Effects of GnRH Antagonist/Letrozole Stimulation Protocol on Outcomes of Intracytoplasmic Sperm Injection Cycles in Poor Ovarian Responders

Yıl 2018, , 13 - 17, 01.05.2018

İşıl Kasapoğlu , Pınar Türk Cihan Çakır , Esra Şen , Berrin Avcı , Gürkan Uncu

https://doi.org/10.32708/uutfd.429393

Öz

In this retrospective study it was aimed to compare the effects of letrozole added GnRH antagonist controlled ovarian hyperstimulation (COH) protocol to the intracytoplasmic sperm injection (ICSI) cycle outcomes comparing with previous antagonist COH cycles, in patients with diminished ovarian reserve (DOR) and who did not achieved live birth, Twenty-six patients who underwent COH for ICSI between June 2013 and December 2015 were included in the study. Using the electronic database, the COH protocol characterictics of 26 patients who underwent ICSI with indications of DOR were determined. When letrozole was added in the early follicular phase to the conventional antagonist stimulation protocol, in 26 patients previously performed embryo transfer resulting without live birth , total gonadotrophine dose used was significantly lower in the letrozole cycles (p = 0.035), besides number of the retrieved oocyte, mature oocyte, fertilization rate, number of embryos obtained, transferred embriyo numbers, frozen embriyo numbers and clinical pregnancy rates did not show any significant difference comparing with previous antagonist cycles.

Anahtar Kelimeler

Diminished ovarian reserve, Intracytoplasmic sperm injection, GnRH antagonist, Letrozol

Düşük Over Rezervli Hastalarda GnRH Antagonist/Letrozol Stimülasyon Protokolünün Kullanılmasının İntrasitoplazmik Sperm Enjeksiyonu Siklus Sonuçlarına Etkisi

Öz

Bu retrospektif çalışmada daha önce düşük ovaryan rezerv (DOR) endikasyonu ile intrasitoplazmik sperm enjeksiyonu (ICSI) siklusu yapıl-ması amacı ile antagonist protokoller ile kontrollü ovaryan hiperstimülasyon (KOH) uygulanmış ve canlı doğum elde edilemeyen hastalarda, takip eden stimülasyon siklusunda antagonist protokole aromataz inhibitörü olan letrozol eklenmesinin siklus sonuçlarına etkisi önceki tedavi siklusları ile karşılaştırılarak değerlendirilmesi hedeflenmiştir. Çalışmaya Haziran 2013- Aralık 2015 yılları arasında ICSI için KOH uygula-nan 26 hasta dahil edildi. Elektronik veri tabanı kullanılarak, DOR endikasyonu ile ICSI uygulanmış olan 26 hastanın KOH protokolü karak-tarestikleri belirlendi. Önceki KOH siklusları sonrası embriyo transferi yapılarak canlı doğum elde edilemeyen 26 hastaya takip eden tedavi sikluslarında erken folliküler fazda konvansiyonel antagonist stimülasyon protokolüne letrozol eklendiğinde önceki KOH siklusları ile karşılaştırıldığında; kullanılan total gonadotropin dozu anlamlı olarak düşerken (p= 0.035), elde edilen oosit, matür oosit, döllenme oranı, elde edilen embriyo sayısı, transfer edilen embriyo sayıları, dondurulan embriyo sayıları ve klinik gebelik oranların anlamlı farklılık göstermediği tespit edildi.

Anahtar Kelimeler

Letrozol, Düşük over rezervi, Intrasitoplazmik sperm enjeksiyonu, GnRH antagonist

Kaynakça

• 1.Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assistedconception following poor ovarian response to gonadotrophinstimulation. Br J Obstet Gynaecol 1997;104(5):521–527.
• 2.Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbe-ma JD, te Velde ER. Predictors of poor ovarian response in invitro fertilization: a prospective study comparing basal markersof ovarian reserve. Fertil Steril 2002;77:328–336.
• 3.Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinicalmanagement of low ovarian response to stimulation for IVF: asystematic review. Hum Reprod Update 2003;9(1):61–76.
• 4.Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA,Bahceci M. Conception rates following assisted reproduction inpoor responder patients: a retrospective study in 300 consecuti-ve cycles. Reprod Biomed Online 2003;6 (4):439–443.
• 5.Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G,Gianaroli L. ESHRE working group on poor ovarian responsedefinition. ESHRE consensus on the definition of ‘poor respon-se’ to ovarian stimulation for in vitro fertilization: the Bolognacriteria. Hum Reprod 2011;26:1616–1624.
• 6.Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattachar-ya S. Interventions for ‘poor responders’ to controlled ovarianhyper stimulation (COH) in in-vitro fertilisation (IVF). Cochra-ne Database Syst Rev 2010.
• 7.Ubaldi FM, Rienzi L, Ferrero S. Management of poor respon-ders in IVF. Reprod BioMed Online 2005; 10: 235-246.
• 8.Winer EP, Hudis C, Burstein HJ, Chlebowski RT, Ingle JN,Edge SB, et al. American Society of Clinical Oncology tech-nology assessment on the use of aromatase inhibitors as adju-vant therapy for women with hormone receptor–positive breastcancer: status report 2002. J Clin Oncol 2002;20:3317–3327.
• 9.Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J,et al. Androgen receptor gene expression in the primate ovary:cellular localization, regulation, and functional correlations. JClin Endocrinol Metab 1998;83:2479–2485.
• 10. 10.Mitwally MF, Casper RF, Diamond MP. The role of aroma-tase inhibitors in ameliorating deleterious effects of ovarianstimulation on outcome of infertility treatment. Reprod BiolEndocrinol 2005;3:54.
• 11.Yarali H, Esinler I, Polat M, Bozdag G, Tiras B. Antago-nist/letrozole protocol in poor ovarian responders for intracy- toplasmic sperm injection: a comparative study with the micro-dose flare-up protocol. Fertil Steril 2009;92(1):231–235.
• 12.Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S,Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 tre-atment cycles. Hum Reprod 2011;26 (7):1768–1774.
• 13.Schoolcraft WB, Surrey ES, Minjarez DA, Stevens JM, Gard-ner DK. Management of poor responders: can outcomes be im-proved with a novel gonadotropin-releasing hormone antago-nist/letrozole protocol? Fertil Steril 2008;89:151–156.
• 14.Surrey ES, Schoolcraft WB. Evaluating strategies for improv-ing ovarian response of the poor responder undergoing assisted reproductive techniques. Fertil Steril 2000;73:667–676.
• 15.Akhtar M, Njar VC, Wright JN. Mechanistic studies on aroma-tase and related C-C bond cleaving P-450 enzymes. J Steroid Biochem Mol Biol 1993;44:375–387.
• 16.Murray AA, Gosden RG, Allison V, Spears N. Effect of andro-gens on the development of mouse follicles growing in vitro. J Reprod Fertil 1998;113:27–33.
• 17.Garcia-Velasco JA, Moreno L, Pacheco A, Guillen A, Duque L,Requena A, et al. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril 2005;84: 82–87.
• 18.Kapoor M, Hurwitz J, Polotsky A, Richlin S, Chi L, LeondiresM. Letrozole in combination with gonadotropins decreases can-cellation rates and improves ongoing pregnancy rates per trans-fer in poor responders. Fertil Steril 2007;88:100.
• 19.Oktay K, Cil A, Oktem O, Bang H. Continuous combined letrozole-FSH stimulation requires less FSH with similar out-comes compared to standard ovarian stimulation regimens for IVF. Fertil Steril 2005;84-94.
• 20.Mahbod Ebrahimi M.D., Firouzeh Akbari-Asbagh M.D., Mo-jgan Ghalandar-Attar M.D. Letrozole + GnRH antagonist sti-mulation protocol in poor ovarian responders undergoing int-racytoplasmic sperm injection cycles: An RCT.Int. J. Reprod BioMed.2017; 15:101-108.
• 21.Xiao J, Chang Sh, Chen Sh. The effectiveness of gonadotropin-releasing hormone antagonist in poor ovarian responders un-dergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril 2013; 100: 1594-1601.
• 22.Fasouliotis SJ , Laufer N, Sabbagh-Ehrlich Sh, Lewin A, Hur-witz A, Simon A. Gonadotropin-Releasing Hormone (GnRH)-Antagonist Versus GnRH-Agonist in Ovarian Stimulation of Poor Responders Undergoing IVF. J Assist Reprod Genet 2003; 20: 455-460.
• 23.Sekhon L, Lee JA, Whitehouse M, Copperman AB, Grunfeld L.Letrozole as an adjunct in GnRH antagonist cycles improves IVF outcomes in poor responders. Fertil Steril 2014; 102: 221.