University of California San Francisco
NYU School of Medicine
As you’ll see, we have a detailed course on the IVF process here and the major decisions doctors and patients need to make therein.
Effectively there are 5–10 major steps and milestones in the IVF process, and as you can see in the sample below (which you may recognize from earlier lessons), after each milestone, intending parents have fewer eggs/embryos to work with. For many reasons, experts think of the IVF process as a funnel.
During each step, there is often a decision to be made. In our dedicated course, you’ll hear more about each, but for the moment, we’ll focus on the ones that are germain to using donor eggs.
Generally speaking in IVF, the more eggs that are retrieved, the higher the odds of success. However, after 20 eggs or more, IVF success rates plateau. To some extent, the same can be true for donor egg cycles. As you can see in one study published in the major European fertility publication, Human Reproduction, after a donor produced at least 15–20 eggs, rates of success didn’t dramatically increase.
Some doctors may see this as a rationale for pushing higher doses of drug (which doesn’t lower the odds of success), while others may see this as justification for taking a more measured approach, since amongst most patients, pushing for higher doses of eggs raises the risk the donor will hyperstimulate.
As a result, many doctors will want to prescribe 150–250 IU (international units) of drug per day while others will push for higher doses, especially if the donor’s profile reveals she’ll respond less well to drugs and will need more. Typically, higher drug doses will increase the total drug bill.
Next, there are multiple combinations of fertility drugs the donor can take leading up to a retrieval. The two most common “protocols” are the “antagonist” protocol and the “long agonist” protocol. Generally speaking, most doctors tend to put donors on the “antagonist” protocol, which can help assuage the risk the donor would be at risk for hyperstimulation or the retrieval would need to be cancelled. To learn more about doses and protocols, go to our dedicated lesson here.
Once eggs are retrieved, they must be fertilized with sperm. Clinics have two techniques available, each with their trade-offs.
ICSI, or intracytoplasmic sperm injection, involves an andrologist selecting a sperm and injecting it directly into the eggs.
Conventional insemination involves surrounding the egg with sperm and allowing circumstances to determine which sperm fertilizes the egg.
We have a dedicated course here to the subject, but on balance, this is how we view the tradeoffs.
For patients using frozen eggs, who have a severe form of male factor infertility or who plan to have genetic testing on their embryos to rule out a single gene disorder, they must use ICSI to fertilize their donor eggs. Most other patients get to decide which approach they’d prefer.
Once eggs are fertilized and they’re grown into embryos, tests like PGT-A exist to help determine if the embryo has the correct number of chromosomes and is more likely to lead to a successful transfer.
Credible clinicians tend to disagree on the value of PGT-A and when it’s most productive. We have a dedicated course on the subject here, and below, we outline the trade-offs.
In the context of using donor eggs, the debate persists but the points of debate can be narrowed. The main value PGT-A provides is that it helps improve the odds the clinic will select an embryo to transfer that leads to a birth. But as you can see in the data below, collected from 34 clinics across three continents, the benefits are most apparent when the person providing eggs is over the age of 35.
The reality is most egg donors in most countries are comfortably younger than the 35 year age cut-off highlighted above. Below is an example of the age breakdown of donors in the United States. As a result, many doctors wonder whether the added cost, effort or risk of PGT-A can be justified. Again, credible experts disagree on the matter.
That said, there are many circumstances where PGT-A may seem like a more appropriate step.
For intending parents doing both donor egg and surrogacy the total cost and effort to coordinate is significant. If PGT-A can minimize the risk of a failed transfer, it's likely easier to justify.
For intending parents committed to having multiple children, PGT-A will raise visibility into whether embryos they plan to store (and rely upon later) are highly unlikely to work. Knowing this information earlier on, rather than years down the line, would be useful.
For intending parents using the eggs of a donor who may be over the age of 35, the argument to use PGT-A becomes more compelling. This is more likely to be the case when intending parents use the eggs of a “known donor” who may be ideal for a number of reasons (e.g. genetic connection, know the person well) but their age or egg quality is not necessarily one of them.
Once embryos have been created, they’ll be transferred. A major question intending parents face is how many embryos to transfer during each transfer.
As you’ve seen, many donor egg recipients have multiple embryos at their disposal. Many are understandably fatigued and motivated to ensure the first transfer leads to a live birth. Given this, and the higher-than-normal likelihood embryos-from-donor-eggs will lead to a live birth, twin rates are exceptionally high. Twin rates correlate with prematurity.
We can’t overstate the risks associated with multiple gestation pregnancies, which can impact the welfare of the person carrying and of the offspring. Below, we characterize some of the better-run studies on a few of the issues.
What is lost on many of us is that if we transfer two embryos at once or one-at-a-time using a second transfer (if necessary), the total rates of success are the same, as highlighted in this Swedish study below. And yet, the risk we offload by doing a single embryo transfer strategy is substantial. The price many of us pay for a second transfer (again, if it’s even needed) is typically 5% of the total donor egg IVF cycle.