Uterine Transplantations - again in the news
By Norbert Gleicher, MD., who is the Medical and Laboratory Director as well as Chief Scientist at the Center for Human Reproduction (CHR). He can be reached through The Reproductive Times at Hello@ReproductiveTimes.com.
Briefing: For most women who, for whatever reason, are missing their uterus, having a genetically autologous child (made with use of their own eggs) requires the use of a so-called gestational carrier (GC) who has somebody else’s embryo transferred into her uterus, carries the pregnancy through delivery and then hands off the offspring to the couple that created the embryo. A still very small number of women, however, are now taking up the opportunity of having/receiving a uterine transplant from another person in the hope of carrying their pregnancy on their own. Considering high percentages of transplant failures and procedure-related morbidity of donors and recipients, as well as exorbitant costs, uterine transplants have remained controversial. A report from several U.S. transplant centers involving 32 such patients is the impetus for this article.
Do you know what an Absolute Uterine Factor is? If not, we believe you are not alone! An “Absolute Uterine Factor”—clearly also deserving of an acronym (i.e., AUF), is nothing but an absent uterus. Yes, an absent uterus and an AUF are one and the same! Then why all of the semantics? One explanation is because an absent uterus would not sound important enough as an indication for the performance of uterine transplants.
One can only admire the impeccable stepwise research over many years by Swedish investigators under the amazing leadership of Mats Bränström, MD, starting with years of animal studies before taking the procedure to a human trial and achieving in 2012 not only long-term tolerance of the transplant (a first human uterine transplant that had to be removed was performed already in 2000 in Saudi Arabia) but in 2014 also the first delivery of a healthy offspring in Australia.
At the same time and from the very beginning several experts in the infertility made the argument that just because something can be done, does not mean it should be done, as certain things may just not be worthwhile doing. And—at least within reproductive medicine—there is no better example for such a circumstance than the amazing ability of achieving successful uterine transplants which then allow recipients of these transplants to go through pregnancy and delivery. A recently published report of several U.S. centers on the IVF practice in patients with AUF undergoing uterus transplants only further reaffirmed this position on ethical, clinical, and financial grounds.1
The study included 31 transplant recipients at mean age of 31.0 ± 4.7 years who before their surgery completed between 1 and 4 oocyte retrievals, banking 3-24 by PGT-A untested embryos or 2-10 by PGT-A as euploid reported embryos. Additional post-transplant retrievals were required in 19% of patients for a total of 16 cycles (2-4 per patient). PGT-A was used in 74% of patients.
A total of 72 autologous embryo transfers occurred in 23 women, with 70 using frozen and 2 cycles using fresh embryos. The live birth rate per cycle was 25/72 (34.72%) after 1st embryo transfer; it was 13/23 (56.52%) and rose to 17/23 (73.91%) after the 2nd transfer. In comparison to matched non-transplant IVF patients, there was no difference in obstetrical outcomes, nor were there any outcome differences between uterine transplants from living or deceased donors.
Those, of course, are outstanding IVF cycle outcomes, even considering the young age of the patient population. However, it took an accompanying Reflection article2 to point out the following: 8/31 (25.81%) had a uterine graft failure. Per intent to treat, above noted live birth rates, therefore, would only have been 41.94% after a 1st transfer and 54.84% after the 2nd transfer, though still very respective outcomes. More importantly, however, the authors of this commentary also pointed out that most recently available U.S. data for IVF cycles using gestational carriers reported a 52.4% live birth rate.3
In practical terms this means as the authors correctly stated that the use of a gestational carrier—the current standard method of helping women with AUF to have autologous children—still represents the most optimal treatment for them. And that does not even at all considers the morbidity for living uterus donors, morbidity from removal surgery of the transplanted uterus once a patient has completed childbearing and, of course, the dramatically higher costs of uterine transplantations, which still greatly exceed by many multiples the quite significant costs of a gestational carrier.
Therefore, it seems worth repeating: Just because we can do something does not mean we should do it!
References
1. Walter et al., Fertil Steril 2024;122(3)-404
2. Pereira N, Lindheim SR. Fertil Steril 2024;122(3):435-436
3. Traub et al., Am J Obstet Gynecol. 2024. S0002-9378(24)00553-2.doi: 10.1016/j.ajog.2024.04.027. Online ahead of print.