Assisted Hacthing

One of the most frustrating aspects of assisted reproductive technology for patients and fertility professionals alike is having to deal with failure. This is especially true in couples who have attempted assisted reproductive procedures many times, and also in those whose time is running out because of their age. Now, a recently developed technique, assisted hatching, is offering new hope to couples who fall into these categories.

Assisted hatching was developed from the observation that embryos which had a thin zona pellucida (shell) had a higher rate of implantation during in vitro fertilization. It was postulated that creating a minor defect in the zona might result in a greater chance of the embryo "hatching," or shedding its shell, allowing for a better chance of implantation in the endometrium.

Initial controlled trials at New York-Cornell Medical College showed a marked increase in implantation in women over age 35 and particularly over 38 or with an elevated FSH level on day 3 of the menstrual cycle. Couples with multiple failed IVF cycles also appear to benefit from assisted hatching. Assisted hatching may be helpful in these infertile couples because their embryos lack sufficient energy to complete the "hatching" process. It is thought that some women may fail multiple cycles of IVF because their eggs have a thicker shell, therefore they have a better prognosis with assisted hatching. In addition, hatched embryos implant one day early, which may allow a greater opportunity for implantation to occur.

he addition of assisted hatching to the standard IVF protocol does add extra laboratory manipulation and therefore added costs. There is a small risk of damage to the embryo during the micromanipulation process or at the time of transfer, and there is a slight increase in identical twinning . There is a greater chance of fetal complications and abnormalities in some identical twins. A rare complication of identical twinning is conjoined or "Siamese" twins. We have not observed a higher rate of identical twins than with routine IVF. This may relate to whether a large enough opening is made in the zona to prevent pinching of the embryo during the hatching process.

The assisted hatching procedure, like ICSI, is carried out by a technique known as micromanipulation. In small dishes the embryos, which now contain an average of six to eight cells, are stabilized by a holding pipette, while on the opposite side a small pipette containing acidified Tyrode's solution creates a small defect in the zona. The size of the defect is critical; if it is too small it may pinch off the embryo during hatching and either reduce the chance of implantation or cause identical twinning. The embryos are then rinsed to remove any excess acid solution and returned to the incubator for a few hours before transfer into the uterus.

This relatively small variation in the IVF procedure has yielded dramatic results. Since all micromanipulation in the 1994 report was lumped together, we need to rely on our experience and reports from the literature to determine AH's effect. In our experience, we were impressed by three very apparent findings.

(1.) First, we discovered that there is a learning curve for this procedure that requires a certain amount of experience with the technique before patients can reap the maximum benefits.

(2.) Our second conclusion was that assisted hatching not only improves the success rate of the patients with the poorest chance of pregnancy because of their age, previous failure or elevated FSH level, but it can also make these "poor prognosis" patients almost as likely to succeed as any patient going through in vitro fertilization.

• In our own experience, in 1995, 133 procedures on poor-prognosis patients yielded 57 clinical pregnancies (43%) and 46 live births (35%). A "take home baby rate" of 35 percent is very close to what we were achieving with our average patients at that time.
• As one would expect, we had the best "take home" baby rates in the under age 40 group with a success rate of 47% (64/138) ongoing or delivered pregnancies per retrieval in 1994, 1995 and part of 1996. During this period, ongoing and delivery rates were 23.1% at age 40 (6/26), 25% at 41 (10/41), and 44% (7/16) at 42.

(3.) Thus, our third observation is that assisted hatching is most effective through age 42. We feel that patients over age 42 would be better served by egg donation if they are willing to accept the concept. It is important to remember that these observations are preliminary and made on the basis of a small number of cases and we will need the confirmation of our and other's ongoing experience.

The bottom line for couples who fall into the "poor prognosis" category because of age (but under age 43), previously failed cycles or elevated FSH levels on the third day of their menstrual cycle is that they should consider adding assisted hatching to the regular regimen of in vitro fertilization. It is important to be sure that the center they choose has enough experience with the technique to assure they have passed the early part of the learning curve and are achieving an enhanced success rate. Finally, couples in which the woman has passed her 43rd birthday should consider egg donation as the most likely method to achieve success.

LASER Assisted Hatching (LAH)

Diode laser is very effective in certain ART procedures like sperm immobilization, zona thinning, zona drilling, assisted hatching, polar body and blastomere biopsy for Pre-Implantation Genetic Screening (PGS) & Pre-Implantation Genetic Diagnosis (PGD), fragment removal etc.

In Vitro Maturation (IVM)

Recently it has been made possible to retrieve immature egg from very small size follicle of about 12mm size which does not require gonadotrophin stimulation. This leads to substantial cost effectiveness of the treatment cycle. Also, this will prevent ovarian hyper stimulation syndrome (OHSS) like dreaded complication. Still the IVM media is costlier and ICSI becomes mandatory.

Holding pipette on left, hatching needle on right As the shell (or zona pellucida) around the embryo is dissolved, the needle is advanced to the left until a small opening is made

 

Who should be treated with assisted hatching?

The most commonly used indications for assisted hatching with an in vitro fertilization case are

• Age factor - Couples having IVF with the female partner's age over 37
• Egg quantity and quality factor - Couples in which the female's day 3 follicle stimulating hormone (FSH) level is elevated
• Embryo quality factor - Couples having IVF with poor quality embryos (excessive fragmentation or slow rates of cell division)
• Zona factor - Couples having IVF with embryos that have a thick outer shell (zona pellucida)
• failures - Couples having IVF that have had one or more previous IVF cycles that failed

In our IVF clinic, we use assisted hatching on just about all cases - because we think it increases the pregnancy and delivery rates.

How is assisted hatching performed?

• The embryo is held with a specialized holding pipette.
• A very delicate, hollow needle is used to expel an acidic solution against the outer "shell" (zona pellucida) of the embryo.
• A small hole is made in the shell by digesting it with the acidic solution.
• The embryo is then washed and put back in culture in the incubator.
• The embryo transfer procedure is done shortly after the hatching procedure. Embryo transfer places the embryos in the woman's uterus where they will hopefully implant and develop to result in a live birth.

Pregnancy rates

Pregnancy rates for in vitro fertilization procedures with assisted hatching have been shown in some published studies to be higher than for IVF without hatching. There is an improvement in the rate of embryo implantation and pregnancy in our IVF clinic with the use of assisted hatching. Apparently, this benefit is not seen in all IVF programs.

It is possible to damage embryos with hatching and lower the pregnancy rate in a program. Therefore, it is essential that if assisted hatching is done, it must be expertly performed by properly trained embryologists.

The actual pregnancy and live birth rates seen in an individual IVF center will vary according to the hatching technique used, the overall quality of the laboratory, the skill of the individual performing the hatching, the embryo transfer skills of the physician, and other factors.

Over the past 15 years there have been great advances in the field of IVF. Thanks to new technologies and procedures, IVF treatments are now becoming more and more successful, even for couples with a poor fertility prognosis. Introduced in the 1990s, assisted hatching is a procedure that can help to improve your chances of IVF success. Available at most fertility clinics nationwide, the procedure is specifically recommended for couples who are most at risk for poor IVF outcomes.

What is Assisted Hatching?

Assisted hatching is a relatively new technique used during certain IVF procedures. It is performed in order to help an embryo hatch out of its protective layering and implant into the uterus.

During the initial stages of development, your embryo is contained in a layer of proteins, known as the zona pellicuda. The zona pellicuda is designed to protect the embryo until it reaches the blastocyst stage of development. In order to successfully implant into the uterine lining, the embryo needs to hatch out of this zona pellicuda and attach to the walls of the uterus.

Sometimes, embryos have a difficult time hatching out of their protective layer. This can occur if the zona pellicuda is too thick or if the embryo does not have enough energy to break through the layer. Assisted hatching attempts to help these embryos break out away from the zona pellicuda by creating a small hole in this outer lining.

How is Assisted Hatching Performed?

Assisted hatching is a very delicate procedure, requiring immense skill. It is performed using micromanipulation techniques, under a microscope, during the fourth day of embryo development.

The embryo is first placed in a petrie dish containing culture solution. A special pipette is then used to hold the embryo in place. The embryologist takes a hollow needle that contains an acidic solution and places it next to the zona pellicuda. A tiny bit of this acidic solution is released from the needle so that it comes into contact with the zona pellicuda. This acidic solution begins to slowly digest the protective layering, creating a small hole. The embryo is then washed in a special solution and placed back inside an incubator until embryo transfer can take place.

Who Can Use Assisted Hatching?

Assisted hatching techniques aren't suitable for every couple. Instead, the procedure is typically recommended for

• women over the age of 37
• women with elevated FSH on day 3 of their menstrual cycle
• couples who have experienced failed IVF cycles
• couples whose embryos have a particularly thick zona pellicuda

Risks Associated with Assisted Hatching

Unfortunately, there are some risks associated with assisted hatching procedures. In particular, assisted hatching procedures do seem to increase the likelihood that you will have identical twins (also known as monozygotic twins). This is because the micromanipulation technique used to break through the zona pellicuda can sometimes cause the embryo to split into two identical halves. There is also an increased risk of

• damage to the embryo, potentially causing death
• fetal complications
• physical deformity
• conjoined twins

The procedure can sometimes also cause complications for the mother, including

• high blood pressure
• infection
• nausea
• mood swings

These side effects are the result of the steroids and antibiotics that you must take during the transfer procedure. Because the protective layer surrounding the embryo has been compromised, it is essential that you take medications to slow your immune system down and to prevent infection of the embryo.

Advantages of the Assisted Hatching Procedure

any couples elect to pursue assisted hatching during their IVF procedures. This is because the technique is associated with a number of benefits including

• fewer embryos required for transfer
• increased implantation success rates
• allows for blastocyst culture>

Disadvantages of the Assisted Hatching Procedure

• Unfortunately, assisted hatching does have its drawbacks. Specifically, assisted hatching is
• only suitable for certain groups of women
• very difficult to perform and requires immense skills
• can be associated with an increased risk of dangerous pregnancy complications

Success Rates of Assisted Hatching

Assisted hatching is associated with a fairly high success rate, especially when performed by a skilled micromanipulator. In fact, pregnancy rates are as high as 49% in women who are between the ages of 35 and 39. Women who are over the age of 40 generally have lower success rates, but assisted hatching still provides them with a better opportunity for conception than would IVF performed without the procedure.