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Fertility Treatment Options for Women With Polycystic Ovary Syndrome. 多囊卵巢综合征妇女的生育治疗选择。
Pub Date : 2019-12-27 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119890867
Shital Sawant, Priya Bhide

Polycystic ovary syndrome is the most common endocrinological disorder in women of reproductive age. It is commonly associated with anovulatory subfertility, for which there are a range of treatment options available to help them conceive. These options are given in a step-wise manner with an appropriate selection of patients to maximise success rates with minimal complications. This review discusses the importance and involvement of multidisciplinary care when offering treatment to women with subfertility. Multidisciplinary care gives an excellent opportunity to identify, assess risk, and potentially prevent future morbidities and complications while treating women for fertility issues. We have also summarised the various options available for fertility treatment: pharmacological treatments, nonpharmacological intervention, and assisted reproductive technology.

多囊卵巢综合征是育龄妇女最常见的内分泌疾病。它通常与无排卵性不孕有关,有一系列的治疗选择可以帮助他们怀孕。这些选择以循序渐进的方式给予适当的患者选择,以最大限度地提高成功率和最小的并发症。这篇综述讨论了多学科护理的重要性和参与提供治疗妇女生育能力低下。多学科护理提供了一个极好的机会来识别,评估风险,并潜在地预防未来的发病率和并发症,同时治疗妇女生育问题。我们还总结了生育治疗的各种选择:药物治疗、非药物干预和辅助生殖技术。
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引用次数: 17
Techniques of Cryopreservation for Ovarian Tissue and Whole Ovary. 卵巢组织及全卵巢冷冻保存技术。
Pub Date : 2019-12-03 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119884945
Amir Arav, Pasquale Patrizio

Cryopreservation of ovarian tissue has been considered experimental for many years, but very recently the American Society of Reproductive Medicine is reviewing the process and perhaps soon will remove the label of "experimental" and recognize it as an established method for preserving female fertility when gonadotoxic treatments cannot be delayed or in patients before puberty or when there is desire to cryopreserve more than just few oocytes. This article discusses in detail the 3 methodologies used for cryopreservation: (a) slow freezing, (b) directional freezing, and (c) vitrification.

卵巢组织的冷冻保存多年来一直被认为是实验性的,但最近美国生殖医学协会正在审查这一过程,也许很快就会取消“实验性”的标签,并承认它是一种既定的方法,用于保存女性生育能力,当促性腺毒素治疗不能延迟时,或者在青春期前的患者中,或者当希望冷冻保存的不仅仅是几个卵母细胞时。本文详细讨论了用于冷冻保存的3种方法:(a)缓慢冷冻,(b)定向冷冻和(c)玻璃化。
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引用次数: 17
An Exploratory Analysis of Factors Associated With Interest in Postpartum Intrauterine Device Uptake Among Pregnant Women and Couples in Kigali, Rwanda. 卢旺达基加利孕妇和夫妇产后对宫内节育器摄取感兴趣的相关因素的探索性分析。
Pub Date : 2019-12-03 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119886843
Vanessa Da Costa, Rosine Ingabire, Robertine Sinabamenye, Etienne Karita, Victoria Umutoni, Alexandra Hoagland, Susan Allen, Ellen Mork, Rachel Parker, Jeannine Mukamuyango, Lisa Haddad, Julien Nyombayire, Kristin M Wall

Background: The desire to space or prevent future pregnancies is high among postpartum women in Rwanda. However, the use of long-acting reversible contraception (LARC), especially the highly effective and cost-effective copper intrauterine device (IUD), is very low, whereas the rates of unintended pregnancy are high. This study aims to identify factors associated with pregnant women's and couple's interest in receiving a postpartum intrauterine device (PPIUD) within 6 weeks after delivery.

Methods: A total of 150 pregnant women or couples attending antenatal care (ANC) in Kigali, Rwanda participated in this cross-sectional study. After participating in a postpartum LARC counseling session, surveys assessed participants' demographics, pregnancy experiences and desires, and PPIUD knowledge, attitudes, practices, and interest. Multivariable logistic regression was used to model factors associated PPIUD interest within 6 weeks postpartum.

Results: Although only 3% of women had ever used an IUD previously, 124 (83%) women were interested in receiving a PPIUD after counseling. Self-reporting physical side effects (adjusted odds ratio [aOR], 0.21; 95% confidence interval [CI], 0.06-0.75) and infection (aOR, 0.19; 95% CI, 0.04-0.85) as disadvantages to the IUD were significantly associated with no interest in receiving a PPIUD. Interest did not differ by male involvement.

Conclusion: Recommendations to increase PPIUD uptake include educating pregnant women and couples about the method during ANC and addressing client myths and misconceptions about the IUD. This strategy allows pregnant women and couples to make informed decisions about their future contraception use, reduce unmet need for family planning, and reduce unintended pregnancy.

背景:卢旺达产后妇女中间隔怀孕或防止未来怀孕的愿望很高。然而,长效可逆避孕(LARC),特别是高效、经济的铜质宫内节育器(IUD)的使用率非常低,而意外妊娠的发生率却很高。本研究旨在确定孕妇和夫妇在产后6周内接受产后宫内节育器(PPIUD)的相关因素。方法:在卢旺达基加利参加产前保健(ANC)的150名孕妇或夫妇参加了这项横断面研究。在参加产后LARC咨询会议后,调查评估了参与者的人口统计数据、怀孕经历和愿望、PPIUD知识、态度、实践和兴趣。采用多变量logistic回归对产后6周内PPIUD兴趣相关因素进行建模。结果:虽然只有3%的女性曾经使用过宫内节育器,但124名(83%)女性在咨询后对接受PPIUD感兴趣。自我报告的身体副作用(校正优势比[aOR], 0.21;95%可信区间[CI], 0.06-0.75)和感染(aOR, 0.19;95% CI, 0.04-0.85),因为宫内节育器的缺点与接受PPIUD的兴趣显著相关。兴趣并没有因为男性的参与而有所不同。结论:建议增加PPIUD的使用,包括在ANC期间对孕妇和夫妇进行方法教育,并解决客户对IUD的误解和误解。这一战略使孕妇和夫妇能够就今后使用避孕药具作出知情决定,减少未满足的计划生育需求,并减少意外怀孕。
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引用次数: 5
Setting Up a Cryopreservation Programme for Immature Testicular Tissue: Lessons Learned After More Than 15 Years of Experience 建立未成熟睾丸组织冷冻保存计划:超过15年经验的教训
Pub Date : 2019-11-01 DOI: 10.1177/1179558119886342
A. Braye, H. Tournaye, E. Goossens
Young boys undergoing gonadotoxic treatments are at high risk of spermatogonial stem cell (SSC) loss and fertility problems later in life. Stem cell loss can also occur in specific genetic conditions, eg, Klinefelter syndrome (KS). Before puberty, these boys do not yet produce sperm. Hence, they cannot benefit from sperm banking. An emerging alternative is the freezing of testicular tissue aiming to preserve the SSCs for eventual autologous transplantation or in vitro maturation at adult age. Many fertility preservation programmes include cryopreservation of immature testicular tissue, although the restoration procedures are still under development. Until the end of 2018, the Universitair Ziekenhuis Brussel has frozen testicular tissues of 112 patients between 8 months and 18 years of age. Testicular tissue was removed in view of gonadotoxic cancer treatment (35%), gonadotoxic conditioning therapy for bone marrow transplantation (35%) or in boys diagnosed with KS (30%). So far, none of these boys had their testicular tissue transplanted back. This article summarizes our experience with cryopreservation of immature testicular tissue over the past 16 years (2002-2018) and describes the key issues for setting up a cryopreservation programme for immature testicular tissue as a means to safeguard the future fertility of boys at high risk of SSC loss.
接受促性腺毒素治疗的年轻男孩在以后的生活中存在精子干细胞(SSC)丢失和生育问题的高风险。干细胞损失也可能发生在特定的遗传条件下,例如,Klinefelter综合征(KS)。在青春期之前,这些男孩还不能产生精子。因此,他们不能从精子库中受益。一种新兴的替代方法是冷冻睾丸组织,目的是保存ssc,以便最终在成年时进行自体移植或体外成熟。许多生育保存方案包括低温保存未成熟睾丸组织,尽管恢复程序仍在发展中。截至2018年底,布鲁塞尔齐肯豪斯大学已经冷冻了112名8个月至18岁患者的睾丸组织。考虑到促性腺毒性癌症治疗(35%),骨髓移植促性腺毒性调理治疗(35%)或诊断为KS的男孩(30%),睾丸组织被切除。到目前为止,这些男孩的睾丸组织都没有被移植回来。本文总结了过去16年(2002-2018)未成熟睾丸组织冷冻保存的经验,并描述了建立未成熟睾丸组织冷冻保存计划的关键问题,以保障SSC丢失高风险男孩的未来生育能力。
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引用次数: 26
The Source of Polycystic Ovarian Syndrome 多囊卵巢综合征的来源
Pub Date : 2019-08-01 DOI: 10.1177/1179558119871467
C. Raperport, R. Homburg
The source of polycystic ovarian syndrome (PCOS) is much debated and is likely to be multifactorial. There is an apparent familial inheritance with first-degree relatives of sufferers more likely to be affected. Twin studies have suggested a genetic cause but candidate genes are yet to be verified. Genes affecting insulin resistance, steroid hormone production, and inflammatory cytokine responses have all been implicated. Current thinking supports the theory that exposure to environmental factors in utero predisposes a female foetus to hyperandrogenism, insulin resistance, and polycystic ovaries in adult life. Which environmental factors have an impact on the foetus and the mechanisms of exposure are still to be confirmed. Animal studies have shown a clear correlation between hyperexposure of the foetus to androgens in utero and future development of a PCOS pattern of symptoms. Placental aromatases should neutralise androgens from the maternal circulation and prevent them reaching the foetal circulation. Our hypothesis is that the high maternal anti-Mullerian hormone (AMH) levels in PCOS block the placental aromatase and allow passage of testosterone through the placenta. This maternal testosterone acts on the foetal ovaries and ‘programmes’ them to recruit more preantral follicles and so produce higher AMH levels when they become functional at around 36 weeks of gestation. The high AMH concentrations in PCOS also seem to increase luteinizing hormone release and inhibit follicle stimulating hormone action on aromatase, so adding to the hyperandrogenic environment of adult PCOS.
多囊卵巢综合征(PCOS)的来源备受争议,可能是多因素的。有一种明显的家族遗传,患者的一级亲属更容易受到影响。双胞胎研究表明了遗传原因,但候选基因尚未得到证实。影响胰岛素抵抗、类固醇激素产生和炎症细胞因子反应的基因都有牵连。目前的观点支持这样一种理论,即子宫内暴露于环境因素会使女性胎儿在成年后出现高雄激素症、胰岛素抵抗和多囊卵巢。哪些环境因素对胎儿有影响以及暴露的机制仍有待证实。动物研究表明,胎儿在子宫内过度暴露于雄激素与多囊卵巢综合征症状模式的未来发展之间存在明确的相关性。胎盘芳香酶应该中和来自母体循环的雄激素,防止它们到达胎儿循环。我们的假设是,多囊卵巢综合征中母体抗苗勒管激素(AMH)水平高,阻断了胎盘芳香化酶,使睾酮通过胎盘。母体的睾酮作用于胎儿卵巢,并“规划”它们招募更多的卵泡,从而在妊娠36周左右卵泡开始发挥功能时产生更高的AMH水平。多囊卵巢综合征中AMH的高浓度似乎也增加了促黄体生成素的释放,抑制了促卵泡激素对芳香化酶的作用,从而增加了成人多囊卵巢综合征的高雄激素环境。
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引用次数: 23
How Will the New Global Polycystic Ovary Syndrome Guideline Change Our Clinical Practice? 新的全球多囊卵巢综合症指南将如何改变我们的临床实践?
Pub Date : 2019-07-03 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119849605
Susie Jacob, Adam H Balen

Polycystic ovary syndrome (PCOS) is a far reaching condition that has a number of reproductive and general health implications. There has been much debate in recent years about the diagnosis and definition of PCOS and a plethora of studies assessing its management, ranging from the psychosocial aspects of the conditions, to the treatment of hyperandrogenism, anovulatory infertility, and the long-term metabolic and reproductive consequences. There has been a need to synthesise the evidence and produce an international consensus guideline for all aspects of the management of PCOS and this was achieved with the publication of the International evidence-based guideline for the assessment and management of polycystic ovary syndrome. The guideline is broadly categorised into 5 sections, which focus on diagnosis, holistic management and safe, effective fertility treatment. This article summarises the key points of the guidance and brings the management of PCOS up to date for the 21st century.

多囊卵巢综合症(PCOS)是一种影响深远的疾病,对生殖健康和全身健康都有影响。近年来,人们对多囊卵巢综合症的诊断和定义争论不休,对其治疗方法的评估研究也层出不穷,从疾病的社会心理方面,到高雄激素、无排卵性不孕症的治疗,以及长期代谢和生殖后果,不一而足。因此,有必要对证据进行综合,并针对多囊卵巢综合症管理的各个方面制定一份国际共识指南,《多囊卵巢综合症评估与管理国际循证指南》的出版实现了这一目标。该指南大致分为 5 个部分,分别侧重于诊断、整体管理和安全有效的生育治疗。本文总结了该指南的要点,并将多囊卵巢综合症的治疗方法推向 21 世纪。
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引用次数: 0
Potential Mechanisms of Ovarian Protection with Gonadotropin-Releasing Hormone Agonist in Breast Cancer Patients: A Review 促性腺激素释放激素激动剂对乳腺癌患者卵巢保护的潜在机制综述
Pub Date : 2019-07-01 DOI: 10.1177/1179558119864584
F. Poggio, M. Lambertini, C. Bighin, B. Conte, E. Blondeaux, A. D’Alonzo, C. Dellepiane, G. Buzzatti, C. Molinelli, F. Boccardo, L. Del Mastro
The use of chemotherapy in premenopausal cancer patients may lead to chemotherapy-induced premature ovarian failure. Pharmacological temporary ovarian suppression obtained with the gonadotropin-releasing hormone agonist (GnRHa) administered concomitantly with chemotherapy has been investigated as a technique capable to reduce the gonadotoxicity, reducing the risk of developing premature menopause. In recent years, important evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients. However, in women interested in fertility preservation, this is not an alternative to cryopreservation strategies, which remains the first option to be proposed. The purpose of this review is to summarize the mechanisms of GnRHa in the preservation of fertility in premenopausal cancer patient candidates to receive chemotherapy, highlighting the areas of doubt that require further investigation.
绝经前癌症患者使用化疗可能导致化疗诱导的卵巢早衰。与化疗同时使用促性腺激素释放激素激动剂(GnRHa)获得的药理学暂时卵巢抑制已被研究为一种能够降低促性腺毒性的技术,降低过早绝经的风险。近年来,关于这种策略的有效性和安全性的重要证据已经出现,现在应该被认为是绝经前乳腺癌患者卵巢功能保护的标准选择。然而,对于对保留生育能力感兴趣的女性来说,这并不是冷冻保存策略的替代选择,冷冻保存策略仍然是第一选择。本综述的目的是总结GnRHa在保留绝经前癌症患者接受化疗的生育能力方面的机制,强调需要进一步研究的疑问领域。
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引用次数: 21
Anti-Müllerian Hormone in Fertility Preservation: Clinical and Therapeutic Applications. 抗<s:1>勒氏杆菌激素在维持生育能力中的临床和治疗应用。
Pub Date : 2019-06-14 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119854755
Charlotte Sonigo, Isabelle Beau, Nadine Binart, Michael Grynberg

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor (TGF)-beta family and a key regulator of sexual differentiation and folliculogenesis. While the serum AMH level has been used in reproductive medicine as a biomarker of quantitative ovarian reserve for more than 20 years, new potential therapeutic applications of recombinant AMH are emerging, notably in the field of oncofertility. Indeed, it is well known that chemotherapy, used to treat cancer, induces ovarian follicular depletion and subsequent infertility. Animal models have been used widely to understand the effects of different cytotoxic agents on ovarian function, and several hypotheses regarding chemotherapy gonadotoxicity have been proposed, that is, it might have a direct detrimental effect on the primordial follicles constituting the ovarian reserve and/or on the pool of growing follicles secreting AMH. Recently, a new mechanism of chemotherapy-induced follicular depletion, called the "burn-out effect," has been proposed. According to this theory, chemotherapeutic agents may lead to a massive growth of dormant follicles which are then destroyed. As AMH is one of the factors regulating the recruitment of primordial follicles from the ovarian reserve, recombinant AMH administration concomitant with chemotherapy might limit follicular depletion, therefore representing a promising option for preserving fertility in women suffering from cancer. This review reports on the potential usefulness of AMH measurement as well as AMH's role as a therapeutic agent in the field of female fertility preservation.

勒氏激素(anti - llerian hormone, AMH)是转化生长因子(TGF)- β家族的成员,是性分化和卵泡发生的关键调节因子。虽然血清AMH水平作为定量卵巢储备的生物标志物已在生殖医学中使用了20多年,但重组AMH的新的潜在治疗应用正在出现,特别是在肿瘤生育领域。事实上,众所周知,用于治疗癌症的化疗会导致卵巢卵泡衰竭和随后的不孕症。动物模型已被广泛用于了解不同细胞毒性药物对卵巢功能的影响,并提出了几种关于化疗促性腺毒性的假设,即它可能对构成卵巢储备的原始卵泡和/或对分泌AMH的生长卵泡池产生直接的有害影响。最近,有人提出了一种化疗诱导的卵泡衰竭的新机制,称为“衰竭效应”。根据这一理论,化疗药物可能导致休眠卵泡的大量生长,然后被破坏。由于AMH是调节卵巢储备中原始卵泡募集的因素之一,重组AMH与化疗联合使用可能会限制卵泡的消耗,因此代表了一种有希望的选择,以保持患有癌症的妇女的生育能力。本文综述了AMH测量的潜在用途,以及AMH作为一种治疗药物在女性生育能力保存领域的作用。
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引用次数: 20
Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo. 体外基于干细胞的卵巢组织重建和体内卵巢再生的女性生育能力保存。
Pub Date : 2019-05-23 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119848007
Taichi Akahori, Dori C Woods, Jonathan L Tilly

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells-referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute "artificial" ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

从历史上看,为诊断为癌症的妇女提供在完成细胞毒性治疗后拥有基因匹配孩子的前景的方法,主要集中在现有的卵母细胞群上,作为临床管理不孕症的唯一资源。在这方面,选择性卵母细胞和胚胎冷冻保存,以及治疗后自体卵巢皮质组织移植,作为年轻女孩和面临癌症的育龄妇女的选择,已经获得了广泛的支持。此外,已经提出使用卵巢保护疗法,包括促性腺激素释放激素激动剂和鞘氨醇-1-磷酸类似物,作为保护卵巢内现有卵母细胞免受放射治疗和许多化疗方案引起的副作用损伤的另一种方法。这一观点随着大量报道的发表而改变,这些报道称,包括人类在内的许多哺乳动物的成年卵巢中含有一种罕见的产生卵母细胞的生殖细胞——被称为雌性种系细胞或卵母干细胞(osc)。这一新的研究路线推动了对产生新的卵母细胞的前景的研究,而不是与现有的卵母细胞一起工作,作为一种维持或恢复女性癌症幸存者生育能力的新方法。在这里,我们概述了世界各地实验室的工作历史,这些工作的重点是提高我们对OSCs生物学的理解,以及如何使用这些细胞在体外重建“人工”卵巢组织或在体内再生受损的卵巢组织,作为未来的生育能力保存选择。
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引用次数: 23
FertiPROTEKT, Oncofertility Consortium and the Danish Fertility-Preservation Networks - What Can We Learn From Their Experiences? FertiPROTEKT、肿瘤生育联盟和丹麦生育保护网络-我们可以从他们的经验中学到什么?
Pub Date : 2019-04-30 eCollection Date: 2019-01-01 DOI: 10.1177/1179558119845865
Michael von Wolff, Claus Yding Andersen, Teresa K Woodruff, Frank Nawroth

Fertility preservation is an increasingly important discipline. It requires close coordination between reproductive medicine specialists, reproductive biologists, and oncologists in various disciplines. In addition, it represents a particular health policy challenge, since fertility-protection measures are to be understood as a treatment for side effects of gonadotoxic treatments and would therefore normally have to be reimbursed by health insurance companies. Therefore, it is inevitable that fertility-preservation activities should organise themselves into a network structure both as a medical-logistic network and as a professional medical society. The necessary network structures can differ significantly at regional, national, and international level, as the size of the regions to be integrated and the local cultural and geographical conditions, as well as the political conditions are very different. To address these issues, the current review aims to point out the basic importance and the chances but also the difficulties of fertility-protection networks and give practical guidance for the development of such network structures. We will not only discuss network structures theoretically but also present them based on three established, different sized networks, such as the Danish Network (www.rigshospitalet.dk), representing a centralised network in a small country; the German-Austrian-Swiss network FertiPROTEKT® (www.fertiprotekt.com), representing a centralised as well as decentralised network in a large country; and the Oncofertility® Consortium (www.oncofertility.northwestern.edu), representing a decentralised, internationally oriented network, primarily serving the transfer of knowledge among its members.

保持生育能力是一门越来越重要的学科。这需要生殖医学专家、生殖生物学家和各个学科的肿瘤学家之间的密切协调。此外,这是一个特殊的卫生政策挑战,因为生育保护措施被理解为治疗性腺毒性治疗的副作用,因此通常必须由健康保险公司报销。因此,生育保护活动不可避免地要组织成一个网络结构,既是一个医疗后勤网络,也是一个专业的医疗社会。必要的网络结构在区域、国家和国际层面可能有很大差异,因为要整合的区域的规模、当地的文化和地理条件以及政治条件都非常不同。为了解决这些问题,本次审查旨在指出生育保护网络的基本重要性、机会和困难,并为发展此类网络结构提供实际指导。我们不仅将从理论上讨论网络结构,还将基于三个已建立的、不同规模的网络来介绍它们,例如丹麦网络(www.rigshospitalet.dk),它代表了一个小国的中央网络;德国-奥地利-瑞士网络FertiPROTEKT®(www.FertiPROTEKT.com),代表着一个大国的集中和分散网络;以及Oncofertility®Consortium(www.oncomptility.northwest.edu),代表一个分散的、面向国际的网络,主要服务于其成员之间的知识转让。
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引用次数: 0
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Clinical Medicine Insights-Reproductive Health
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