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Cumulative live birth rates in low-prognosis women.
Hum Reprod. 2019 06 04; 34(6):1030-1041.HR

Abstract

STUDY QUESTION

Do cumulative live birth rates (CLBRs) over multiple IVF/ICSI cycles confirm the low prognosis in women stratified according to the POSEIDON criteria?

SUMMARY ANSWER

The CLBR of low-prognosis women is ~56% over 18 months of IVF/ICSI treatment and varies between the POSEIDON groups, which is primarily attributable to the impact of female age.

WHAT IS KNOWN ALREADY

The POSEIDON group recently proposed a new stratification for low-prognosis women in IVF/ICSI treatment, with the aim to define more homogenous populations for clinical trials and stimulate a patient-tailored therapeutic approach. These new criteria combine qualitative and quantitative parameters to create four groups of low-prognosis women with supposedly similar biologic characteristics.

STUDY DESIGN, SIZE, DURATION

This study analyzed the data of a Dutch multicenter observational cohort study including 551 low-prognosis women, aged <44 years, who initiated IVF/ICSI treatment between 2011 and 2014 and were treated with a fixed FSH dose of 150 IU/day in the first treatment cycle.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Low-prognosis women were categorized into one of the POSEIDON groups based on their age (younger or older than 35 years), anti-Müllerian hormone (AMH) level (above or below 0.96 ng/ml), and the ovarian response (poor or suboptimal) in their first cycle of standard stimulation. The primary outcome was the CLBR over multiple complete IVF/ICSI cycles, including all subsequent fresh and frozen-thawed embryo transfers, within 18 months of treatment. Cumulative incidence curves were obtained using an optimistic and a conservative analytic approach.

MAIN RESULTS AND THE ROLE OF CHANCE

The CLBR of the low-prognosis women was on average ~56% over 18 months of IVF/ICSI treatment. Younger unexpected poor (n = 38) and suboptimal (n = 179) responders had a CLBR of ~65% and ~68%, respectively, and younger expected poor responders (n = 65) had a CLBR of ~59%. The CLBR of older unexpected poor (n = 41) and suboptimal responders (n = 102) was ~42% and ~54%, respectively, and of older expected poor responders (n = 126) ~39%. For comparison, the CLBR of younger (n = 164) and older (n = 78) normal responders with an adequate ovarian reserve was ~72% and ~58% over 18 months of treatment, respectively. No large differences were observed in the number of fresh treatment cycles between the POSEIDON groups, with an average of two fresh cycles per woman within 18 months of follow-up.

LIMITATIONS, REASONS FOR CAUTION

Small numbers in some (sub)groups reduced the precision of the estimates. However, our findings provide the first relevant indication of the CLBR of low-prognosis women in the POSEIDON groups. Small FSH dose adjustments between cycles were allowed, inducing therapeutic disparity. Yet, this is in accordance with current daily practice and increases the generalizability of our findings.

WIDER IMPLICATIONS OF THE FINDINGS

The CLBRs vary between the POSEIDON groups. This heterogeneity is primarily determined by a woman's age, reflecting the importance of oocyte quality. In younger women, current IVF/ICSI treatment reaches relatively high CLBR over multiple complete cycles, despite reduced quantitative parameters. In older women, the CLBR remains relatively low over multiple complete cycles, due to the co-occurring decline in quantitative and qualitative parameters. As no effective interventions exist to counteract this decline, clinical management currently relies on proper counselling.

STUDY FUNDING/COMPETING INTEREST(S)

No external funds were obtained for this study. J.A.L. is supported by a Research Fellowship grant and received an unrestricted personal grant from Merck BV. S.C.O., T.C.v.T., and H.L.T. received an unrestricted personal grant from Merck BV. C.B.L. received research grants from Merck, Ferring, and Guerbet. K.F. received unrestricted research grants from Merck Serono, Ferring, and GoodLife. She also received fees for lectures and consultancy from Ferring and GoodLife. A.H. declares that the Department of Obstetrics and Gynaecology, University Medical Centre Groningen received an unrestricted research grant from Ferring Pharmaceuticals BV, the Netherlands. J.S.E.L. has received unrestricted research grants from Ferring, Zon-MW, and The Dutch Heart Association. He also received travel grants and consultancy fees from Danone, Euroscreen, Ferring, AnshLabs, and Titus Healthcare. B.W.J.M. is supported by an National Health and Medical Research Council Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, and Guerbet. He also received a research grant from Merck BV and travel support from Guerbet. F.J.M.B. received monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands) and Ferring Pharmaceuticals BV (the Netherlands) for advisory work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development, and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare.

TRIAL REGISTRATION NUMBER

Not applicable.

Authors+Show Affiliations

Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.Department of Reproductive Medicine, Maastricht University Medical Centre, P. Debyelaan 25, HX Maastricht, The Netherlands.Centre for Reproductive Medicine, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, GZ Groningen, The Netherlands.Centre for Reproductive Medicine, Amsterdam University Medical Centre, Free University of Amsterdam, De Boelelaan, HV Amsterdam, The Netherlands.Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Henri Dunantstraat 1, GZ 's-Hertogenbosch, The Netherlands.Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, GA Nijmegen, T he Netherlands.Centre for Reproductive Medicine, Amsterdam University Medical Centre, University of Amsterdam, Meibergdreef 9, AZ Amsterdam, The Netherlands.Department of Obstetrics and Gynaecology, Isala Clinics, Dokter Spanjaardweg 27-29, 8025 BT Zwolle, The Netherlands.Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.Department of Obstetrics and Gynaecology, Monash University, Scenic Blvd & Wellington Road, Clayton, VIC, Australia.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan, CX Utrecht, The Netherlands.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31125412

Citation

Leijdekkers, Jori A., et al. "Cumulative Live Birth Rates in Low-prognosis Women." Human Reproduction (Oxford, England), vol. 34, no. 6, 2019, pp. 1030-1041.
Leijdekkers JA, Eijkemans MJC, van Tilborg TC, et al. Cumulative live birth rates in low-prognosis women. Hum Reprod. 2019;34(6):1030-1041.
Leijdekkers, J. A., Eijkemans, M. J. C., van Tilborg, T. C., Oudshoorn, S. C., van Golde, R. J. T., Hoek, A., Lambalk, C. B., de Bruin, J. P., Fleischer, K., Mochtar, M. H., Kuchenbecker, W. K. H., Laven, J. S. E., Mol, B. W. J., Torrance, H. L., & Broekmans, F. J. M. (2019). Cumulative live birth rates in low-prognosis women. Human Reproduction (Oxford, England), 34(6), 1030-1041. https://doi.org/10.1093/humrep/dez051
Leijdekkers JA, et al. Cumulative Live Birth Rates in Low-prognosis Women. Hum Reprod. 2019 06 4;34(6):1030-1041. PubMed PMID: 31125412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cumulative live birth rates in low-prognosis women. AU - Leijdekkers,Jori A, AU - Eijkemans,Marinus J C, AU - van Tilborg,Theodora C, AU - Oudshoorn,Simone C, AU - van Golde,Ron J T, AU - Hoek,Annemieke, AU - Lambalk,Cornelis B, AU - de Bruin,Jan Peter, AU - Fleischer,Kathrin, AU - Mochtar,Monique H, AU - Kuchenbecker,Walter K H, AU - Laven,Joop S E, AU - Mol,Ben Willem J, AU - Torrance,Helen L, AU - Broekmans,Frank J M, AU - ,, PY - 2018/10/22/received PY - 2019/03/10/revised PY - 2019/5/28/pubmed PY - 2020/7/16/medline PY - 2019/5/25/entrez KW - Bologna criteria KW - IVF/ICSI KW - POSEIDON criteria KW - anti-Müllerian hormone KW - cumulative live birth KW - female age KW - low prognosis KW - ovarian reserve KW - ovarian stimulation KW - poor ovarian response SP - 1030 EP - 1041 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 34 IS - 6 N2 - STUDY QUESTION: Do cumulative live birth rates (CLBRs) over multiple IVF/ICSI cycles confirm the low prognosis in women stratified according to the POSEIDON criteria? SUMMARY ANSWER: The CLBR of low-prognosis women is ~56% over 18 months of IVF/ICSI treatment and varies between the POSEIDON groups, which is primarily attributable to the impact of female age. WHAT IS KNOWN ALREADY: The POSEIDON group recently proposed a new stratification for low-prognosis women in IVF/ICSI treatment, with the aim to define more homogenous populations for clinical trials and stimulate a patient-tailored therapeutic approach. These new criteria combine qualitative and quantitative parameters to create four groups of low-prognosis women with supposedly similar biologic characteristics. STUDY DESIGN, SIZE, DURATION: This study analyzed the data of a Dutch multicenter observational cohort study including 551 low-prognosis women, aged <44 years, who initiated IVF/ICSI treatment between 2011 and 2014 and were treated with a fixed FSH dose of 150 IU/day in the first treatment cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Low-prognosis women were categorized into one of the POSEIDON groups based on their age (younger or older than 35 years), anti-Müllerian hormone (AMH) level (above or below 0.96 ng/ml), and the ovarian response (poor or suboptimal) in their first cycle of standard stimulation. The primary outcome was the CLBR over multiple complete IVF/ICSI cycles, including all subsequent fresh and frozen-thawed embryo transfers, within 18 months of treatment. Cumulative incidence curves were obtained using an optimistic and a conservative analytic approach. MAIN RESULTS AND THE ROLE OF CHANCE: The CLBR of the low-prognosis women was on average ~56% over 18 months of IVF/ICSI treatment. Younger unexpected poor (n = 38) and suboptimal (n = 179) responders had a CLBR of ~65% and ~68%, respectively, and younger expected poor responders (n = 65) had a CLBR of ~59%. The CLBR of older unexpected poor (n = 41) and suboptimal responders (n = 102) was ~42% and ~54%, respectively, and of older expected poor responders (n = 126) ~39%. For comparison, the CLBR of younger (n = 164) and older (n = 78) normal responders with an adequate ovarian reserve was ~72% and ~58% over 18 months of treatment, respectively. No large differences were observed in the number of fresh treatment cycles between the POSEIDON groups, with an average of two fresh cycles per woman within 18 months of follow-up. LIMITATIONS, REASONS FOR CAUTION: Small numbers in some (sub)groups reduced the precision of the estimates. However, our findings provide the first relevant indication of the CLBR of low-prognosis women in the POSEIDON groups. Small FSH dose adjustments between cycles were allowed, inducing therapeutic disparity. Yet, this is in accordance with current daily practice and increases the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: The CLBRs vary between the POSEIDON groups. This heterogeneity is primarily determined by a woman's age, reflecting the importance of oocyte quality. In younger women, current IVF/ICSI treatment reaches relatively high CLBR over multiple complete cycles, despite reduced quantitative parameters. In older women, the CLBR remains relatively low over multiple complete cycles, due to the co-occurring decline in quantitative and qualitative parameters. As no effective interventions exist to counteract this decline, clinical management currently relies on proper counselling. STUDY FUNDING/COMPETING INTEREST(S): No external funds were obtained for this study. J.A.L. is supported by a Research Fellowship grant and received an unrestricted personal grant from Merck BV. S.C.O., T.C.v.T., and H.L.T. received an unrestricted personal grant from Merck BV. C.B.L. received research grants from Merck, Ferring, and Guerbet. K.F. received unrestricted research grants from Merck Serono, Ferring, and GoodLife. She also received fees for lectures and consultancy from Ferring and GoodLife. A.H. declares that the Department of Obstetrics and Gynaecology, University Medical Centre Groningen received an unrestricted research grant from Ferring Pharmaceuticals BV, the Netherlands. J.S.E.L. has received unrestricted research grants from Ferring, Zon-MW, and The Dutch Heart Association. He also received travel grants and consultancy fees from Danone, Euroscreen, Ferring, AnshLabs, and Titus Healthcare. B.W.J.M. is supported by an National Health and Medical Research Council Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, and Guerbet. He also received a research grant from Merck BV and travel support from Guerbet. F.J.M.B. received monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands) and Ferring Pharmaceuticals BV (the Netherlands) for advisory work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development, and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Not applicable. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/31125412/Cumulative_live_birth_rates_in_low_prognosis_women_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dez051 DB - PRIME DP - Unbound Medicine ER -