Definition of a clinical strategy to enhance the efficacy, efficiency and safety of egg donation cycles with imported vitrified oocytes.
- 作者列表："Rienzi L","Cimadomo D","Maggiulli R","Vaiarelli A","Dusi L","Buffo L","Amendola MG","Colamaria S","Giuliani M","Bruno G","Stoppa M","Ubaldi FM
STUDY QUESTION:Which is the most suitable clinical strategy in egg donation IVF cycles conducted with imported donated vitrified oocytes? SUMMARY ANSWER:The importation, and allocation, of at least eight vitrified eggs per couple during an egg donation cycle is associated with a high cumulative live birth delivery rate per cycle, as well as the confident adoption of a single blastocyst transfer strategy to minimize the risk of multiple pregnancies. WHAT IS KNOWN ALREADY:IVF using donor eggs is commonly used worldwide to treat women who are unable to conceive with their own oocytes. In 2014, the Constitutional Court (n.162/2014) gave permission for gamete donation to be allowed for ART in Italy. Initially recommended as a therapeutic approach for premature ovarian insufficiency, the use of donated oocytes has become more and more common. In countries such as Italy, fresh oocyte donation is theoretically possible, but practically impossible due to the lack of donors. In fact, the Italian law does not allow reimbursement to the young women, who can only voluntarily donate their eggs. Therefore, Italian IVF centers have established several collaborations with international oocyte cryo-banks. The most popular workflow involves the importation of donated oocytes that have been vitrified. However, recent evidence has questioned the overall efficacy of such an approach. This is because detrimental effects arising from oocyte vitrification and warming might reduce the number of eggs available for insemination, with a consequential reduction in the achievable live birth rate per cycle. STUDY DESIGN, SIZE, DURATION:This was a longitudinal cohort study, conducted between October 2015 and December 2018 at two private IVF centers. Overall, 273 couples were treated (mean maternal age: 42.5 ± 3.5 years, range: 31-50 years; mean donor age: 25.7 ± 4.2, 20-35 years) with oocytes purchased from three different Spanish egg banks. PARTICIPANTS/MATERIALS, SETTING, METHODS:We performed an overall analysis, as well as several sub-analyses clustering the data according to the year of treatment (2015-2016, 2017 or 2018), the number of warmed (6, 7, 8 or 9) and surviving oocytes (≤4, 5, 6, 7, 8 or 9) and the cycle strategy adopted (cleavage stage embryo transfer and vitrification, cleavage stage embryo transfer and blastocyst vitrification, blastocyst stage embryo transfer and vitrification). This study aimed to create a workflow to maximize IVF efficacy, efficiency, and safety, during egg donation cycles with imported vitrified oocytes. The primary outcome was the cumulative live birth delivery rate among completed cycles (i.e. cycles where at least a delivery of a live birth was achieved, or no embryo was produced/left to transfer). All cycles, along with their embryological, obstetric and neonatal outcomes, were registered and inspected. MAIN RESULTS AND THE ROLE OF CHANCE:The survival rate after warming was 86 ± 16%. When 6, 7, 8 and 9 oocytes were warmed, 94, 100, 72 and 70% of cycles were completed, resulting in 35, 44, 69 and 59% cumulative live birth delivery rates per completed cycle, respectively. When ≤4, 5, 6, 7, 8 and 9 oocytes survived, 98, 94, 85, 84, 66 and 68% of cycles were completed, resulting in 16, 46, 50, 61, 76 and 60% cumulative live birth delivery rates per completed cycle, respectively. When correcting for donor age, and oocyte bank, in a multivariate logistic regression analysis, warming eight to nine oocytes resulted in an odds ratio (OR) of 2.5 (95% CI: 1.07-6.03, P = 0.03) for the cumulative live birth delivery rate per completed cycle with respect to six to seven oocytes. Similarly, when seven to nine oocytes survived warming, the OR was 2.7 (95% CI: 1.28-5.71, P < 0.01) with respect to ≤6 oocytes. When cleavage stage embryos were transferred, a single embryo transfer strategy was adopted in 17% of cases (N = 28/162); the live birth delivery rate per transfer was 26% (n = 43/162), but among the pregnancies to term, 28% involved twins (n = 12/43). Conversely, when blastocysts were transferred, a single embryo transfer strategy was adopted in 96% of cases (n = 224/234) with a 30% live birth delivery rate per transfer (N = 70/234), and the pregnancies to term were all singleton (n = 70/70). During the study period, 125 babies were born from 113 patients. When comparing the obstetric outcomes for the cleavage and blastocyst stage transfer strategies, the only significant difference was the prevalence of low birthweight: 34 versus 5%, respectively (P < 0.01). However, several significant differences were identified when comparing singleton with twin pregnancies; in fact, the latter resulted in a generally lower birthweight (mean ± SD: 3048 ± 566 g versus 2271 ± 247 g, P < 0.01), a significantly shorter gestation (38 ± 2 versus 36 ± 2 weeks, P < 0.01), solely Caesarean sections (72 versus 100%, P = 0.02), a higher prevalence of low birthweight (8 versus 86%, P < 0.01), small newborns for gestational age (24 versus 57%, P = 0.02) and preterm births (25 versus 86%, P < 0.01). LIMITATIONS, REASONS FOR CAUTION:This retrospective study should now be confirmed across several IVF centers and with a greater sample size in order to improve the accuracy of the sub-analyses. WIDER IMPLICATIONS OF THE FINDINGS:Single blastocyst transfer is the most suitable approach to achieve high success rates per procedure, thereby also limiting the obstetric complications that arise from twin pregnancies in oocyte donation programs. In this regard, the larger the cohort of imported donated vitrified oocytes, the more efficient the management of each cycle. STUDY FUNDING/COMPETING INTEREST(S):None. TRIAL REGISTRATION NUMBER:None.
研究问题:采用进口玻璃化卵母细胞进行卵子捐献IVF周期，哪一种临床策略最合适? 简要回答:在一个卵子捐献周期中，每对夫妇至少输入和分配8个玻璃化卵子，这与高累积活产出率相关，同时也与自信地采用单个囊胚转移策略以最小化多胎妊娠的风险相关。 已知的是:使用捐赠的卵子进行体外受精在世界范围内普遍用于治疗无法用自己的卵母细胞受孕的妇女。2014年，意大利宪法法院(n.162/2014)批准将gamete捐赠用于艺术品。最初被推荐作为治疗卵巢功能不全的方法，捐献的卵母细胞的使用已经变得越来越普遍。在意大利这样的国家，新的卵母细胞捐献在理论上是可能的，但由于缺乏捐献者，实际上是不可能的。事实上，意大利法律不允许补偿年轻女性，她们只能自愿捐献卵子。因此，意大利体外受精中心已经与国际卵母细胞冷冻库建立了几项合作。最流行的工作流程涉及已玻璃化的捐献卵母细胞的输入。然而，最近的证据对这种方法的整体效果提出了质疑。这是因为卵母细胞玻璃化和变暖所产生的有害影响可能会减少可用于授精的卵子数量，从而降低每周期可达到的活产率。 研究设计、规模、持续时间:这是一项纵向队列研究，在2015年10月至2018年12月期间在两个私人试管婴儿中心进行。总共有273对夫妇接受了治疗(平均母亲年龄:42.5±3.5岁，范围:31-50岁;平均供体年龄:25.7±4.2岁(20-35岁)，卵母细胞购自西班牙三家不同的卵子银行。 参与者/材料、设置方法:我们进行了全面分析,以及几个sub-analyses集群数据根据治疗的年(2015 - 2016年,2017年或2018年),温暖的数量(6、7、8、9)和幸存的卵母细胞(≤4、5、6、7、8、9)和周期策略采用(卵裂阶段胚胎移植和玻璃化,卵裂阶段胚胎移植和囊胚玻璃化,胚泡期胚胎移植和玻璃化)。本研究旨在创建一个工作流程，以最大限度地提高体外受精的效率、效率和安全性，在卵子捐赠周期与进口玻璃化卵母细胞。主要结果是在完成的周期(即至少完成了一次活产的周期，或未产生/未留下胚胎进行移植的周期)中累积的活产率。所有的周期，连同他们的胚胎学，产科和新生儿的结果，都进行了登记和检查。 主要结果与机会的作用:升温后存活率为86±16%。当加热6、7、8和9个卵母细胞时，94、100、72和70%的周期完成，每个完整周期的累计活产率分别为35、44、69和59%。当≤4、5、6、7、8、9卵母细胞存活时，完成98、94、85、84、66、68%的周期，每完成一个周期的累计活产率分别为16、46、50、61、76、60%。在多变量logistic回归分析中，当校正供体年龄和卵母细胞库时，8 - 9个卵母细胞变暖，每完成一个周期的累积活产率与6 - 7个卵母细胞的比值比(OR)为2.5 (95% CI: 1.07-6.03, P = 0.03)。相似地，当7 ~ 9个卵母细胞在升温条件下存活时，OR为2.7 (95% CI: 1.28-5.71, P < 0.01)，而≤6个卵母细胞存活。卵裂期胚胎转移时，17%采用单胚转移策略(N = 28/162);每次转移的活产率为26% (n = 43/162)，但在足月妊娠中，28%涉及双胞胎(n = 12/43)。相反，当胚泡被转移时，96%的病例(n = 224/234)采用单一胚胎转移策略，每转移一次有30%的活产率(n = 70/234)，妊娠至足月均为单例(n = 70/70)。在研究期间，113名患者中有125名婴儿出生。当比较卵裂和囊胚阶段转移策略的产科结果时，唯一显著的差异是低出生体重的患病率:34与5%，分别(P < 0.01)。然而，在比较单胎和双胎妊娠时发现了几个显著的差异;事实上,后者通常导致低出生体重(平均数±标准差:3048±566克和2271±247 g、P < 0.01),显著缩短妊娠(38±2和36±2周,P < 0.01),单纯剖腹产(100%和72,P = 0.02),更高的患病率低出生体重(8 86%,P < 0.01),小新生儿胎龄(24个和57%,P = 0.02)和早产(25和86%,P < 0.01)。 局限性，谨慎的理由:为了提高亚分析的准确性，这项回顾性研究现在应该在几个试管婴儿中心和更大的样本量得到确认。 这些发现的更广泛的含义是:单个囊胚移植是实现每次手术的高成功率的最合适的方法，从而也限制了卵母细胞捐赠项目中双胞胎妊娠产生的产科并发症。在这方面，进口捐赠的玻璃化卵母细胞数量越多，对每个周期的管理就越有效。 研究资金/竞争利益(S):没有。 试验注册号码:没有。
METHODS:BACKGROUND:Controlled ovarian stimulation (COS) has a negative effect on the endometrial receptivity compared with natural menstrual cycle. Whether it's necessary to postpone the first frozen embryo transfer (FET) following a freeze-all strategy in order to avoid any residual effect on endometrial receptivity consequent to COS was inconclusive. OBJECTIVE:The purpose of this retrospective study was to explore whether the delayed FET improve the live birth rate and neonatal outcomes stratified by COS protocols after a freeze-all strategy. METHODS:A total of 4404 patients who underwent the first FET cycle were enrolled in this study between April 2014 to December 2017, and were divided into immediate (within the first menstrual cycle following withdrawal bleeding) or delayed FET (waiting for at least one menstrual cycle and the transferred embryos were cryopreserved for less than 6 months). Furthermore, each group was further divided into two subgroups according to COS protocols, and the pregnancy and neonatal outcomes were analyzed between the immediate and delayed FET following the same COS protocol. RESULTS:When FET cycles following the same COS protocol, there was no significant difference regarding the rates of live birth, implantation, clinical pregnancy, multiple pregnancy, early miscarriage, premature birth and stillbirth between immediate and delayed FET groups. Similarly, no significant differences were found for the mean gestational age, the mean birth weight, and rates of low birth weight and very low birth weight between the immediate and delayed FET groups. The sex ratio (male/female) and the congenital anomalies rate also did not differ significantly between the two FET groups stratified by COS protocols. CONCLUSION:Regardless of COS protocols, FET could be performed immediately after a freeze-all strategy for delaying FET failed to improve reproductive and neonatal outcomes.
METHODS:OBJECTIVE:To evaluate the effect of oral diosmin on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) and explore the value of diosmin in preventing and treating OHSS. METHOD:A retrospective study of women attending a reproductive center in Guangzhou, China, between September and December 2016. The inclusion criterion was previous cancellation of embryo transfer after oocyte retrieval during IVF owing to a high risk of OHSS. The women were divided into two groups depending on whether they received oral diosmin (1000 mg twice daily for 10 days) after oocyte retrieval (diosmin group) or not (control group). Apart from diosmin, both groups underwent the same treatment. Baseline information and data related to OHSS were compared. RESULTS:Overall, 146 women were included: 74 in the diosmin group and 72 in the control group. The incidence of moderate-to-severe OHSS in the diosmin and control groups was 5/74 (6.2%) and 14/72 (13.4%), respectively (P=0.027). The control group included four cases of paracentesis due to ascites; there were no cases of paracentesis or severe OHSS in the diosmin group. CONCLUSION:Oral administration of diosmin effectively reduced both the incidence of moderate-to-severe OHSS and the severity of OHSS among high-risk women.
METHODS::Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.