I perceive the extension of female reproductive lifespan as one of the most significant and potentially rewarding pursuits in biomedical research. Is oocyte cryopreservation a viable strategy?
Great post! A few thoughts from a fertility specialist. Firstly, U.S. data (available at SART.org and from the CDC) shows that live birth rates (LBR) are higher with fresh donor eggs vs frozen donor eggs, which is a better comparison because it removes infertility as a confounder. But this is kind of a moot point because obviously you have to freeze if you are doing this for fertility preservation. Secondly, pregnancy success rates with frozen embryos are greater than with frozen eggs. So, for women who are partnered or plan to use donor sperm anyway, embryo freezing might be a better option. It also allows for genetic testing on the embryo (euploid embryos have higher implantation rates). Obviously this is more expensive than freezing eggs and of course requires that you commit to a sperm source sooner than you would like. Better yet if you make enough eggs, freeze both eggs and embryos! Thirdly, mathematical modeling studies show that the optimal time for egg freezing for women may be early to mid-thirties (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457646/). Older than that, it's much less successful and for younger women in their 20s, they may undergo the risks of the procedure and expense without ever needing to use those eggs. Another consideration is desired family size. For women who want more than one child and start their families later in life, egg and/or embryo freezing may be even more cost-effective (https://pubmed.ncbi.nlm.nih.gov/36175208/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457614/).
Thank you so much, these are all great points! The donor egg thing is particularly interesting, did not think of that.
Re: frozen embryos: do you have any link to papers reporting success rates? I wonder if the higher success rates are a selection thing. In the sense that once you have a frozen embryo you are already eliminating the possibility of having not been able to produce an embryo. But if you take all women who attempt to have an embryo frozen, would the success rates still be higher? (hope the question makes sense)
The SART data is not so granular to allow comparison of success rates of embryo transfers using frozen donor eggs to frozen-thawed embryos using fresh donor eggs. But yes, it is possible that there is selection bias with frozen embryos vs eggs. But it is also possible that the success rate difference is due to using fresh vs frozen-thawed eggs to create the embryos in the first place.
Great piece! The similarity of outcomes with frozen and fresh eggs shows how much using vitrification vs slow freezing (from 2006+) has helped improve egg thawing rates, making egg freezing a much more viable option. I also like the section on the future and Gameto's work to make IVM success rates higher. Another "moonshot" startup in the fertility space is ConceptionBio (https://conception.bio) who are trying to convert stem cells to eggs. If they succeed the female reproductive span will be significantly extended.
Fantastic article, thank you so much. Extremely informative.
I have a question: in your paper you make it clear that women freezing eggs in their early 30s have a good chance at eventually achieving pregnancy. According to the study that you analysed, "women who retrieve more than 20 oocytes before the age of 38 have a ~70% chance of conceiving".
And yet in the 2nd part of the article, when discussing "The Future", you make a case that women should freeze their eggs in their 20s. You give the scenario of a 35 year old woman, who should have frozen her eggs in her 20s.
How should we reconcile these 2 ideas? Thank you so much again!
Thanks that's a good question. This specific study has the issue that you didn't have enough women in the pre 38 categ to see if being in your 20s is better than early 30s. My expectation based on other priors is that yes.
That makes sense thank you. It would also be my guess that freezing in one's 20s is better than early 30s, but then the question is: how much better is it? Is the difference substantial? I hope we'll soon have more data to answer this question and all the other good questions you raise in your paper.
According to Steve Hsu, young women (early twenties) doing commercially motivated egg donations sometimes have 60-100 eggs harvested in a single cycle. He mentioned this in his podcast with Dwarkesh Patel. Since this increases the chance of success without increasing cost of extraction or storage, it adds to the incentive for such early intervention.
Another note: 40 year old women still have, on average, 8,000 immature eggs in their ovaries. The problem at that age is quality, not quantity.
Harvesting that many eggs has a high risk of OHSS, so it is considered not best medical practice to purposely give doses of hormones that are so high that that many eggs are expected to be matured. It's not an exact science, and some younger women or women with PCOS have higher than expected numbers of mature oocytes on typical dosing. But routinely harvesting 50-100 is medically questionable.
You should have mentioned Brigitte Adams in your article. The poster child of "Freeze your eggs, Free your career" froze 11 eggs in her late 30s.
"Two eggs failed to survive the thawing process. Three more failed to fertilize. That left six embryos, of which five appeared to be abnormal. The last one was implanted in her uterus. On the morning of March 7, she got the devastating news that it, too, had failed.
Adams was not pregnant, and her chances of carrying her genetic child had just dropped to near zero. She remembers screaming like “a wild animal,” throwing books, papers, her laptop — and collapsing to the ground."
She ended up having a baby with a donor egg. Basically she became a surrogate mother. And about your example of women doctors. You might want to read this story:
I'm not bashing your article. I posted links to reputable news sources on this topic. And Brigitte Adams is famous precisely because she was on the cover of Businessweek magazine gloating about her frozen eggs. But just a few years after being the poster girl of egg freezing, all 11 of her eggs failed. I'm sure that she makes enough money to do multiple IVF cycles to freeze more eggs. And also freeze them with different companies because "don't put all your eggs in one basket.". But she never did that.
I'm definitely pro egg freezing and I'm all for IVF and embryo selection with PGS. The article on infertile women doctors clearly shows the problem. If women doctors don't even know how small their fertility window is, what do you think are the odds that a "HR lady" know this?
It's good that you're writing this to raise awareness though. Kudos to you.
Great post! A few thoughts from a fertility specialist. Firstly, U.S. data (available at SART.org and from the CDC) shows that live birth rates (LBR) are higher with fresh donor eggs vs frozen donor eggs, which is a better comparison because it removes infertility as a confounder. But this is kind of a moot point because obviously you have to freeze if you are doing this for fertility preservation. Secondly, pregnancy success rates with frozen embryos are greater than with frozen eggs. So, for women who are partnered or plan to use donor sperm anyway, embryo freezing might be a better option. It also allows for genetic testing on the embryo (euploid embryos have higher implantation rates). Obviously this is more expensive than freezing eggs and of course requires that you commit to a sperm source sooner than you would like. Better yet if you make enough eggs, freeze both eggs and embryos! Thirdly, mathematical modeling studies show that the optimal time for egg freezing for women may be early to mid-thirties (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457646/). Older than that, it's much less successful and for younger women in their 20s, they may undergo the risks of the procedure and expense without ever needing to use those eggs. Another consideration is desired family size. For women who want more than one child and start their families later in life, egg and/or embryo freezing may be even more cost-effective (https://pubmed.ncbi.nlm.nih.gov/36175208/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457614/).
Thank you so much, these are all great points! The donor egg thing is particularly interesting, did not think of that.
Re: frozen embryos: do you have any link to papers reporting success rates? I wonder if the higher success rates are a selection thing. In the sense that once you have a frozen embryo you are already eliminating the possibility of having not been able to produce an embryo. But if you take all women who attempt to have an embryo frozen, would the success rates still be higher? (hope the question makes sense)
The SART data is not so granular to allow comparison of success rates of embryo transfers using frozen donor eggs to frozen-thawed embryos using fresh donor eggs. But yes, it is possible that there is selection bias with frozen embryos vs eggs. But it is also possible that the success rate difference is due to using fresh vs frozen-thawed eggs to create the embryos in the first place.
thank you very much, will check this out!
Great piece! The similarity of outcomes with frozen and fresh eggs shows how much using vitrification vs slow freezing (from 2006+) has helped improve egg thawing rates, making egg freezing a much more viable option. I also like the section on the future and Gameto's work to make IVM success rates higher. Another "moonshot" startup in the fertility space is ConceptionBio (https://conception.bio) who are trying to convert stem cells to eggs. If they succeed the female reproductive span will be significantly extended.
Thank you. I’ve actually written abt conception in an earlier broader piece abt fertility! I agree they’re great!
Fantastic article, thank you so much. Extremely informative.
I have a question: in your paper you make it clear that women freezing eggs in their early 30s have a good chance at eventually achieving pregnancy. According to the study that you analysed, "women who retrieve more than 20 oocytes before the age of 38 have a ~70% chance of conceiving".
And yet in the 2nd part of the article, when discussing "The Future", you make a case that women should freeze their eggs in their 20s. You give the scenario of a 35 year old woman, who should have frozen her eggs in her 20s.
How should we reconcile these 2 ideas? Thank you so much again!
Thanks that's a good question. This specific study has the issue that you didn't have enough women in the pre 38 categ to see if being in your 20s is better than early 30s. My expectation based on other priors is that yes.
That makes sense thank you. It would also be my guess that freezing in one's 20s is better than early 30s, but then the question is: how much better is it? Is the difference substantial? I hope we'll soon have more data to answer this question and all the other good questions you raise in your paper.
According to Steve Hsu, young women (early twenties) doing commercially motivated egg donations sometimes have 60-100 eggs harvested in a single cycle. He mentioned this in his podcast with Dwarkesh Patel. Since this increases the chance of success without increasing cost of extraction or storage, it adds to the incentive for such early intervention.
Another note: 40 year old women still have, on average, 8,000 immature eggs in their ovaries. The problem at that age is quality, not quantity.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008772 (see figure 1)
Harvesting that many eggs has a high risk of OHSS, so it is considered not best medical practice to purposely give doses of hormones that are so high that that many eggs are expected to be matured. It's not an exact science, and some younger women or women with PCOS have higher than expected numbers of mature oocytes on typical dosing. But routinely harvesting 50-100 is medically questionable.
You should have mentioned Brigitte Adams in your article. The poster child of "Freeze your eggs, Free your career" froze 11 eggs in her late 30s.
"Two eggs failed to survive the thawing process. Three more failed to fertilize. That left six embryos, of which five appeared to be abnormal. The last one was implanted in her uterus. On the morning of March 7, she got the devastating news that it, too, had failed.
Adams was not pregnant, and her chances of carrying her genetic child had just dropped to near zero. She remembers screaming like “a wild animal,” throwing books, papers, her laptop — and collapsing to the ground."
https://www.washingtonpost.com/news/national/wp/2018/01/27/feature/she-championed-the-idea-that-freezing-your-eggs-would-free-your-career-but-things-didnt-quite-work-out/
She ended up having a baby with a donor egg. Basically she became a surrogate mother. And about your example of women doctors. You might want to read this story:
https://www.nytimes.com/2021/09/13/health/women-doctors-infertility.html
25% of women doctors end up infertile. I would love to see what percentage of female doctors end up childless.
why would I include these examples? My piece makes it clear for a woman with her characteristics the chance of birth is <50%
I'm not bashing your article. I posted links to reputable news sources on this topic. And Brigitte Adams is famous precisely because she was on the cover of Businessweek magazine gloating about her frozen eggs. But just a few years after being the poster girl of egg freezing, all 11 of her eggs failed. I'm sure that she makes enough money to do multiple IVF cycles to freeze more eggs. And also freeze them with different companies because "don't put all your eggs in one basket.". But she never did that.
I'm definitely pro egg freezing and I'm all for IVF and embryo selection with PGS. The article on infertile women doctors clearly shows the problem. If women doctors don't even know how small their fertility window is, what do you think are the odds that a "HR lady" know this?
It's good that you're writing this to raise awareness though. Kudos to you.
Thanks, makes sense. I guess I rely on people to understand these percentages and their implications? I know not everyone does, but yeah...
Like the procedure looks better than I thought but it’s still far from guaranteed live birth