D'Uva Maristella, Di Micco Pierpaolo, Strina Ida, Alviggi Carlo, Iannuzzo Mariateresa, Ranieri Antonio, Mollo Antonio, De Placido Giuseppe
Dipartimento di Scienze Ostetriche Ginecologiche e Medicina della Riproduzione, Area Funzionale di Medicina della Riproduzione ed Endoscopia Ginecologica, University of Naples Federico II, Italy.
Thromb J. 2007 Jul 11;5:10. doi: 10.1186/1477-9560-5-10.
Hyperhomocysteinemia has been described as a risk factor for unexplained recurrent pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-homocysteine pathway such as MTHFR C677T gene polymorphism. However, the association between hyperhomocysteinemia and sterility problems have been underlined only for recurrent pregnancy loss while a relationship between hyperhomocysteinemia and female sterility is still matter of discussion.
This study sought to find out a possible relationship between sterility (primary sterility or secondary sterility due to recurrent pregnancy loss) and homocysteine metabolism.
We selected 20 patients with recurrent pregnancy loss, 20 patients with unexplained female sterility and 20 healthy women as control group. Several whole blood samples were collected by venipuncture. Firstly homocysteinemia and other related variables were tested (i.e. folate and vitamin B12 levels); thereafter DNA was extracted by a further whole blood sample collected in EDTA in order to screen MTHFR C677T gene polymorphism. Statistical analysis was performed by chi square test; differences were considered to be significant if p < 0.05.
The median fasting total plasma homocysteine concentration was 19.2 +/- 6.14 microM for patients with recurrent pregnancy loss, while was 21.05 +/- 8.78 microM for patients with unexplained sterility, vs 7.85 +/- 3.31 microM of control group (p < 0.05). Fifteen patients with unexplained female sterility showed MTHFR C677T homozigosity vs 17 with recurrent pregnancy loss and 3 in the control group (p < 0.05). On the other hand no significant differences were found in the levels of vitamin B 12 in the three groups, while reduced folate concentrations were found in women with unexplained female sterility and recurrent pregnancy loss (p < 0.05 vs control group.
MTHFR C677T gene polymorphism is frequent in the studied populations. These data raise questions on the role of the homocysteine metabolism in sterility problems. Even though increased homocysteine (i.e. > 15 microM) and MTHFR C677T homozigosity have already been described as risk factors for recurrent pregnancy loss, few studies evaluated their role in women with unexplained sterility. Further studies on larger series are needed to better understand the role of homocysteine metabolism, including folate metabolism, in this clinical setting.
高同型半胱氨酸血症已被描述为不明原因复发性流产的一个危险因素。同型半胱氨酸水平升高可能是由于饮食中叶酸和维生素B12摄入不足，以及甲硫氨酸-同型半胱氨酸途径中的遗传缺陷，如亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性。然而，高同型半胱氨酸血症与不育问题之间的关联仅在复发性流产中得到强调，而高同型半胱氨酸血症与女性不育之间的关系仍存在争议。
本研究旨在找出不育（原发性不育或因复发性流产导致的继发性不育）与同型半胱氨酸代谢之间的可能关系。
我们选择了20例复发性流产患者、20例不明原因女性不育患者以及20名健康女性作为对照组。通过静脉穿刺采集多份全血样本。首先检测高同型半胱氨酸血症及其他相关变量（即叶酸和维生素B12水平）；此后，从另一采集于乙二胺四乙酸（EDTA）的全血样本中提取DNA，以筛查MTHFR C677T基因多态性。采用卡方检验进行统计分析；若p < 0.05，则认为差异具有统计学意义。
复发性流产患者空腹血浆总同型半胱氨酸浓度中位数为19.2±6.14微摩尔/升，不明原因不育患者为21.05±8.78微摩尔/升，而对照组为7.85±3.31微摩尔/升（p < 0.05）。15例不明原因女性不育患者表现为MTHFR C677T纯合子，复发性流产患者中有17例，对照组中有3例（p < 0.05）。另一方面，三组维生素B12水平未发现显著差异，而不明原因女性不育和复发性流产患者的叶酸浓度降低（与对照组相比p < 0.05）。
MTHFR C677T基因多态性在所研究人群中较为常见。这些数据引发了关于同型半胱氨酸代谢在不育问题中作用的疑问。尽管同型半胱氨酸水平升高（即> 15微摩尔/升）和MTHFR C677T纯合子已被描述为复发性流产的危险因素，但很少有研究评估它们在不明原因不育女性中的作用。需要对更大样本量进行进一步研究，以更好地了解同型半胱氨酸代谢，包括叶酸代谢，在这种临床情况下的作用。
