利用遺傳疾病發生率及近親交配係數探討精卵捐贈活產數之限制

Abstract

使用匿名捐贈者的精卵是人工生殖手術中的一個方法，然而在多次使用同一捐贈者的精卵時，卻可能會衍生出一些風險。從文獻探討可以發現，學者擔心的風險主要集中在「近親交配的問題」上，這個問題除了倫理、道德、法律因素上的考量之外，從生物醫學的角度擔心的是這些人的後代得到遺傳疾病的機率可能會較一般人高。但是當精卵捐贈的供給與需求不平衡時，許多人會想要利用多次使用同一捐贈者的細胞來解決問題；然而，各國對於這方面的規定差異甚大，法國的上限是5次，英國是10次，西班牙是6次，台灣是1次，荷蘭卻高達25次，這些限制的訂定多半沒有科學上明確的道理說明；因此，本研究嘗試從統計學的角度，採用遺傳疾病發生率及近親交配係數為觀點，提出可允許最大活產數之選擇策略。 本文在修正過去學者估計近親交配次數的模式後，並提出估算其變異數之方法；再從機率的觀點出發，提出依不同疾病之遺傳模式特色，估計其因精卵捐贈而導致疾病發生率的方法，在給定一可容許的發生率之下，或是將發生率再轉換成醫療照護成本並給定成本上限，即可決定可允許之最大活產數。從結果可以發現，盛行率較高之疾病受同一捐贈者細胞多次使用的影響較大，若考量此類疾病的影響，則需降低可允許之最大活產數；另外，從因artificial insemination by donor (AID)而導致的疾病發生率與族群中疾病盛行率的比值來看，隱性遺傳疾病受到同一捐贈者細胞多次使用的影響較大。此外，本文也延續de Boer et al. (1995)和Curie-Cohen (1980)的想法使用近親交配係數做探討，但不同於這些學者之觀點，本研究採用族群之觀點來估計近親交配係數，在給定一閾值後，便可得知可允許之最大活產數；結果顯示，當族群中現有的近親交配係數愈高時，可允許最大活產數就會愈少；當族群中表徵因素的同型交配行為愈強烈時，可允許最大活產數也會愈少。

Using anonymous donors’ gametes, a treatment in assisted reproductive technology (ART), may result in inadvertent consanguineous mating, especially when a single donor’s gametes are multiply used. Unwitting consanguinities between offspring of one single donor and his or her unknown relatives may lead to higher risks of transmission of hereditary diseases. However, when supply and demand of artificial insemination by donor (AID) are unbalanced, multiple use of one single donor’s gametes becomes a solution. In that case, its influence on medical and genetic aspects should be carefully evaluated, as well as its social, cultural and legal implications. The choice of maximum number of offspring per donor varies greatly in different countries. For example, the limit in France is 5, 10 in UK, 6 in Spain, 1 in Taiwan, and 25 in The Netherlands. Most of these limits, however, do not result from specific scientific studies. In this study, two approaches are discussed for setting the maximum number of live births per donor. First, I incorporate the risk of certain hereditary disease in the computation of number of consanguinities to evaluate the possible elevation of incidence and prevalence. For any given disease of interest, I construct its incidence due to donor insemination (DI) from probabilistic perspective. Based on information from disease characteristics, population data, donor statistics, and tolerable increased incidence or medical costs, one can decide the figure for the maximal limit. The results show that there will be more new cases due to AID when the prevalence is high. In addition, when using the ratio of incidence to prevalence as the criterion, the risk owing to DI of autosomal recessive inheritance disease is higher than that of disease of other mode of inheritance. The second approach, following the same idea from de Boer et al. (1995) and Curie-Cohen (1980), adopts the population perspective to derive coefficient of inbreeding including DI. The modification includes adding the current constant coefficient of inbreeding in a given society with no AID children, and an extra coefficient of inbreeding due to AID with respect to the number of live births per donor. Then, maximum number of live births per donor will be decided by setting a threshold for the tolerable coefficient of inbreeding. The results indicate that the larger coefficient of inbreeding in a population without AID is, the smaller number of live births per donor is and the more significantly assortive mating for phenotype is, the smaller number of live births per donor is.