The data from the present survey show that the prevalence of genetic testing and the protocol for the tests are not standardized and differ across human sperm banks in different regions of China.
In recent years, the cost of molecular genetic tests has greatly reduced due to the emergence of next-generation sequencing technologies, which have allowed for the analysis of a large number of genes and the concurrent evaluation of hundreds of mutations. Hence, some reproductive centers and patients have called for the implementation of more extensive genetic screening of sperm donors in human sperm banks. Cryos International is the largest sperm bank in the world that supplies frozen donor sperm to over 100 countries. They employ a bespoke extensive carrier screening panel that screens males for 46 genetic disorders. In contrast, none of the human sperm banks in China that participated in this study use carrier screening panels for donors. This is probably because the sperm banks in china recruit donors for Chinese only, more important, there is no bespoke extensive carrier screening panel for Chinese people yet. The carrier frequency of disease-related genes identified at the Translational Medicine Center of Children’s Hospital of Fudan University is more similar for the East Asian population than those for the European population, as reported by the Exome Aggregation Consortium. The differences in carrier frequency among different populations indicate the need to establish a panel of genes that is specific to the Chinese population for genetic testing. However, there is also considerable debate within the sperm banking community as to whether sperm donors should undergo expanded carrier screening [4, 13]. According to reports from some countries, testing of a higher number of genes meant that fewer donors would be eligible. Additionally, the heads of some sperm banks consider that carrier screening is expensive and considerably adds to the cost of screening a sperm donor. Despite this, carrier screening is a powerful tool, especially in certain high-risk ethnic populations.
Present study showed there are 10 banks in China are using NGS (Next-Generation Sequencing) to test specific genetic now. However, as we know, it cannot be detected by NGS in some specific genes mutations, for example: HBA1、HBA2、SMA etc. Therefore, the gap-PCR method is used for detecting thalassemia-related genes. Also, to our knowledge, the hemoglobin electrophoresis was used for detect thalassemia-related genes in sperm bank 14, 19 and 21, these banks test all donors thalassemia. However, the thing is, different methods would show different detection rates and interpretations. Also, they all have advantages and limitations . Therefore, it is very necessary to uniform and standardize the methods of specific genetic testing in human sperm banks.
In the present study, two human sperm banks in China used whole-exome sequencing to screen sperm donor and donor–recipient matches. The GJB2 mutation was the most common pathogenic mutation found in sperm donors. The data from the two sperm banks showed that 18.6% and 14.4% of qualified sperm donors in China were carriers of pathogenic variants of GJB2. This is higher than the carrier frequencies for GJB2 that were previously reported [15, 16]. However, this is not surprising, as previous studies on carrier frequencies tested for known mutations, whereas the exome sequencing at these two clinics explored the entire coding region of most genes. Accordingly, the carrier frequencies of GJB2 should not be over-interpreted, as different GJB2 pathogenic variants are associated with various phenotypes of hearing loss. For instance, both p.V37I homozygotes and compound heterozygous p.V37I variants of GJB-2 indicate a significantly higher risk of developing hearing loss. Conversely, heterozygous p.V37I variants alone do not increase the risk of hearing loss . Nonetheless, the frequency of GJB2 variants should be a matter of concern in sperm donors in China, along with the frequency of thalassemia- and spinal muscular atrophy-related gene variants. At the time of this study, an increasing number of human sperm banks in China reported that additional genetic tests were under development. Increased public awareness and increasing requests for special tests are likely to influence genetic testing at sperm banks in China in the future.
Genetic counseling is an integral part of genetic testing of sperm donors. In 1996, a study reported that 6 out of 16 (37.5%) sperm banks had a genetic counselor on their staff . In 2013, it was documented that 7 of 13 (53.8%) sperm banks already have genetic counsellors, although mostly in part-time positions . The present study found that 25 out of 26 (96.2%) sperm banks had genetic counselors on their staff (with six of them in part-time positions), and 20 of the 26 (76.9%) sperm banks had more than one genetic counselor on their staff. This denotes a positive trend in human sperm banks across China. Unfortunately, our data also indicated that not all of the counsellors had adequate qualifications. Comparing with European and American countries, it gets starting late in development of genetic counselor in China. Therefore, there is no standard guidelines for being a qualified genetic counsellors yet. Be specific, it is not difficult of being a genetic counsellor in China. He or she needs to participate some courses and training regardless their previous degrees or background. Also, the organizer could come from folk not official. Even majority of them claimed they have been trained well but normally the course last 2-3 days only.it can be seemed as a gentics-related meetings. In another hand, there is no official paper materials yet also. They could follow any curriculum. In a word, no standardized in China yet. Genetic counselors who are not trained in genetics may not be able to prepare a donor for the results and or be able to provide support to the donor for sharing this information with their at-risk relatives . This is probably why some sperm banks in China believed that there was no need to inform the donor of the results. However, the authors believe that it is unethical to withhold the genetic testing results from a donor, as they would be unaware of the risks of bearing progeny in the future. Hence, it is important to have a qualified genetic counselor who is capable of explaining the risks based on the genetic test results and the limitations of each test. A professional genetic counselor would also be able to provide accurate information and obtain the informed consent of sperm donors in the appropriate way. Therefore, it is highly recommended to establish a standardized genetic counseling procedure and training book official as soon as possible, at the same time, the organizer has to be professional enough. Then, more and more qualified counselors could be the staff in banks in the near future.
Genetic testing of sperm donors was introduced in China much after it was initiated in other countries. In the United States, sperm banks frequently cite the guidelines of organizations such as the American Society of Reproductive Medicine and the American College of Medical Genetics. In Europe, too, sperm banks have been following the official guidelines of the European Union. In the present study, 12 sperm banks (46.2%) followed the genetic screening guidelines of the NHFPCC, but 11 sperm banks (42.3%) did not follow any standard guidelines. The majority of the sperm banks reported that they are not currently considering additional genetic tests for sperm donors because there are no official guidelines for the genetic evaluation of sperm donors. Hence, it is necessary to develop a consensus on genetic testing of sperm donors in China, so that all sperm banks can benefit from specific and clear practical recommendations with regard to the genetic screening of donors and the disclosure of test results. To achieve this, it is important to engage academics and practitioners in the field of genetics to gather information, discuss, and come to a consensus about the guidelines that must be established. The important questions that need to be answered are: (a) Which genetic tests should be performed on sperm donors? (b) Which genetic disorders should be tested through an extensive carrier screening panel specific for the Chinese population? (c) Should donors with mutations of unclear significance be eliminated? (d) Should the results of the genetic tests be disclosed to donors?
The present study has certain limitations such as survey recipients were asked to forward the survey to an appropriate staff member who would be most suited to answering the online questionnaire, which might have led to self-selection bias. In addition, the sperm bank in some provinces was relatively small, the number of qualified sperm donors was few, hence, and the findings in these sperm banks might have led to bias.