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Current Therapeutic Options for Controlled Ovarian Stimulation in Assisted Reproductive Technology

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Abstract

Assisted reproduction technologies have substantially advanced since the birth of the first in vitro fertilization baby, and innovations within in vitro fertilization laboratories have been of paramount importance for the overall assisted reproduction technology success rates. However, one of the milestones in the history of in vitro fertilization is irrefutably the introduction of conventional ovarian stimulation. The objective of the present review is to provide an update on conventional ovarian stimulation, by giving an overview of treatment milestones, together with the latest innovations currently being investigated. The realization of an assisted reproduction technology treatment depends on many steps that can be medically manipulated and must be harmoniously combined, starting from the follicular phase and ending with luteal phase support. New technologies in the pharmaceutical sector are fundamental to optimize efficiency and tailor treatment approaches to individual needs. The present review aims to offer physicians a useful summary of the more recent publications and to facilitate the translation of research findings into daily clinical practice.

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References

  1. Polyzos NP, Drakopoulos P, Parra J, Pellicer A, Santos-Ribeiro S, Tournaye H, 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(661–70):e1.

    Google Scholar 

  2. Maheshwari A, McLernon D, Bhattacharya S. Cumulative live birth rate: time for a consensus? Hum Reprod. 2015;30(12):2703–7.

    PubMed  Google Scholar 

  3. Castelló D, Motato Y, Basile N, Remohí J, Espejo-Catena M, Meseguer M. How much have we learned from time-lapse in clinical IVF? Mol Hum Reprod. 2016;22(10):719–27.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  5. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340(8810):17–8.

    CAS  PubMed  Google Scholar 

  6. Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science. 1981;212(4495):681–2.

    CAS  PubMed  Google Scholar 

  7. Edwards RG, Steptoe PC, Purdy JM. Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br J Obstet Gynaecol. 1980;87(9):737–56.

    CAS  PubMed  Google Scholar 

  8. Macklon NS, Stouffer RL, Giudice LC, Fauser BCJM. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006;27(2):170–207.

    PubMed  Google Scholar 

  9. Groenewoud ER, Macklon NS, Cohlen BJ. Cryo-thawed embryo transfer: natural versus artificial cycle: a non-inferiority trial (ANTARCTICA trial). BMC Womens Health. 2012;12:27.

    PubMed  PubMed Central  Google Scholar 

  10. Groenewoud ER, Cantineau AEP, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013;19(5):458–70.

    PubMed  Google Scholar 

  11. Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102(1):19–26.

    CAS  PubMed  Google Scholar 

  12. Drakopoulos P, Blockeel C, Stoop D, Camus M, De Vos M, 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 

  13. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108(3):393–406.

    PubMed  Google Scholar 

  14. Maddock WO, Leach RB, Tokuyama I, Paulsen CA, Roy WR. Effects of hog pituitary follicle-stimulating hormone in women: antihormone formation and inhibition of ovarian function. J Clin Endocrinol Metab. 1956;16(4):433–48.

    CAS  PubMed  Google Scholar 

  15. Gemzell CA. Induction of ovulation with human pituitary gonadotrophins. Fertil Steril. 1962;13:153–68.

    CAS  PubMed  Google Scholar 

  16. Santi D, Casarini L, Alviggi C, Simoni M. Efficacy of follicle-stimulating hormone (FSH) alone, FSH + luteinizing hormone, human menopausal gonadotropin or FSH + human chorionic gonadotropin on assisted reproductive technology outcomes in the “personalized” medicine era: a meta-analysis. Front Endocrinol. 2017;8:114.

    Google Scholar 

  17. Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006;21(12):3217–27.

    CAS  PubMed  Google Scholar 

  18. Devroey P, Pellicer A, Nyboe Andersen A, Arce JC. A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Fertil Steril. 2012;97(3):561–71.

    CAS  PubMed  Google Scholar 

  19. Al-Inany HG, Abou-Setta AM, Aboulghar MA, Mansour RT, Serour GI. Efficacy and safety of human menopausal gonadotrophins versus recombinant FSH: a meta-analysis. Reprod Biomed Online. 2008;16(1):81–8.

    CAS  PubMed  Google Scholar 

  20. van Wely M, Kwan I, Burt AL, Thomas J, Vail A, Van der Veen F, et al. Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles: a Cochrane review. Hum Reprod Update. 2012;18(2):111.

    PubMed  Google Scholar 

  21. ESHRE Reproductive Endocrinology Guidelines Group. Ovarian stimulation for IVF/ICSI: guideline of the European Society of Human Reproduction and Embryology. Belgium: ESHRE; 2019.

    Google Scholar 

  22. Lunenfeld B. Historical perspectives in gonadotrophin therapy. Hum Reprod Update. 2004;10(6):453–67.

    CAS  PubMed  Google Scholar 

  23. Howles CM. Genetic engineering of human FSH (Gonal-F). Hum Reprod Update. 1996;2(2):172–91.

    CAS  PubMed  Google Scholar 

  24. Martinez G, Sanguineti F, Sepulveda J, Dorey J, Arici A, Patrizio P. A comparison between follitropin α filled by mass and follitropin a filled by bioassay in the same egg donors. Reprod Biomed Online. 2011;22(S1):S20–S2222.

    PubMed  Google Scholar 

  25. Lunenfeld B, Bilger W, Longobardi S, Alam V, D’Hooghe T, Sunkara S. The development of gonadotropins for clinical use in the treatment of infertility. Front Endocrinol. 2019;10:429.

    Google Scholar 

  26. Tulppala M, Milla A, Tuuri T, Vilska S, Foudila T, Hakala-Ala-Pietilä T, et al. Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study. Hum Reprod. 1999;14(11):2709–15.

    CAS  PubMed  Google Scholar 

  27. Bordewijk EM, Mol F, van der Veen F, Van Wely M. Required amount of rFSH, HP-hMG and HP-FSH to reach a live birth: a systematic review and meta-analysis. Hum Reprod Open. 2019;2019(3):1–12.

    Google Scholar 

  28. The European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endocrinol Metab. 1998;83(5):1507–14.

    Google Scholar 

  29. Lehert P, Kolibianakis EM, Venetis CA, Schertz J, Saunders H, Arriagada P, et al. Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis. Reprod Biol Endocrinol. 2014;12:17.

    PubMed  PubMed Central  Google Scholar 

  30. Humaidan P, Chin W, Rogoff D, D’Hooghe T, Longobardi S, Hubbard J, et al. Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders. Hum Reprod. 2017;32(7):1537–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015;30(9):2005–8.

    CAS  PubMed  Google Scholar 

  32. Polyzos NP, Drakopoulos P. Management strategies for POSEIDON’s Group 1. Front Endocrinol. 2019;10:679.

    Google Scholar 

  33. Alviggi C, Conforti A, Esteves SC, Andersen CY, Bosch E, Buhler K, et al. Recombinant luteinizing hormone supplementation in assisted reproductive technology: a systematic review. Fertil Steril. 2018;109(4):644–64.

    CAS  PubMed  Google Scholar 

  34. Fares FA, Suganuma N, Nishimori K, LaPolt PS, Hsueh AJ, Boime I. Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit. Proc Natl Acad Sci USA. 1992;89(10):4304–8.

    CAS  PubMed  Google Scholar 

  35. Boostanfar R, Shapiro B, Levy M, Rosenwaks Z, Witjes H, Stegmann BJ, et al. Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation pr. Fertil Steril. 2015;104(1):94–103.e1.

    CAS  PubMed  Google Scholar 

  36. Devroey P, Boostanfar R, Koper NP, Mannaerts BMJL, Ijzerman-Boon PC, Fauser BCJM. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009;24(12):3063–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Griesinger G, Boostanfar R, Gordon K, Gates D, McCrary Sisk C, Stegmann BJ. Corifollitropin alfa versus recombinant follicle-stimulating hormone: an individual patient data meta-analysis. Reprod Biomed Online. 2016;33(1):56–60.

    CAS  PubMed  Google Scholar 

  38. Corifollitropin alfa Ensure Study Group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online. 2010;21(1):66–76.

    Google Scholar 

  39. Drakopoulos P, Vuong TNL, Ho NAV, Vaiarelli A, Ho MT, Blockeel C, et al. Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial. Hum Reprod. 2017;32(11):2225–33.

    CAS  PubMed  Google Scholar 

  40. Polyzos NP, Corona R, Van De Vijver A, Blockeel C, Drakopoulos P, Vloeberghs V, et al. Corifollitropin alfa followed by hpHMG in GnRH agonist protocols: two prospective feasibility studies in poor ovarian responders. Gynecol Endocrinol. 2015;31(11):885–90.

    CAS  PubMed  Google Scholar 

  41. Errazuriz J, Romito A, Drakopoulos P, Frederix B, Racca A, De Munck N, et al. Cumulative live birth rates following stimulation with corifollitropin alfa compared with hp-hMG in a GnRH antagonist protocol in poor ovarian responders. Front Endocrinol. 2019;10:175.

    Google Scholar 

  42. 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):124–40.

    PubMed  Google Scholar 

  43. Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-Müllerian hormone and antral follicle count as biomarkers of ovarian response. Hum Reprod Update. 2015;21(6):698–710.

    CAS  PubMed  Google Scholar 

  44. Nyboe Andersen A, Nelson SM, Fauser BCJM, García-Velasco JA, Klein BM, Arce JC, et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017;107(2):387–96.e4.

    CAS  PubMed  Google Scholar 

  45. Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, et al. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind phase 3 safety trial. Reprod Biomed Online. 2019;38(2):195–205.

    CAS  PubMed  Google Scholar 

  46. Barbieri RL. The endocrinology of the menstrual cycle. Methods Mol Biol. 2014;1154:145–69.

    CAS  PubMed  Google Scholar 

  47. Fleming R, Adam AH, Barlow DH, Black WP, MacNaughton MC, Coutts JR. A new systematic treatment for infertile women with abnormal hormone profiles. Br J Obstet Gynaecol. 1982;89(1):80–3.

    CAS  PubMed  Google Scholar 

  48. Huirne JAF, Lambalk CB. New drug classes gonadotropin-releasing-hormone-receptor antagonists. Lancet. 2001;358(9295):1793–803.

    CAS  PubMed  Google Scholar 

  49. Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in-vitro fertilisation using buserelin and gonadotropins. Lancet. 1984;324(8414):1284–5.

    Google Scholar 

  50. Lambalk CB, Banga FR, Huirne JA, Toftager M, Pinborg A, Homburg R, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017;23(5):560–79.

    CAS  PubMed  Google Scholar 

  51. Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4:CD001750.

    PubMed  Google Scholar 

  52. Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update. 2006;12(2):159–68.

    CAS  PubMed  Google Scholar 

  53. Youssef M, Van Der Veen F, Van Wely M. GnRHa to trigger final oocyte maturation: a time to reconsider. Hum Reprod. 2010;25(2):559.

    CAS  PubMed  Google Scholar 

  54. Kol S, Humaidan P, Alsbjerg B, Engmann L, Benadiva C, Garcia-Velasco JA, et al. The updated Cochrane review 2014 on GnRH agonist trigger: repeating the same errors. Reprod Biomed Online. 2015;30(6):563–5.

    CAS  PubMed  Google Scholar 

  55. Casper RF. Introduction: gonadotropin-releasing hormone agonist triggering of final follicular maturation for in vitro fertilization. Fertil Steril. 2015;103(4):865–6.

    PubMed  Google Scholar 

  56. Kolibianakis EM, Schultze-Mosgau A, Schroer A, van Steirteghem A, Devroey P, Diedrich K, et al. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists. Hum Reprod. 2005;20(10):2887–922.

    CAS  PubMed  Google Scholar 

  57. Humaidan P, Polyzos NP, Alsbjerg B, Erb K, Mikkelsen AL, Elbaek HO, et al. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod. 2013;28(9):2511–21.

    CAS  PubMed  Google Scholar 

  58. Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26(10):2593–7.

    PubMed  Google Scholar 

  59. Toftager M, Bogstad J, Løssl K, Prætorius L, Zedeler A, Bryndorf T, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017;32(3):556–67.

    CAS  PubMed  Google Scholar 

  60. Wildt L, Hutchison S, Marshall G, Pohl R, Knobil E. On the site of action of progesterone in the blockade of the estradiol-induced gonadotropin discharge in the rhesus monkey. Endocrinology. 1981;109(4):1293–4.

    CAS  PubMed  Google Scholar 

  61. Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017;23(2):211–20.

    CAS  PubMed  Google Scholar 

  62. 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.

    PubMed  Google Scholar 

  63. Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015;104(1):62–70.e3.

    CAS  PubMed  Google Scholar 

  64. Chen Q, Wang Y, Sun L, Zhang S, Chai W, Hong Q, et al. Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders. Reprod Biol Endocrinol. 2017;15(1):1–9.

    CAS  Google Scholar 

  65. Beguería R, García D, Vassena R, Rodríguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019;34(5):872–80.

    PubMed  Google Scholar 

  66. 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.

    PubMed  PubMed Central  Google Scholar 

  67. Nargund G, Datta AK, Fauser BCJM. Mild stimulation for in vitro fertilization. Fertil Steril. 2017;108(4):558–67.

    PubMed  Google Scholar 

  68. Labarta E, MartÍnez-Conejero JA, Alamá P, Horcajadas JA, Pellicer A, Simón C, et al. 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;26:1813–25.

    CAS  PubMed  Google Scholar 

  69. Simón C, Cano F, Valbuena D, Remohí J, Pellicer A. Implantation: 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.

    PubMed  Google Scholar 

  70. 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.

    CAS  PubMed  Google Scholar 

  71. Teramoto S, Kato O. Minimal ovarian stimulation with clomiphene citrate: a large-scale retrospective study. Reprod Biomed Online. 2007;15(2):134–48.

    CAS  PubMed  Google Scholar 

  72. Yilmaz S, Yilmaz Sezer N, Gönenç IM, Ilhan SE, Yilmaz E. Safety of clomiphene citrate: a literature review. Cytotechnology. 2018;70(2):489–95.

    CAS  PubMed  Google Scholar 

  73. Bechtejew TN, Nadai MN, Nastri CO, Martins WP. Clomiphene citrate and letrozole to reduce follicle-stimulating hormone consumption during ovarian stimulation: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017;50(3):315–23.

    CAS  PubMed  Google Scholar 

  74. Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol. 2005;23(3):619–29.

    CAS  PubMed  Google Scholar 

  75. Akhtar M, Njar VCO, Neville WJ. Mechanistic studies on aromatase and related C–C bond cleaving P-450 enzymes. J Steroid Biochem Mol Biol. 1993;44(4–6):375–87.

    CAS  PubMed  Google Scholar 

  76. Mitwally MF, Casper RF. Aromatase inhibitors in ovulation induction. Semin Reprod Med. 2004;22(1):61–78.

    CAS  PubMed  Google Scholar 

  77. Fauser B, Devroey P, Yen SSC, Gosden R, Crowley WF, Baird DT, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod. 1999;14(11):2681–6.

    CAS  PubMed  Google Scholar 

  78. Revelli A, Chiadò A, Dalmasso P, Stabile V, Evangelista F, Basso G, et al. “Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial. J Assist Reprod Genet. 2014;31(7):809–15.

    PubMed  PubMed Central  Google Scholar 

  79. Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, et al. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod. 2004;19(9):2031–5.

    CAS  PubMed  Google Scholar 

  80. Bastu E, Buyru F, Ozsurmeli M, Demiral I, Dogan M, Yeh J. A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response. Eur J Obstet Gynecol Reprod Biol. 2016;203:30–4.

    CAS  PubMed  Google Scholar 

  81. Biljan M, Hemmings R, Brassard N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertil Steril. 2005;84(Suppl. 1):S95.

    Google Scholar 

  82. Shao Y-H, Tulandi T. Letrozole and unexplained infertility: a contemporary meta-analysis. J Obstet Gynaecol Can. 2019;41(6):832–4.

    PubMed  Google Scholar 

  83. Lainas TG, Sfontouris IA, Venetis CA, Lainas GT, Zorzovilis IZ, Tarlatzis BC, et al. 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.

    CAS  PubMed  Google Scholar 

  84. Ferraretti AP, La Marca A, Fauser BCJM, 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(7):1616–24.

    CAS  Google Scholar 

  85. Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, 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.

    PubMed  Google Scholar 

  86. Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update. 2003;9(1):61–766.

    CAS  PubMed  Google Scholar 

  87. Morgia F, Sbracia M, Schimberni M, Giallonardo A, Piscitelli C, Giannini P, et al. 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.

    CAS  PubMed  Google Scholar 

  88. Polyzos NP, Blockeel C, Verpoest W, De Vos M, Stoop D, Vloeberghs V, et al. 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.

    CAS  PubMed  Google Scholar 

  89. Busnelli A, Papaleo E, Del Prato D, La Vecchia I, Iachini E, Paffoni A, et al. A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria. Hum Reprod. 2015;30(2):315–22.

    PubMed  Google Scholar 

  90. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol. 1999;181(5 Pt 1):1263–9.

    CAS  PubMed  Google Scholar 

  91. Taylor H, Pal L, Seli E. Speroff’s clinical gynecologic endocrinology and infertility. 9th ed. Philadelphia: Wolters Kluwer Health; 2019.

    Google Scholar 

  92. Goldzieher JW, Stanczyk FZ. Oral contraceptives and individual variability of circulating levels of ethinyl estradiol and progestins. Contraception. 2008;78(1):4–9.

    CAS  PubMed  Google Scholar 

  93. Huirne JAF, van Loenen ACD, Donnez J, Pirard C, Homburg R, Schats R, et al. Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study. Reprod Biomed Online. 2006;13(2):235–45.

    CAS  PubMed  Google Scholar 

  94. Cédrin-Durnerin I, Bständig B, Parneix I, Bied-Damon V, Avril C, Decanter C, et al. Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol. Hum Reprod. 2007;22(1):109–16.

    PubMed  Google Scholar 

  95. Rombauts L, Healy D, Norman RJ, Speirs A, Watkins B, Yovich J, et al. A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients. Hum Reprod. 2006;21(1):95–103.

    CAS  PubMed  Google Scholar 

  96. Barmat LI, Chantilis SJ, Hurst BS, Dickey RP. A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization. Fertil Steril. 2005;83(2):321–30.

    CAS  PubMed  Google Scholar 

  97. Kolibianakis EM, Papanikolaou EG, Camus M, Tournaye H, Van Steirteghem AC, Devroey P. Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial. Hum Reprod. 2006;21(2):352–7.

    CAS  PubMed  Google Scholar 

  98. Biljan MM, Mahutte NG, Dean N, Hemmings R, Bissonnette F, Tan SL. Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent implantation and pregnancy rates. Fertil Steril. 1998;70(6):1063–9.

    CAS  PubMed  Google Scholar 

  99. Garcia-Velasco JA, Bermejo A, Ruiz F, Martinez-Salazar J, Requena A, Pellicer A. Cycle scheduling with oral contraceptive pills in the GnRH antagonist protocol vs the long protocol: a randomized, controlled trial. Fertil Steril. 2011;96(3):590–3.

    CAS  PubMed  Google Scholar 

  100. Huirne JA, Hugues JN, Pirard C, Fischl F, Sage JC, Pouly JL, et al. Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb study. Hum Reprod. 2006;21(6):1408–15.

    CAS  PubMed  Google Scholar 

  101. Farquhar C, Rombauts L, Kremer JAM, Lethaby A, Ayeleke RO. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2017;5:CD006109.

    PubMed  Google Scholar 

  102. Kim CH, You RM, Kang HJ, Ahn JW, Jeon I, Lee JW, et al. GnRH antagonist multiple dose protocol with oral contraceptive pill pretreatment in poor responders undergoing IVF/ICSI. Clin Exp Reprod Med. 2011;38(4):228–33.

    PubMed  PubMed Central  Google Scholar 

  103. Bakas P, Hassiakos D, Grigoriadis C, Vlahos NF, Liapis A, Creatsas G. Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old. Gynecol Endocrinol. 2014;30(11):825–9.

    CAS  PubMed  Google Scholar 

  104. Pan JX, Liu Y, Ke ZH, Zhou CL, Meng Q, Ding GL, et al. Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess. Gynecol Endocrinol. 2015;31(4):332–6.

    CAS  PubMed  Google Scholar 

  105. Özmen B, Şükür YE, Seval MM, Ateş C, Atabekoʇlu CS, Sönmezer M, et al. Dual suppression with oral contraceptive pills in GnRH antagonist cycles for patients with polycystic ovary syndrome undergoing intracytoplasmic sperm injection. Eur J Obstet Gynecol Reprod Biol. 2014;183:137–40.

    PubMed  Google Scholar 

  106. Hwang JL, Seow KM, Lin YH, Huang LW, Hsieh BC, Tsai YL, et al. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod. 2004;19(9):1993–2000.

    CAS  PubMed  Google Scholar 

  107. Decanter C, Robin G, Thomas P, Leroy M, Lefebvre C, Soudan B, et al. First intention IVF protocol for polycystic ovaries: does oral contraceptive pill pretreatment influence COH outcome? Reprod Biol Endocrinol. 2013;11(1):1–9.

    Google Scholar 

  108. Wei D, Shi Y, Li J, Wang Z, Zhang L, Sun Y, et al. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome. Hum Reprod. 2017;32(2):354–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Bellver J, Albert C, Labarta E, Pellicer A. Early pregnancy loss in women stimulated with gonadotropin-releasing hormone antagonist protocols according to oral contraceptive pill pretreatment. Fertil Steril. 2007;87(5):1098–101.

    CAS  PubMed  Google Scholar 

  110. Andersen AN, Witjes H, Gordon K, Mannaerts B. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod. 2011;26(12):3413–23.

    CAS  PubMed  Google Scholar 

  111. Montoya-Botero P, Martinez F, Rodríguez-Purata J, Rodríguez I, Coroleu B, Polyzos N. The effect of type of oral contraceptive pill and duration of use on fresh and cumulative live birth rates in IVF/ICSI cycles. Hum Reprod. 2020;35(4):826–36.

    PubMed  Google Scholar 

  112. Guivarc’h-Levêque A, Homer L, Arvis P, Broux PL, Moy L, Priou G, et al. Programming in vitro fertilization retrievals during working days after a gonadotropin-releasing hormone antagonist protocol with estrogen pretreatment: does the length of exposure to estradiol impact on controlled ovarian hyperstimulation outcomes? Fertil Steril. 2011;96(4):872–6.

    PubMed  Google Scholar 

  113. Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003;18(12):2698–703.

    CAS  PubMed  Google Scholar 

  114. Fanchin R, Cunha-Filho JS, Schonäuer LM, Kadoch IJ, Cohen-Bacri P, Frydman R. Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens. Fertil Steril. 2003;79(2):316–21.

    PubMed  Google Scholar 

  115. Cédrin-Durnerin I, Guivarc’h-Levêque A, Hugues JN. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012;97(6):1359–64.e1.

    PubMed  Google Scholar 

  116. Blockeel C, Engels S, De Vos M, Haentjens P, Polyzos NP, Stoop D, et al. Oestradiol valerate pretreatment in GnRH-antagonist cycles: a randomized controlled trial. Reprod Biomed Online. 2012;24(3):272–80.

    CAS  PubMed  Google Scholar 

  117. Dragisic KG, Davis OK, Fasouliotis SJ, Rosenwaks Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. Fertil Steril. 2005;84(4):1023–6.

    CAS  PubMed  Google Scholar 

  118. Chang EM, Han JE, Won HJ, Kim YS, Yoon TK, Lee WS. Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization. J Assist Reprod Genet. 2012;29(3):225–30.

    PubMed  Google Scholar 

  119. Shastri SM, Barbieri E, Kligman I, Schoyer KD, Davis OK, Rosenwaks Z. Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide. Fertil Steril. 2011;95(2):592–5.

    CAS  PubMed  Google Scholar 

  120. Griesinger G, Felberbaum R, Diedrich K. GnRH-antagonists in reproductive medicine. Arch Gynecol Obstet. 2005;273(2):71–8.

    CAS  PubMed  Google Scholar 

  121. Fanchin R, Branco AC, Kadoch IJ, Hosny G, Bagirova M, Frydman R. Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation. Fertil Steril. 2004;81(6):1554–9.

    CAS  PubMed  Google Scholar 

  122. Blockeel C, Riva A, De Vos M, Haentjens P, Devroey P. Administration of a gonadotropin-releasing hormone antagonist during the 3 days before the initiation of the in vitro fertilization/intracytoplasmic sperm injection treatment cycle: impact on ovarian stimulation: a pilot study. Fertil Steril. 2011;95(5):1714–9.e2.

    CAS  PubMed  Google Scholar 

  123. Viardot-Foucault V, Nadarajah S, Lye WK, Tan HH. GnRH antagonist pre-treatment: one centre’s experience for IVF-ICSI cycle scheduling. Reprod Biomed Online. 2015;30(4):366–72.

    CAS  PubMed  Google Scholar 

  124. Castillo JC, Humaidan P, Bernabeu R. Pharmaceutical options for triggering of final oocyte maturation in ART. Biomed Res Int. 2014;2014:580171.

    PubMed  PubMed Central  Google Scholar 

  125. Humaidan P, Nelson SM, Devroey P, Coddington CC, Schwartz LB, Gordon K, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod. 2016;31(9):1997–2004.

    CAS  PubMed  Google Scholar 

  126. Casarini L, Lispi M, Longobardi S, Milosa F, La Marca A, Tagliasacchi D, et al. LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling. PLoS One. 2012;7(10):e46682.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Abbara A, Clarke SA, Dhillo WS. Novel concepts for inducing final oocyte maturation in in vitro fertilization treatment. Endocr Rev. 2018;39(5):593–628.

    PubMed  PubMed Central  Google Scholar 

  128. Induction of final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment: recombinant HCG versus urinary HCG. The European Recombinant Human Chorionic Gonadotrophin Study Group. Hum Reprod. 2000;15(7):1446–51.

  129. Chang P, Kenley S, Burns T, Denton G, Currie K, DeVane G, et al. Recombinant human chorionic gonadotropin (rhCG) in assisted reproductive technology: results of a clinical trial comparing two doses of rhCG (Ovidrel) to urinary hCG (Profasi) for induction of final follicular maturation in in vitro fertilization-embryo t. Fertil Steril. 2001;76(1):67–74.

    CAS  PubMed  Google Scholar 

  130. Youssef MA, Abou-Setta AM, Lam WS. Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles. Cochrane Database Syst Rev. 2016;4:CD003719.

    PubMed  Google Scholar 

  131. Nakano R, Mizuno T, Kotsuji F, Katayama K, Wshio M, Tojo S. “Triggering” of ovulation after infusion of synthetic luteinizing hormone releasing factor (LRF). Acta Obstet Gynecol Scand. 1973;52(3):269–72.

    CAS  PubMed  Google Scholar 

  132. Gonen Y, Balakier H, Powell W, Casper RF. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab. 1990;71(4):918–22.

    CAS  PubMed  Google Scholar 

  133. Itskovitz J, Boldes R, Levron J, Erlik Y, Kahana L, Brandes JM. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril. 1991;56(2):213–20.

    CAS  PubMed  Google Scholar 

  134. Atef A, Francois P, Christian V, Marc-Andre S. The potential role of gap junction communication between cumulus cells and bovine oocytes during in vitro maturation. Mol Reprod Dev. 2005;71(3):358–67.

    CAS  PubMed  Google Scholar 

  135. Kol S. Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome. Fertil Steril. 2004;81(1):1–5.

    CAS  PubMed  Google Scholar 

  136. Blockeel C, Drakopoulos P, Santos-Ribeiro S, Polyzos NP, Tournaye H. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016;31(3):491–7.

    PubMed  Google Scholar 

  137. Oktay K, Turkcuoglu I, Rodriguez-Wallberg KA. GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. Reprod Biomed Online. 2010;20(6):783–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Fauser BC, de Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J, et al. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002;87(2):709–15.

    CAS  PubMed  Google Scholar 

  139. Griffin D, Feinn R, Engmann L, Nulsen J, Budinetz T, Benadiva C. Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril. 2014;102(2):405–9.

    CAS  PubMed  Google Scholar 

  140. Son WY, Chung JT, Chian RC, Herrero B, Demirtas E, Elizur S, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008;23(9):2010–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Fabris AM, Cruz M, Legidos V, Iglesias C, Muñoz M, García-Velasco JA. Dual triggering with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin in patients with a high immature oocyte rate. Reprod Sci. 2017;24(8):1221–5.

    CAS  PubMed  Google Scholar 

  142. Ben-Haroush A, Sapir O, Salman L, Altman E, Garor R, Margalit T, et al. Does “dual trigger” increase oocyte maturation rate? J Obstet Gynaecol. 2019;71:1–3.

    Google Scholar 

  143. Kasum M, Kurdija K, Orešković S, Čehić E, Pavičić-Baldani D, Škrgatić L. Combined ovulation triggering with GnRH agonist and hCG in IVF patients. Gynecol Endocrinol. 2016;32(11):861–5.

    CAS  PubMed  Google Scholar 

  144. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Thomas S. Gonadotropin-releasing hormone agonist combined with a reduced dose of human chorionic gonadotropin for final oocyte maturation in fresh autologous cycles of in vitro fertilization. Fertil Steril. 2008;90(1):231–3.

    CAS  PubMed  Google Scholar 

  145. Humaidan P, Bungum L, Bungum M, Andersen CY. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online. 2006;13(2):173–8.

    CAS  PubMed  Google Scholar 

  146. Santos-Ribeiro S, Mackens S, Popovic B, Polyzos N, Racca A, Drakopoulos P, et al. Implantation enhancement by elective cryopreservation of all viable embryos (ICE): randomized controlled trial (RCT) comparing the two safest approaches in IVF/ICSI for high-responders. Hum Reprod. 2018;33:110.

    Google Scholar 

  147. Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92(3):1235–316.

    CAS  PubMed  Google Scholar 

  148. Jayasena CN, Comninos AN, Narayanaswamy S, Bhalla S, Abbara A, Ganiyu-Dada Z, et al. Acute and chronic effects of kisspeptin-54 administration on GH, prolactin and TSH secretion in healthy women. Clin Endocrinol (Oxf). 2014;81(6):891–8.

    CAS  Google Scholar 

  149. Jayasena CN, Abbara A, Comninos AN, Nijher GMK, Christopoulos G, Narayanaswamy S, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Investig. 2014;124(8):3667–77.

    CAS  PubMed  Google Scholar 

  150. Dosouto C, Haahr T, Humaidan P. Advances in ovulation trigger strategies. Panminerva Med. 2019;61(1):42–51.

    PubMed  Google Scholar 

  151. Fatemi HM, Popovic-Todorovic B, Papanikolaou E, Donoso P, Devroey P. An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update. 2007;13(6):581–90.

    CAS  PubMed  Google Scholar 

  152. Csapo AI, Pulkkinen MO, Ruttner B, Sauvage J, Wiest W. The significance of the human corpus luteum in pregnancy maintenance: I. Preliminary studies. Am J Obs Gynecol. 1972;112(8):1061–7.

    CAS  Google Scholar 

  153. Smitz J, Devroey P, Camus M, Deschacht J, Khan I, Staessen C, et al. The luteal phase and early pregnancy after combined GnRH-agonist/HMG treatment for superovulation in IVF or GIFT. Hum Reprod. 1988;3(5):585–90.

    CAS  PubMed  Google Scholar 

  154. Beckers NG, Laven JS, Eijkemans MJ, Fauser BC. Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization. Hum Reprod. 2000;15(1):43–9.

    CAS  PubMed  Google Scholar 

  155. Delcour C, Robin G, Delesalle A-S, Drumez E, Plouvier P, Dewailly D, et al. Weekly intramuscular progesterone for luteal phase support in women receiving oocyte donation is associated with a decreased miscarriage rate. Reprod Biomed Online. 2019;39(3):446–51.

    CAS  PubMed  Google Scholar 

  156. Miles R, Paulson R, Lobo R, Press M, Dahmoush L, Sauer M. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994;62(3):485–90.

    CAS  PubMed  Google Scholar 

  157. Bulletti C, De Ziegler D, Flamigni C, Giacomucci E, Polli V, Bolelli G, et al. Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod. 1997;12(5):1073–9.

    CAS  PubMed  Google Scholar 

  158. Cicinelli E, De Ziegler D. New hypotheses. Transvaginal progesterone: evidence for a new functional 'portal system' flowing from the vagina to the uterus. Hum Reprod Update. 1999;5(4):365–72.

    CAS  PubMed  Google Scholar 

  159. van der Linden M, Buckingham K, Farquhar C, Kremer JAM, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015;7:CD009154.

    Google Scholar 

  160. Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014;29(8):1706–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Schindler AE. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas. 2009;65(Suppl. 1):S3–11.

    CAS  PubMed  Google Scholar 

  162. Tournaye H, Sukhikh GT, Kahler E, Griesinger G. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017;32(5):1019–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Griesinger G, Blockeel C, Sukhikh G, Patki A, Dhorepatil B, Yang D-Z, et al. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018;123:10–87.

    Google Scholar 

  164. Yang D-Z, Griesinger G, Wang W, Gong F, Liang X, Zhang H, et al. A phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): results from the Chinese mainland subpopulation. Gynecol Endocrinol. 2019;3:1–9.

    Google Scholar 

  165. Watters M, Noble M, Child T, Nelson S. Short versus extended progesterone supplementation for luteal phase support in fresh IVF cycles: a systematic review and meta-analysis. Reprod Biomed Online. 2019;40(1):143–50.

    PubMed  Google Scholar 

  166. Soliman S, Daya M, Collins J, Hughes E. The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. Fertil Steril. 1994;61(6):1068–76.

    CAS  PubMed  Google Scholar 

  167. Mochtar MH, Hogerzeil HV, Mol BW. Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial. Hum Reprod. 1996;11(8):1602–5.

    CAS  PubMed  Google Scholar 

  168. Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002;17(9):2287–99.

    CAS  PubMed  Google Scholar 

  169. Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;3:CD004830.

    Google Scholar 

  170. Fatemi HM, Popovic-Todorovic B, Humaidan P, Kol S, Banker M, Devroey P, et al. Severe ovarian hyperstimulation syndrome after gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze-all” approach in GnRH antagonist protocol. Fertil Steril. 2014;101(4):1008–111.

    CAS  PubMed  Google Scholar 

  171. Haahr T, Roque M, Esteves SC, Humaidan P. GnRH agonist trigger and LH activity luteal phase support versus hCG trigger and conventional luteal phase support in fresh embryo transfer IVF/ICSI cycles-a systematic PRISMA review and meta-analysis. Front Endocrinol (Lausanne). 2017;8:116.

    Google Scholar 

  172. Pirard C, Donnez J, Loumaye E. GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study. Hum Reprod. 2006;21(7):1894–900.

    CAS  PubMed  Google Scholar 

  173. Tesarik J, Hazout A, Mendoza C. Luteinizing hormone affects uterine receptivity independently of ovarian function. Reprod Biomed Online. 2003;7(1):59–64.

    CAS  PubMed  Google Scholar 

  174. Bar-Hava I, Mizrachi Y, Karfunkel-Doron D, Omer Y, Sheena L, Carmon N, et al. Intranasal gonadotropin-releasing hormone agonist (GnRHa) for luteal-phase support following GnRHa triggering, a novel approach to avoid ovarian hyperstimulation syndrome in high responders. Fertil Steril. 2016;106(2):330–3.

    CAS  PubMed  Google Scholar 

  175. Wiser A, Klement AH, Shavit T, Berkovitz A, Koren RR, Gonen O, et al. Repeated GnRH agonist doses for luteal support: a proof of concept. Reprod Biomed Online. 2019;39(5):770–6.

    CAS  PubMed  Google Scholar 

  176. Çakar E, Tasan HA, Kumru P, Cogendez E, Usal NT, Kutlu HT, et al. Combined use of oestradiol and progesterone to support luteal phase in antagonist intracytoplasmic sperm injection cycles of normoresponder women: a case-control study. J Obstet Gynaecol. 2019;104:1–6.

    Google Scholar 

  177. Farhi J, Weissman A, Steinfeld Z, Shorer M, Nahum H, Levran D. Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2000;73(4):761–6.

    CAS  PubMed  Google Scholar 

  178. Drakakis P, Loutradis D, Vomvolaki E, Stefanidis K, Kiapekou E, Anagnostou E, et al. Luteal estrogen supplementation in stimulated cycles may improve the pregnancy rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer. Gynecol Endocrinol. 2007;23(11):645–52.

    CAS  PubMed  Google Scholar 

  179. Ghanem ME, Sadek EE, Elboghdady LA, Helal AS, Gamal A, Eldiasty A, et al. The effect of luteal phase support protocol on cycle outcome and luteal phase hormone profile in long agonist protocol intracytoplasmic sperm injection cycles: a randomized clinical trial. Fertil Steril. 2009;92(2):486–93.

    CAS  PubMed  Google Scholar 

  180. Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008;89(3):554–61.

    CAS  PubMed  Google Scholar 

  181. Fatemi H, Kolibianakis E, Camus M, Tournaye H, Donoso P, Papanikolaou E, et al. Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial. Hum Reprod. 2006;21(10):2628–32.

    CAS  PubMed  Google Scholar 

  182. Kwon S-K, Kim C-H, Lee K-H, Jeon IK, Ahn J-W, Kim S-H, et al. Luteal estradiol supplementation in gonadotropin-releasing hormone antagonist cycles for infertile patients in vitro fertilization. Clin Exp Reprod Med. 2013;40(3):131–4.

    PubMed  PubMed Central  Google Scholar 

  183. Huang N, Situ B, Chen X, Liu J, Yan P, Kang X, et al. Meta-analysis of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2015;103(2):367–73.e5.

    CAS  PubMed  Google Scholar 

  184. Ismail Madkour WA, Noah B, Abdel Hamid AMS, Zaheer H, Al-Bahr A, Shaeer M, et al. Luteal phase support with estradiol and progesterone versus progesterone alone in GnRH antagonist ICSI cycles: a randomized controlled study. Hum Fertil (Camb). 2016;19(2):142–9.

    CAS  Google Scholar 

  185. Leão Rogériode Barros F, Esteves Sandro C. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics. https://doi.org/10.6061/clinics/2014(04)10. Available from: https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322014000400279&lng=en

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Authors and Affiliations

  1. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

    Annalisa Racca & Panagiotis Drakopoulos

  2. Department of Surgical and Clinical Science, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium

    Annalisa Racca & Panagiotis Drakopoulos

  3. Department of Reproductive Medicine, Dexeus University Hospital, Barcelona, Spain

    Ana Raquel Neves & Nikolaos P. Polyzos

  4. Coimbra Hospital and University Centre, Coimbra, Portugal

    Ana Raquel Neves

  5. Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Nikolaos P. Polyzos

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  1. Annalisa Racca
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Racca Annalisa, Drakopoulos Panagiotis, Neves Ana Raquel, and Polyzos P. Nikolaos have no conflicts of interest that are directly relevant to the content of this article.

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Racca, A., Drakopoulos, P., Neves, A.R. et al. Current Therapeutic Options for Controlled Ovarian Stimulation in Assisted Reproductive Technology. Drugs 80, 973–994 (2020). https://doi.org/10.1007/s40265-020-01324-w

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