Egg freez­ing is an advanced form of assisted repro­duc­tive tech­nol­ogy. It com­monly entails freez­ing of mature unfer­til­ized human egg. If the egg sur­vive thaw­ing, its then fer­til­ized with a sin­gle sperm by direct injec­tion (intra­cy­to­plas­mic sperm injec­tion or ICSI). In this post I dis­cuss the his­tory, biol­ogy and suc­cess of egg freez­ing. No opin­ions, just the facts ma’am.

Biol­ogy. The egg is dif­fer­ent from any cell in the body. Its the largest in size and has high water con­tents. Its sur­round­ing mem­brane does not allow water to pass eas­ily. Its the only cell in the body that has its DNA spread in the form of a flimsy struc­ture called the spin­dle (as opposed to other cells where DNA is enclosed in a nuclear membrane)

When the egg is frozen two things take place: water inside the egg form crys­tals and the con­cen­tra­tion of salts inside the egg markedly increase. The two changes dis­rupt the inner struc­ture of the egg and make the egg swell and some­times burst. In lieu of its spe­cial struc­ture the egg has been a very elu­sive cell to freeze. Cry­opro­tec­tants (Kryo-Protek’tant) are syn­thetic sub­stances added to the freez­ing cock­tail to reduce these effects.

Short His­tory. There was great inter­est in freez­ing human repro­duc­tive cells and tis­sue. Human sperm freez­ing was avail­able since 1950. It took almost 50 years for egg freez­ing to be a read­ily avail­able option. The first suc­cess­ful preg­nancy from a thawed human egg was reported in 1986. But it was not until the late 90s that egg freez­ing was reported rou­tinely and only by few cen­ters world­wide. One non-scientific event  helped in pop­u­lar­iz­ing egg freez­ing, the pas­sage in 1994 of an Ital­ian law that pre­vents IVF cen­ters from insem­i­nat­ing more than three eggs forced physi­cians to freeze the rest of the eggs unfer­til­ized. Many of the early stud­ies on egg freez­ing came from Italy, a fact that limit gen­er­al­iz­abil­ity of the results of these stud­ies (they should be applied with cau­tion out­side Italy). A new method for egg freez­ing was also pro­posed recently : rapid freez­ing (vitrification)

Meth­ods. Two tech­niques are avail­able slow freez­ing and vit­ri­fi­ca­tion. Sim­ply described vit­ri­fi­ca­tion is an ultra-rapid freez­ing method (drops the tem­per­a­ture from room tem­per­a­ture to –170°C). The water inside the cell changes into a solid state with­out for­ma­tion of ice crys­tals. Pre­lim­i­nary reports on vit­ri­fi­ca­tion indi­cate that this method greatly improve the sur­vival of eggs when they are warmed, when com­pared to slow freez­ing. The newer vit­ri­fi­ca­tion method require the use of high con­cen­tra­tion of cry­opro­tec­tants (the com­pounds that pro­tect the cell from ice for­ma­tion) and the use of spe­cial plas­tic instru­ment that allows rapid drop of tem­per­a­ture (most suc­ce­ful instru­ment so far is called cryotop).

Clin ic al per­spec­tive. Women con­sider egg freez­ing in one of two sit­u­a­tions fer­til­ity preser­va­tion for med­ical indi­ca­tion or fer­til­ity exten­sion for social rea­sons. Egg freez­ing require stim­u­la­tion of the ovary with fer­til­ity med­ica­tion for about 10 to 14 days. Con­ven­tional med­ica­tion are used except in estro­gen sen­si­tive can­cer  e.g. breast can­cer where spe­cial pro­to­cols for stim­u­la­tion are used to reduce estro­gen expo­sure. Vagi­nal egg retrieval is then per­formed as usual in IVF. Eggs are frozen four to five hours later using slow freez­ing or vit­ri­fi­ca­tion. When a women comes back to use the eggs e.g. after can­cer cure, eggs are thawed and sur­viv­ing eggs are fer­til­ized using hus­band or donor sperm through ICSI. Embryo devel­op­ment is observed and embryos are trans­ferred in the cleav­age stage (day 3) or blas­to­cyst stage (day 5 or 6). The uterus has to be pre­pared using estro­gen and prog­es­terone to be ready for implan­ta­tion. Because embryo implan­ta­tion is lower than that of frozen embryos, usu­ally one extra embryo is trans­ferred than what is usu­ally rec­om­mended (e.g. two instead of one embryo)

Suc­cess of egg freez­ing. I reviewed all stud­ies pub­lished in the lit­er­a­ture world wide regard­ing egg freez­ing of non-donor oocytes. The most impor­tant num­ber for women con­sid­er­ing egg freez­ing is ongo­ing and live birth per thawed egg. In other words what is the poten­tial for a preg­nancy beyond 20 weeks or a deliv­ery for each egg thawed? This will also allow com­par­i­son with the poten­tial for frozen embryo. Please com­pare the first and third col­umn of the table.

Slow freez­ing is com­pared to vit­ri­fi­ca­tion and vit­ri­fi­ca­tion using more recent tech­nique cry­otop method

With slow freez­ing only about 2/3 of the eggs sur­vive freez­ing com­pared to 90% with cry­otop vit­ri­fi­ca­tion. 3/4 of eggs fer­til­ize with slow freez­ing ver­sus 90% for cry­otop. Most impor­tantly about 1.8% of eggs thawed result in an ongo­ing preg­nancy if the egg was frozen with the slow freez­ing method ver­sus about 7.5% with cry­otop vit­ri­fi­ca­tion. Because of the lim­ited poten­tial of thawed egg, the pro­ce­dure is offered to younger women with good response to fer­til­ity medication.

Embryo freez­ing suc­cess rate in the US is about 30% per cycle. Each thawed embryo has a 15% chance to pro­duce a live birth (cal­cu­lated from The Cen­ter for Dis­ease Con­trol and Pre­ven­tion data in women 37 year old or younger). In short cry­otop vit­ri­fi­ca­tion yields 1/2 the poten­tial for an ongo­ing preg­nancy when com­pared to frozen embryos, in expert hands. The major­ity of the stud­ies were con­ducted in Europe (no large stud­ies from the united states).

Safety of egg freez­ing. Mod­ern egg freez­ing does not appear to carry dan­gers to mother or chil­dren. This is how­ever, based on sev­eral hun­dreds to about one thou­sand chil­dren borne using this tech­nol­ogy and after a short term fol­low up. There are no long term data on the health babies borne from frozen eggs e.g . at five years after birth.

In sum­mary egg freez­ing is an advanced tech­nol­ogy that opens new avenues for women and pro­mote their repro­duc­tive choice and deci­sion mak­ing. Women con­sid­er­ing this tech­nol­ogy should, how­ever, be aware of its true poten­tial as iden­ti­fied from sci­en­tific stud­ies. I dont know of any pub­lished stud­ies using egg freez­ing for fer­til­ity extension.