Genetic evaluation of oocyte donors: recipient couple preferences and outcome of testing

Transcription

1 GENETICS Genetic evaluation of oocyte donors: recipient couple preferences and outcome of testing Valerie L. Baker, M.D., a,b Heather M. Rone, B.S., a and Geoffrey David Adamson, M.D. a a Fertility Physicians of Northern California, San Jose; and b Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Stanford University Medical Center, Stanford, California Objective: To report preferences of recipient couples for genetic testing of their oocyte donors. Design: Observational report of results from a genetic testing options form implemented as part of routine care. Setting: Private practice. Patient(s): Recipients and oocyte donors. Intervention(s): Recipient couples completed a form before screening of their oocyte donor that outlined required screening and recommended tests that the couple could accept or decline. Couples were given information about carrier frequency, risk to their child if results were abnormal, and cost. Main Outcome Measure(s): Percentage of couples accepting optional testing. Result(s): Of the 63 couples with data available from their first testing-options form, 42 (67%) accepted and 21 (33%) declined fragile X testing, whereas 34 (54%) accepted and 29 (46%) declined karyotyping. When asked whether they would accept additional testing of their donor if it was recommended by a genetic counselor, 15 (24%) said that they would accept additional testing regardless of cost, 35 (56%) declined, and 13 (20%) indicated that their decision would depend on the cost. In many cases, history was elicited by the genetic counselor or test results were obtained that influenced further testing, decisions to proceed, or provided information important for the child. Conclusion(s): Recipient couples sometimes chose to decline tests that we recommended but did not require, despite the relatively low cost of this testing compared with the total cost of the oocyte donation cycle. (Fertil Steril Ò 2008;90: Ó2008 by American Society for Reproductive Medicine.) Key Words: Oocyte donation, genetic testing, patient preferences The American Society for Reproductive Medicine (ASRM) has published guidelines regarding appropriate screening for oocyte donors, which include minimum standards for genetic screening (1, 2). These standards include genetic screening by history, with cystic fibrosis (CF) screening recommended for all donors and carrier-specific screening tests recommended on the basis of the donor s ethnicity. In addition, according to the ASRM guidelines, the donor and the donor s first-degree relatives should not have any major Mendelian or multifactorial disorder or any significant familial disease with a major genetic component. Genetic screening of oocyte donors also is practiced internationally (3). Despite widespread practice, little is known about the preferences of recipient couples regarding genetic screening of egg donors. To our knowledge, this is the first study to report the preferences of recipient couples for genetic testing of egg donors. We also sought to ascertain how these test results influenced the decision to proceed with the donors and what additional information would be provided by the genetic consult and testing that may be important for the child. Received April 6, 2007; revised and accepted October 30, V.L.B. has received research support from Institute Biochimique (IBSA), Switzerland. H.M.R. is an employee of Fertility Physicians of Northern California. G.D.A. is CEO and a shareholder of Advanced Reproductive Care, Palo Alto, CA, and his spouse is a shareholder of Advanced Reproductive Care. G.D.A. is a physician and an owner of Fertility Physicians of Northern California, has received research support from IBSA, has been a speaker for Ferring Pharmaceuticals, Suffern, NY, and is on the LabCorp Advisory Board, Morrisville, NC. Reprint requests: Valerie L. Baker, M.D., Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Stanford University Medical Center, 300 Pasteur Drive, Room HH333, Stanford, California (FAX: ; vlbaker@ stanford.edu). MATERIALS AND METHODS In June 2005, after consultation with several genetic counselors, we implemented a revised program for genetic evaluation of egg donors. Although we previously had been adhering to ASRM 2002 guidelines for genetic screening of egg donors (1), the new program was more extensive than it had been in the past and incorporated couples preferences into the decisions regarding what tests would be performed. Data are presented for cycles in which donors were screened from June 2005 through December 2006 (n ¼ 75 cycles) /08/$34.00 Fertility and Sterility â Vol. 90, No. 6, December doi: /j.fertnstert Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.

2 Information regarding genetic risk assessment initially was discussed with each recipient couple at the time of their pretreatment consultation with their primary physician. Each recipient couple subsequently was asked to complete a form entitled Testing Options for Donors that was developed by the first author (V.L.B.) in consultation with genetic counselors. Each couple completed this form before the donor was seen for her screening visit. A summary of the information provided in this form is presented in Table 1. On the form, couples were provided with specific information regarding the carrier frequency, the nature of the diseases, and the costs of testing. The testing options were categorized into two groups. Required testing for all donors and the recipient couples, on the basis of the ASRM guidelines, always was performed. The recipient couples were not given an option of declining the required evaluation of the donor. The second group of tests were recommended tests that were recommended on the basis of carrier frequency and severity of disease (e.g., fragile X, peripheral blood chromosome analysis), ethnicity, and personal or medical history of the donor. The couples could decline these recommended tests on the form. However, if additional testing was recommended for a particular donor on the basis of ethnicity or personal or medical history, this information was communicated to the couple to obtain their permission for additional testing. The required evaluation included interview of the donor by a genetic counselor, CF mutation analysis, complete blood count, and hemoglobin electrophoresis. Couples were provided with a brochure explaining CF mutation analysis. Fragile X and peripheral blood chromosome analysis (karyotype) for the donor always were recommended but were not required. These tests were not discussed specifically in the ASRM 2002 guidelines (1) but were listed as optional in the ASRM 2006 guidelines (2). Because these tests were not included as routine tests in the ASRM 2002 guidelines, we had not previously been recommending screening for karyotype and fragile X for all egg donors. We added fragile X to the list of routine recommended tests because of its relatively high frequency, even in women with no family history of fragile X or mental retardation (carrier frequency is 1/259) and because of the potential serious consequences of having a donor who is a carrier of fragile X (i.e., increased risk of mental retardation in offspring). The physicians and genetic counselors debated at length over whether to include karyotype analysis in the recommended panel of tests. Eventually, it was decided that the implications of an abnormal karyotype were great enough to warrant its inclusion in the generally recommended panel of tests, despite the expected low frequency of abnormal results. The couples also were informed that additional testing might be recommended after the donor was interviewed by a genetic counselor. This additional testing might be recommended on the basis of the donor s ethnicity, personal medical history, or reported family history. On the form, couples had the options of declining additional testing, of allowing the tests to be ordered at the donor screening visit if the cost of the tests did not exceed $650, or of allowing additional tests to be ordered regardless of the cost. Obtaining the recipient couples permission for this additional testing allowed us to order the test immediately after the donor completed her genetic consult, without needing to ask the donor to return for another blood draw. However, if a serious issue arose after history was obtained from the donor, we contacted the recipient couple and explained the issue and the additional followup recommended, even if the couple initially had declined the additional testing on the form. The donor interview was conducted over the phone with a genetic counselor. Although tests were ordered for the donor according to couple preference and not donor preference, the genetic counselor did explain the nature of the tests to the donor. The intended parents were provided with a written summary of the genetic risk assessment of their donor. This written report included the risk of all chromosome abnormalities and specifically the risk of Down s syndrome on the basis of the donor s age, the risk of open neural-tube defects, and the background risk of any birth defect (quoted as 3% 4%). The risks for hemoglobinopathy, CF, and fragile X (if performed) were included after the test results were obtained. The report also included other risks on the basis of the history and/or additional testing. Genetic counseling was offered to couples after completion of tests for the donor and the intended father but was not required. If a donor had abnormal test results, these were reviewed with her by the genetic counselor and, in most cases, also by the physician who had screened the donor. Unless anonymous donor sperm was used, the intended father underwent routine testing that included CF, complete blood count, and hemoglobin electrophoresis. There was no routine genetic risk assessment of the intended father by a genetic counselor. If an abnormality in the oocyte donor s testing was found, it was recommended that the intended father also be interviewed by a genetic counselor. Cystic fibrosis mutation analysis was performed, initially using an assay that tests for 86 mutations and later using a test for 97 mutations, which has a higher detection rate for Hispanics and African-Americans. Complete blood count and hemoglobin electrophoresis were performed by Quest Diagnostics (Lyndhurst, NJ) or LabCorp (Burlington, NC), by using standard methodology. Fragile X testing was performed by using a protocol that included both Southern blot and polymerase chain reaction analysis. The inclusion of the Southern blot improves the sensitivity of the test for alleles with larger repeat size, whereas polymerase chain reaction is more accurate for lower repeat ranges. The test is designed to identify the number of CGG repeats in the FMR1 gene. The test result is reported as normal (<45 repeats), intermediate (45 54 repeats), premutation ( repeats), or full mutation (>200 repeats) Baker et al. Genetic evaluation of egg donors Vol. 90, No. 6, December 2008

3 TABLE 1 Summary of information provided to recipient couples on the Testing Options for Donors form. Procedures and tests Required Interview of the donor by a genetic counselor Frequency of abnormality Cost Description NA $150 The genetic counselor makes recommendations for additional testing based on the donor s family and medical history Cystic fibrosis carrier status Caucasian 1/25 $195 Cystic fibrosis causes chronic lung and digestive problems as well as poor growth. With a negative test result, the risk that your donor is a carrier will be significantly reduced Asian 1/90 Complete blood count and quantitative hemoglobin electrophoresis Recommended Fragile X carrier status Blood chromosome analysis (karyotyping) Additional genetic testing based on family history Follow-up genetic consultation Not given Not given Screens for inherited blood disorders such as thalassemia 1/260 normal women $255 Fragile X is one of the most common forms of mental retardation. If your donor is a carrier, there is an up to 50% chance of having a child with the disease 2 to 5 per 1,000 $300 Karyotyping determines whether your donor has an abnormal arrangement of her chromosomes, which increases the risk of miscarriage and having a child will have the wrong number of chromosomes, leading to diseases like Down s syndrome Dependent on the disorder Not given Additional testing may be recommended by the genetic counselor based on the donor s reported family history a NA $150 If the donor s genetic screening evaluation is normal, our standard practice is to inform you and proceed with the cycle. However, you have the option to review the results with the genetic counselor before moving forward Note: NA ¼ not applicable. a Recipient couples are given options to accept regardless of cost, to accept if the cost is <$650, or to decline testing even if recommended by the genetic counselor. Baker. Genetic evaluation of egg donors. Fertil Steril Fertility and Sterility â 2093

4 Peripheral blood chromosome analysis was performed by using standard methodology. Specialized genetic testing on the basis of the donor s ethnicity, personal medical history, or family history, if required, was sent to appropriate laboratories. The couple s preferences, the results of genetic evaluation, and the impact of these results on the decision to proceed with the donor were recorded. The completion of this form and ordering of tests with respect to preference became (and still is) part of routine care in our clinic. Therefore, no separate informed consent was obtained from the couples for the completion of this form. There was no identifying information in the data set that was used for research. A detailed description of our study was reviewed by the Western Institutional Review Board, which found that our study qualified for an exemption from the requirement for IRB review under federal regulation 45 CFR x RESULTS Demographic characteristics of the female recipient and the donor are presented in Table 2. In some cases, a recipient couple filled out a testing-options form more than once because their first donor did not pass screening or because a cycle was unsuccessful. Demographic data for each recipient are presented only once (thus, there are data for 64 recipients in Table 2 for 75 cycles). Cycles were performed with anonymous donors, except in five cases. Most of the intended mothers were in their 40s and were nulliparous, with longstanding infertility. The intended mother who was 56 years of age used a gestational carrier and was married to a man in his 30s. Most donors were in their 20s and were also nulliparous. The majority of recipients and donors in our practice are Caucasian, although many are Asian. The indication for egg donation in all but two cases was diminished ovarian reserve. Two recipients chose egg donation as a result of having abnormal karyotypes. In Table 3, data for the first cycle for each recipient couple are presented separately from the data for the second cycle. Of the 63 couples with available data from their first testing-options form, 42 (67%) accepted and 21 (33%) declined fragile X testing, whereas 34 (54%) accepted and 29 (46%) declined karyotyping. When asked whether they would accept additional testing of their donor if recommended by a genetic counselor, 15 (24%) said that they would accept additional testing regardless of cost, 35 (56%) declined, and 13 (20%) indicated that their decision would depend on the cost and the implications of the test. Data for preferences of couples who underwent screening of a second donor (n ¼ 10) or third donor (n ¼ 1) also are presented in Table 3. Second cycles were necessary for these couples because of lack of pregnancy (n ¼ 5), because of donor s noncompliance or decision not to proceed (n ¼ 3), or because of exclusion of the initial donor as a result of unsatisfactory screening results (n ¼ 3). The preferences for most couples remained consistent in the second cycle. However, four couples tended to want increased testing in their second cycle. One couple declined fragile X and karyotyping in the first cycle and requested this testing in the second cycle. Two couples stated that additional testing was cost dependent in the first cycle but accepted the additional testing regardless of cost in the second cycle. One couple declined additional testing in their first cycle but accepted additional testing dependent on cost in the second cycle. Only one couple had inconsistent results (accepted fragile X and additional testing dependent on cost in the first cycle but declined fragile X and accepted additional testing regardless of cost in the second cycle). TABLE 2 Demographic baseline characteristics of donors and recipients. Parameter Donor n Recipient n Age 25.2 (20 33, 3.0) (32 56, a 4.25) 64 Gravidity 0.7 (0 5, 1.1) (0 6, 1.7) 64 Parity 0.4 (0 3, 0.7) (0 3, 0.6) 64 Years infertile NA 4.6 (1 16, 3.0) 63 b Education 14.8 (12 19, 1.9) (12 24, 2.2) 61 b Ethnicity of intended mother (%) Caucasian Asian Hispanic Unspecified Note: Data for age, gravidity, parity, years infertile, and education are presented as mean (range, SD). NA ¼ not applicable. a Intended mother, 56 years of age, used a gestational carrier. b Data are missing for one and three patients, respectively, in these two categories. Baker. Genetic evaluation of egg donors. Fertil Steril Baker et al. Genetic evaluation of egg donors Vol. 90, No. 6, December 2008

5 TABLE 3 Preferences selected by recipient couples on the Testing Options for Donors form and responses recorded by recipient couples at the time of their second attempted (n [ 10) or third attempted (n [ 1) cycle. Parameter Accepted Declined Cost dependent n Preferences selected on the form Fragile X 42 (66.7) 21 (33.3) NA 63 a Karyotype 34 (54) 29 (46) NA 63 a Additional 15 (23.8) 35 (55.6) 13 (20.6) 63 a Responses recorded at the time of the 2nd or 3rd attempted cycle Fragile X 10 (90.9) 1 (9.1) NA 11 Karyotype 7 (63.6) 4 (36.4) NA 11 Additional 5 (45.5) 2 (18.2) 4 (36.4) 11 Note: Data are n (%). NA ¼ not available. a Data are missing for one answer in each category. Baker. Genetic evaluation of egg donors. Fertil Steril Results of the testing and the influence of the tests on the couple s decision to proceed are presented in Table 4. Three donors were found to be carriers for CF, and their recipients decided to proceed with the cycles after the intended fathers were tested and found not to be CF carriers. If the intended father s initial CF screen had been performed for only 25 mutations, the analysis was repeated with screening for a greater number of mutations. One donor had an abnormal mean corpuscular volume (MCV), which led to determining that she was a carrier for alpha thalassemia. That cycle was canceled for reasons independent of test results (noncompliance of the donor). Of the 52 recipients who indicated on their questionnaire that they wanted their donors to be tested for fragile X, 49 donors tested negative, 1 donor tested positive for a premutation, and 2 donors had their cycles canceled before genetic testing was performed. The recipient couples decided against proceeding with the donor whose testing revealed the premutation. One recipient couple, who originally had declined fragile X testing, had their donor tested per recommendations of the genetic counselor as a result of a family history of mental retardation, and that donor also tested negative for fragile X. TABLE 4 Impact of results from genetic testing on the recipient couple s decision to proceed with the donor. Parameter Normal (n) Abnormal (n) Impact on cycle Required test results a Cystic fibrosis carrier testing 70 3 Proceeded with donor CBC with MCV 72 1 Cycle canceled (donor noncompliance) Hemoglobin electrophoresis 73 0 Recommended test results a Fragile X carrier status 50 b 1 New donor chosen in one case of abnormality Karyotype 41 b 0 Additional testing of donor 3 c 1 Proceeded with donor Note: MCV ¼ mean corpuscular volume. a In two cases, the tests planned based on recipient-couple preferences were not performed because the cycles were canceled before testing. b In four cases (1 for fragile X and 3 for karyotype), analyses initially were declined by the couple and then were accepted only after the donor was evaluated by a genetic counselor who made an especially strong recommendation for testing on the basis of history. c Other testing of the donor based on ethnicity was strongly recommended but was declined in three additional cases that therefore have no results available. Baker. Genetic evaluation of egg donors. Fertil Steril Fertility and Sterility â 2095

6 Of the 41 recipients who accepted blood chromosome analysis for their donors, 38 donors had normal karyotypes, none had abnormal karyotype, and 3 were not tested because the cycles were canceled before testing. In addition, 3 other donors were tested after the donors were evaluated by a genetic counselor, even though karyotyping initially had been declined by the recipient couples. All 3 of these donors also had normal karyotypes. In a total of 11 cases, additional testing on the basis of the donor s family history or ethnicity was recommended by the genetic counselor after interview of the donor, with results available in 8 cases (Table 4). Four of these cases in which specific strong recommendations were made have just been discussed (1 for fragile X and 3 for karyotype). Tay-Sachs enzyme testing was recommended and performed in two cases, which both yielded normal results. In one case, Tay-Sachs DNA testing was recommended but declined. In three cases, an Ashkenazi Jewish panel was recommended but was performed in only one case, which yielded normal results. After reporting a paternal grandfather with hemochromatosis, one donor was tested and found to have the Cys282Tyr mutation in the hemochromatosis gene. The intended father then was tested and found to have the His63Asp mutation. The recipient couple decided to proceed with this donor after consultation with a genetic counselor regarding the risk for an affected child and the nature of the potential abnormalities. In addition to these 11 cases, in 1 case, the donor had an indeterminate Tay-Sachs result from a prior cycle, and the intended father was advised to be tested and was found to be normal; therefore, the couple decided to proceed with that donor. Among the 36 donors who previously had cycled in another program, few had completed a detailed genetic evaluation. In only 3 cases could it be confirmed that a formal evaluation of the donor by a genetic counselor had been performed, and none of those donors had been tested for fragile X or karyotype. Only 1 donor had been tested previously for fragile X and karyotype, 1 had been tested for fragile X only, and 4 previously had had a karyotype only. Other potentially valuable information was provided to the recipient couples regarding the donor s family history for a variety of diseases with a potential genetic component. These diseases included rheumatoid arthritis, lupus (n ¼ 2), osteoporosis, stroke, heart disease (n ¼ 16), hypertension (n ¼ 4), congenital heart defect (n ¼ 2), bundle branch block, diabetes (n ¼ 7), glaucoma, epilepsy, colon cancer (n ¼ 3), ovarian cancer, pancreatic cancer, breast cancer (n ¼ 5), asthma, Crohn s disease, Alzheimer s disease (n ¼ 2), attention deficit disorder, bipolar disorder (n ¼ 2), alcoholism, depression, mental retardation, thyroid cancer (n ¼ 2), Grave s disease, and leukemia. In each case, a description of the likely inheritability was provided on the basis of relationship of the relative to the donor, the age of onset, and the number of family members affected. In some cases, the couple had a follow-up consultation with the genetic counselor to better define the risk. No significant family history was noted for 20 donors. Some problems were reported, but environmental rather than genetic factors were thought to be responsible (e.g., hearing loss after meningitis, lung cancer in a heavy smoker). In other cases, the history was not considered to be significant because the relationship of the affected individual to the donor was so distant that the risk would not be greater than that in the general population. DISCUSSION Our analyses revealed that couples vary regarding their preferences about genetic evaluation of their donors. It was somewhat surprising to us to find how frequently couples chose to decline recommended tests, especially given the relatively low cost of this testing compared with the total cost of the egg donation cycle. It also was clear from this study that the outcome of the genetic evaluation of the donor may alter the couple s decision to proceed with a particular donor, may influence what tests the intended father undergoes, and often provides information that may be important for the child. It should be noted, however, that because of the small number of cases with abnormal findings, the reactions of recipient couples to abnormal results in our study may not accurately predict what would occur in a general population. Although our sample size is modest, our study is the first to report on recipient-couple preferences for genetic testing of oocyte donors. There is no published information regarding how intended parents view the tradeoff between the additional cost and complexity of testing vs. the value of having the information. One study reported that of couples undergoing IVF using their own eggs, 71% had no interest in receiving formal genetic counseling despite the fact that two thirds of the couples had at least one identified genetic risk factor (4). This finding is consistent with our experience, in which most couples did not wish to have formal genetic counseling to review the results of the donor and intended father s testing. A limitation of our study is that it is difficult to ascertain how well each couple understood the options that were presented to them and what factors may have influenced their decisions. It is possible that some couples spent more time discussing genetic testing with their physician or egg donor coordinator than did other couples, a factor that may have made these couples more likely to accept testing. Couple preferences may have varied if the cost of testing were different, which also might have bee true for different centers or for different points in time. There are multiple reasons that a careful genetic evaluation of egg donors is warranted. Because most cycles are performed with anonymous donors, the screening process is really the only opportunity that most recipient couples have to obtain information that may be important to the health of their offspring. A written summary of the donor s family history and results of testing can become an important part of the child s medical record. Although not all couples may elect to 2096 Baker et al. Genetic evaluation of egg donors Vol. 90, No. 6, December 2008

7 disclose the use of egg donation to their child (5), this genetic history may prove valuable for future medical reasons. Another reason that genetic evaluation is warranted is to maximize the chance of the birth of a healthy child. Because the choice of a particular donor in most cases is elective, it appears reasonable to exclude donors who carry increased risk of transmitting a serious disease, especially if the genetic assessment of the intended father for that disease also suggests an increased combined risk. However, if the risk of having an affected child will be low, it may be reasonable to include the donor after appropriate genetic counseling of the intended parents and the donor, as noted in one study describing inclusion of heterozygotes for CF in the egg donor pool (6). Finally, one other reason that careful genetic evaluation of egg donors is warranted is that a program may be more protected legally if an abnormal child is born and it can shown that the program performed a careful genetic evaluation before initiating the cycle and informed the couple if there did appear to be an increased risk associated with a particular donor. Despite the importance of genetic evaluation, some programs may not be following even minimum guidelines for evaluation. A survey of IVF programs registered as members of the Society for Assisted Reproductive Technology was published in 1999 (7). Although most programs who responded did follow ASRM recommendations for genetic screening of oocyte donors, a siginificant percentage did not use well-established testing at the time. On the basis of this 1999 survey and the limited prior genetic evaluation that we noted for donors who previously had donated, a follow-up survey is warranted, as is education of programs that are not performing evaluation. As more genetic tests become available, it will be important to continually reevaluate which tests should be recommended. Fragile X is one example of a test that increasingly is being recognized as important. The American College of Obstetricians and Gynecologists recommends testing of women with premature diminished ovarian reserve for fragile X (8). The test appears to have a high degree of acceptance among women with such ovarian dysfunction (9).It obviously is a different issue to decide whether or not the test should be performed for egg donors who do not have diminished ovarian reserve. However, it appears reasonable to include fragile X testing among the recommended tests for egg donors, given the implications of abnormal testing, its relatively high frequency in the general population, and the fact that carriers in the egg donor pool may not yet have developed diminished ovarian reserve because of their young age. Fragile X testing of egg donors has been advocated by some in the past (10). According to the ASRM 2006 Minimum Genetic Screening for Gamete Donors, fragile X testing may be performed at the discretion of the individual program (2). The issue of whether to include karyotype in routine genetic evaluation of donors certainly can be debated, given the low frequency of abnormal results. The ASRM guidelines consider routine karyotyping of donors to be optional. However, some investigators have suggested that the incidence of abnormal karyotype results among oocyte donors may be higher than generally is thought, perhaps especially if donors are strongly motivated to donate as a result of familial history of infertility that could be associated with chromosomal rearrangements or mosaicism (11). There are no universally agreed-upon standards that provide specific guidance regarding when a donor should be excluded. According to the ASRM 2006 guidelines, donors should be excluded if the donor herself or her first-degree relatives (parents, siblings, or offspring) have any major Mendelian disorder, any major malformation with a multifactorial or polygenic cause such as a heart malformation, and any significant disease with a major genetic component. The donor may still be included if she has a first-degree relative with a chromosomal abnormality, as long as her karyotype is normal. One large international distributor of donor sperm (Cryos in Denmark [12]) has a general policy of keeping the risk for transmission of genetic disease below the risk in the average population and is in favor of screening donors for problems that are becoming part of routine screening as part of preconception family planning in the general population. However, Cryos (12) also points out that we cannot make the risk of abnormality zero and that as more tests become available, it is going to be difficult to decide where to draw the line about what tests to perform. Guidance from organizations such as ASRM will continue to be critical in helping programs to decide what is medically reasonable to recommend. Two recent reviews of potentially relevant case law offer some insight into what the nature of legal liability may be with respect to genetic testing of oocyte donors (13, 14). Claims for wrongful birth against the physician may be brought by parents who have a child with a severe defect that could have been predicted by genetic screening of the donor. The parents may assert that if they had been informed that a genetic test was available, they would have wanted this test to be performed and would have not chosen a particular donor who had an abnormal result. In past wrongful-birth claims that have not involved oocyte donation, the parents damage claims primarily have been for recovery of the extra costs of providing care for their disabled child with special needs. Courts in North America have recognized the validity of a cause of action for wrongful-birth claims in cases of evaluations that can be performed during pregnancy. However, claims for wrongful life have not been commonly recognized by the same courts. A wrongful-life claim asserts that the child is entitled to compensation because of a lifetime need for extraordinary care. A wrongful-life claim may be filed if the parents are deceased, if the statute of limitations on wrongful birth is expired, or if lifelong support is needed for a child and a wrongful-birth award only covered the child until he or she reached the age of majority. The awards made in these wrongful-birth or wrongful-life suits could include recovery for specific damages only (e.g., medical expenses) or could include compensation for emotional harm. For these Fertility and Sterility â 2097

8 claims to be successful, it would be necessary for the plaintiff to prove that the physician was negligent in performing duties (did not practice within the established minimum standard of care) and that the established breach of duty caused the injury. Obviously, it is not possible, and the established minimum standard does not require, that a physician identify and disclose every possible birth defect. However, it will be prudent for physicians who are performing oocyte donation to be certain to remain current regarding the standard of care. Furthermore, if a donor consciously and willfully fails to provide accurate genetic information and it is proven that this misinformation directly influences a couple s decision to select that donor, the donor also could possibly face a wrongful-birth or wrongful-life suit. One other issue that deserves further consideration is whether to consider the couple s preferences in making the decision about which tests to perform. It may be more cost effective and simpler just to order tests than to provide counseling for couples about their options. Furthermore, routine testing without considering the couple s preferences may prevent guilt that some couples may experience if they decline a test and then have a child born with a particular disorder such as fragile X. However, our study suggests that some couples may wish to accept a low level of risk rather than spend the additional resources for testing, whereas other couples want more complete testing. A program s legal liability also may be reduced if it is the couple s choice to decline the test and an abnormality results (13). A combination of required, recommended, and other optional tests may end up being the best compromise as the number of possible genetic tests increases. Future research also should examine the donor s preference with respect to genetic screening and examine the psychological impact and effect of this testing on the donor s future reproductive choice. In our opinion, the donor should be provided with information about the tests and have the option of declining genetic testing. It is possible that donors may decline genetic-disease screening because they fear receiving abnormal results and rejection. However, donors may feel pressure to agree to being tested. Sensitive counseling is important if abnormal results are found, because donors may be totally unprepared for bad news. It also is important to note that there may be benefit to the donor and her future partner in discovering a genetic abnormality before their first desired conception. In conclusion, we strongly recommend that oocyte donor programs continue to use or implement formal genetic evaluation of egg donors, with interviews by a genetic counselor and testing as recommended by ASRM 2006 guidelines as a minimum. A written report should be provided to the recipient couples, to become part of the child s medical record, assuming that the couple is going to disclose their use of oocyte donation to the child in the future. The inclusion of couples preferences may increase acceptability for bearing the cost of genetic testing. Careful genetic evaluation of oocyte donors will help programs to maximize the probability that these cycles will result in the births of healthy children. REFERENCES 1. American Society for Reproductive Medicine. Minimal genetic screening for gamete donors. 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Survey of genetic screening for oocyte donors. Fertil Steril 1999;71: American College of Obstetricians and Gynecologists Committee on Genetics. ACOG committee opinion. No. 338: Screening for fragile X syndrome. Obstet Gynecol 2006;107: Pastore LM, Karns LB, Pinkerton JV, Silverman LM, Williams CD, Camp TR. Acceptance of fragile X premutation genetic screening in women with ovarian dysfunction. Am J Obstet Gynecol 2006;194: Spence WC, Black SH, Fallon L, Maddalena A, Cummings E, Menapace-Drew G, et al. Molecular fragile X screening in normal populations. Am J Med Genet 1996;64: Ravel C, Letur H, Lannou DL, Barthelemy C, Bresson JL, Siffroi JP, et al. High incidence of chromosomal abnormalities in oocyte donors. Fertil Steril 2007;87: Cryos International. Available at: donor-semen/screening.aspx. Accessed on March 9, Carey KN, McCartney J. Wrongful life and wrongful birth: legal aspects of failed testing in oocyte donation. Penn Bioeth J 2005;1: Roth R. Congenital disabilities and the law. Clin Perinatol 2007;34: Baker et al. Genetic evaluation of egg donors Vol. 90, No. 6, December 2008