KALİTELİ EMBRİYO TRANSFERİNE RAĞMEN BAŞARISIZ IVF SİKLUSU OLAN KADINLARDA İN VİTRO FERTİLİZASYON (IVF) TEDAVİSİ BOYUNCA İV LİPİD (SMOFLIPID®) KULLANIMININ ETKİSİ: VAKA KONTROL ÇALIŞMASI

Öz

Amaç: Tekrarlayan implantasyon başarısızlığı (RIF) zorlu bir gerçek olduğundan, bu sorunun üstesinden gelmek için farklı terapötik immünomodülatör ajanların etkileri araştırılmaktadır. Bu çalışma, intralipidin RIF'li IVF hastalarının gebelik sonuçları üzerindeki etkisini değerlendirmeyi amaçlamıştır. Yöntemler: Katılımcıların 116'sı sadece kısa antagonist protokolünü alan kontrol grubuna, 106'sı ise intravenöz lipid (SMOFlipid®) verilerek intralipid grubunda yer aldı. İntralipid, embriyo transferinin olduğu gün, pozitif gebelik testinin olduğu gün verildi ve gebeliğin onuncu haftasına kadar haftalık olarak devam edildi. İmplantasyon oranı, biyokimyasal gebelik oranı, klinik gebelik oranı ve canlı doğum oranı değerlendirildi. Bulgular: Pozitif gebelik testi, klinik gebelik oranı ve canlı doğum oranı İntralipid grubunda istatistiksel olarak anlamlıydı (p<0,001) (sırasıyla %50,9'a karşı %22,4, %41.5'e karşı %19,8, %29,2'ye karşı %10,3) ). İmplantasyon, spontan abortus, çoğul gebelik ve kimyasal gebelik oranları açısından gruplar arasında anlamlı fark yoktu (p>0.05). Sonuçlar: Bu çalışma, intralipid tedavisinin, sadece standart IVF protokolü uygulanan hastalara kıyasla RIF'li hastalarda daha iyi gebelik sonuçlarına sahip olduğunu ortaya koymuştur. RIF'li hastalarda intralipidin rutin kullanımını önermek için daha ileri prospektif çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• in vitro fertilizasyon
• İntravenöz Lipid Emülsiyonları
• Embriyo İmplantasyonları

Effect of Intravenous Lipid (SMOFLIPID®) Use along in Vitro Fertilization (IVF) Treatment in Women with Failed IVF Cycles Despite Good Quality Embryo Transfer

Öz

Objectives: Since recurrent implantation failure (RIF) is a challenging fact, effects of different therapeutic immunomodulatory agents are being investigated to overcome this problem. This study aimed to evaluate the effect of intralipid on pregnancy outcomes of IVF patients with RIF. Methods: 116 of the participants who received only the short antagonist protocol allocated in the control group, whereas 106 patients were in intralipid group by additionally receiving intravenous lipid (SMOFlipid®). Intralipid was given on the day of embryo transfer, on the day of positive pregnancy test and continued weekly until the tenth week of pregnancy. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate and live birth rate were evaluated. Results: The positive pregnancy test, clinical pregnancy rate and live birth rate were statistically significantly higher (p<0.001) in the intralipid group (50.9% vs. 22.4%, 41.5% vs. 19.8%, 29.2% vs. 10.3%, respectively). There was no significantly difference between groups in terms of implantation, spontaneous abortion , multiple pregnancy and chemical pregnancy rates (p>0.05). Conclusions: This study revealed that intralipid therapy has better pregnancy outcomes in patients with RIF compared to patients undergo standard IVF protocol only. Further prospective studies are needed to suggest the routine use of intralipid in patients with RIF.

Anahtar Kelimeler

• In Vitro Fertilization
• Intravenous Lipid Emulsions
• Embryo Implantations

Kaynakça

1. 1. Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet. 2012;29:1227–1239.
2. 2. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018;16(1):121.
3. 3. Rinehart J. Recurrent implantation failure: definition. J Assist Reprod Genet 2007;24(7):284-7.
4. 4. Kumar P, Mahajan S. Preimplantation and post implantation therapy for the treatment of reproductive failure. J Hum Reprod Sci 2013;6(April (2)):88–92
5. 5. Chaouat G, Dubanchet S, Ledee N. Cytokines: important for implantation? J Assist Reprod Genet. 2007;24:491–505.
6. 6. Li J, Chen Y, Liu C, Hu Y, Li L. Intravenous immunoglobulin treatment for repeated IVF/ICSI failure and unexplained infertility: a systematic review and a meta-analysis. Am J Reprod Immunol 2013;70:434–47.
7. 7. Zeyneloglu HB, Tohma YA, Onalan G, Moran U. Granulocyte colony-stimulating factor for intracytoplasmic sperm injection patients with repeated implantation failure: which route is best? J Obstet Gynaecol. 2019:1-5.
8. 8. Roussev RG, Acacio B, Ng SC, Coulam CB. Duration of intralipid’s suppressive effect on NK cell’s functional activity. Am J Reprod Immunol. 2008;9(3) 258–63 60.

9. 9. Tan BK, Vandekerckhove P, Kennedy R, Keay SD. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG. 2005;112(6):773-80.
10. 10. Klek S, Szczepanek K, Scislo L, Walewska E, Pietka M, et al. Intravenous lipid emulsions and liver function in adult chronic intestinal failure patients: results from a randomized clinical trial. Nutrition. 2018;55-56:45-50..
11. 11. Ozen SB, Celebi SH, Coskun D, Gungor I, Inan G. Effect of Intravenous lipid administration on calcium therapy in verapamil toxicity. Bratisl Lek Listy. 2019;120(10):789
12. 12. Singh N, Davis AA, Kumar S, Kriplani A. The effect of administration of intravenous Intravenous lipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: A randomised controlled trial. Eur J Obstet Gynecol Reprod Biol. 2019;240:45-51.
13. 13. Al-Zebeidi J, Agdi M, Lary S, Al-Obaid S, Salim G, et al. Effect of empiric intravenous Intravenous lipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial. Gynecol Endocrinol. 2019:1-4
14. 14. Achilli C, Duran-Retamal M, Saab W, Serhal P, Seshadri S. The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2018;110(6):1089-100.
15. 15. Nobijari FF, Arefi SS, Moini A, Taheripanah R, Fazeli E, et al. Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure. Zygote. 2019;27(4):214-8.
16. 16. Liu S, Diao L, Huang C, Li Y, Zeng Y, et al. The role of decidual immune cells on human pregnancy. J Reprod Immunol. 2017;124:44-53.
17. 17. Ledee N, Prat-Ellenberg L, Petitbarat M, Chevrier L, Simon C, et al. Impact of prednisone in patients with repeated embryo implantation failures: Beneficial or deleterious? J Reprod Immunol. 2018;127:11-5.
18. 18. Allahbadia GN. Intravenous lipid Infusion is the Current Favorite of Gynecologists for Immunotherapy. J Obstet Gynaecol India. 2015;65(4):213-7
19. 19. Ledee N, Vasseur C, Petitbarat M, Chevrier L, Vezmar K, et al. Intravenous lipid(R) may represent a new hope for patients with reproductive failures and simultaneously an over-immune endometrial activation. J Reprod Immunol. 2018;130:18-22.
20. 20. Dakhly DM, Bayoumi YA, Sharkawy M, Gad Allah SH, Hassan MA, et al. Intravenous lipid supplementation in women with recurrent spontaneous abortion and elevated levels of natural killer cells. Int J Gynaecol Obstet. 2016;135(3):324-7.
21. 21. Asif S, Al Ahwany H, Bhave Chittawar P, et al. Immune therapies for women with history of unsuccessful implantation undergoing IVF/ICSI treatment - A Cochrane collaboration systematic review. Abstracts of the 34th Annual meeting of the ESHRE, Barcelona, 2018. Hum Reprod 2018;33 (suppl. (1)) i84.
22. 22. Al-Zebeidi J, Sahar Lary S, Al-Jaroudi D. The effect of fat emulsion intralipid 20% in reproductive outcome for patients with multiple implantation failure. Int J Women’s Health Reprod Sci. 2017;6: 144–149.
23. 23. Check JH, Check DL. Intravenous intralipid therapy is not beneficial in having a live delivery in women aged 40–42 years with a previous history of miscarriage or failure to conceive despite embryo transfer undergoing in vitro fertilization-embryo transfer. Clin Exp Obstet Gynecol. 2016;43:14–15.