Assisted hatching at the Portland Hospital fertility unit

By Sammy Lee, Meryl Santis, Alastair McClure, Julian Norman-Taylor and Dickinson Cowan.

Much has been written over the years about assisted  hatching.  During the early 90s, Jacques Cohen demonstrated that assisted hatching with embryo co-culture could produce improved results for fertility patients. The rationale behind assisted hatching is that some embryos are unable to implant because they fail to hatch. Embryos fail to hatch for a number of reasons:
 

• The embryo fails to develop (it either arrests-stops growing or the development is abnormal and the embryo fails to become a blastocyst.

• The embryo becomes a blastocyst, but is unable to "expand", This failure to expand means that it is unable to put enough pressure on the zona pellucida (the outer membrane) so that it may escape.

• The embryo becomes a blastocyst, but is unable to hatch because, even though it develops into an "expanded blastocysta, the zona pellucida does not break. This would leave the potentially viable embryo trapped inside the zona.

• The zona pellucida may be too thick.

• The zona pellucida may be too hard.

• Hard zona are usually detected by discoloration.

• Abnormal zona may also be spotted by an unusual opaqueness or by the presence of large numbers of sperm attached to it.

• There are likely to be other, as yet unknown reasons; the above should not be considered to be an exhaustive and inclusive list of reasons for failure to hatch or to implant.

In cases where it is thought that there is problem with hatching, a procedure
resulting in the opening up of a hole of some description into the zona pellucida (assisted hatching), might help. There are a number of different methods of assisted hatching:
 

• Using a pipette filled with Acid Tyrodes. The acid filled pipette is brought up close to the zona peltucida. Once close up, acid is released slowly from the pipette until a hole in the zona pellucida visibly opens up. Thls hole is usually between 10-20 microns in size, which can be big enough to allow premature hatching of the embryo. Some practitionners also argue that the acid may also be harmful to the embryo itself.

• Jacques Cohen's original method described the use of a sharp glass needle, similar to the shape and size of a standard ICSI (sperm microinjection) needle. This needle was used to lance the zona pellucida. Once achieved, the needle would be used in a slicing motion producing abrasion up against the hotding pipette until a substantial gash had been introduced into the zona. Once again, premature hatching may be a potential hazard of this method, but there would be no potential harm from any acid.

• Another increasingly popular method is the laser. Here, a special laser is fitted to the microscope. Then the embryo(s) to be hatched are lined up under the sights of the laser. A brief pulse of energy then results in a hole appearing in the zona. The lazer may be applied with precision, so a hole as large as 20 microns might be created or a very gentle nick could be placed into the zona pellucida. This is an highly elegant method, but a very expensive one. All the other methods are relatively low cost, but a laser costs over £12 000.

• The method used at the Portland Hospital is similar to Dr Cohen's, but the abrasion part of the process is omitted. An ICSI needle is simply used to put two small perforations into the zona peltucida (5-10 microns only in diameter). The method is simple, cost effective, safe and efficient. Premature hatching is highly unlikely, the embryos are not exposed to any chemicals and the simple method is completed in less than 5 minutes, just before embryo transfer.

Assisted hatching is a simple procedure. It is usually done just prior to embryo transfer and may be done at any stage from 4 cell to blastocyst. It must be borne in mind though that different units and different embryotogists have different opinions and there are bound to be units which have a policy that only 8 cell embryos will be hatched etc. etc.
 

At the Portland Hospital Fertility Unit (PHFU), assisted hatching was first done in 1998. A patient who had had more than 3 previous failed IVF cycles was in a quandary as to what else might be done to help her have a chance of a child. After a lengthy discussion, it was agreed that she and her partner would be guinea pigs. They volunteered to be the PHFUs first assisted hatching (AH) patients. The couple were delighted nine months later to be the proud parents of a baby boy! The PHFUs first AH baby. Since then, AH has become a fairly routine procedure in the unit, although even after three years, we have still only done 75 AH cycles. Hatching is offered selectively; usually only after 3 failed lVF cycles or where the female partner is over 38 years old. Additionally, indications such as thick, discoloured or disfigured zonas are used as filters for those having AH.
 

Results are shown below.

Table. Showing outcomes for treatments with and without (controls) assisted hatching. Data from HFEA 1998 for different age groups is included for comparison.
 

                            AVERAGE  CYCLES     LIVE
                                  AGE                            BIRTHS
Assisted Hatching      37               75               17 (22.7%)
Controls                      33               75               14 (18.7%)
HFEA 1998                 37           3918             528 (13.5%)
HFEA 1998                 33           5645           1050 (18.9%)

For comparison, data has also been taken form the HFEA report of live births in the UK for 1998 in similar age groups to the AH patients. Control cases done at the same time as the AH cases have been paired to provide further data for comparison. It is interesting to note that on average, patients having AH were 4 years older than patients who did not receive AH. The live birth rate for AH patients here at the PHFU was significantfy higher (22.7% vs 13.5%) than for 37-38 year olds as a whole in the UK during 1998.

Assisted hatching is now established technology here at the PHFU. The results are most encouraging. Assisted reproduction technology does not stand still. Here at the PHFU we continuously strive to improve success rates for our patients. The search continues and we hope that progress and new methods that will help to improve our success rates will occur regularly.