Oocyte and embryo freezing prior to chemotherapy and/or radiotherapy
Embryo or oocyte cryopreservation is an established procedure.
It should be discussed with all young women about to undergo potentially sterilising chemotherapy or pelvic radiation. It may be suitable for young women who:
Embryo freezing is well established in fertility practice, and is highly successful with over 80% of good quality embryos expected to survive the thawing process. With improvements in freeze-thawing techniques, and survival rates of oocytes when thawed of approximately 60%, oocyte freezing is now a viable alternative for a young woman not in a long-standing relationship. Neither technique will guarantee fertility, and the process of ovarian stimulation and oocyte retrieval requires two to three weeks before the start of chemotherapy or pelvic radiotherapy.
These techniques may be unsuitable for younger patients because:
- oestrogen sensitive tumours may require the amendment of the stimulation protocol with aromatase inhibitors or partial oestrogen agonists such as tamoxifen
- the patient must be sufficiently medically stable to tolerate an anaesthetic
- the patient must be in a stable relationship
- the ovaries must be accessible for an egg collection and
- the patient must be able to tolerate vaginal ultrasound examination to observe follicular development, precluding younger adolescents from this technique.
Likelihood of success
The success of IVF and embryo freezing, and subsequently replacing the thawed embryo after completion of cancer therapy, is dependant on the age of the patient undergoing the IVF treatment. Currently in Australia the chance of a live birth per thawed embryo replaced in a woman under 30 years of age is about 25 to 30 percent.
With the process of oocyte freezing, it would generally be expected that for every 10 oocytes of good quality obtained at the retrieval procedure, ultimately two or three embryos may result, with implantation rates similar to those from frozen embryos.
Risks and side effects
The side-effects of ovarian stimulation relate to the oestrogenic effects during the stimulation phase of the treatment cycle. Younger women are particularly at risk of the side-effect of ovarian hyperstimulation syndrome (OHSS), where the patient has a florid response to the stimulation, suffers with profound abdominal distension with ascites and is at risk of thrombosis. OHSS can be severe and lead to cycle cancellation, however there are several ways to mitigate against its effects (Humaidan) and now it is rare to cancel an IVF cycle for this reason. There also are increased risks for a medically unwell patient undergoing IVF related to the anaesthetic and the oocyte collection procedure, such as haemorrhage, thrombosis and infection.
There is a theoretical concern about the risk of ovarian stimulation and associated elevations in oestradiol on tumour cell growth in young women with oestrogen receptor positive breast cancers. While there is no published evidence suggesting that a single IVF cycle increases the risk, the use of an aromatase inhibitor or tamoxifen during the stimulation cycle as a form of ‘protection’ or as the only form of stimulation has been described in multiple reports.
In the absence of specific studies addressing this issue, the consensus is that in a patient with ‘good prognosis’ disease, who understands the theoretical concerns and the lack of absolute evidence of safety, and for whom preserving oocytes or embryos is of the utmost importance, most oncologists would not advise against a cycle of stimulation.
There is also a ‘social risk’ to frozen embryos: that the couple may separate and the former male partner may no longer consent to the stored embryos being used; or if there is a new male partner he may not be comfortable to use the embryos.
There is limited public funding of fertility preservation techniques within Australia and this will vary according to treatment location.
The future of cryopreservation
Vitrification is increasingly being used for the freezing of oocytes and embryos and preliminary evidence suggests that the outcomes are better than the older traditional forms of cryopreservation.
A new technique called in-vitro maturation of oocytes (IVM) involves collection of immature oocytes from small follicles, generally early in the menstrual cycle with limited or no ovarian stimulation. This may have particular benefit for younger patients, especailly those with limited time prior to the commencement of chemotherapy or young women with an oestrogen sensitive tumour, but currently is still considered investigational. Thus the technique is only available in a few centres within Australia in a research setting.
Safety of embryo and oocyte freezing
In relation to children resulting from the replacement of the frozen embryos, or the subsequently fertilised frozen oocytes or vitrified oocytes resulting from IVM, the evidence is reassuring. However it is possible that children born as a result of IVF have a minimally increased risk of congenital abnormalities compared to naturally conceived children  and studies of the long term outcomes of children born from IVM treatment are limited .
- Wennerholm UB, Soderstrom-Anttila V, Bergh C, Aittomaki K, Hazekamp J, Nygren KG, et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod 2009;24:2158-2172.
- Smith GD, Serafini PC, Fioravanti J, Yadid I, Coslovsky M, Hassun P, et al. Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification. Fertil Steril 2010 Nov;94(6):2088-95 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20171613.
- Hart R. Preservation of fertility in adults and children diagnosed with cancer. BMJ 2008 Oct 27;337:a2045 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18955375.
- Oktem O, Oktay K. Fertility preservation for breast cancer patients. Semin Reprod Med 2009;27:486-492.
- Wang YA CG, Sullivan EA. Assisted reproductive technology in Australia and New Zealand 2008. Cat. no. PER 49. Canberra: AIHW 2010 Abstract available at http://www.aihw.gov.au/publication-detail/?id=6442468391&tab=2.
- Oktay K, Buyuk E, Davis O, Yermakova I, Veeck L, Rosenwaks Z. Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen. Hum Reprod 2003 Jan;18(1):90-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12525446.
- Shalom-Paz E, Almog B, Shehata F, Huang J, Holzer H, Chian RC, et al. Fertility preservation for breast-cancer patients using IVM followed by oocyte or embryo vitrification. Reprod Biomed Online 2010 Oct;21(4):566-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20822957.
- Sutcliffe AG, Ludwig M. Outcome of assisted reproduction. Lancet 2007 Jul 28;370(9584):351-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17662884.
- Buckett WM, Chian RC, Holzer H, Dean N, Usher R, Tan SL. Obstetric outcomes and congenital abnormalities after in vitro maturation, in vitro fertilization, and intracytoplasmic sperm injection. Obstet Gynecol 2007;110:885-891.