ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil.
Anatolia IVF, Ankara, Turkey.
Hum Reprod. 2021 Jul 19;36(8):2157-2169. doi: 10.1093/humrep/deab152.
What is the cumulative delivery rate (CDR) per aspiration IVF/ICSI cycle in low-prognosis patients as defined by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria?
The CDR of POSEIDON patients was on average ∼50% lower than in normal responders and varied across POSEIDON groups; differences were primarily determined by female age, number of embryos obtained, number of embryo transfer (ET) cycles per patient, number of oocytes retrieved, duration of infertility, and BMI.
The POSEIDON criteria aim to underline differences related to a poor or suboptimal treatment outcome in terms of oocyte quality and quantity among patients undergoing IVF/ICSI, and thus, create more homogenous groups for the clinical management of infertility and research. POSEIDON patients are presumed to be at a higher risk of failing to achieve a live birth after IVF/ICSI treatment than normal responders with an adequate ovarian reserve. The CDR per initiated/aspiration cycle after the transfer of all fresh and frozen-thawed/warmed embryos has been suggested to be the critical endpoint that sets these groups apart. However, no multicenter study has yet substantiated the validity of the POSEIDON classification in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment using real-world data.
STUDY DESIGN, SIZE, DURATION: Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women with infertility between 22 and 42 years old in their first IVF/ICSI cycle of standard ovarian stimulation whose fresh and/or frozen embryos were transferred until delivery of a live born or until all embryos were used. Patients were retrospectively classified according to the POSEIDON criteria into four groups based on female age, antral follicle count (AFC), and the number of oocytes retrieved or into a control group of normal responders (non-POSEIDON). POSEIDON patients encompassed younger (<35 years) and older (35 years or above) women with an AFC ≥5 and an unexpected poor (<4 retrieved oocytes) or suboptimal (4-9 retrieved oocytes) response to stimulation, and respective younger and older counterparts with an impaired ovarian reserve (i.e. expected poor responders; AFC <5). Non-POSEIDON patients were those with AFC ≥5 and >9 oocytes retrieved. CDR was computed per one aspirated cycle. Logistic regression analysis was carried out to examine the association between patient classification and CDR.
The CDR was lower in the POSEIDON patients than in the non-POSEIDON patients (33.7% vs 50.6%; P < 0.001) and differed across POSEIDON groups (younger unexpected poor responder [Group 1a; n = 212]: 27.8%, younger unexpected suboptimal responder [Group 1b; n = 1785]: 47.8%, older unexpected poor responder [Group 2a; n = 293]: 14.0%, older unexpected suboptimal responder [Group 2b; n = 1275]: 30.5%, younger expected poor responder [Group 3; n = 245]: 29.4%, and older expected poor responder [Group 4; n = 623]: 12.5%. Among unexpected suboptimal/poor responders (POSEIDON Groups 1 and 2), the CDR was twice as high in suboptimal responders (4-9 oocytes retrieved) as in poor responders (<4 oocytes) (P = 0.0004). Logistic regression analysis revealed that the POSEIDON grouping, number of embryos obtained, number of ET cycles per patient, number of oocytes collected, female age, duration of infertility and BMI were relevant predictors for CDR (P < 0.001).
LIMITATIONS, REASONS FOR CAUTION: Our study relied on the antral follicle count as the biomarker used for patient classification. Ovarian stimulation protocols varied across study centers, potentially affecting patient classification.
POSEIDON patients exhibit lower CDR per aspirated IVF/ICSI cycle than normal responders; the differences are mainly determined by female age and number of oocytes retrieved, thereby reflecting the importance of oocyte quality and quantity. Our data substantiate the validity of the POSEIDON criteria in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment. Efforts in terms of early diagnosis, prevention, and identification of specific interventions that might benefit POSEIDON patients are warranted.
STUDY FUNDING/COMPETING INTEREST(S): Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. J.F.C. declares receipt of statistical services fees from ANDROFERT Clinic. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. P.H. declares receipt of unrestricted research grants from Merck, Ferring, Gedeon Richter and IBSA and lecture fees from Merck, Gedeon Richter and Med.E.A. C.A. declares receipt of unrestricted research grants from Merck and lecture fees from Merck. The remaining authors have no conflicts of interest to disclose.
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根据患者导向策略涵盖个体卵母细胞数（POSEIDON）标准，低预后患者每抽吸 IVF/ICSI 周期的累积妊娠率（CDR）是多少？
POSEIDON 患者的 CDR 平均比正常反应者低约 50%，且在 POSEIDON 组之间存在差异；差异主要由女性年龄、获得的胚胎数量、每位患者的胚胎移植（ET）周期数、获得的卵母细胞数量、不孕持续时间和 BMI 决定。
POSEIDON 标准旨在强调在接受 IVF/ICSI 的患者中，卵母细胞质量和数量方面与不良或次优治疗结局相关的差异，从而为不孕症的临床管理和研究创建更同质的组。POSEIDON 患者在接受 IVF/ICSI 治疗后实现活产的可能性被认为高于具有足够卵巢储备的正常反应者。已经提出，每抽吸/IVF 周期转移所有新鲜和冷冻/解冻/变暖胚胎后的累积妊娠率是区分这些组的关键终点。然而，尚无多中心研究使用真实世界数据证实 POSEIDON 分类在确定 IVF/ICSI 治疗中低预后相关亚人群方面的有效性。
研究设计、规模、持续时间：涉及巴西、土耳其和越南的三个生育诊所的 9073 名患者的多中心基于人群的回顾性队列研究，这些患者在 2015 年至 2017 年期间接受了第一次 IVF/ICSI 周期的标准卵巢刺激，新鲜和/或冷冻胚胎一直转移到分娩或使用所有胚胎。根据 POSEIDON 标准，患者被分为四组，基于女性年龄、窦卵泡计数（AFC）和获得的卵母细胞数量或正常反应者（非 POSEIDON）控制组。POSEIDON 患者包括年龄较小（<35 岁）和年龄较大（35 岁或以上）的女性，AFC≥5 且刺激反应异常差（<4 个卵母细胞）或次优（4-9 个卵母细胞），以及各自的卵巢储备受损（即预期的反应不良者；AFC<5）的对应物。非 POSEIDON 患者是指 AFC≥5 和>9 个卵母细胞。计算每抽吸周期的 CDR。进行逻辑回归分析以检查患者分类与 CDR 之间的关联。
POSEIDON 患者的 CDR 低于非 POSEIDON 患者（33.7% vs 50.6%；P<0.001），且在 POSEIDON 组之间存在差异（年轻意外反应不良组[第 1a 组；n=212]：27.8%，年轻意外反应不佳组[第 1b 组；n=1785]：47.8%，年龄较大意外反应不良组[第 2a 组；n=293]：14.0%，年龄较大意外反应不佳组[第 2b 组；n=1275]：30.5%，年轻预期反应不良组[第 3 组；n=245]：29.4%，年龄较大预期反应不良组[第 4 组；n=623]：12.5%。在意外反应不良/不佳组（POSEIDON 组 1 和 2）中，反应不佳（<4 个卵母细胞）的患者的 CDR 是反应不佳（4-9 个卵母细胞）患者的两倍（P=0.0004）。逻辑回归分析显示，POSEIDON 分组、获得的胚胎数量、每位患者的 ET 周期数、收集的卵母细胞数量、女性年龄、不孕持续时间和 BMI 是 CDR 的相关预测因子（P<0.001）。
局限性、谨慎原因：我们的研究依赖于窦卵泡计数作为用于患者分类的生物标志物。研究中心的卵巢刺激方案不同，可能会影响患者分类。
POSEIDON 患者的每抽吸 IVF/ICSI 周期的 CDR 低于正常反应者；差异主要由女性年龄和获得的卵母细胞数量决定，反映了卵母细胞质量和数量的重要性。我们的数据证实了 POSEIDON 标准在确定 IVF/ICSI 治疗中低预后相关亚人群方面的有效性。需要努力进行早期诊断、预防，并确定可能使 POSEIDON 患者受益的特定干预措施。
研究资金/利益冲突：默克公司（Merck KGaA，德国达姆施塔特）提供的无限制研究者发起的研究资助（MS200059_0013）。该资助者在研究设计、数据收集、分析、发表决定或手稿准备方面没有任何作用。S.C.E. 宣布从默克和 Med.E.A. 获得无限制的研究赠款和演讲费。H.Y. 宣布从默克、默克 Sharp 和 Dohme（MSD）和 Ferring 获得演讲费和会议费，并从 MSD 和 Ferring 获得研究赠款。J.F.C. 宣布从 ANDROFERT 诊所获得统计服务费。T.M.H. 从默克、MSD 和 Ferring 获得演讲费和会议费。P.H. 宣布从默克、Ferring、Gedeon Richter 和 IBSA 获得无限制的研究赠款和演讲费，并从 Merck、Gedeon Richter 和 Med.E.A. 获得演讲费。其余作者没有利益冲突需要披露。
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