Tarlatzis Basil C, Bili Helen
Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Aristotle University, Thessaloniki, Greece.
Expert Opin Drug Saf. 2004 Jan;3(1):39-46. doi: 10.1517/14740338.3.1.39.
The widespread application of protocols using gonadotropin-releasing hormone (GnRH) agonists or antagonists in assisted reproduction treatment has led to an increasing number of pregnancies exposed to these drugs. This issue has raised scepticism as to the safety of these medications, concerning both pregnant women and their offspring. The main parameters that can be studied to ensure the safety of GnRH analogues include: a) systemic and local reactions to the medication; b) incidence of ovarian hyperstimulation syndrome (OHSS); c) direct effect on oocytes and embryos; and d) the health of those children exposed. So far, no systemic side effects and no major local reactions have been reported following the use of GnRH agonists or third-generation antagonists. On the other hand, the incidence of OHSS seems to be higher with GnRH agonist protocols compared to conventional or GnRH antagonist protocols. The recent cloning of the GnRH receptor has led to the demonstration of GnRH receptor gene expression in the human ovary, although the existence of GnRH receptors per se remains controversial. Similarly, the potential direct effect of GnRH analogues on the follicles and oocytes remains a matter of debate. The incidence of miscarriage and the health of children born as a result of in vitro fertilisation (IVF) treatment do not appear to be influenced by the GnRH agonist treatment. This also seems to be the case for the GnRH antagonists, although the available information on this issue is still limited. Therefore, most of the accumulated data concerning the safety of the GnRH analogues are encouraging, and no serious side effects have been reported. On the other hand, as no definite conclusions about the safety of these drugs can be drawn until now, continued assessment of the aforementioned parameters in long-term follow-up studies is recommended.
促性腺激素释放激素（GnRH）激动剂或拮抗剂方案在辅助生殖治疗中的广泛应用，导致越来越多的孕妇接触到这些药物。这一问题引发了对这些药物安全性的质疑，涉及孕妇及其后代。为确保GnRH类似物的安全性可研究的主要参数包括：a）药物的全身和局部反应；b）卵巢过度刺激综合征（OHSS）的发生率；c）对卵母细胞和胚胎的直接影响；d）接触这些药物的儿童的健康状况。到目前为止，使用GnRH激动剂或第三代拮抗剂后尚未报告有全身副作用和重大局部反应。另一方面，与传统方案或GnRH拮抗剂方案相比，GnRH激动剂方案的OHSS发生率似乎更高。GnRH受体的近期克隆已证实其在人卵巢中的基因表达，尽管GnRH受体本身的存在仍存在争议。同样，GnRH类似物对卵泡和卵母细胞的潜在直接影响仍是一个有争议的问题。体外受精（IVF）治疗导致的流产发生率和出生儿童的健康状况似乎不受GnRH激动剂治疗的影响。GnRH拮抗剂似乎也是如此，尽管关于这一问题的现有信息仍然有限。因此，关于GnRH类似物安全性的大多数累积数据是令人鼓舞的，尚未报告有严重副作用。另一方面，由于目前还无法就这些药物的安全性得出明确结论，建议在长期随访研究中继续评估上述参数。
