Facts

On March 18, 2003, plaintiff Eve Rubell first presented to USC Reproductive Endocrinology & Infertility (USC RE&I) for in vitro fertilization (IVF). Richard Paulson, M.D., is the Director of USC RE&I, and the only physician at USC RE&I who counseled and treated the plaintiff.

By March 18, 2003, Rubell had been trying to become pregnant without success for 2.5 years. Her Kaiser physicians had provided her with a listing of IVF centers in the local area, from which she chose to engage Dr. Paulson. Almost immediately after beginning a first round of IVF in April 2003, Rubell was referred to Dr. Jacqueline Siegel-Bartelt of Kaiser for a genetics consultation following an ophthalmology eye finding (corneal swirling) suggestive of Fabry's disease carrier status.

This diagnosis was shortly thereafter confirmed by blood testing genetic analysis performed by GeneDx. Dr. Siegel-Bartelt, who was aware of Rubell's consultations with USC RE&I for in vitro fertilization, recommended pre-implantation genetic diagnosis (PGD) for either fetal sex selection (by Fluorescent In-Situ Hybridization "FISH" testing) or for the specific Fabry mutation (by PCR testing).

Due to the identification by GeneDx of the specific Fabry mutation of Rubell's DNA, it was recommended to her that each embryo be genetically tested using a technique called polymerase chain reaction (PCR). PCR is designed to identify a specific genetic abnormality at a certain locus of a DNA strand obtained from a single cell from each embryo. Dr. Siegel-Bartelt recommended that Mark Hughes, M.D. of Genesis Genetics in Detroit, Mich. perform the PGD/PCR procedure.

On Sept. 8, 2003, Dr. Paulson harvested Rubell's eggs and Jose Bergero’s sperm. The next day, through a process called intracytoplasmic sperm injection (ICSI) Rubell's eggs was fertilized resulting in six successfully fertilized eggs/embryos. The embryos were then cultured until day three, Sept. 11, when Dr. Sergei Evsikov arrived at USC RE&I to perform a single-cell biopsy of each of the six developing embryos. Those single-cells, referred to as blastomeres, were then sent via special courier to Dr. Hughes' PCR laboratory in Detroit for PCR testing.

On Sept. 13, the PGD Transfer Report from Genesis Genetics Institute indicated that embryos numbers two and five, which each contained one normal and one Fabry gene, were carriers of the maternal mutation (i.e. carrier females). Two of the other embryos were predicted to be males affected by Fabry disease and no results were obtained from the remaining two embryos.

After reviewing the PGD Transfer Report and discussing the results with Dr. Paulson, Rubell and Bergero chose to implant embryos numbers two and five, predicted to be female carriers of Fabry disease, resulting in one successful implantation and pregnancy.

Following successful implantation, Rubell declined an amniocentesis and it was not until after an ultrasound revealed her fetus was a male and a blood test indicated increased risk of Down’s syndrome, that Rubell changed her mind and agreed to an amniocentesis in December 2003. Unfortunately, this amniocentesis indicated a male fetus afflicted with Fabry's disease. The results were shared with Rubell on Jan. 5, 2004, but the couple, Rubell and Bergero, indicated that they elected to continue the pregnancy despite knowing that their child would be afflicted with Fabry’s disease.

On May 31, Gabriel Bergero was delivered and his Fabry's status was later confirmed by genetic testing.

PLAINTIFF'S CONTENTIONS:
The plaintiff contended that the most likely source of the error in this case was either a sample mix-up, resulting in the wrong embryo being implanted, or DNA contamination at the USC RE&I laboratory due to insufficient DNA contamination prevention procedures and protocols. Sample switching was a known problem with PCR testing. Labs which did PCR testing routinely had a "second set of eyes" i.e. a second person watching all embryo transfers to make sure such mixup did not occur. No such technique was used at USC. After USC erroneously implanted a male with Fabry disease, USC began using the "second pair of eyes" precaution.

The plaintiff also contended that misinformation was conveyed to Kaiser Permanente as well as to Ms. Rubell. USC wrote Kaiser stating that "our laboratory has had excellent results with PGD" (preimplantation genetic diagnosis) when in fact according to the lab director, USC had done only "one or two" such PGD tests. Ms. Rubell was not informed that there were other labs which had performed "20 to 40 times as many" PCR tests as USC, or that the major lab for such testing had performed about 800 such tests.

The plaintiff contended that FISH testing, a more reliable test for determining the gender of an embryo, should have been performed by itself or in conjunction with PCR testing, which would have required a second cell be biopsied from the three-day-old embryo, to make certain that only female embryos were implanted.

At the time, it was thought that female carriers experienced far less serious manifestations of the disease and therefore it was more important to prevent the implantation of an affected male embryo than it was to avoid the implantation of a carrier female. Therefore, the plaintiff contended that the outcome of this case could have been avoided by simply making certain that only female embryos were implanted.

The plaintiff contended that Dr. Paulson did not obtain an informed consent from Rubell and Bergero because Dr. Paulson did not inform them of the fact that USC RE&I had performed only two previous PCR tests and seven previous FISH tests prior to Rubell's testing in September 2003.

Plaintiff additionally contended that the equipment on which embryo biopsies were performed was used after exposure to ambient air for many months without decontamination from DNA.

Plaintiff finally contended that as it was found that USC had erroneously implanted a male with Fabry disease, USC dropped its PCR program and did not restart it for 2.5 years.

DEFENDANT'S CONTENTIONS:
The defendant contended that preimplantation genetic diagnosis, and specifically PCR testing, was an emerging and cutting edge technology in 2003. The lack of extensive prior experience by USC RE&I in performing PCR testing was similar to the experience by other IVF laboratories in Southern California.

Rubell and Bergero's goal in having preimplantation genetic diagnosis performed was to eliminate the Fabry disease gene from their descendants. PCR, rather than FISH could only accomplish this goal for gender testing, as FISH would have an equal chance of resulting in a carrier female child. It was only after the PGD testing results showed that none of the six embryos were unaffected with Fabry disease, that Rubell and Bergero opted to implant a predicted carrier female, rather than undergo a new round of fertilization and testing to obtain an unaffected embryo.

There was no evidence of a sample mix-up or DNA contamination during the testing and implantation process at USC RE&I. There was no deviation from the IVF or PGD protocols implemented at USC RE&I, nor was there any evidence of DNA contamination in the media blank samples sent to Dr. Hughes for testing along with the single-cell blastomeres.

The most likely explanation for the bad outcome of the testing in this case was due to either an unknown failure in the technology of the PCR testing, unavoidable DNA contamination from maternal cumulus cells, or mosaicism of the embryo tested (that the single-cell tested from one of the embryos was not representative of the other cells in the embryo nor of the resulting child).

Settlement Discussions

The plaintiffs demanded $7 million; the defendant offered $1 million. The department chief settled before trial for $500,000.

Specials in Evidence

$14 million (present value cost of lifetime Fabrazyme treatment)

Injuries

As this is a wrongful life case, no general damages or loss of future earnings potential damages could be sought. The only damages that could be claimed by plaintiff are the medical expenses associated with the future care and treatment of Gabriel Bergero due to his Fabry's disease. Accordingly, the economic damage in this case at most is the cost of providing enzyme replacement therapy (Fabrazyme) to him during his lifetime.

Result

Defense verdict.

Other Information

Wrongful life care precludes recovery of anything other than the extraordinary medical costs associated with the treatment of plaintiff's Fabry's disease.

Deliberation

one day

Poll

11-1

Length

19 days