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The Ovarian Response After Follicular Versus Luteal Phase Stimulation with a Double Stimulation Strategy

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Abstract

The double-ovarian stimulation strategy has been proposed to optimize the number of oocytes retrieved within the shortest possible timeframe. The objective of this study is to explore the effectiveness of luteal phase (LP) ovarian stimulation as compared to the previous follicular phase (FP) stimulation in a double stimulation strategy. We conducted an observational cohort study of women scheduled for a double stimulation protocol between March 2014 and June 2017, who had completed the FP controlled ovarian stimulation (COS 1) and started the LP stimulation (COS 2) in the same cycle. Women received equivalent daily doses of gonadotropins in combination with GnRH-antagonist protocol for both the COS 1 and the COS 2 performed during the same cycle. Ovulation was triggered using GnRH-agonist in the two stimulations. The primary outcome was the number of oocytes retrieved. A total of 77 patients were included in the analysis. The number of oocytes retrieved after COS 1 was significantly higher than after the COS 2 (5.25 ± 3.38 for COS 1 versus 3.83 ± 3.14 for COS 2; p = 0.001). The duration of the stimulation was significantly shorter, the total dose of injected gonadotropins was significantly lower, and the estradiol level on the trigger day was significantly higher with COS 1 as compared to COS 2. Stimulation during the LP in a double-successive stimulation strategy results in a lower ovarian response as compared to the FP equivalent daily dose stimulation.

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References

  1. Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW. Can you ever collect too many oocytes? Hum Reprod. 2015;30(1):81–7.

    Article  Google Scholar 

  2. Drakopoulos P, Blockeel C, Stoop D, Camus M, Vos MD, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31(2):370–6.

    PubMed  Google Scholar 

  3. Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28(10):2728–34.

    Article  Google Scholar 

  4. Kok JD, Looman CW, Weima SM, te Velde ER. A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome. Digest World Core Med J. 2006;85(4):918–24.

    Google Scholar 

  5. Sunkara SK, Rittenberg V, Rainefenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26(7):1768–74.

    Article  Google Scholar 

  6. Tsampras N, Gould D, Fitzgerald CT. Double ovarian stimulation (DuoStim) protocol for fertility preservation in female oncology patients. Hum Fertil. 2017;20(4):248–53.

    Article  Google Scholar 

  7. Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, et al. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod BioMed Online. 2014;29(6):684–91.

    Article  Google Scholar 

  8. Liu C, Jiang H, Zhang W, Yin H. Double ovarian stimulation during the follicular and luteal phase in women ≥38 years: a retrospective case-control study. Reprod BioMed Online. 2017;35(6):678–84.

    Article  CAS  Google Scholar 

  9. Ubaldi FM, Vaiarelli A, Alviggi C, Trabucco E, Zullo F, Capalbo A, et al. Double stimulation in a single menstrual cycle increases the number of oocytes retrieved in poor prognosis patients undergoing IVF treatment. Prospective study with historical control. Fertil Steril. 2015;104(3):e322–2.

    Article  Google Scholar 

  10. Zhang J. Luteal phase ovarian stimulation following oocyte retrieval: is it helpful for poor responders? Reprod Biol Endocrinol. 2015;13:76.

    Article  Google Scholar 

  11. Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003;80(1):116–22.

    Article  Google Scholar 

  12. Demirtas E, Elizur SE, Holzer H, Gidoni Y, Son WY, Chian RC, et al. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients. Reprod BioMed Online. 2008;17(4):520–3.

    Article  Google Scholar 

  13. Wang Y. Luteal-phase ovarian stimulation versus conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study. Clin Endocrinol. 2015;104(3):e328–8.

    Article  Google Scholar 

  14. Chen H, Wang Y, Lyu Q, Ai A, Fu Y, Tian H, 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(5):1194–1201.e2.

    Article  CAS  Google Scholar 

  15. Martínez F, Clua E, Devesa M, Rodríguez I, Arroyo G, González C, 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(5):1307–11.

    Article  Google Scholar 

  16. von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, et al. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009;92(4):1360–5.

    Article  Google Scholar 

  17. Ubaldi FM, Capalbo A, Vaiarelli A, Cimadomo D, Colamaria S, Alviggi C, et al. Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation. Fertil Steril. 2016;105(6):1488–95.e1.

    Article  Google Scholar 

  18. Alviggi C, Andersen CY, Buhler K, Conforti A, De PG, Esteves SC, et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016;105(6):1452–3.

    Article  Google Scholar 

  19. De Ziegler D, Gayet V, Aubriot FX, Fauque P, Streuli I, Wolf JP, et al. Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes. Fertil Steril. 2010;94(7):2796–9.

    Article  Google Scholar 

  20. Vaiarelli A, Cimadomo D, Trabucco E, Vallefuoco R, Buffo L, Dusi L, 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.

    Article  Google Scholar 

  21. Boots CE, Meister M, Cooper AR, Hardi A, Jungheim ES. Ovarian stimulation in the luteal phase: systematic review and meta-analysis. J Assist Reprod Genet. 2016;33(8):971–80.

    Article  CAS  Google Scholar 

  22. Sighinolfi G, Sunkara SK, La Marca A. New strategies of ovarian stimulation based on the concept of ovarian follicular waves: from conventional to random and double stimulation. Reprod BioMed Online. 2018;37(4):489–97.

    Article  Google Scholar 

  23. Ortega I, García-Velasco JA, Pellicer A. Ovarian manipulation in ART: going beyond physiological standards to provide best clinical outcomes. J Assist Reprod Genet. 2018;35(10):1751–62 https://doi.org/10.1007/s10815-018-1258-6.

    Article  Google Scholar 

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Acknowledgments

The authors wish to thank staff members of our department’s operating room for their expert assistance with data collection. The authors also gratefully acknowledge Valerie Blanchet, Julia Gonnot, and Celie Cervantes for unabatedly managing the patient database.

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Authors and Affiliations

  1. Department of GynaecologyObstetrics II and Reproductive Medicine Paris, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Université Paris Descartes, Paris, France

    Mathilde Bourdon, Pietro Santulli, Chloé Maignien, Louis Marcellin, Yulian Chen & Charles Chapron

  2. Institut Cochin, INSERM U1016, Laboratoire d’immunologie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Mathilde Bourdon, Pietro Santulli & Louis Marcellin

  3. Service d’Histologie-Embryologie-Biologie de la Reproduction, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique – Hôpitaux de Paris (AP- HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Université Paris Descartes, Paris, France

    Khaled Pocate-Cheriet

  4. Institut Cochin, INSERM U1016, Département de “Génetique, Développement et Cancer”, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Louis Marcellin & Charles Chapron

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  1. Mathilde Bourdon
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  2. Pietro Santulli
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  3. Chloé Maignien
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  4. Khaled Pocate-Cheriet
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  5. Louis Marcellin
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  6. Yulian Chen
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  7. Charles Chapron
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Contributions

M.B., P.S. and Y.C. were involved in substantial contributions to conception and design, acquisition of data, drafting and revising the article, and final approval of the version to be published; P.S. and C.C. were involved in substantial contributions to conception and study design, revising the article critically for important intellectual content and final approval of the version to be published; C.M., K.PC., and L.M. were involved in contributions to acquisition of data and final approval of the version to be published.

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Correspondence to Pietro Santulli.

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ESM 1

S1 Table Baseline characteristics of the per protocol (PP) population. IVF in vitro fertilization, BMI body mass index, FSH follicle-stimulating hormone, LH luteinizing hormone, AMH anti-Mϋllerian hormone, AFC antral follicle count – Data are the mean ± standard deviation or n (%), unless specified otherwise; NA not applicable (DOCX 59 kb)

ESM 2

S2 Table Follicular (COS 1) and luteal phase (COS 2) ovarian stimulation characteristics in the subgroup of infertile women. ITT (intention to treat) population, all of the women who had received the COS 1 and started the COS 2 in the subgroup of infertile women (n = 53 women); PP (per protocol) population, all of the women who completed both the COS 1 and 2 in the subgroup of infertile women (n = 47 women); MII, metaphase II oocytes; a at triggering day; Data are the mean ± standard deviation or n (%); p paired Student’s t-test t Student’s t-test (DOCX 51 kb)

ESM 3

S3 Table Follicular (COS 1) and luteal phase (COS 2) ovarian stimulation characteristics in the subgroup of fertility preservation women. ITT (intention to treat) population, all of the women who had received the COS 1 and started the COS 2 in the subgroup of fertility preservation women (n = 24 women); PP (per protocol) population: all of the women who completed both the COS 1 and 2 in the subgroup of fertility preservation women (n = 23 women); MII, metaphase II oocytes; a at triggering day; Data are the mean ± standard deviation or n (%); p paired Student’s t-test t Student’s t-test (DOCX 54 kb)

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Bourdon, M., Santulli, P., Maignien, C. et al. The Ovarian Response After Follicular Versus Luteal Phase Stimulation with a Double Stimulation Strategy. Reprod. Sci. 27, 204–210 (2020). https://doi.org/10.1007/s43032-019-00012-9

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  • DOI: https://doi.org/10.1007/s43032-019-00012-9

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