced reproductive technologies while others, of course, may not. However, we emphasize the importance of allowing patients to make their own decisions about family in the presence of the best available clinical data, and, as close to the time of diagnosis as possible, when the most options are available ().
Figure 3 Options for fertility preservation and for conception. A timeline of cancer and motherhood events is shown at the top of the flow chart. Patients meeting referral criteria should see a reproductive endocrinologist as soon after diagnostic biopsy as possible. (more ...)
An attempt to preserve a patient’s fertility before treatment offers the best chance of a successful pregnancy after treatment. Established techniques, such as embryo cryopreservation, or experimental techniques, such as oocyte cryopreservation, ovarian tissue cryopreservation, or ovarian suppression therapy can be used before commencing cancer treatment.
AS CO currently recommends the use of embryo cryopreservation whenever possible. 30
Survival rates per thawed embryo range from 35% to 90% and implantation rates of these embryos range from 8% to 30%.29
Embryo cryopreservation requires a sperm source, whereas oocyte cryopreservation does not, offering a very useful alternative to women who are single at diagnosis. Live birth rates after thawing cryopreserved oocytes were once as low as 2–5% per thawed oocyte, but new freezing techniques have dramatically improved the live birth rate of cryopreserved oocytes to approximately 40% per cycle started, near that of cryopreserved embryos.31–33
Currently available experimental alternatives for fertility preservation include tissue cryopreservation and in vitro
maturation (IVM). Ovarian tissue cryopreservation involves a surgical procedure to remove all or part of the ovary, potentially offering an option for prepubertal girls and for women who require emergent treatment and cannot harvest eggs at the time of diagnosis. When thawed, this tissue provides the possibility of re-implantation or perhaps–in the future–complete in vitro
growth. In addition to use before treatment, ovarian tissue cryopreservation may be one of the only available procedural options for fertility preservation once treatment commences.34
IVM involves egg harvest before treatment from antral follicles 4–12 mm in diameter, in the absence of stimulation, and subsequent maturation of oocytes in vitro
. IVM also offers a viable option for prepurbertal girls and women facing emergent treatment. The procedure can be performed at any time in the menstrual cycle. Implantation rates of embryos from IVM are less than half that of embryos from oocytes matured in vivo.35
The use of ovarian suppression therapy remains controversial. In 2009 a randomized study of 78 patients with cancer reported decreased rates of amenorrhea and normalization of serum markers of ovarian function. 36
This study is interesting, although it is limited by short follow up (8 months after last chemotherapy) and lack of fertility as an outcome. Additionally, the results are considered controversial because of small sample size and higher than expected adverse outcomes in the control group.37
Another small randomized trial investigating the effect of GnRH agonist use together with an escalated chemotherapy regimen known as BEA COPP was stopped early because all patients in both study arms had very low AMH levels at 12 months of follow up.38
This study was limited by lack of a proper control group, by absence of fertility as an outcome, and by concerns that the treatment regimen (escalated BEA COPP) may be particularly gonadotoxic. Until larger randomized trials with longer follow up are conducted and a greater focus on both fertility and recurrence rates are included in trials, we view the use of GnRH agonists as a possible yet experimental option. We do not recommend GnRH agonists as replacement for more proven methods of fertility preservation, and contend that it should be considered only for patients enrolled under experimental protocol.
Following cancer treatment, and after a period of 2–5 years of disease-free survival, natural conception can be attempted. If fertility preservation was not performed, ovarian stimulation and oocyte harvest for embryo or oocyte cryopreservation can be attempted, but this is associated with diminished success.39
If natural conception is unsuccessful, and fertility preservation was performed before treatment, cryopreserved oocytes and/or embryos may be thawed and transferred to the patient. Additionally, cryopreserved tissues can also be transplanted back to the patient. To date, transpositions of cryopreserved tissue have led to approximately 10 births worldwide.40
In patients who do not respond to the abovementioned options, or who electively choose not to undergo fertility preservation before cancer treatment, may also consider options such as oocyte and/or embryo donation or adoption. Patients who either had a hysterectomy or who underwent pelvic radiation may wish to consider surrogacy.