International Journal of Infertility & Fetal Medicine

Register      Login

VOLUME 13 , ISSUE 1 ( January-April, 2022 ) > List of Articles

REVIEW ARTICLE

POSEIDON 1 and 2: Probable Causes and Proposed Treatment Strategies? An Evidence-based Update

Atri Pal

Citation Information : Pal A. POSEIDON 1 and 2: Probable Causes and Proposed Treatment Strategies? An Evidence-based Update. Int J Infertil Fetal Med 2022; 13 (1):23-27.

DOI: 10.5005/jp-journals-10016-1257

License: CC BY-NC 4.0

Published Online: 19-01-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Aim and objective: To elucidate the cause of poor ovarian response to controlled ovarian hyperstimulation during in vitro fertilization in women with good ovarian reserve and the potential treatment options for them. Background: There has been a steady increase in number of in vitro fertilization (IVF) cycles being performed across the world. An important step of IVF is controlled ovarian hyperstimulation (COH), with an aim to achieve multifollicular response. Conventionally the protocol and gonadotropin dose is tailored to ensure adequate oocyte yield and minimize complications. Studies suggest that maximizing oocyte yield increases the cumulative LBR. However, in spite of high dose of gonadotropin usage during COH, many women have poor response (<4 oocytes retrieved) and/or low oocyte yield (4–9 oocytes retrieved). Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) criteria to classify poor responders were introduced in 2016 to achieve better stratification of poor responders and achieve an individualized treatment approach for the patients. Review results: Some of the proposed reasons include suboptimal gonadotropin dose, gonadotropin receptor resistance due to gonadotropin receptor polymorphism and issues with ovulation trigger. Two most studied single nucleotide polymorphism are those at position 307 and 680 of exon 10 of Follicle stimulating hormone receptor. Some studies have demonstrated that homozygous Asparagine at position 680 required lesser gonadotropin dose and had more oocyte yield in normoovulatory women compared with other variants at position 680. However, other studies have reported contradictory findings. Similarly contradictory results have been reported from various studies regarding ovarian response with respect to variants at locus 307. Some of the proposed treatments for patients with unexpected responders include increasing the dose of Inj. FSH, adding Inj. Luteinizing hormone receptor (LH) to ovarian stimulation, use of dual trigger, synchronizing the follicular cohort, use of adjuvants during IVF, and dual stimulation. Conclusion: The exact reason for such a response is still unclear although role of FSH/LH polymorphism has been studied extensively. However, no specific FSH/LH polymorphism has been consistently been associated with such unexpected hyporesponse. There is no high quality evidence for other proposed treatment options.


HTML PDF Share
  1. Yovich JL. Founding pioneers of IVF update: innovative researchers generating livebirths by 1982. Reprod Biol 2020;20(1):111–113. DOI: 10.1016/j.repbio.2019.12.008
  2. Mills M, Rindfuss RR, McDonald P, et al. Why do people postpone parenthood? Reasons and social policy incentives. Hum Reprod Update 2011;17(6):848–860. DOI: 10.1093/humupd/dmr026
  3. de Graaff AA, Land JA, Kessels AG, et al. Demographic age shift toward later conception results in an increased age in the subfertile population and an increased demand for medical care. Fertil Steril 2011;95(1):61–63. DOI: 10.1016/j.fertnstert.2010.05.013
  4. De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2015: results generated. Hum Reprod Open 2020;2020(1):hoz038. DOI: 10.1093/hropen/hoz038
  5. Malhotra N, Shah D, Pai R, et al. Assisted reproductive technology in India: a 3 year retrospective data analysis. J Hum Reprod Sci 2013;6(4):235–240. DOI: 10.4103/0974-1208.126286
  6. Fauser BC, Devroey P, Yen SS, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999;14(11):2681–2686. DOI: 10.1093/humrep/14.11.2681
  7. La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update 2014;20(1):124–140. DOI: 10.1093/humupd/dmt037
  8. Polyzos NP, Drakopoulos P, Parra J, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including ∼15,000 women. Fertil Steril 2018;110(4):661–670. DOI: 10.1016/j.fertnstert.2018.04.039
  9. Zhao Z, Shi H, Li J, et al. Cumulative live birth rates according to the number of oocytes retrieved following the “freeze-all” strategy. Reprod Biol Endocrinol 2020;18(1):14. DOI: 10.1186/s12958-020-00574-3
  10. Oudendijk JF, Yarde F, Eijkemans MJ, et al. The poor responder in IVF: is the prognosis always poor?: a systematic review. Hum Reprod Update 2012;18:1–11. DOI: 10.1093/humupd/dmr037
  11. Patrizio P, Vaiarelli A, Setti L, et al. How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics. Reprod Biomed Online 2015;30:581–592. DOI: 10.1016/j.rbmo.2015.03.002
  12. Gonda KJ, Domar AD, Gleicher N, et al. Insights from clinical experience in treating IVF poor responders. Reprod Biomed Online 2018;36(1):12–19. DOI: 10.1016/j.rbmo.2017.09.016
  13. Blumenfeld Z. What is the best regimen for ovarian stimulation of poor responders in ART/IVF?. Front Endocrinol 2020;11:192. DOI: 10.3389/fendo.2020.00192
  14. Polyzos NP, Devroey P. A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? Fertil Steril 2011;96:1058–1061. DOI: 10.1016/j.fertnstert.2011.09.048
  15. Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011;26:1616–1624. DOI: 10.1093/humrep/der092
  16. Ke H, Chen X, Liu YD, et al. Cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the bologna criteria. J Huazhong Univ Sci Technolog Med Sci 2013; 33:418–22. DOI: 10.1007/s11596-013-1134-7
  17. Esteves SC, Roque M, Bedoschi GM, et al. Defining low prognosis patients undergoing assisted reproductive technology: POSEIDON criteria—the why. Front Endocrinol 2018;9:461. DOI: 10.3389/fendo.2018.00461
  18. Esteves SC, Carvalho JF, Martinhago CD, et al. Estimation of age-dependent decrease in blastocyst euploidy by next generation sequencing: development of a novel prediction model. Panminerva Med 2018;61(1):3–10. DOI: 10.23736/S0031-0808.18.03507-3
  19. Humaidan P, Alviggi C, Fischer R, et al. The novel POSEIDON stratification of ‘Low prognosis patients in Assisted Reproductive Technology’ and its proposed marker of successful outcome. F1000Res 2016;5:2911. DOI: 10.12688/f1000research.10382.1
  20. Conforti A, Esteves SC, Cimadomo D, et al. Management of women with an unexpected low ovarian response to gonadotropin. Front Endocrinol 2019;10:387. DOI: 10.3389/fendo.2019.00387
  21. Alviggi C, Conforti A, Esteves SC, et al. Understanding ovarian hypo-response to exogenous gonadotropin in ovarian stimulation and its new proposed marker—the Follicle-To-Oocyte (FOI) Index. Front Endocrinol 2018;9:589. DOI: 10.3389/fendo.2018.00589
  22. Daly AK. Pharmacogenetics and human genetic polymorphisms. Biochem J 2010;429(3):435–449. DOI: 10.1042/BJ20100522
  23. Brookes AJ. The essence of SNPs. Gene 1999;234:177–186. DOI:10.1016/s0378-1119(99)00219-x
  24. Achrekar SK, Modi DN, Desai SK, et al Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women. Fertil Steril 2009;91(2):432–439 DOI: 10.1016/j.fertnstert.2007.11.093
  25. Lindgren I, Bååth M, Uvebrant K, et al. Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization. Hum Reprod 2016;31(3):672–683. DOI: 10.1093/humrep/dev342
  26. Perez Mayorga M, Gromoll J, Behre HM, et al. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab 2000;85(9):3365–3369. DOI: 10.1210/jcem.85.9.6789
  27. Simoni M, Nieschlag E, Gromoll J. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Hum Reprod Update 2002;8(5):413–421. DOI: 10.1093/humupd/8.5.413
  28. Huang X, Li L, Hong L, et al. The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation. Clin Endocrinol (Oxf) 2015;82(4):577–583. DOI: 10.1111/cen.12573
  29. Behre HM, Greb RR, Mempel A, et al. Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genomics 2005;15(7):451–456. DOI: 10.1097/01.fpc.0000167330.92786.5e
  30. Laven JS, Mulders AG, Suryandari DA, et al. Follicle-stimulating hormone receptor polymorphisms in women with normogonadotropic an ovulatory infertility. Fertil Steril 2003;80(4):986–992. DOI: 10.1016/s0015-0282(03)01115-4
  31. Yan Y, Gong Z, Zhang L, et al. Association of follicle-stimulating hormone receptor polymorphisms with ovarian response in Chinese women: a prospective clinical study. PLoS One 2013;8(10):e78138. DOI: 10.1371/journal.pone.0078138
  32. Dolfin E, Guani B, Lussiana C, et al. FSH-receptor Ala307Thr polymorphism is associated to polycystic ovary syndrome and to a higher responsiveness to exogenous FSH in Italian women. J Assist Reprod Genet 2011;28(10):925–930. DOI: 10.1007/s10815-011-9619-4
  33. Lensen SF, Wilkinson J, Leijdekkers JA, et al. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI). Cochrane Database Syst Rev 2018;2(2): CD012693. DOI: 10.1002/14651858.CD012693.pub2
  34. Drakopoulos P, Santos-Ribeiro S, Bosch E, et al. The effect of dose adjustments in a subsequent cycle of women with suboptimal response following conventional ovarian stimulation. Front Endocrinol 2018;9:361. DOI: 10.3389/fendo.2018.00361
  35. Conforti A, Esteves SC, Di Rella F, et al. The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis. Reprod Biol Endocrinol 2019;17(1):18. DOI: 10.1186/s12958-019-0460-4
  36. Alviggi C, Conforti A, Esteves SC, et al. Recombinant luteinizing hormone supplementation in assisted reproductive technology: a systematic review. Fertil Steril 2018;109(4):644–664. DOI: 10.1016/j.fertnstert.2018.01.003
  37. Lin MH, Wu FS, Lee RK, et al. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril 2013;100(5):1296–1302. DOI: 10.1016/j.fertnstert.2013.07.1976
  38. Haas J, Bassil R, Samara N, et al. GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study. Hum Reprod 2020;35(7):1648–1654. DOI: 10.1093/humrep/deaa107
  39. Chern CU, Li JY, Tsui KH, et al. Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: a retrospective cohort study. PLoS One 2020;15(7):e0235707. DOI: 10.1371/journal.pone.0235707
  40. Lin MH, Wu FS, Hwu YM, et al. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve. Reprod Biol Endocrinol 2019;17(1):7. DOI: 10.1186/s12958-018-0451-x
  41. Eftekhar M, Naghshineh E, Neghab N, et al. A comparison of dual triggering (by administration of GnRH agonist plus HCG) versus HCG alone in poor ovarian responders in ART outcomes. Middle East Fertil Soc J 2018;23(4):350–353.41. DOI: 10.1016/j.mefs.2018.04.011
  42. Khalife D, Awwad J, Ghunaim S, et al. Dual triggering of final oocyte maturation in poor ovarian responders: a prospective randomized controlled trial. Fertil Steril 2019;112(3):e28–e29. DOI: 10.1016/j.fertnstert.2019.07.207
  43. Farquhar C, Rombauts L, Kremer JA, et al. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 2017;5(5):D006109. DOI: 10.1002/14651858.CD006109.pub3
  44. Cozzolino M, Cecchino GN, Troiano G, et al. Growth hormone cotreatment for poor responders undergoing in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2020;114(1):97–109. DOI: 10.1016/j.fertnstert.2020.03.007
  45. Nagels HE, Rishworth JR, Siristatidis CS, et al. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev 2015;26(11):CD009749. DOI: 10.1002/14651858.CD009749.pub2
  46. Kamath MS, Mascarenhas M, Franik S, et al. Clinical adjuncts in in vitro fertilization: a growing list. Fertil Steril 2019;112(6):978–986 DOI: 10.1016/j.fertnstert.2019.09.019
  47. Vaiarelli A, Cimadomo D, Ubaldi N, et al. What is new in the management of poor ovarian response in IVF?. Curr Opin Obstet Gynecol 2018;30(3):155–162. DOI: 10.1097/gco.0000000000000452
  48. Vaiarelli A, Cimadomo D, Trabucco E, et al. Double stimulation in the same ovarian cycle (DuoStim) to maximize the number of oocytes retrieved from poor prognosis patients: a multicenter experience and SWOT analysis. Front Endocrinol 2018;9:317. DOI: 10.3389/fendo.2018.00317
  49. Alsbjerg B, Haahr T, Elbaek HO, et al. Dual stimulation using corifollitropin alfa in 54 Bologna criteria poor ovarian responders–a case series. Reprod Biomed Online 2019;38(5):677–682. DOI: 10.1016/j.rbmo.2019.01.007
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.