Since I'm on a roll, it's time for another research-based post. Today's topic: artificial oocyte activation (AOA). The fundamental premise, as butchered by my non-scientific self, is that an egg must be activated by the sperm in order for fertilization to occur. Activation is typically caused when the sperm oocyte-activating factor, phospholipase C zeta is delivered to the egg by the sperm. Eggs that are receptive to this factor then generate an oscillation in calcium levels. This in turn leads to a resumption in meiotic activity. Fertilization failure occurs when these oscillations in calcium levels are not triggered, whether due to sperm or egg issues.
Going back at least 20 years, researchers discovered that exposing a fertilized egg to calcium rich environments can trigger fertilization. This is true in cases where fertilization didn't happen in that specific egg, and in cases where prior retrievals resulted in fertilization failure, but subsequent retrievals, using calcium, show fertilization.
As a ballpark, fertilization rates after ICSI should be about 75%. After our catastrophic 1 of 5 fertilized cycle, which in turn followed cycles where only 2 of 3 fertilized, I was concerned about our fertilization. There is research out there showing that high sperm dna fragmentation is correlated with lower fertilization. The same is true of low morphology. (Like all research subjects, there are also papers showing that neither of those things is true!). End result, I requested that we use AOA. Here's the research on it.
This 2019 Fertility and Sterility article grouped eggs by cause of fertilization failure: severe sperm related activation failure, less severe sperm-related activation failure, and assumed egg related activation failure. Fertilization rates went from 10% to 70%, 15% to 63%, and 18% to 57% across those three groups, when AOA was used. Live birth rates went from 0% to 41%, 22%, and 22% across the groups. I suspect this is the basis for my RE's statement that AOA only helps with sperm-related issues, although a benefit was seen in egg-related cases, too.
Article text: https://www.fertstert.org/action/showPdf?pii=S0015-0282%2819%2930330-9
Because there are few things better than a good meta-analysis, here's a 2017 Fert Steril article meta-analyzing AOA using 14 studies with over 1,500 ICSI cycles. It found the incidence of clinical pregnancy was 37% in the AOA group and 16% in the non-AOA group. The live birth rate was 27% versus 9%. The part that I find really interesting was that the fertilization rate was 59% versus 47%, which is significant given the sample size, but I question the practical significance. Blastocyst formation was 50% in the AOA group and 10% in the ICSI group. I suppose that explains the difference in live birth!
Article text: https://www.fertstert.org/article/S0015-0282(17)30488-0/pdf
Looking specifically at DOR patients, this 2015 Fertil Steril found no difference in results. However, only an average of 2 eggs were retrieved in both the AOA and the control group. The study population specifically excluded couples with male factor infertility, abnormal sperm parameters, or a history of prior fertilization failure. In my mind, this wasn't a useful study, since the population didn't have fertilization issues. There were some other oddities, such as retrieval being 32-34 hours post trigger, and the use of unusual protocols for DOR patients (long lupron).
Article text: https://www.fertstert.org/action/showPdf?pii=S0015-0282%2815%2901675-1
Finally, a 2018 Human Reproduction article. This looked at couples with two or more past cycles with less than 30% fertilization, or 100% abnormal sperm morphology. This study looked at SrCl2 and calcimycin separately. Both treatments produced higher fertilization (49%, 42%) than plain ICSI (27%). Live birth was also better (42%, 36%, 23%). Differences were found in which activation medium worked based upon cause of fertilization issues.
Article abstract: https://pubmed.ncbi.nlm.nih.gov/30099496/
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