AMSTERDAM (EGMN) —Two drugs that inhibit uterine contractions might provide a novel approach to improving implantation rates in patients undergoing IVF, according to early research reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“Contractions of the uterus are more frequent in IVF cycles compared to normal menstrual cycles, and a higher frequency of contractions around the time of embryo transfer is associated with a more negative impact on pregnancy outcomes,” reported Dr. Christophe Blockeel of the Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

“We’ve learned that uterine contractions are actually in many cases expelling somewhere between 15%-50% of embryos after transfer,” commented Roger Pierson, Ph.D., a collaborator in the study, and professor of obstetrics, gynecology and reproductive sciences at the University of Saskatchewan, Saskatoon, Canada.

“Regardless of which catheter you use, or whether or not you use ultrasound, you are still irritating the uterus and it doesn’t matter how gentle you are, some women are going to respond with advanced uterine contractions,” he said in an interview.

The study, which was conducted in oocyte donors and was funded by Ferring Pharmaceuticals, examined the effect of the selective oxytocin antagonist barusiban and the mixed oxytocin/vasopressin antagonist atosiban versus placebo on luteal phase uterine contractions. Study participants were 125 oocyte donors who had undergone controlled ovarian stimulation, oocyte retrieval, and luteal phase supplementation with progesterone.

Women were randomized to either barusiban (41 women, IV bolus 9 mg, IV infusion 2.16 mg/h), atosiban (42 women, IV bolus 6.75 mg, IV infusion 18 mg/h) or placebo on day 2 after oocyte retrieval.

Transvaginal ultrasounds lasting at least 5 minutes were obtained after retrieval on Day 1, 14 times on Day 2 (pretreatment, 8 times before mock embryo transfer, 3 times after mock embryo transfer, and 2 times post infusion), and on Day 5.

With both medications, the frequency of uterine contractions remained stable during the first 2 days after retrieval, followed by a significant decrease noted in both treatment groups that lasted for about 3 hours.

“These medications are quite short acting, so they need to be administered an hour or two before transfer just to get the uterus settled to facilitate implantation,” explained Dr. Pierson, who is also a consultant for Ferring.

Without the control medication the frequency of uterine contractions can be as high as 6 or 7 per minute after embryo transfer, he said, adding that the ideal is somewhere around 1 to 1.5 contractions per minute.

“This is a very new approach to improving implantation and quite different,” he explained. While atosiban is already used to treat preterm labor, barusiban was specifically developed to treat uterine contractions in IVF, and another similar medication is being developed by the company.

“Both barusiban and atosiban are very well tolerated drugs, however, toxicology tests are still needed before we can use these drugs in patients undergoing embryo transfer rather than donors,” Dr. Blockeel said. Optimal dosing also needs further investigation.

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

阿姆斯特丹(EGMN) ——根据在欧洲人类生殖与胚胎学协会年会上所报告的早期研究，2种抑制子宫收缩的药物可能为改善接受IVF治疗患者的着床率提供了一种新的方法。

 

比利时布鲁塞尔大学医院生殖医学中心的Christophe Blockeel 博士报道，“与正常月经周期相比，在IVF周期子宫收缩变得更加频繁；胚胎移植时子宫收缩频率越高，对妊娠结局的影响越不利。”

 

Roger Pierson博士评论说，“我们得知，实际上许多病例出现子宫收缩，某些情况下，移植后可排出15%~50%的胚胎。”Roger Pierson博士是加拿大萨斯喀彻温省大学产科、妇科和生殖科学系的教授，也是研究的合作者。

 

“无论你使用哪种胚胎移植管，抑或你是否使用超声，你仍然是在刺激子宫，而且不管你操作如何轻柔，一些妇女仍将会伴随出现进行性子宫收缩，”他在一次采访中说。

 

这项由Ferring制药公司资助的、在卵母细胞供者中进行的研究调查了与安慰剂相比，选择性催产素受体拮抗剂barusiban以及催产素/加压素复合拮抗剂atosiban对黄体期子宫收缩的影响。研究参与者为125例接受控制性卵巢刺激、卵母细胞提取和黄体期补充黄体酮的卵母细胞供者。

 

这些妇女在卵母细胞提取后第2天被随机分配接受barusiban (41例妇女，静脉团注9 mg，静脉输注 2.16 mg/h)、atosiban (42例妇女，静脉团注6.75 mg，静脉输注18 mg/h)或者安慰剂治疗。

 

在卵母细胞提取后第1天对受试者进行经阴道超声检查，第2天对其进行14次经阴道超声检查(治疗前1次、模拟胚胎移植前8次、模拟胚胎移植后3次、输注后2次)，第5天再对其进行经阴道超声检查，经阴道超声检查的时间至少持续5分钟。

 

通过使用以上2种药物，子宫收缩频率在卵母细胞提取后前2天保持稳定；随后，2个治疗组受试者的子宫收缩频率出现显著下降，持续约3h。

 

“这些药物相当短效，所以需要在胚胎移植前1h或2h注射这些药物，才可解决子宫收缩问题，从而促进着床。”Pierson博士解释说，他还是Ferring制药公司的顾问。

 

他说，若没有控制药物，胚胎移植后子宫收缩频率则可高达6~7次/min；他补充说，大约1~1.5次/min是比较理想的。

 

“这是一种用于改善着床的非常新的方法，完全不同于其他方法，”他解释说。atosiban已被用于治疗早产，barusiban被专门开发用于治疗IVF患者的子宫收缩，与此同时，公司正在开发另一个类似药物。

 

Blockeel博士说，“barusiban和atosiban的耐受性极佳，然而，在我们可将这些药物用于治疗那些接受胚胎移植的患者而不是供者之前，仍然需要对其进行毒理学试验。还需要对其最佳剂量进行进一步研究。”

 

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