成本和技术促使更多人使用冷冻卵子
2013-01-14 20:11:28   来源：医学论坛网   作者：  评论：0 点击：

目前越来越多的人开始采用冷冻捐赠卵子来完成体外受精(IVF)，这种技术在公众认知度和接受度方面大有引爆流行的趋势。

　　近年来，这种被称为“玻璃化”的卵子冷冻技术取得了很大的进展，在活产率方面获得了令人鼓舞的结果，可以与新鲜卵子捐赠周期的结果相媲美。除此之外，采用冷冻卵子的IVF可显著降低成本，而且医疗界的接受度也越来越高，这必将推动冷冻捐赠卵子库的发展。

　　北美“My Egg Bank”的医学总监Daniel B. Shapiro博士表示：“这种技术现已被人们非常迅速、非常广泛地接受了。” “My Egg Bank”是一个涵盖了美国各地卵子库的多中心网络，包括亚特兰大、西雅图和奥兰多。

Zsolt Peter Nagy博士

　　作为My Egg Bank的合作方，美国生殖生物学会的科学总监Zsolt Peter Nagy博士称，冷冻卵子技术已经有几十年的历史了，1986年首个使用冷冻保存卵母细胞的婴儿诞生。但当时这种技术的效率较差，可能需要100~150个卵子才能成功妊娠1次。Nagy博士说：“这样的效率水平一直持续了20年左右。”

　　但是，自从科学家开始尝试改进卵子冷冻技术之后，事情就开始发生变化了。大约在2006年实现了一次技术突破，一种名为“玻璃化”的新技术问世。虽然玻璃化的具体方法有很多，但通常都需通过冷冻保护剂和快速冷却程序以凝固卵子，避免形成冰晶体。许多玻璃化方法都需要将卵母细胞直接暴露于液氮。

　　在一项比较玻璃化卵母细胞与新鲜卵母细胞的随机对照试验中，研究者发现从600名受者的结局数据来看，两种技术的受精率、着床率和妊娠率并无显著差异。玻璃化卵子每次移植的妊娠率为55.4%，新鲜卵子的妊娠率为55.6%(Hum. Reprod. 2010;25:2239-46)。

　　位于美国马里兰州罗克维尔的卵子库“Donor Egg Bank”的CEO Heidi Hayes说，正是这些研究结果引起了人们对冷冻捐赠卵子库的关注。该卵子库于2012年3月向受者开放供其使用。Hayes女士说：“如今这种技术已经大大改进，新技术的问世将给整个领域带来翻天覆地的变化。”

　　美国生殖医学会(ASRM)在新版指南中也指出，采用玻璃化和慢冻法的成熟卵母细胞冷冻保存技术已经不再是一种实验性方法，这也进一步推动了该领域的发展。负责起草该指南的ASRM实践委员会主席Samantha M. Pfeifer博士称，该技术“实验性质”的取消意味着临床医生在准备将冷冻卵子用于IVF周期时无需再告知患者这是一种实验性技术。这还意味着机构审查委员会(IRB)也无需参与知情同意程序。

　　但ASRM并不支持冷冻卵子库的建设。虽然指南称许多支持使用卵母细胞冷冻保存技术的高质量证据都是在捐赠卵母细胞周期中获得的，但尚需更多关于捐赠人群安全性和效率的临床特定数据才能推荐捐赠卵子库的全面建设。ASRM的声明的确建议那些因接受化疗存在不孕高风险的癌症患者使用卵母细胞冷冻保存技术。

　　Pfeifer博士说，使用冷冻卵子具有许多优势，比如我们可以对卵子进行检疫以筛查传染病。但就如何使用冷冻卵子而言，依然存在一些问题，比如这些卵子可以冷冻多长时间？可以存活多久？

　　快速推进冷冻卵子捐赠库的全面建设还存在另一种担忧：不是每家机构都有能力冷冻卵子。同时任职于美国宾夕法尼亚大学妇产科学系的Pfeifer 博士说：“有人担心政府会突然强制要求每个人都使用冷冻卵子；我们真的还没有做好准备。在这种技术成为我们国家的标准操作之前，还有许多事情要做。”第一步就是取消“实验性”标签。她说：“如今这种技术已经不再是实验性质，现实的情况是人们将开始使用这种技术。”

　　即便没有ASRM的全力支持，建设冷冻捐赠卵子库的呼声也是越来越高。Shapiro博士指出，成本是重要因素之一。使用新鲜捐赠卵子的IVF 费用大约为每周期26,000~44,000美元，具体价格取决于各地市场以及是否聘请了代理人去寻找捐赠者。Shapiro博士说，费用涨得很快，因为需要给每个人都支付费用，包括捐赠者、代理人以及实施这一技术的诊所。

　　相比之下，北美My Egg Bank是向其附属机构“出售”卵子，每周期费用约为16,500美元，包括捐赠成本、玻璃化以及解冻卵子的技术支持等所有费用。其他卵子库也宣传称其出售的冷冻周期费用只有新鲜IVF周期的一半左右。

　　Shapiro博士指出，而且许多卵子库还会提供某些类型的保障。例如，My Egg Bank就保证向受者提供2个高质量的胚胎。大约20%的患者可能不能获得2个高质量的胚胎，如果妊娠不成功，那么My Egg Bank会向其免费提供另一个周期。此外，My Egg Bank还提供一个名为“Frozen Egg Advantage”的计划，如果患者已经支付了5个周期的费用仍未成功，则保证退款。也就是说，5个周期结束时，患者要么抱着宝宝回家，要么拿到治疗费用的全额退款。

　　Shapiro博士说：“患者只需要简单算一下，很快就会得出结论，在我们这里做几个冷冻周期的累计妊娠几率比在其他任何地方做1个新鲜IVF周期的几率都要高，而且费用还更低。”

　　Nagy博士补充道，操作便利是人们选择冷冻卵子的另一个因素。在采用新鲜卵子捐赠这一传统技术时，卵子捐赠者和受者的周期必须同步，只有这样才能保证卵子取出后能立即受精并移植。“如今我们可以对捐赠卵子进行冷冻处理，那么卵子捐赠与卵子移植的操作就可以分开进行了。”

　　RESOLVE：美国国家不孕协会总裁兼CEO Barbara Collura指出，这样做可以消除一些程序上的不确定性，也能减轻患者的压力。她曾经亲耳听到一些不孕患者抱怨，由于其捐赠者的中途退出，她们不得不一切都重头来过。Collura女士说：“她们选择一名卵子捐赠者，她们的一生都会因此发生改变。这些事情听起来没有什么特别的，但当患者已经38、39或者40岁时，已经被不孕困扰多年，那么能够使用玻璃化的捐赠卵母细胞并且能在自己准备好的时候使用，那真的是太好了。”

　　Hayes女士说，冷冻卵子库也给患者在选择卵子捐赠者时提供了更多的选择。这也是冷冻卵子技术越来越受青睐的因素之一。她说：“抛开成本不谈，捐赠者是她们重点考虑的一大因素。”这不仅仅是数量的问题，这还涉及种族和民族多样性的问题。使用新鲜卵子捐赠时，很难找到与受者某些种族背景相匹配的捐赠者。但如果使用冷冻卵子捐赠的话，建立一个更加多样化的数据库对于卵子库而言会更加容易。就Donor Egg Bank USA而言，他们正在与夏威夷的一个附属项目合作，希望找到更多的亚洲捐赠者以纳入其卵子库。

　　Hayes女士说：“我认为，由于文化背景的不同，某些种族背景的女性可能不太愿意捐赠卵子。而来自这些种族的受者同样渴望生个宝宝，以延续家族的血脉。”

　　虽然某些圈子对冷冻卵子技术的兴趣越来越大，但公众对于冷冻卵子捐赠这一模式的整体认知度还是很低的。Hayes女士认为，鉴于越来越多的患者在网上分享了其使用冷冻捐赠卵子的成功经历，社会媒体应该可以帮助这种技术成为一种主流方法。“成功生下宝宝的人越多，谈论这件事的人就越多，那么选择使用冷冻卵子的人就会越来越多。”

　　By: MARY ELLEN SCHNEIDER, Internal Medicine News Digital Network

　　The use of frozen donor eggs to assist with in vitro fertilization is on the rise, and it could be headed toward a tipping point in terms of public awareness and acceptance.

　　Advances in an egg freezing method known as vitrification have shown encouraging results in terms of live births, rivaling the results seen with fresh egg donation cycles. Add to that the significantly lower cost of in vitro fertilization (IVF) using frozen eggs and the increasing acceptance in the medical community, and it’s a recipe for growth in frozen donor egg banking.

　　"There’s been very rapid and very wide acceptance of this," said Dr. Daniel B. Shapiro, the medical director of My Egg Bank North America, a multicenter network of egg banks with locations throughout the United States including Atlanta, Seattle, and Orlando.

The technology to freeze eggs has been around for decades, with the first baby born as a result of a cryopreserved oocyte reported in 1986. But the process was inefficient then and between 100 and 150 eggs might be needed to get a single pregnancy, according to Zsolt Peter Nagy, Ph.D., the scientific director for Reproductive Biology Associates, which is a partner in My Egg Bank.

　　"That was the level of efficiency for about 20 years," said Dr. Nagy said.

　　But the landscape started to change when scientists began experimenting with improvements to the egg freezing technique. A breakthrough came around 2006 with the use of a new process called vitrification. Although there are various methods of vitrification, it generally involves using a cryo-protectant and rapid cooling to solidify the cell without forming ice crystals. Many of the vitrification methods call for directly exposing the oocytes to liquid nitrogen.

　　In a randomized controlled trial of 600 recipients, which compared vitrified to fresh oocytes, researchers found no significant differences in fertilization, implantation, or pregnancy rates. Pregnancy rates per transfer were 55.4% for vitrified eggs, compared to 55.6% for fresh eggs (Hum. Reprod. 2010;25:2239-46).

　　It’s these types of results that are fueling the interest in frozen donor egg banking, said Heidi Hayes, CEO of Donor Egg Bank USA, a Rockville, Md.–based bank that opened for recipient use in March 2012.

　　"That is what changed it. Now it can be done successfully," Ms. Hayes said. "It’s going to change the field as a whole because of the new technology."

　　The field got another boost when the American Society for Reproductive Medicine (ASRM) issued a new guideline saying that the cryopreservation of mature oocytes – using both vitrification and slow-freeze protocols – was no longer experimental.

　　Removing the experimental designation means that practices wishing to use frozen eggs in IVF cycles won’t have to counsel patients that the procedure is experimental. It also means that an Institutional Review Board (IRB) won’t have to be involved in the informed consent process. That’s a significant change because a lot of practices don’t have access to an IRB, said Dr. Samantha M. Pfeifer, chair of the Practice Committee of the ASRM, which wrote the guidelines.

　　But ASRM is not endorsing frozen egg banking. Although the guidelines state that much of the best data supporting the use of oocyte cryopreservation was in the setting of donor oocyte cycles, the group said it would need more clinic-specific data on the safety and efficiency in the donor population before it could recommend universal donor banking. The ASRM statement does recommend oocyte cryopreservation for cancer patients who are at high risk for infertility because of chemotherapy.

　　There are a lot of advantages to moving toward frozen eggs, Dr. Pfeifer said, such as the ability to quarantine eggs to check for communicable diseases. But there are also lingering questions about how to use frozen eggs, she said. For instance, how long can these eggs be frozen and still be viable?

　　The other concern with moving rapidly toward universal donor banking with frozen eggs is that not every practice has the capability to freeze eggs. "There was some concern that if there was a sudden mandate from the government that everyone [would have] to use frozen eggs; we’re not equipped to do that yet," said Dr. Pfeifer of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia. "A lot of things have to happen before that can become a standard procedure in this country."

　　The first step is removing the experimental label, she said. "Now that it’s not experimental, the reality is that people will be using this technique."

　　Even without a full-scale endorsement from the ASRM, momentum for frozen donor egg banking has been picking up. The cost is a big part of that, Dr. Shapiro said.

　　The price tag for a cycle of IVF using fresh donor eggs can run anywhere between $26,000 and $44,000, depending on the local market and whether an agent has been hired to find a donor. The cost rises quickly because everyone has to get paid, Dr. Shapiro said, including the donor, the agent, and the clinic performing the procedure.

　　In contrast, My Egg Bank North America "sells" its cycles to its affiliate practices for $16,500, which includes all the donor costs, vitrification, and technical assistance with the thawing of the eggs. Other egg banks also advertise the availability of frozen cycles at about half the cost of fresh IVF cycles.

　　And many of the banks offer some type of guarantee. For instance, at My Egg Bank, recipient patients are guaranteed two high-quality embryos. About 20% of patients don’t get two high-quality embryos so they are offered another cycle at no cost if no pregnancy results, Dr. Shapiro said. My Egg Bank also offers a program called "Frozen Egg Advantage," which offers a money-back guarantee when patients pay for five cycles. Patients either go home with a baby or get full reimbursement of treatment expenses at the end of five cycles.

　　"People sit down and they do a simple little [math]," he said. "They quickly come to the conclusion that a couple of cycles with us gives a higher cumulative likelihood of pregnancy than one fresh cycle any place else, and it still comes out less."

　　Convenience is another factor. Traditionally with fresh egg donation, both the egg donor and recipient would have to synchronize their cycles so that once the eggs are retrieved, they could be immediately fertilized and transferred. "When you have the possibility to freeze the donor eggs, then basically you can disconnect the egg donation from receiving those eggs," Dr. Nagy said.

　　That has the potential to take some of the uncertainty and stress out of the process for patients, said Barbara Collura, president and CEO of RESOLVE: The National Infertility Association. She has heard first-hand from infertile women who have had to start over when their donor dropped out of the process.

　　"They pick out an egg donor, and then she gets into law school and her whole life changes and she’s no longer available," Ms. Collura said. "Those things happen and they sound very trite, but when you’re 38, 39, 40 and you’ve been at this already for several years, having the ability to use a vitrified donated oocyte and to be able to use that when you’re ready, is amazing."

　　Frozen egg banking also may offer women greater choice when it comes to choosing an egg donor. That’s another factor that is driving the increasing popularity of this option, said Ms. Hayes of Donor Egg Bank USA.

　　"Cost aside, the donor is the most important factor to them," she said.

　　It’s not just about numbers, Ms. Hayes said, it’s also about ethnic and racial diversity. With fresh donation, it can be difficult to match recipients with donors of certain ethnic backgrounds. With frozen donation, it becomes logistically easier for egg banks to spend time building a more diverse database. At Donor Egg Bank USA, they are working with an affiliate program in Hawaii with the hopes of getting more Asian donors into the bank.

　　"I think culturally there are some women of ethnic background that are less likely to donate eggs," Ms. Hayes said. "These recipients, they want a baby as much as any other couple does. You want your baby to mirror your family."

　　Despite the growing interest in select circles, general awareness of the frozen egg donation model is fairly low. Ms. Hayes said she thinks social media will help it get into the mainstream as more women talk online about their success with frozen donor eggs.

　　"The more women have babies, the more they’ll talk about it, and the more people will utilize a frozen egg as an option," she said.