Hot TopicState of the art on oocyte cryopreservation in female cancer patients: A critical review of the literature
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Background
Among patients diagnosed with malignant cancers worldwide, 3–10% are under 40 years of age. Cancer in reproductive age is twice as frequent in females than in males [1], [2]. Important advances in cancer treatments have led to increased survival rates over the past years; conversely these therapies expose patients to potential long term adverse effects, including infertility [3]. The maintenance of future fertility is considered of great importance by patients. At the time of cancer diagnosis,
Procedural challenges for cryopreserving the oocytes
Mature oocytes (metaphase II, MII) are fragile cells and numerous challenges should be overcome for obtaining a successful cryopreservation procedure and subsequent storage. The oocyte is the largest human cell, with subsequent low surface area to volume ratio. The overall effect is that oocytes are likely to retain water during freezing and they are particularly vulnerable to physical injury by intracellular ice formation during the cryopreservation process.
Moreover, addition or dilution of
Different methods for oocyte cryopreservation
The available methods for oocyte cryopreservation are slow freezing (or controlled-rate cryopreservation) and vitrification [43]. In slow freezing cryopreservation, oocytes are slowly cooled to below the freezing point in the presence of low concentrations of cryoprotectant agents (e.g. sugars, propanediol). This allows to reduce intracellular ice formation and structural damage due to solute concentrations and osmotic stress [44], [45]. The term “vitrification” refers to any process resulting
Efficacy and safety of oocyte cryopreservation
The efficacy and safety of oocyte cryopreservation can be inferred from available data especially in two populations: infertile women and oocyte donors.
During the first decades of use, overall success of both slow-cooling and vitrification techniques was low compared to in vitro fertilization (IVF) with unfrozen oocytes. In 2006 Oktay et al. reported a live birth rate per oocyte of 1.9% after slow freezing and 2.0% after vitrification [59]. Subsequently, four randomized controlled trials
Efficacy of oocyte cryopreservation in cancer patients
Although oocyte cryopreservation is routinely used as a method for fertility preservation, specific data on the success of the procedure in female cancer patients are limited so far. A first reason for this observation is that oocyte cryopreservation has been widely used from no more than 10 years. Second, after oocyte cryopreservation, women need time to treat their oncological disease before attempting to have a pregnancy. Third, not all the women who cryopreserved will decide to use their
Ovarian response to stimulation in cancer patients
The effect of cancer on patients’ ovarian reserve and consequently on the response to COS is a key factor for the success of oocyte cryopreservation.
In 2012, a systematic review and meta-analysis performed by Friedler et al. [80] compared the outcomes of 227 COS cycles in female cancer patients with those of 1258 cycles in infertile patients. The study showed that less oocytes were retrieved in patients with cancer as compared to the infertile non oncologic population (11.7 ± 7.5 vs. 13.5 ± 8.4, P <
Finding the ideal candidate for oocyte cryopreservation
During oncofertility counseling, when discussing the efficacy of the available methods for fertility preservation, the ability to estimate the success of the proposed technique is essential. Anti-Mullerian hormone (AMH) and antral follicle count (AFC) are widespread used markers of ovarian reserve in the general population and can be used as predictors of response to COS in ART procedures, also in cancer patients [87]. In the study by Lee et al. including 41 women with breast cancer that
Counseling in difficult cases: old and very young women
Since the risk of cancer treatment-related infertility increases with age, women with the highest probability of developing permanent amenorrhea are often also the ones in which fertility preservation treatments have the lowest chances of success. In facing these situations, a proper oncofertility counseling by fertility specialists is crucial. Hence, a personalized counseling to provide all the information regarding risks, benefits and success rates is mandatory before subjecting a patient to
Conclusions
Physicians should offer fertility preservation to women facing gonadotoxic therapies, with an adequate counseling within a multidisciplinary contest that includes a fertility specialist (see Fig. 1). During oncofertility counseling, all the options, both standard and experimental ones, should be presented with an estimate of their efficacy and safety adjusted on the characteristics and needs of the patient, including a discussion on the possibility of delaying treatment initiation.
Oocyte
Conflict of interest
The authors declare no conflict of interest.
Funding
This research did not receive any specific grant from founding agencies in the public, commercial, or not-for-profit sectors.
Author contribution
All the authors contributed to the preparation of the manuscript. The final version of the manuscript has been read and approved by all the authors before its submission.
Acknowledgments
No writing assistance was utilized in the production of the manuscript.
Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at Institut Jules Bordet, in Brussels (Belgium).
This work was partially supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC; investigator grant number: 2013–14272).
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