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Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study

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Abstract

Introduction

Luteal phase ovarian stimulation (LPOS) has been proven a feasible protocol for infertile patients. High progesterone level in the luteal phase could physiologically inhibit premature luteinizing hormone surge, from which poor ovarian responders (PORs) could obtain benefits. Therefore, we aimed to compare clinical outcomes between LPOS and follicular phase ovarian stimulation (FPOS) protocol in PORs undergoing in vitro fertilization (IVF).

Methods

This prospective pilot study was performed at one tertiary center from January 2016 to October 2017. A total of 60 PORs who met Bologna criteria and undergoing IVF were enrolled. Thirty PORs were allocated to the LPOS group and 30 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics, and pregnancy outcomes were compared between the two groups.

Results

The length of stimulation was significantly longer in the LPOS group than in the FPOS group. The numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, and day-3 embryos were significantly higher in the LPOS group than in the FPOS group. Conversely, we could not find any significant difference for clinical pregnancy rate, ongoing pregnancy rate, abortion rate, and cancellation rate. The multivariate analysis showed that only LPOS (p = 0.007) was significantly associated the possibility to retrieve three or more oocytes, whereas basal follicle-stimulating hormone (FSH) < 8 IU/l (p = 0.103) and antral follicle count (AFC) ≥ 3 (p = 0.143) did not significantly affect this event.

Conclusion

LPOS allows improved oocyte retrieval and oocyte quality in PORs with respect to FPOS, despite comparable pregnancy outcomes. LPOS may be considered a feasible option for oocytes accumulation in PORs.

Trial Registration

ClinicalTrials.gov identifier, NCT03238833

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References

  1. 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;96:1058–61.e7.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Yang S, Chen X, Zhen X, et al. The Prognosis of IVF in Poor Responders Depending on the Bologna Criteria: A Large Sample Retrospective Study from China. Biomed Res Int. 2015;2015:296173.

    PubMed  PubMed Central  Google Scholar 

  4. Polyzos NP, Nwoye M, Corona R, et al. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014;28:469–74.

    Article  PubMed  Google Scholar 

  5. La Marca A, Grisendi V, Giulini S, et al. Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a validation study. J Assist Reprod Genet. 2015;32:931–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sunkara SK, Coomarasamy A, Faris R, Braude P, Khalaf Y. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial. Fertil Steril. 2014;101:147–53.

    Article  PubMed  CAS  Google Scholar 

  7. Hu L, Bu Z, Guo Y, Su Y, Zhai J, Sun Y. Comparison of different ovarian hyperstimulation protocols efficacy in poor ovarian responders according to the Bologna criteria. Int J Clin Exp Med. 2014;7:1128–34.

    PubMed  PubMed Central  Google Scholar 

  8. Kummer NE, Weitzman VN, Benadiva CA, Schmidt DW, Engmann LL, Nulsen JC. In vitro fertilization outcomes in patients experiencing a premature rise in luteinizing hormone during a gonadotropin-releasing hormone antagonist cycle. Fertil Steril. 2011;95:2592–4.

    Article  PubMed  CAS  Google Scholar 

  9. Allegra A, Marino A, Coffaro F, et al. GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial. Hum Reprod. 2007;22:101–8.

    Article  PubMed  CAS  Google Scholar 

  10. Reichman DE, Zakarin L, Chao K, Meyer L, Davis OK, Rosenwaks Z. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril. 2014;102:99–102.

    Article  PubMed  CAS  Google Scholar 

  11. Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine (Baltimore). 2015;94:e909.

    Article  CAS  Google Scholar 

  12. Zhu X, Ye H, Fu Y. Use of Utrogestan during controlled ovarian hyperstimulation in normally ovulating women undergoing in vitro fertilization or intracytoplasmic sperm injection treatments in combination with a “freeze all” strategy: a randomized controlled dose-finding study of 100 mg versus 200 mg. Fertil Steril. 2017;107:379–86.e4.

    Article  PubMed  CAS  Google Scholar 

  13. Kuang Y, Chen Q, Hong Q, et al. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014;29:684–91.

    Article  PubMed  Google Scholar 

  14. Dong J, Wang Y, Chai WR, et al. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017;124:1048–55.

    Article  PubMed  CAS  Google Scholar 

  15. Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012;18:73–91.

    Article  PubMed  Google Scholar 

  16. Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013;100:1673–80.

    Article  PubMed  Google Scholar 

  17. Sönmezer M, Türkçüoğlu I, Coşkun U, Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil Steril. 2011;95:2125.e9–11.

    Article  CAS  Google Scholar 

  18. Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011;95:64–7.

    Article  PubMed  Google Scholar 

  19. von Wolff M, Thaler CJ, Frambach T, et al. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009;92:1360–5.

    Article  CAS  Google Scholar 

  20. Nayak SR, Wakim AN. Random-start gonadotropin-releasing hormone (GnRH) antagonist-treated cycles with GnRH agonist trigger for fertility preservation. Fertil Steril. 2011;96:e51–4.

    Article  PubMed  CAS  Google Scholar 

  21. Kuang Y, Hong Q, Chen Q, et al. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014;101:105–11.

    Article  PubMed  CAS  Google Scholar 

  22. Martinez F, Clua E, Devesa M, et al. Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes. Fertil Steril. 2014;102:1307–11.

    Article  PubMed  CAS  Google Scholar 

  23. Chen H, Wang Y, Lyu Q, et al. Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles. Fertil Steril. 2015;103:1194–201.e2.

    Article  PubMed  CAS  Google Scholar 

  24. Wang N, Wang Y, Kuang Y. Luteal-phase ovarian stimulation vs conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study. Clin Endocrinol (Oxf). 2016;84:720–8.

    Article  CAS  Google Scholar 

  25. Qin N, Chen Q, Hong Q, et al. Flexibility in starting ovarian stimulation at different phases of the menstrual cycle for treatment of infertile women with the use of in vitro fertilization or intracytoplasmic sperm injection. Fertil Steril. 2016;106:334–41.e1.

    Article  PubMed  Google Scholar 

  26. Wang N, Wang Y, Chen Q, et al. Luteal-phase ovarian stimulation vs conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study. Clin Endocrinol (Oxf). 2016;84:720–8.

    Article  CAS  Google Scholar 

  27. Wu Y, Zhao FC, Sun Y, Liu PS. Luteal-phase protocol in poor ovarian response: a comparative study with an antagonist protocol. J Int Med Res. 2017;45:1731–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Wei LH, Ma WH, Tang N, Wei JH. Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol: a retrospective study. Taiwan J Obstet Gynecol. 2016;55:50–4.

    Article  PubMed  Google Scholar 

  29. Li Y, Yang W, Chen X, Li L, Zhang Q, Yang D. Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response. Gynecol Endocrinol. 2016;32:74–7.

    Article  PubMed  CAS  Google Scholar 

  30. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.

    Article  Google Scholar 

  31. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–83.

  32. Zheng Y, Dong X, Huang B, Zhang H, Ai J. The artificial cycle method improves the pregnancy outcome in frozen-thawed embryo transfer: a retrospective cohort study. Gynecol Endocrinol. 2015;31:70–4.

    Article  PubMed  Google Scholar 

  33. Ubaldi F, Vaiarelli A, D’Anna R, Rienzi L. Management of poor responders in IVF: is there anything new? Biomed Res Int. 2014;2014:352098.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Loutradis D, Drakakis P, Vomvolaki E, Antsaklis A. Different ovarian stimulation protocols for women with diminished ovarian reserve. J Assist Reprod Genet. 2007;24:597–611.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Schimberni M, Morgia F, Colabianchi J, et al. Natural-cycle in vitro fertilization in poor responder patients: a survey of 500 consecutive cycles. Fertil Steril. 2009;92:1297–301.

    Article  PubMed  Google Scholar 

  36. Li J, Xu Y, Zhou G, Guo J, Xin N. Natural cycle IVF/IVM may be more desirable for poor responder patients after failure of stimulated cycles. J Assist Reprod Genet. 2011;28:791–5.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kadoch IJ, Phillips SJ, Bissonnette F. Modified natural-cycle in vitro fertilization should be considered as the first approach in young poor responders. Fertil Steril. 2011;96:1066–8.

    Article  PubMed  Google Scholar 

  38. Kato K, Takehara Y, Segawa T, et al. Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort. Reprod Biol Endocrinol. 2012;10:35.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Rombauts L, Suikkari AM, MacLachlan V, Trounson AO, Healy DL. Recruitment of follicles by recombinant human follicle-stimulating hormone commencing in the luteal phase of the ovarian cycle. Fertil Steril. 1998;69:665–9.

    Article  PubMed  CAS  Google Scholar 

  40. Kansal Kalra S, Ratcliffe S, Gracia CR, Martino L, Coutifaris C, Barnhart KT. Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders. Reprod Biomed Online. 2008;17:745–50.

    Article  PubMed  Google Scholar 

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Acknowledgements

We are very grateful to our study participants for their cooperation. The authors wish to acknowledge Dr. Antonio Simone Laganà for his role in data analysis and for the insightful suggestions aimed at improving the manuscript.

Funding

No funding or sponsorship was received for this study or publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Li-Te Lin, Salvatore Giovanni Vitale, San-Nung Chen, Zhi-Hong Wen, Hsiao-Wen Tsai, Chyi-uei Chern, and Kuan-Hao Tsui have nothing to disclose. The authors alone are responsible for the content and writing of the paper.

Compliance with Ethics Guidelines

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institution ethical committee of Kaohsiung Veterans General Hospital and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Data Availability

Available from the corresponding author on reasonable request.

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Correspondence to Salvatore Giovanni Vitale or Kuan-Hao Tsui.

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Lin, LT., Vitale, S.G., Chen, SN. et al. Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study. Adv Ther 35, 847–856 (2018). https://doi.org/10.1007/s12325-018-0713-1

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