Lastly, referral pathways, procedures, and work instruction forms were developed. In the past, referral to fertility experts were informal and consisted only of a phone call, which resulted in a lack of shared information between the specialist and the physician. Having a formalized process of referral streamlined the process.

The researchers compared the prebundling cohort to the postbundling cohort and found that the postbundling cohort was more likely to have a documented discussion about infertility risk and was more likely to be referred to a fertility specialist, resulting in improved fertility preservation outcomes. Notably, while the researchers found that documented fertility discussions increased in both genders, the greatest improvement in fertility discussion postbundling was with female patients. However, males were still more significantly likely to be referred to a fertility specialist than females.


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The authors suspect that one reason for the gender disparity is that preserving female fertility is more technically difficult than preserving male fertility. Male fertility preservation is relatively quick and noninvasive. In contrast, the only nonexperimental method of female fertility preservation is oocyte collection and cryopreservation, which can be a month-long invasive procedure where the young woman is given fertility drugs to stimulate egg production. The eggs are then collected using multiple vaginal ultrasounds and vaginal egg retrieval, which may make some families and patients uncomfortable. In addition, a delay in cancer treatment may not be possible for all patients and relatively few oocytes actually survive the cryopreservation and thawing process.5 

One alternative is ovarian tissue freezing, which although it is still considered experimental has resulted in the birth of at least 70 healthy babies.6 During the outpatient procedure, one ovary is surgically removed and the outer surface that contains the immature egg follicles is frozen in strips. These strips can be transplanted back into the woman at a later date when she is cancer free. The hope is that the immature follicles will begin to develop as they would in a normal ovary. The first live human birth from this procedure was reported in 2004.7 However, the success of this procedure has largely been with tissue frozen after puberty. The first case of successful pregnancy and birth following ovarian tissue frozen before puberty was recently reported and demonstrates the feasibility of the procedure even after 13 years of cryopreservation. Re-implantation of cryopreserved ovarian tissue might not be possible for every patient as there may be an increased risk of re-introducing cancerous cells for some types of cancer.

Another more experimental procedure, which has not yet resulted in live human birth is in vitro follicle maturation, where instead if re-implanting the tissue, the immature follicles are grown to maturity in the lab. The mature egg can then be fertilized in the lab and the embryo implanted into the uterus. 

Healthcare professionals may be more likely to encourage fertility preservation in males than females because current female fertility preservation options are often considered experimental with no proven benefit, and therefore not worth the delay in treatment.8 More advances for female fertility preservation are needed, so that delays in treatment are reduced and female fertility preservation is comparable to males.8 However, females should still be made aware of their available fertility preservation options. Bundling interventions such as these just might be the first and easiest step to bridging the fertility preservation gender gap.

References

1. Schover LR. Patient attitudes toward fertility preservation. Pediatr Blood Cancer. 2009;53(2):281-284.

2. Letourneau JM, Ebbel EE, Katz PP, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118(6):1710-1717.

3. Barlevy D, Wangmo T, Elger BS, Ravitsky V. Attitudes, beliefs, and trends regarding adolescent oncofertility discussions: a systematic literature review. J Adolesc Young Adult Oncol. 2016;5(2):119-134.

4. Bradford NK, Walker R, Henney R, Inglis P, Chan RJ. Improvements in clinical practice for fertility preservation among young cancer patients: results from bundled interventions [published online ahead of print September 21, 2017]. J Adolesc Young Adult Oncol. doi: 10.1089/jayao.2017.0042

5. Bagchi A, Woods EJ, Critser JK. Cryopreservation and vitrification: recent advances in fertility preservation technologies. Expert Rev Med Devices. 2008;5(3):359-370.

6. Silber S. Ovarian tissue cryopreservation and transplantation: scientific implications. J Assist Reprod Genet. 2016;33(12):1595-1603.

7. Donnez J, Dolmans MM, Demylle D, et al. Live birth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364(9443):1405-1410.

8. Barlevy D, Elger BS, Wangmo T, Ravitsky V. Adolescent oncofertility discussions: recommendations from a systematic literature review. AJOB Empir Bioeth. 2007;8(2):106-115.