Detailed inform­a­tion and a list of ref­er­ences can be found in Chapter 3.2 of the FertiPROTEKT book, “Indic­a­tions and fertility pre­ser­va­tion methods for onco­lo­gic­al and non-onco­lo­gic­al disorders”, which can be down­loaded free of charge.

BACKGROUND

Before the start of chemo­ther­apy and / or radio­ther­apy, egg ells (oocytes) can be frozen (cryo­p­reserved) in a fer­til­ized or unfer­til­ized state. Cryo­p­reser­va­tion of unfer­til­ized oocytes or embryos after in vitro fer­til­iz­a­tion (IVF) and / or intracyto­plas­mic sperm injection (ICSI) are estab­lished repro­duct­ive medicine tech­niques that can be used for fertility pre­ser­va­tion in patients before chemotherapy.

Two different methods are used: the slow freezing method and vit­ri­fic­a­tion, which is ultra-fast freezing.

EGG CELL COLLECTION

So that enough egg cells (oocytes) can be cryo­p­reserved (unfer­til­ized and / or fer­til­ized), ovarian stim­u­la­tion is necessary, which can start at any point during the cycle and requires a time frame of about two weeks. On average, about 13 oocytes can be collected before chemo­ther­apy. However, the number of collected oocytes decreases sig­ni­fic­antly above 35 years of age. A detailed present­a­tion of stim­u­la­tion tech­niques, their effect­ive­ness, risks, and costs can be found here.

CRYOPRESERVATION OF EGG CELLS

+ PRONUCLEAR STAGE (FERTILIZED EGG CELLS)

In contrast to the cryo­p­reser­va­tion of unfer­til­ized oocytes, cryo­p­reser­va­tion of fer­til­ized oocytes with 2 pronuclei (pro­nuc­lear stage), i.e. one day after egg col­lec­tion, is a long-estab­lished suc­cess­ful method and is an essential part of assisted repro­duct­ive medicine tech­niques. The highly reliable thawing rate of 73–95% and a pregnancy rate of 20 to 32% after cryo­p­reser­va­tion and thawing are probably due to the absence of the spindle apparatus after the com­ple­tion of meiosis. Cryo­p­reser­va­tion can either be performed as a slow freezing process, which is char­ac­ter­ized by simple and well repro­du­cible handling using an automatic freezing programme, or as part of vitrification.

+ CRYOPRESERVATION OF UNFERTILIZED EGG CELLS

After the estab­lish­ment of freezing unfer­til­ized eggs as a clinical procedure had failed for over 2 decades, vit­ri­fic­a­tion brought the desired break­through. Neither the American Society for Repro­duct­ive Medicine (ASRM) nor the European society (ESHRE) guidelines describe any reser­va­tions about this method, since neither an increased rate of chro­mo­somal disorders (disorders of the genetic material) nor con­gen­it­al abnor­mal­it­ies have been iden­ti­fied up to now.

However, it should be noted that in the age range of 25 to 42 years, the fer­til­iz­a­tion rate decreases con­tinu­ously and cryo­p­reser­va­tion of unfer­til­ized oocytes should be performed in patients under 35 years of age since the number of oocytes decreases due to the age-related reduction in the ovarian reserve.

If unfer­til­ized oocytes are later thawed as part of a fertility treatment, con­ven­tion­al in vitro fer­til­iz­a­tion (IVF) is no longer possible because the cumulus cells (sur­round­ing cells) are removed before cryo­p­reser­va­tion to assess the maturity of the oocyte. Intracyto­plas­mic sperm injection (ICSI) is therefore used for fer­til­iz­a­tion, even if is the semen analysis is normal.

PRACTICE SUMMARY

The intro­duc­tion of new stim­u­la­tion protocols and the estab­lish­ment of vit­ri­fic­a­tion allow the col­lec­tion of egg cells within about 2 weeks, which can then be cryo­p­reserved in an unfer­til­ized and fer­til­ized state. Because it is recom­men­ded that at least some of the egg cells should be frozen in an unfer­til­ized state, even for couples in a stable rela­tion­ship, vit­ri­fic­a­tion is an indis­pens­able pre­requis­ite in the imple­ment­a­tion fertility pre­ser­va­tion techniques.