Q From U: Assisted Hatching

Submitted by FertilityLab Wed 03/07/2012

I get a lot of questions from you (Q from U) about assisted hatching so here is more on that topic.

What is assisted hatching (AH) ? Assisted hatching is a technique used by embryologists to produce an opening in the outer shell of the egg called the zona pellucida. We talk about hatching in two contexts. Normal embryos, left to their own devices will hatch on their own as shown in the picture below. The embryo must escape or hatch from the zona or it can’t implant into the endometrial lining of the uterus. Receptors on the embryo and on the maternal cells must be free to interact with each other and cause implantation to occur. If the embryo is trapped in the zona after transfer, that can’t happen.

So if the embryo will normally hatch on it’s own, why does an embryologist ever open the zona artificially? The procedure of assisted hatching was developed by a Dutch embryologist ,Jacques Cohen, PhD in the early 1990′s. Dr. Cohen moved to the US in the early days of IVF here and is one of the most highly respected pioneers in micromanipulation techniques (ICSI and AH). Dr. Cohen writes about his early successes and concerns regarding assisted hatching in this review and this paper. He developed the AH technique because he noticed that some embryos grown in vitro had zonas which remained thick, instead of thinning naturally as the embryo grew and expanded. This natural thinning of the zona at the same time as the swelling growth (expansion) of the blastocyst work together to breach the zona and release the blastocyst. If the zona stays thick, the embryo may be trapped inside and fail to implant.

What methods exist for assisted hatching? The original methods involved making a mechanical slit in the zona with microneedles (also called partial zona dissection) or alternatively, the use of a chemical solution (acid Tyrodes solution) to dissolve the zona. A stream of acid Tyrodes is released onto the surface of the zona and the zona dissolves until the technician stops the stream and retracts the hatching pipette containing the acid solution. Both of these methods required very high levels of technical skill to avoid damaging the embryo and have largely been replaced in most programs by almost idiot-proof laser hatching (point and shoot) technology. You can see a video of a laser in action on the Hamilton-Thorne manufacturer website and also below. Lasers are relatively expensive which is the only drawback of this relatively safe technology compared to older methods of assisted hatching.

Click here to view the embedded video.

Why is assisted hatching ordered? The most common indications for AH are maternal age (over 37 years of age), elevated FSH levels which can negatively impact egg quality, thick zona pellucida (the original indication), slow embryo progression, lots of fragmentation (fragments can sometimes be removed during the hatching procedure) , previous failed IVF cycles and cryopreserved embryos which may have hardened zonas from the freezing solutions used and the freezing process itself.

Other reasons for ordering assisted hatching is patient preference (e.g. they were successful several years ago using AH and want to do everything the same) and (cynically) there is a procedure code for hatching so labs can charge separately for it.

Is it always needed? No. Hatching was a much more useful technique in the bad old days of cell culture when we could only grow embryos for three days in culture and the medias were not optimized for embryo growth. There is evidence to suggest that zona hardening and failure to thin may have been an unintended consequence of these early culture methods. These concerns and the observations of persistently thick zonas in culture is what prompted Dr. Cohen to want to breach the zona for the embryo since it might not bbe able to breach a hardened zona through simple expansion. There is no evidence that the newer culture systems that support embryo growth to the blastocyst stage result in thick zonas. We routinely see embryos growing to relatively huge sizes with zonas strained to almost invisible thinness just prior to spontaneous hatching in vitro. Frankly, a bigger problem today may be that embryos hatch before we get them into the catheter and back into Mom.

Assisted hatching of thawed cryopreserved embryos may still be beneficial for implantation according to some studies. Cryopreservation by some methods may cause zona hardening and assisted hatching could theoretically bypass hatching difficulties for these embryo. Most programs would rather hatch “just in case” rather than having to try to explain to the patient why her frozen embryo transfer didn’t work, but her friend who had AH, did get pregnant.

Does AH make everyone (patients and doctors) feel like they have done everything they can to ensure hatching (and hopefully pregnancy) will occur? Yes. Because we can’t be sure that it is unnecessary, it is often done “just in case”. What’s the downside? The technician may not be skilled enough and damage the embryo. Or the hatching will work “too well” and the zona will be lost prior to transfer, making the embryo more “sticky” and possibly harder to move around and pick up with handling pipettes. Zona-free embryos may be more likely to be retained in the catheter and may be less protected from shear forces in the catheter during pick up and transfer. Some studies have suggested that the risk of monozygotic twins is higher in assisted hatched embryos, possibly because the inner cell mass is torn into two, causing twins. Twin pregnancies, especially if the placental structures are shared among twins (monoamniotic, monchorionic twins), tend to have more obstetrical complications and poorer outcomes than singleton pregnancies.

The good news is that AH is much easier for the technician (and therefore safer for the embryo) with the advent of laser technology. AH is probably used more than absolutely required because the only obvious indications it will be helpful (a big fat zona) is rarely seen. AH is more often done for “just in case” reasons, or if you will, as insurance against “failure to hatch”.

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