Arizona Center for Fertility Studies Offers Laser Technology

Laser Assisted Hatching (LAH)

The advent of the laser has allowed the development of precision techniques to manipulate embryos for enhanced fertility. Laser-assisted hatching (LAH) can potentially enhance implantation/pregnancy rates or turn around a history of failure for embryos to implant themselves in the uterine wall.

Arizona Center for Fertility Studies strongly believes that laser technology is state of the art technology for any embryos that undergo Assisted Hatching (AH), embryo biopsy for Chromosome Abnormality / Single Gene Mutations or Gender or Sex Selection and prior to transferring Cryopreserved or Frozen Embryos FET).

Arizona Center for Fertility Studies embryologist, Andrew Barker, is one of a number of reproductive embryologists in the country that is highly skilled in using the laser on human embryos.

Laser-assisted hatching (LAH) is used to help the embryo hatch from its protective outer shell, the zona pellucida, and promote implantation in the uterine wall after embryo transfer. Laser-assisted hatching uses a highly focused infrared laser beam to remove a very small section of the zona pellucida, or outer wall of an embryo, in very precise increments. Prior to the clinical availability of the laser-assisted hatching, only mechanical or chemical methods could be used for assisted hatching of human embryos in clinical settings. Laser-assisted hatching requires less handling of the embryo than these other assisted hatching methods. Also, laser-assisted hatching is faster than the other methods and, therefore, the embryo spends less time outside the incubator.

Indications for laser-assisted hatching (LAH)

Laser-assisted hatching (LAH) is not currently recommended for routine use in all in-vitro fertilization patients, and several factors should be considered in determining candidates for laser-assisted hatching. These include age, hormonal status, embryo quality, number of in-vitro fertilization attempts, and whether frozen embryos are being implanted.

• Age - Women over 37 years old. Arizona Center for Fertility Studies actually believes that all embryos, whether day 3 or blastocysts, should undergo laser-assisted hatching to improve implantation/pregnancy rates
• Hormonal Status - Women with an elevated baseline level of FSH
• Embryo Quality - Women with poor prognosis embryos, including conditions such as a thick zona pellucida, slow cell division rate, or high-cell fragmentation
• In-Vitro Fertilization Attempts - Women who have failed 1 or more In-Vitro Fertilization cycles. Arizona Center for Fertility Studies believes that laser-assisted hatching should be done on the first In-Vitro Fertilization attempt so a second attempt may not be needed
• Frozen Embryos - Women using either day 3 or blastocyst frozen/thawed embryos, which may have hardened zona pellucida as a result of the freezing process. Arizona Center for Fertility Studies does laser-assisted hatching on all frozen embryo transfers (FET)

Laser-Assisted Biopsy (LAB)

Laser-Assisted Biopsy (LAB) is used at Arizona Center for Fertility Studies to facilitate removal of a cell or blastomere from an embryo undergoing pre-implantation genetic diagnosis (PGD/PGS) for chromosome testing, single gene mutation testing or gender/sex selection. There are two current methods used for embryo biopsy:

• Blastomere Biopsy
• Trophectoderm Biopsy.

Blastomere Biopsy

Blastomere biopsy, the most common method of embryo biopsy, involves the removal of one blastomere when the embryo reaches the eight-cell stage, typically at the third day of development.

Trophectoderm Biopsy

Recently, trophectoderm biopsy is gaining popularity as an alternative method of embryo biopsy. Since trophectoderm cells are extra-embryonic tissue, they do not become part of the fetus but do become part of supporting structures, such as the placenta and membranes. Trophectoderm biopsy takes place at the blastocyst (day 5 or 6) stage of development, as the trophectoderm is beginning to herniate through the zona pellucida. Instead of removing an individual blastomere or cell, several trophectoderm cells are removed.

As a result of our experience over the last several years doing 23-chromosome microarray; and now what seems to be conclusive evidence that embryos can "self-correct", Arizona Center for Fertility Studies strongly recommends only doing biopsies on day 5-6 embryos (blastocysts) using laser-directed TE (trophectoderm) biopsy. This means that after the blastocyst is biopsied, it will undergo cryopreservation and be transferred in a subsequent frozen embryo transfer (FET) the following cycle. Although this means that the couple will need to wait a cycle to do the transfer, there are a number of advantages of doing a TE biopsy as opposed to a day 3 biopsy.

1. First and foremost, it eliminates dealing with the possibility of "self-correction", which Arizona Center for Fertility Studies has observed happens more commonly than would be expected. Arizona Center for Fertility Studies was in a unique situation to be able to re-biopsy normal appearing day 5-6 blastocysts at no charge. Most clinics are not able to do this and if they are doing day 3 biopsy and the chromosomes come back abnormal, they have to discard the embryos because without re-biopsy there is no way to know if they "self-corrected" and it is too risky to just assume they did. If a patient feels strongly that she wants to do a day 3 biopsy, in order to avoid a FET and has developmentally normal blastocysts that come back chromosomally abnormal, Arizona Center for Fertility Studies will still do a TE biopsy, at no charge, and cryopreserve the embryo(s) and wait for the results of the TE biopsy. If the re-biopsy is normal, she will be able to do a future FET if needed. Although Arizona Center for Fertility Studies strongly recommends day 5-6 TE biopsy for PDG/PGS with subsequent FET, the couple will not have to worry about discarding "normal" embryos.
2. Several other reasons to do day 5-6 laser directed TE biopsy is that there is evidence to suggest that embryos do better in group culture through the blastocyst stage than to be separated on day 3, which they have to be to if a day 3 biopsy is done.
3. Additionally, day 3 biopsy has an increased chance of failed amplification (see below) because only one cell is being removed. With a TE biopsy you can safely remove 3-4 cells, which eliminates the risk of failed amplification and gives a more accurate interpretation.
4. Also, by doing TE biopsy and cryopreservation, with subsequent FET, the patient can be stimulated more aggressively to make more eggs/embryos and be triggered with lupron, rather than with hCG, and completely avoid the risk of ovarian hyperstimulation syndrome (OHSS).
5. Finally, the couple only pays for TE biopsy if the embryos reach the blastocyst stage. If a day 3 biopsy is done, all embryos need to undergo a biopsy, since you do not know which ones will develop into blastocysts. With TE biopsy, if the embryos do not reach the blastocyst stage, which is of course not a good sign, at least you are not paying to have PGD/PGS done.

In Arizona Center for Fertility Studies experience, all these advantages collectedly add up to higher success rates when using PGD/PGS, and is the reason Arizona Center for Fertility Studies now strongly recommends only doing TE biopsy, cryopreservation and subsequent next cycle FET on all patients undergoing PGD/PGS. The one exception is in our out of state patients, unless they can make a return trip. Our success rates are still very good with day 3 biopsy but Arizona Center for Fertility Studies would prefer day 5 TE biopsy.

Indications for Laser-Assisted Embryo Biopsy (LAB):

Laser-Assisted Embryo Biopsy (LABis not currently recommended for routine use in all in-vitro fertilization patients, and several factors should be considered in determining candidates for LAB. Arizona Center for Fertility Studies strongly believes that Laser-Assisted Embryo Biopsy (LAB should be done on all embryos for the following indications:

• Carriers of Single Gene Disorders (genetic disorders like cystic fibrosis, muscular dystrophy, sickle cell anemia, Rh factor and many more)- These patients benefit from PGD/PGS by reducing the risk of conceiving an affected baby
• Recurrent Miscarriage - Fertile couples with repeated miscarriages (PRL) should be evaluated for the presence of a chromosomal abnormality. The female or male partner may be a carrier of a balanced translocation or be an aneuploid mosaic
• Unsuccessful In-Vitro Fertilization (IVF) Cycles - Couples with repeated unsuccessful In-Vitro Fertilization (IVF) cycles should be evaluated for the presence of a chromosome abnormality. The female or male partner may be a carrier of a balanced translocation or be an aneuploid mosaic
• Unexplained Infertility - The most probable cause of unexplained infertility or history of repeated pregnancy loss is a chromosome abnormality. The male or female partner (evaluation of the female) may be a carrier of a translocation or be an aneuploid mosaic
• Aneuploidy (embryos with chromosome abnormalities that result in a miscarriage or unsuccessful attempt at In-Vitro Fertilization (IVF), most commonly Down’s Syndrome) or Advanced maternal Age - women of advanced maternal age (> 35) are at a higher risk of producing aneuploid embryos, resulting in implantation failure, a higher risk of miscarriage or the birth of a child with a chromosome abnormality (e.g. Down syndrome)
• Gender or sex selection - Couples wanting to determine the sex of each of their embryos for gender selection

Is Laser Technology Safe?

Arizona Center for Fertility Studies believes that laser is safe for human embryos do to the patented Isotherm Rings™ on our laser that prevent potential harmful effects on blastomeres (the cells of the embryo) adjacent to the zona pellucida (wall of the embryo) due to heat from the laser drilling.

The Isotherm Rings™ appear on our embryologist’s computer screen as a series of six concentric circles of varying colors (below) and indicate the maximum temperature reached at the ring diameter at various laser pulse durations (2^nd picture below). At longer pulse duration, it is apparent that temperatures radiate farther into the center of the embryo, increasing the likelihood of blastomere damage. Arizona Center for Fertility Studies embryologist uses the orange ring (second from center) as an indicator of the drill hole size at the selected pulse duration.

With this interactive Isotherm Rings™ feature, Arizona Center for Fertility Studies can now "see" the heating and drill hole size and eliminate the temperature "guesswork."

Note how the heat penetrates further into the embryo as the pulse length increases. So even if the actual drill hole (orange ring) does not come close to the blastomeres, the blastomeres are exposed to the heat generated by the laser beam at longer pulse lengths. By using the Isotherm Rings™ feature of our laser, our embryologist can "see" the heat conduction prior to treatment and adjust the pulse length and embryo positioning accordingly, so as NOT to damage the embryo.

Arizona Center for Fertility Studies is excited about offering this new technology in human reproduction that has become the standard at our clinic.

Pictures and some text - Courtesy of Hamilton Thorne