Al-Shawaf Talha, Zosmer Ariel, Dirnfeld Martha, Grudzinskas Gedis
Barts and The London Centre for Reproductive Medicine, St Bartholomew's Hospital, London, UK.
Drug Saf. 2005;28(6):513-28. doi: 10.2165/00002018-200528060-00004.
Infertility may affect one in six couples; however, the development of the assisted reproduction technique (ART) created the opportunity for a large proportion of the infertile population to bear children. Pharmacological agents are routinely used in ART, and new ones are introduced regularly, with the aim of retrieving multiple oocytes to increase the prospect of pregnancy. The combinations of drugs that are used have specific adverse effects, but it is mostly the combined action of more than one agent that causes the greatest concern. The matter is complicated by the suspicion that some techniques in ART, for example intracytoplasmic sperm injection for severe male infertility problems (including azoospermia), may also contribute to the increase in adverse effects, especially congenital malformation. Gonadotropin releasing hormone (GnRH) agonists are widely used in controlled ovarian hyperstimulation. It may give rise to a short period of estradiol withdrawal symptoms and it may also lead to luteal phase deficiency. Similarly GnRHa antagonists, which have been recently introduced to control ovarian hyperstimulation, can lead to luteal phase deficiency and may cause some local injection site reactions. The more pure form of gonadotropin leads to less local injection site reactions and their main adverse effects are associated with the consequences of multiple ovulations. It has been proposed that gonadotropins may be a factor in the increasing risk of ovarian cancer and possibly breast cancer, but this has not been substantiated. Prion infection is another potential hazard, although no cases have been reported. Ovarian hyperstimulation syndrome is a well recognised complication of controlled ovarian hyperstimulation in ART. It is usually a result of recruitment of a large number of ovarian follicles. Efforts to minimise the incidence of this syndrome and its severity are now well developed. Congenital malformations are another possible adverse effect of fertility drugs, but it is more probable that the increase in congenital abnormality that is reported in ART is because of the population studied, i.e. patients already at high risk of congenital malformation, rather than the fertility drugs used or the technique employed. High order multiple pregnancy and its sequela is a well established complication of controlled ovarian hyperstimulation. This could be a result of multiple ovulations or more than one embryo replacement. Reducing the number of embryos transferred can reduce this more serious adverse effect for expectant mothers and for children conceived from ART.
六对夫妇中可能就有一对受到不孕不育问题的影响；然而，辅助生殖技术（ART）的发展为很大一部分不孕不育人群创造了生育机会。药物制剂在ART中经常使用，并且新的药物也在不断推出，目的是获取多个卵母细胞以增加怀孕的几率。所使用的药物组合具有特定的副作用，但最令人担忧的往往是多种药物的联合作用。ART中的一些技术，例如用于严重男性不育问题（包括无精子症）的胞浆内单精子注射，也可能导致副作用增加，尤其是先天性畸形，这使得情况变得更加复杂。促性腺激素释放激素（GnRH）激动剂广泛用于控制性卵巢过度刺激。它可能会引发短时间的雌二醇撤退症状，还可能导致黄体期缺陷。同样，最近用于控制性卵巢过度刺激的GnRHa拮抗剂也会导致黄体期缺陷，并可能引起一些局部注射部位反应。纯度更高的促性腺激素导致的局部注射部位反应较少，其主要副作用与多个卵泡排卵的后果有关。有人提出促性腺激素可能是卵巢癌以及可能的乳腺癌风险增加的一个因素，但这尚未得到证实。朊病毒感染是另一个潜在风险，尽管尚未有病例报告。卵巢过度刺激综合征是ART中控制性卵巢过度刺激公认的并发症。它通常是大量卵巢卵泡募集的结果。目前已经有很多努力来尽量降低该综合征的发生率及其严重程度。先天性畸形是生育药物的另一个可能的副作用，但ART中报告的先天性异常增加更有可能是因为所研究的人群，即本身就有高先天性畸形风险的患者，而不是所使用的生育药物或采用的技术。高阶多胎妊娠及其后果是控制性卵巢过度刺激公认的并发症。这可能是多个卵泡排卵或移植了不止一个胚胎的结果。减少移植胚胎的数量可以为接受ART治疗的准妈妈及其所孕育的孩子减少这种更严重的副作用。
