Skip to main content

Which Women Are Suitable for Natural and Modified Natural Cycle IVF?

  • Chapter
  • First Online:
Development of In Vitro Maturation for Human Oocytes

Abstract

The term natural cycle in vitro fertilisation (NC-IVF) applies ‘when IVF is carried out with oocytes collected from a woman’s ovary or ovaries in a spontaneous menstrual cycle without administration of any medication at any time during the cycle’.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Nargund G, Fauser BC, Macklon NS, Ombelet W, Nygren K, Frydman R. Rotterdam ICGoTfOSfIVF: the ISMAAR proposal on terminology for ovarian stimulation for IVF. Hum Reprod. 2007;22(11):2801–4.

    Article  CAS  PubMed  Google Scholar 

  2. Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978;2(8085):366.

    Article  CAS  PubMed  Google Scholar 

  3. Verberg MF, Eijkemans MJ, Heijnen EM, Broekmans FJ, de Klerk C, Fauser BC, Macklon NS. Why do couples drop-out from IVF treatment? A prospective cohort study. Hum Reprod. 2008;23(9):2050–5.

    Article  CAS  PubMed  Google Scholar 

  4. Nargund G, Chian RC. ISMAAR: leading the global agenda for a more physiological, patient-centred, accessible and safer approaches in ART. J Assist Reprod Genet. 2013;30(2):155–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Aanesen A, Nygren KG, Nylund L. Modified natural cycle IVF and mild IVF: a 10 year Swedish experience. Reprod Biomed Online. 2010;20(1):156–62.

    Article  PubMed  Google Scholar 

  6. Shaulov T, Velez MP, Buzaglo K, Phillips SJ, Kadoch IJ. Outcomes of 1503 cycles of modified natural cycle in vitro fertilization: a single-institution experience. J Assist Reprod Genet. 2015;32(7):1043–8.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nargund G, Waterstone J, Bland J, Philips Z, Parsons J, Campbell S. Cumulative conception and live birth rates in natural (unstimulated) IVF cycles. Hum Reprod. 2001;16(2):259–62.

    Article  CAS  PubMed  Google Scholar 

  8. Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, Macklon NS, Fauser BC. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22(4):980–8.

    Article  PubMed  Google Scholar 

  9. Hohmann FP, Macklon NS, Fauser BC. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab. 2003;88(1):166–73.

    Article  CAS  PubMed  Google Scholar 

  10. Arce JC, Andersen AN, Fernandez-Sanchez M, Visnova H, Bosch E, Garcia-Velasco JA, Barri P, de Sutter P, Klein BM, Fauser BC. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, Anti-Müllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014; 102(6):1633–1640 e1635.

    Google Scholar 

  11. Baker VL, Brown MB, Luke B, Smith GW, Ireland JJ. Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. Fertil Steril. 2015; 104(5):1145–1152 e1145.

    Google Scholar 

  12. von Wolff M, Kollmann Z, Fluck CE, Stute P, Marti U, Weiss B, Bersinger NA. Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF. Hum Reprod. 2014;29(5):1049–57.

    Article  Google Scholar 

  13. Valbuena D, Martin J, de Pablo JL, Remohi J, Pellicer A, Simon C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril. 2001;76(5):962–8.

    Article  CAS  PubMed  Google Scholar 

  14. Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003;14(5):236–42.

    Article  CAS  PubMed  Google Scholar 

  15. Haouzi D, Assou S, Dechanet C, Anahory T, Dechaud H, De Vos J, Hamamah S. Controlled ovarian hyperstimulation for in vitro fertilization alters endometrial receptivity in humans: protocol effects. Biol Reprod. 2010;82(4):679–86.

    Article  CAS  PubMed  Google Scholar 

  16. Simon C, Cano F, Valbuena D, Remohi J, Pellicer A. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod. 1995;10(9):2432–7.

    Article  CAS  PubMed  Google Scholar 

  17. Labarta E, Martinez-Conejero JA, Alama P, Horcajadas JA, Pellicer A, Simon C, Bosch E. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011;26(7):1813–25.

    Article  CAS  PubMed  Google Scholar 

  18. Pelinck MJ, Keizer MH, Hoek A, Simons AH, Schelling K, Middelburg K, Heineman MJ. Perinatal outcome in singletons after modified natural cycle IVF and standard IVF with ovarian stimulation. Eur J Obstet Gynecol Reprod Biol. 2010;148(1):56–61.

    Article  PubMed  Google Scholar 

  19. Sunkara SK, La Marca A, Seed PT, Khalaf Y. Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes. Hum Reprod. 2015;30(6):1473–80.

    Article  PubMed  Google Scholar 

  20. Hu XL, Feng C, Lin XH, Zhong ZX, Zhu YM, Lv PP, Lv M, Meng Y, Zhang D, Lu XE, et al. High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth. J Clin Endocrinol Metab. 2014;99(6):2217–24.

    Article  CAS  PubMed  Google Scholar 

  21. Xu GF, Zhang JY, Pan HT, Tian S, Liu ME, Yu TT, Li JY, Ying WW, Yao WM, Lin XH, et al. Cardiovascular dysfunction in offspring of ovarian-hyperstimulated women and effects of estradiol and progesterone: a retrospective cohort study and proteomics analysis. J Clin Endocrinol Metab. 2014;99(12):E2494–503.

    Article  CAS  PubMed  Google Scholar 

  22. Pelinck MJ, Hoek A, Simons AH, Heineman MJ. Efficacy of natural cycle IVF: a review of the literature. Hum Reprod Update. 2002;8(2):129–39.

    Article  CAS  PubMed  Google Scholar 

  23. Paulson RJ, Sauer MV, Francis MM, Macaso TM, Lobo RA. In vitro fertilization in unstimulated cycles: the University of Southern California experience. Fertil Steril. 1992;57(2):290–3.

    Article  CAS  PubMed  Google Scholar 

  24. Aboulghar MA, Mansour RT, Serour GA, Amin YM, Sattar MA, Ramzy AM. In vitro fertilization in a spontaneous cycle: a successful simple protocol. J Obstet Gynaecol (Tokyo 1995). 1995; 21(4):337–40.

    Google Scholar 

  25. Heijnen EM, Eijkemans MJ, De Klerk C, Polinder S, Beckers NG, Klinkert ER, Broekmans FJ, Passchier J, Te Velde ER, Macklon NS, et al. A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial. Lancet. 2007;369(9563):743–9.

    Article  PubMed  Google Scholar 

  26. Groen H, Tonch N, Simons AH, van der Veen F, Hoek A, Land JA. Modified natural cycle versus controlled ovarian hyperstimulation IVF: a cost-effectiveness evaluation of three simulated treatment scenarios. Hum Reprod. 2013;28(12):3236–46.

    Article  PubMed  Google Scholar 

  27. Tjon-Kon-Fat RI, Bensdorp AJ, Maas J, Oosterhuis GJE et al. An economic analysis comparing IVF with a single embryo transfer and IVF with amodified natural cycle to IUI with hyperstimulation (the INeS trial). In: 29th annual meeting, European Society of Human Reproduction and Embryology 2013; London; 2013.

    Google Scholar 

  28. Frydman R, Cornel C, de Ziegler D, Taieb J, Spitz IM, Bouchard P. Spontaneous luteinizing hormone surges can be reliably prevented by the timely administration of a gonadotrophin releasing hormone antagonist (Nal-Glu) during the late follicular phase. Hum Reprod. 1992;7(7):930–3.

    Article  CAS  PubMed  Google Scholar 

  29. Rongieres-Bertrand C, Olivennes F, Righini C, Fanchin R, Taieb J, Hamamah S, Bouchard P, Frydman R. Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation. Hum Reprod. 1999;14(3):683–8.

    Article  CAS  PubMed  Google Scholar 

  30. Edwards RG, Lobo R, Bouchard P. Time to revolutionize ovarian stimulation. Hum Reprod. 1996;11(5):917–9.

    Article  CAS  PubMed  Google Scholar 

  31. Nargund G, Doyle PE, Bourne TH, Parsons JH, Cheng WC, Campbell S, Collins WP. Ultrasound derived indices of follicular blood flow before HCG administration and the prediction of oocyte recovery and preimplantation embryo quality. Hum Reprod. 1996;11(11):2512–7.

    Article  CAS  PubMed  Google Scholar 

  32. Nargund G, Bourne T, Doyle P, Parsons J, Cheng W, Campbell S, Collins W. Associations between ultrasound indices of follicular blood flow, oocyte recovery and preimplantation embryo quality. Hum Reprod. 1996;11(1):109–13.

    Article  CAS  PubMed  Google Scholar 

  33. Greco E, Litwicka K, Arrivi C, Varricchio MT, Zavaglia D, Mencacci C, Minasi MG. Accumulation of oocytes from a few modified natural cycles to improve IVF results: a pilot study. J Assist Reprod Genet. 2013;30(11):1465–70.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Muasher SJ, Oehninger S, Simonetti S, Matta J, Ellis LM, Liu HC, Jones GS, Rosenwaks Z. The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome. Fertil Steril. 1988;50(2):298–307.

    Article  CAS  PubMed  Google Scholar 

  35. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. Definition EwgoPOR: ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616–24.

    Article  CAS  PubMed  Google Scholar 

  36. Reyftmann L, Dechaud H, Loup V, Anahory T, Brunet-Joyeux C, Lacroix N, Hamamah S, Hedon B. Natural cycle in vitro fertilization cycle in poor responders. Gynecol Obstet Fertil. 2007;35(4):352–8.

    Article  CAS  PubMed  Google Scholar 

  37. Kolibianakis E, Zikopoulos K, Camus M, Tournaye H, Van Steirteghem A, Devroey P. Modified natural cycle for IVF does not offer a realistic chance of parenthood in poor responders with high day 3 FSH levels, as a last resort prior to oocyte donation. Hum Reprod. 2004;19(11):2545–9.

    Article  PubMed  Google Scholar 

  38. Polyzos NP, Blockeel C, Verpoest W, De Vos M, Stoop D, Vloeberghs V, Camus M, Devroey P, Tournaye H. Live birth rates following natural cycle IVF in women with poor ovarian response according to the Bologna criteria. Hum Reprod. 2012;27(12):3481–6.

    Article  CAS  PubMed  Google Scholar 

  39. Kedem A, Tsur A, Haas J, Yerushalmi GM, Hourvitz A, Machtinger R, Orvieto R. Is the modified natural in vitro fertilization cycle justified in patients with “genuine” poor response to controlled ovarian hyperstimulation? Fertil Steril. 2014;101(6):1624–8.

    Article  PubMed  Google Scholar 

  40. Papaleo E, De Santis L, Fusi F, Doldi N, Brigante C, Marelli G, Persico P, Cino I, Ferrari A. Natural cycle as first approach in aged patients with elevated follicle-stimulating hormone undergoing intracytoplasmic sperm injection: a pilot study. Gynecol Endocrinol. 2006;22(7):351–4.

    Article  PubMed  Google Scholar 

  41. Lainas TG, Sfontouris IA, Venetis CA, Lainas GT, Zorzovilis IZ, Tarlatzis BC, Kolibianakis EM. Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders. Hum Reprod. 2015;30(10):2321–30.

    Article  PubMed  Google Scholar 

  42. Polyzos NP, Drakopoulos P, Tournaye H. Modified natural cycle IVF for poor ovarian responders: rethink before concluding. Hum Reprod. 2016;31(1):221–2.

    Article  CAS  PubMed  Google Scholar 

  43. Kyrou D, Kolibianakis EM, Venetis CA, Papanikolaou EG, Bontis J, Tarlatzis BC. How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2009;91(3):749–66.

    Article  CAS  PubMed  Google Scholar 

  44. Bassil S, Godin PA, Donnez J. Outcome of in-vitro fertilization through natural cycles in poor responders. Hum Reprod. 1999;14(5):1262–5.

    Article  CAS  PubMed  Google Scholar 

  45. Castelo-Branco A, Frydman N, Kadoch J, Le Du A, Fernandez H, Fanchin R, Frydman R. The role of the semi natural cycle as option of treatment of patients with a poor prognosis for successful in vitro fertilization. J Gynecol Obstet Biol Reprod (Paris). 2004;33(6 Pt 1):518–24.

    Article  CAS  Google Scholar 

  46. Matsuura T, Takehara Y, Kaijima H, Teramoto S, Kato O. Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles. J Assist Reprod Genet. 2008;25(4):163–7.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Schimberni M, Morgia F, Colabianchi J, Giallonardo A, Piscitelli C, Giannini P, Montigiani M, Sbracia M. Natural-cycle in vitro fertilization in poor responder patients: a survey of 500 consecutive cycles. Fertil Steril. 2009;92(4):1297–301.

    Article  PubMed  Google Scholar 

  48. Morgia F, Sbracia M, Schimberni M, Giallonardo A, Piscitelli C, Giannini P, Aragona C. A controlled trial of natural cycle versus microdose gonadotropin-releasing hormone analog flare cycles in poor responders undergoing in vitro fertilization. Fertil Steril. 2004;81(6):1542–7.

    Article  CAS  PubMed  Google Scholar 

  49. Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol. 2005;23(19):4347–53.

    Article  CAS  PubMed  Google Scholar 

  50. Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study. J Clin Oncol. 2008;26(16):2630–5.

    Article  CAS  PubMed  Google Scholar 

  51. Wang JG, Guarnaccia M, Weiss SF, Sauer MV, Choi JM. Initial presentation of undiagnosed acute intermittent porphyria as a rare complication of ovulation induction. Fertil Steril. 2006; 86(2):462 e461–63.

    Google Scholar 

  52. Chian RC, Uzelac PS, Nargund G. In vitro maturation of human immature oocytes for fertility preservation. Fertil Steril. 2013;99(5):1173–81.

    Article  CAS  PubMed  Google Scholar 

  53. Lim JH, Yang SH, Xu Y, Yoon SH, Chian RC. Selection of patients for natural cycle in vitro fertilization combined with in vitro maturation of immature oocytes. Fertil Steril. 2009;91(4):1050–5.

    Article  PubMed  Google Scholar 

  54. Humaidan P, Engmann L, Benadiva C. Luteal phase supplementation after gonadotropin-releasing hormone agonist trigger in fresh embryo transfer: the American versus European approaches. Fertil Steril. 2015;103(4):879–85.

    Article  CAS  PubMed  Google Scholar 

  55. Seyhan A, Ata B, Polat M, Son WY, Yarali H, Dahan MH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod. 2013;28(9):2522–8.

    Article  CAS  PubMed  Google Scholar 

  56. Fatemi HM, Popovic-Todorovic B. Implantation in assisted reproduction: a look at endometrial receptivity. Reprod Biomed Online. 2013;27(5):530–8.

    Article  CAS  PubMed  Google Scholar 

  57. Gurbuz AS, Gode F, Ozcimen N, Isik AZ. Gonadotrophin-releasing hormone agonist trigger and freeze-all strategy does not prevent severe ovarian hyperstimulation syndrome: a report of three cases. Reprod Biomed Online. 2014;29(5):541–4.

    Article  PubMed  Google Scholar 

  58. Chian RC, Buckett WM, Abdul Jalil AK, Son WY, Sylvestre C, Rao D, Tan SL. Natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes is a potential approach in infertility treatment. Fertil Steril. 2004;82(6):1675–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. K. Datta MD, MRCOG .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Datta, A.K., Deval, B., Campbell, S., Nargund, G. (2017). Which Women Are Suitable for Natural and Modified Natural Cycle IVF?. In: Chian, RC., Nargund, G., Huang, J. (eds) Development of In Vitro Maturation for Human Oocytes. Springer, Cham. https://doi.org/10.1007/978-3-319-53454-1_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-53454-1_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-53452-7

  • Online ISBN: 978-3-319-53454-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics