Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients
Sandro C. Esteves 1, Hakan Yarali2,3, Lan N. Vuong 4,5,6, Jose´ F. Carvalho7 , Irem Y. O¨ zbek2 , Mehtap Polat2 , Ho L. Le 5,6, Toan D. Pham 5,6, Tuong M. Ho 5,6, Peter Humaidan 8 , and Carlo Alviggi9
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.
Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017.
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).
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.
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.
ART, cumulative delivery rate, embryo transfer, infertility, live birth, life table, POSEIDON criteria, real-world evidence
Review Can we modify assisted reproductive technology practice to broaden reproductive care access?
[ Richard J. Paulsona, Bart C. J. M. Fauserb, Lan T. N. Vuongc, and Kevin Doodyd ]
One of the barriers to access to fertility care is the relative complexity of fertility treatments. If these can be si...
Review Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles
[ Sanchez F1,2, Le AH3,4, Ho VNA3,4, Romero S1,2, Van Ranst H1, De Vos M1, Gilchrist RB5, Ho TM3,4, Vuong LN3,4,6, Smitz J1 ]
To investigate the effectiveness of a biphasic IVM culture strategy at...
Review Antral follicle count and anti-Müllerian hormone to classify low-prognosis women under the POSEIDON criteria: a classification agreement study of over 9000 patients
[ Sandro C Esteves1, Hakan Yarali2,3, Lan N Vuong4,5,6, José F Carvalho7, İrem Y Özbek2, Mehtap Polat2, Ho L Le4,5, Toan D Pham4,5, Tuong M Ho4,5 ]
Review Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment
[ A. Abbara1, R. Islam2, S.A. Clarke1, L. Jeffers1, G. Christopoulos2, A.N. Comninos1, R. Salim2, S.A. Lavery2, T.N.L. Vuong3,4, P. Humaidan5, T.W. Kelsey6, G.H. Trew2, W.S. Dhillo1 ]
Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to th...
Review Top 10 priorities for future infertility research: an international consensus development study
[ J.M.N. Duffy 1,2,*, G.D. Adamson 3, E. Benson 4, S. Bhattacharya 5, S. Bhattacharya 5, M. Bofill 6, K. Brian 7, B. Collura 8, C. Curtis 9, J.L.H. Evers 10, R.G. Farquharson 11, A. Fincham 12, S. Franik 13, L.C. Giudice 14,15, E. Glanville 16, M. Hickey 17, A.W. Horne 18, M.L. Hull 19, N.P. Johnson 19, V. Jordan 6, Y. Khalaf 20, J.M.L. Knijnenburg 21, R.S. Legro 22, S. Lensen 17, J. MacKenzie 23, D. Mavrelos 24, B.W. Mol 25, D.E. Morbeck 6,26, H. Nagels 27, E.H.Y. Ng 28,29, C. Niederberger 30, A.S. Otter31, L. Puscasiu 32,33, S. Rautakallio-Hokkanen 12, L. Sadler 6,16, I. Sarris 1, M. Showell 27, J. Stewart 34, A. Strandell 35, C. Strawbridge 36, A. Vail 37, M. van Wely 38, M. Vercoe 27, N.L. Vuong 39, A.Y. Wang 40, R. Wang 25, J. Wilkinson 37, K. Wong 9, T.Y. Wong 16, C.M. Farquhar 6,27, and the Priority Setting Partnership for Infertility ]
STUDY QUESTION: Can the priorities for future research in infertility be identified?.