Medical treatment is better for adolescents.

Ruptured ectopic pregnancy is the leading cause of morbidity and mortality during the first trimester. Death rates for adolescents are higher than those of adults, mostly due to delays in diagnosis and delays in accessing care.

Methotrexate, a folic acid antagonist that inactivates dihydrofolate reductase, clearly is the preferred treatment for asymptomatic ectopic pregnancy in adults. A recent systematic review demonstrated that treatment success was higher with systemic methotrexate than with laparoscopic salpingostomy, with no significant differences in long-term follow-up, intrauterine pregnancy, or repeat ectopic pregnancy (Clin. Evid. [online] 2009;pii:1406).

The evidence also shows that single-dose methotrexate is more cost effective than laparoscopic salpingostomy. Ten years ago, a study suggested that the difference amounts to $3,000 per resolved ectopic pregnancy, and the difference is likely even greater now (Obstet. Gynecol. 2000;95:407-12).

What do we use for ectopic pregnancy in adult women? Would we even have this debate? Of course we would use methotrexate. Why? Because we avoid the surgery and its complications.

Many of us have had the experience of performing a laparoscopic salpingostomy and ending up having to take the patient’s tubes out. Are we willing to decrease an adolescent woman’s fertility potential?

Another study compared methotrexate and surgery for ectopic pregnancy in both adolescents and adult women. The success rate for methotrexate was 85.5% in adolescents and 87.1% in adults, not significantly different (J. Pediatr. Adolesc. Gynecol. 1996;9:71-3).

Many physicians have the impression that adolescents are not compliant with treatments requiring short-term follow-up. This is based on anecdotes, personal experiences, and studies looking at long-term treatment follow-up – women with diabetes or chronic renal failure, for example. But if you use methotrexate as a short-term treatment, adolescents actually are quite compliant. That same 1996 study showed no significant differences between adolescents and adults in compliance with the rigid study protocol.

Despite the clear evidence that methotrexate is as effective, safe, and appropriate in adolescents as in adults, the evidence also shows that physicians are practicing some sort of age discrimination. A 2009 survey of physicians showed that 66% said they do not apply different criteria for methotrexate treatment in adolescents and adults. But the same survey also showed that only 25% of physicians would be willing to use methotrexate in adolescents (J. Obstet. Gynaecol. Can. 2009;31:254-62).

So what should you do for adolescent women? In my view you should treat them the same as you would an adult. I think it’s wrong to limit all clinically indicated options simply on the basis of the woman’s age.

Dr. Fleming is with the department of obstetrics and gynecology at the University of Ottawa. She said she had no conflicts of interest to disclose.

Surgical treatment is the preferred option.

I acknowledge that the criteria for using methotrexate for asymptomatic ectopic pregnancy are the same in adolescents and adult women. The teens need to be hemodynamically stable. They need to have no contraindications to methotrexate. But – and this is the biggest concern for me in using methotrexate in adolescents – they need to be reliable.

Adolescents need to be compliant with their medical treatment. They have to return again and again for blood work. They have to have rapid access to emergency services. But many of these young women may not have told their parents that they’re pregnant, never mind that they are being treated for ectopic pregnancy. It’s quite a bit harder to keep their parents in the dark with a planned surgical procedure than with a simple methotrexate injection.

The contraindications to methotrexate are the same in adolescents and adults. The long list includes immunodeficiency, liver disease, various blood disorders, renal dysfunction, pulmonary disease, and peptic ulcer. It also includes alcoholism, and we all know that binge drinking is epidemic among adolescents.

A similar pattern holds with the side effects of methotrexate treatment. They’re the same in adolescents and adults, but some of the side effects are arguably more salient in adolescents. Thirty percent of women will have side effects, and these could include stomatitis, neutropenia, pneumonitis, and alopecia (Obstet. Gynecol. 2003;101:778-84). If you’ve ever had to tell a teenage girl that she may end up bald, you might understand why she could prefer a small surgical scar.

Not only are teenagers unreliable, they tend not to like needles, and there are a lot of needles associated with methotrexate treatment. They have to get baseline blood work, and then they get their intramuscular methotrexate injection. On day 4, they have to get a beta human chorionic gonadotropin (hCG) test. Then they’re going to have to come in for weekly hCGs until the test is negative. That takes a mean of 35 days, or five follow-up needle sticks (Am. J. Obstet. Gynecol. 1998;178:1354-8). On top of that, many authors say that if beta hCG hasn’t decreased by 25% by day 7, you should repeat the methotrexate. Well that’s another needle.

Although the 86%-94% success rate with methotrexate seems impressive, that means there is a failure rate of 6%-14% (Fertil. Steril. 1997;67:421-33). You’re sending these adolescents home to get all this follow-up blood work done, and some of them are going to be unreliable and fail to return. The next time you see them, they’re going to be back in the emergency department with a ruptured ectopic pregnancy. It’s potentially a big problem.

On the other hand, laparoscopic salpingostomy is such a nice, easy, straightforward surgery. Laparoscopic management has shown to require less OR time than open surgery and minimal blood loss (Cochrane Database Syst. Rev. 2007:CD000324). Women usually go home the same day, and the recovery time is minimal. The beta hCG drops so quickly that they might need only one additional blood test. For most of them the beta is down by 50% the very next day, and if it’s less than 75%, virtually none of them will have any persistent ectopics or need any further treatment (Fertil. Steril. 1997;68:430-4).

I acknowledge that laparoscopic salpingostomy is more expensive than methotrexate treatment. But you have to be clear about what is your patient’s cost and what is the institution’s cost. I don’t think the institution should come first in these situations. I think the adolescent needs to come first. We’re talking about different types of cost here, and I think life cost is more important than the financial cost.

We know that the risk of a recurrent ectopic pregnancy is the same as with methotrexate. As for the suggestion that there’s a greater fertility risk with laparoscopic salpingostomy, it is a very rare event that we’ll end up having to perform a salpingectomy. Even if we did, we know that it might take them a little longer to get pregnant down the road, but that one tube functions just as well as two.

Dr. Van Eyk is with the division of obstetrics and gynecology at Dalhousie University, Halifax, Nova Scotia. She said she had no conflicts of interest to disclose.

The authors debated this topic at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Dr. Van Eyk and Dr. Fleming emphasized that they were assigned extreme positions for the purposes of debate, and that these do not represent their actual views.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

药物治疗是针对青少年的更优治疗方案

 

异位妊娠破裂是患者在妊娠前3个月内发病和死亡的主要原因。与成人相比，青少年的死亡率更高，这主要是因为医生未能及时作出诊断，以及患者未能及时就医。

 

显然，甲氨蝶呤(一种可使二氢叶酸还原酶失活的叶酸拮抗剂)是用于治疗成人无症状性异位妊娠的首选治疗方案。近期发表的一篇系统性综述表明，甲氨蝶呤全身治疗的成功率较腹腔镜下输卵管造口术高，但二者在长期随访中及子宫内妊娠或重复异位妊娠方面不存在显著差异(Clin. Evid. [online] 2009;pii:1406)。

 

研究证据还表明，使用单剂甲氨蝶呤比腹腔镜下输卵管造口术更具成本效益。10年前的一项研究表明，每治愈1例异位妊娠患者，这两项治疗在费用上的差异便高达3,000美元，而现在这一差异甚至可能更高(Obstet. Gynecol. 2000;95:407-12)。

 

对于成年妇女的异位妊娠，我们应该采用何种治疗方式？我们甚至还会就此问题进行争论吗？毫无疑问我们将会使用甲氨蝶呤。但这是为什么呢？因为我们需要避免手术及其并发症。

 

我们中的许多人都曾有过如下体验，即你为患者实施了腹腔镜下输卵管造口术，但最后却不得不将患者的输卵管切除。我们愿意导致一位青年女性的生育能力受损吗？

 

在另一项研究中，研究者对甲氨蝶呤和外科手术治疗青少年和成年女性异位妊娠的效果进行了比较。使用甲氨蝶呤治疗的青少年和成年人的成功率分别为85.5%和87.1%，无显著差异(J. Pediatr. Adolesc. Gynecol. 1996;9:71-3)。

 

许多医师可能都有这样的印象，即青少年往往不愿接受那些需要进行短期随访的治疗方案。这可能是基于轶事传闻、个人经验以及研究更倾向对那些需要长期治疗的患者(比如，患有糖尿病或慢性肾衰的女性)进行随访调查。但事实上，如果你在短期治疗中使用甲氨蝶呤，则青少年通常都很愿意接受。据1996年发表的同一项研究表明，青少年和成年人对严格研究方案的依从性并不存在显著差异。

 

尽管已有明确证据表明，甲氨蝶呤用于治疗青少年和用于成年人一样有效、安全和恰当，但证据还表明，医生们对青少年存在某种年龄歧视。2009年对医生进行的一项调查表明，有66%的医生说，在甲氨蝶呤用药方面，他们不会对青少年和成人实行不同的标准。但是该研究还显示，仅有25%的医生愿意对青少年使用甲氨蝶呤(J. Obstet. Gynaecol. Can. 2009;31:254-62)。

 

那么，你能为青少年女性做些什么呢？依我看来，在对她们进行治疗时，你应该采用和成人一样的治疗方案。我认为，仅因为女性的年龄因素就对那些理应施行的临床治疗方案进行限制是错误的。

 

Fleming博士目前任职于渥太华大学医院妇产科。她表示自己没有需要披露的利益冲突。

 

手术治疗是首选方案

 

我承认，甲氨蝶呤用于治疗无症状性异位妊娠的标准在青少年和成年女性中是一致的。十几岁的青少年需要保持血流动力学稳定性。她们需要没有甲氨蝶呤的相关禁忌证。但这要求她们是值得信赖的，这是我在应用甲氨蝶呤对青少年进行治疗时最关注的事情。

 

治疗需要保证青少年对治疗方案的依从性。她们不得不多次复诊以接受一次又一次的血液检查。她们不得不迅速接受急诊治疗。但在这类年轻女性中，有许多人并未告知父母自己已经怀孕，更不用说她们正要接受异位妊娠的相关治疗了。在需要对父母隐瞒该事实的前提下，按计划接受外科手术要比简单的注射甲氨蝶呤难以实现得多。

 

青少年和成人应用甲氨蝶呤的禁忌证是一致的。这一长串名单包括免疫缺陷、肝脏疾病、各种各样的血液病、肾功能不全、肺病和消化道溃疡。它还包括酒精中毒，我们都知道，在青少年中酗酒非常普遍。

 

在甲氨蝶呤的治疗不良反应方面也存在类似的模式。这些不良反应在青少年和成人中都是一致的，但是证据表明某些不良反应在青少年中更为显著。30%的女性将会出现不良反应，其中包括口腔炎、中性粒细胞减少、肺炎和脱发(Obstet. Gynecol. 2003;101:778-84)。如果你曾经告知某位十几岁的女孩她最后可能变成一个秃子，那么你可能就会理解她为何可能更愿意接受一个小手术疤痕了。

 

不仅仅是因为十几岁的青少年不够可靠，她们往往不喜欢接受注射治疗，且甲氨蝶呤治疗需要进行多次注射。她们必须接受基线血液检查，再肌肉注射甲氨蝶呤。在第4天，她们还必须接受人绒毛膜促性腺激素(β-HCG)检查。然后她们将不得不每周进行hCG检查，直到检查结果转阴为止。这一过程平均耗时35天，或5次后续注射(Am. J. Obstet. Gynecol. 1998;178:1354-8)。最重要的是，许多作者说在第7天时，如果β-hCG值的下降幅度未达到25%，就需要再次注射甲氨蝶呤。好吧，那又是一次注射。

 

尽管使用甲氨蝶呤治疗高达86%~94%的成功率似乎令人印象深刻，但那意味着还有6%~14%的失败几率(Fertil. Steril. 1997;67:421-33)。你将这些青少年送回家，还必须确保她们完成后续的全部血液检查，但她们中的某些人并不可信且未能复诊。下次你再看见这些患者时，她们可能就因为异位妊娠破裂而再次回到了急诊科。这可能是一个潜在的重大问题。

 

就另一方面而言，腹腔镜下输卵管造口术是一种如此精细且简单易行的手术。与开腹手术相比，腹腔镜手术的手术时间更短且患者失血量更少(Cochrane Database Syst. Rev. 2007:CD000324)。女性通常在手术当天就可以回家，其需要的恢复时间同样极短。患者的β-hCG值下降得如此迅速，以至于她们可能仅需要接受一次额外的血液检查。对于接受手术的大部分女性而言，在手术隔天她们的β-hCG值便下降了50%(如果下降幅度小于75%)，实际上，她们中没有人会存在任何异位妊娠残留，或需要进行进一步治疗(Fertil. Steril. 1997;68:430-4)。

 

我承认，腹腔镜下输卵管造口术比甲氨蝶呤治疗更昂贵。但你必须清楚其中哪一部分是患者承担的费用，哪一部分是医院承担的费用。我不认为在这种情况下医院的利益应该被放在首位。我认为我们应该首先考虑青少年的利益。我们正在讨论不同种类治疗的费用，但我认为生命成本比经济成本要重要得多。

 

我们知道，手术引起异位妊娠复发的风险与使用甲氨蝶呤引发的风险一样。至于有人表示使用腹腔镜下输卵管造口术会带来更高的生育风险，然而事实是，最后不得不进行输卵管切除术的事件发生几率是极小的。即便我们进行了这一手术，我们也知道，这会使她们在将来某个时候花费更长的时间才能受孕，但像双侧输卵管一样，单侧输卵管同样能够发挥功能。

 

Van Eyk博士供职于加拿大新斯科舍省哈利法克斯市达尔豪西大学医院妇产科。她说她没有任何利益冲突需要披露。

 

作者们在北美儿童和青少年妇科学会的年会上就这一议题进行了辩论。Van Eyk博士和Fleming博士强调说，因为辩论的原因，他们被安排采取完全对立的立场，但这并不能代表他们的实际观点。

 

爱思唯尔  版权所有