PPOS vs Antagonist in PGT-A: What a New Study Reveals About Euploidy

Hey there! Let’s chat about something pretty important if you’re navigating the world of IVF, especially if you’re considering Preimplantation Genetic Testing for Aneuploidy (PGT-A). We’re diving into a recent study that compared two popular ways doctors stimulate your ovaries to get those precious eggs: the Progestin-Primed Ovarian Stimulation (PPOS) protocol and the good old Gonadotropin-Releasing Hormone (GnRH) Antagonist protocol.

You know, getting ready for IVF involves a few steps, and one of the big ones is ovarian stimulation. The goal is to help your ovaries produce multiple follicles, each potentially containing an egg. For years, doctors used protocols that involved GnRH agonists to prevent early ovulation. But now, antagonists are super common because they’re simpler and might even reduce the risk of something called Ovarian Hyperstimulation Syndrome (OHSS).

Enter the PPOS protocol. This one uses progestins (like dydrogesterone in this study) right from the start of stimulation. Why? Well, progestins are great at blocking that pesky Luteinizing Hormone (LH) surge from the pituitary gland, which is what triggers ovulation too early. The cool thing about PPOS is it’s often simpler – fewer injections sometimes – and potentially cheaper. The catch? You *have* to freeze all the embryos because the progestins mess with the uterine lining, making it not ready for a fresh transfer.

So, PPOS is often used when a fresh transfer isn’t planned anyway, like in cases of fertility preservation, egg donation, or, you guessed it, when you’re doing PGT-A.

Why PGT-A Matters Here

If you’re doing PGT-A, it means you’re having your embryos tested for chromosomal abnormalities (aneuploidy) before transfer. This is often recommended for women with advanced maternal age, a history of recurrent pregnancy loss, or repeated implantation failure. The hope is to transfer only chromosomally normal (euploid) embryos, which significantly increases the chance of a successful pregnancy and live birth. Since PGT-A takes time, you’re freezing all the embryos anyway while you wait for the results. This makes PPOS a potentially perfect fit!

But here’s where things got a little fuzzy before this study. Some earlier research hinted that maybe, just maybe, using progestins during stimulation might affect the quality of the eggs or embryos, potentially leading to fewer euploid embryos. Other studies said it was totally fine. See? A bit controversial!

Diving into the Study

This is where this particular study comes in, and it’s pretty exciting because it’s a *randomized controlled trial*. That’s the gold standard in research, meaning participants were randomly assigned to one group or the other, which helps make the comparison fair and square.

The researchers rounded up 240 women who were already planning to do PGT-A cycles. These women fit the typical profile for PGT-A:

• Advanced maternal age (38-45 years)
• Recurrent pregnancy loss (two or more miscarriages)
• Repeated implantation failure (several failed embryo transfers)

They split them into two groups: 120 women got the PPOS protocol (using dydrogesterone), and 120 got the Antagonist protocol. They followed standard procedures for stimulation, egg retrieval, fertilization (using ICSI), embryo culture, and blastocyst biopsy for PGT-A. All usable blastocysts were frozen.

The main thing they wanted to compare was the euploidy rate. How did they define that? As the number of euploid blastocysts they got *per injected oocyte*. They also looked at other things like the number of eggs retrieved, fertilization rates, blastocyst formation rates, and importantly, the pregnancy and live birth rates from the *first frozen embryo transfer* cycle using a euploid embryo.

The Big Reveal: Euploidy

Okay, drumroll please… What did they find? When they crunched the numbers, the euploidy rate was comparable between the two groups. It was 12.5% in the PPOS group and 16.0% in the Antagonist group. Now, you might look at those numbers and think, “Hey, 16% is higher than 12.5%!” And yes, it is numerically higher, but the statistical analysis showed that this difference was *not significant* (the P value was greater than 0.05). This means the observed difference could easily be due to random chance, not because one protocol is truly better than the other at producing euploid embryos in this population.

They also looked at the euploid blastocyst rate *per woman*, and again, no significant difference was found (33.3% for PPOS vs. 50.0% for Antagonist – again, not statistically different).

Beyond the Chromosomes

What about all the other stuff? The study found that the number of eggs retrieved, the number of mature eggs, fertilization rates, cleavage rates, and blastocyst formation rates were all similar between the two groups. This is great news because it suggests PPOS doesn’t negatively impact these crucial early steps compared to the antagonist protocol.

Interestingly, they *did* find some differences in hormone levels during stimulation. The PPOS group had a lower total dose of FSH (the stimulating hormone) and higher estradiol and LH levels on the trigger day compared to the antagonist group. This might suggest the pituitary suppression from progestins isn’t *quite* as strong as with the antagonist, but the key takeaway is that these hormonal differences didn’t translate into a difference in the all-important euploidy rate or later outcomes.

Speaking of later outcomes, they followed the women who had at least one euploid blastocyst through their first frozen embryo transfer cycle. And guess what? The positive pregnancy test rate, clinical pregnancy rate (seeing a gestational sac), miscarriage rate, ectopic pregnancy rate, and the live birth rate were all similar between the two groups. This really reinforces the idea that using PPOS for stimulation, when followed by a frozen embryo transfer, doesn’t seem to harm the chances of taking home a baby compared to the antagonist protocol.

Why PPOS Might Be Your Pick (Especially for PGT-A)

So, what does all this mean? Well, for women undergoing PGT-A, this study provides strong evidence that PPOS is a perfectly valid option. It seems to produce a similar number of euploid embryos and leads to comparable live birth rates after frozen transfer as the standard antagonist protocol.

Given that PPOS can be simpler (oral pills instead of just injections) and potentially cheaper, it becomes a really attractive alternative, especially in situations where a freeze-all cycle is already planned. This includes PGT-A cycles, fertility preservation (egg freezing), egg donation cycles, and for women at high risk of OHSS, where a GnRH agonist trigger (which is safer for OHSS but requires freezing) can be used effectively with PPOS.

The study authors note that using the PPOS protocol avoids any potential negative effects that the hormonal environment of a stimulated cycle might have on the uterine lining’s receptivity, since the transfer is delayed.

A Quick Peek at Limitations

No study is perfect, and the authors were upfront about a few things. They used the euploidy rate *per injected oocyte* as the primary outcome, even though they randomized women *individually*. They did include the rate *per woman* as a secondary outcome, which also showed no difference, but it’s worth noting. Also, while 240 women sounds like a lot, they aimed to detect a 5% difference in euploidy rate. Detecting smaller differences might require an even larger study. Finally, this study focused specifically on women doing PGT-A for certain reasons (age, loss, failure). The results might not apply directly to younger women, those on their first IVF cycle, or those without these specific indications.

Putting it All Together

So, there you have it! This randomized controlled trial gives us solid evidence that for women undergoing PGT-A due to advanced maternal age, recurrent pregnancy loss, or repeated implantation failure, the PPOS protocol is just as effective as the GnRH antagonist protocol in terms of producing euploid blastocysts and achieving live births after a frozen embryo transfer.

It’s another great tool in the IVF toolbox, potentially offering a simpler and more cost-effective way to get to that crucial step of having a healthy, chromosomally normal embryo ready for transfer. Always chat with your own doctor about which protocol is best for *your* specific situation, but it’s reassuring to know that PPOS holds up so well in this important comparison.

Source: Springer