ORİJİNAL ARAŞTIRMALAR
Gonadotropin ile Kombine İntrauterin İnseminasyon Sikluslarında Dual Tetiklemenin Klinik Gebelik Sonuçları Üzerine Etkisi
The Effect of Gonadotropin Combined Intrauterine Insemination Cycles with Dual Trigger on Clinical Pregnancy Outcomes
Received Date : 25 Sep 2023
Accepted Date : 27 Dec 2023
Available Online : 28 Dec 2023
Onur YAVUZa, Recep Emre OKYAYa, Aslı AKDÖNERa, Erkan ÇAĞLIYANa, Bülent GÜLEKLİa
aDokuz Eylül Üniversitesi Tıp Fakültesi, Doğum ve Kadın Hastalıkları ABD, İzmir, Türkiye
Doi: 10.24074/tjrms.2023-99673 - Makale Dili: EN
Türk Üreme Tıbbı ve Cerrahisi Dergisi. 2024;8(1):21-6.
ÖZET
Amaç: İnsan koryonik gonadotropin (hCG), son foliküler olgunlaşmayı ve ovulasyonu tetiklemek için intrauterin inseminasyonda (IUI) kullanılan standart bir tedavidir.
Bu çalışmanın amacı, hCG tetikleme uygulamasına gonadotropin salgılatıcı hormon agonisti (GnRHa) eklemenin son oosit olgunlaşması üzerine etkisini ve klinik
gebelik sonuçlarını araştırmaktır. Gereç ve Yöntemler: Bu, üçüncü basamak bir merkezde gerçekleştirilen retrospektif bir kesitsel çalışmadır. Kliniğimizde
gonadotropin ile kombine IUI tedavisi uygulanan toplam 74 primer infertil hasta çalışmaya dahil edildi. Hastalar, ovulasyon tetikleme protokolüne göre iki gruba ayrıldı:
Grup 1 (n=38, 51.3%) rekombinant hCG (rec-hCG) 250 μg ve Grup 2 (n=36, 48.7%) rec-hCG ile birlikte 0.2 mg GnRHa. Her iki gruba, hCG ile ovulasyon tetiklemesini
takiben 32 ile 36 saat içinde IUI uygulandı. Her iki gruba luteal faz desteği için intravajinal yoldan günlük olarak 600 mg mikronize progesteron tedavisi
verildi. Klinik gebelik, transvajinal ultrason ile fetal kalp atışlarına sahip gestasyon kesesinin varlığı olarak tanımlandı. Bulgular: Demografik özellikler, serum bazal
hormon düzeyleri, sperm parametreleri ve siklus özellikleri açısından gruplar benzerdir. Biyokimyasal ve klinik gebelik oranları Grup 1'de 13.2% ve Grup 2'de 27.8%
olarak saptandı. Gruplar arasında istatistiksel olarak anlamlı bir farklılık gözlenmedi. Grup 2'de çoğul gebelik görülmezken, Grup 1'de iki hastada dikoryonik diamniotik
çoğul gebelik meydana geldi. Gruplardaki hastaların hiçbirinde ovaryan hiperstimülasyon sendromu (OHSS) saptanmadı. Sonuç: GnRHa ile birlikte hCG tetikleme
protokolü biyokimyasal ve klinik gebelik oranlarını arttırmaktadır. Ancak bu artış, istatistiksel olarak anlamlı farklılık yaratmamıştır. Gonadotropin ile kombine
IUI sikluslarında dual tetikleme protokolü göz önünde bulundurulmalıdır.
Anahtar Kelimeler: Dual tetikleme; intrauterin inseminasyon; klinik gebelik; ovulasyon indüksiyonu
ABSTRACT
Objective: For intrauterine insemination (IUI), human chorionic gonadotropin (hCG) is a standard treatment used to induce final follicular maturation and ovulation.
The aim of this study was to investigate the effect of addition of gonadotropin-releasing hormone agonist (GnRHa) to human chorionic gonadotropin for final oocyte
maturation on clinical pregnancy outcomes. Material and Methods: This was a retrospective cross-sectional study conducted at a tertiary center. A total of 74 patients
with primary infertility who underwent IUI treatment in our clinic were included. The patients were divided into two groups according to final oocyte maturation protocol:
Group 1 (n=38, 51.3%) received a single-dose injection of recombinant hCG (rec-hCG) 250 μg subcutaneously and Group 2 (n=36, 48.7%) received rec-hCG
combined with 0.2 mg GnRHa. Both groups underwent IUI at 32 to 36 hours following the ovulation trigger with hCG. Both groups received micronized progesterone
600 mg daily through the intravaginal route for luteal phase support. Clinical pregnancy was defined as the presence of gestational sac with fetal heart beat by transvaginal
ultrasound. Results: There was no significant difference in the demographic characteristics, serum basal hormone levels, sperm parameters, and cycle characteristics
between the groups. The rates of biochemical and clinical pregnancy were 13.2% in Group 1 and 27.8% in Group 2, indicating no significant difference. No
multiple pregnancy occurred in Group 2, while two patients in Group 1 had dichorionic diamniotic multiple pregnancy. None of the patients in either group had ovarian
hyperstimulation syndrome (OHSS). Conclusion: Our study results indicate dual trigger may increase the biochemical and clinical pregnancy rates, although it
was not statistically significant. Dual trigger protocol should be considered in patients undergoing IUI.
Keywords: Clinical pregnancy; dual trigger; intrauterine insemination; ovulation induction
REFERANSLAR
- ESHRE Capri Workshop Group. Intrauterine insemination. Hum Reprod Update. 2009;15(3):265-77. [Crossref] [PubMed]
- Babayof R, Margalioth EJ, Huleihel M, Amash A, Zylber-Haran E, Gal M, et al. Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries under- going IVF treatment: a prospective randomized trial. Hum Reprod. 2006;21(5):1260-5. [Crossref] [PubMed]
- Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin sig- nificantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril. 2013;100(5):1296-302. [Crossref] [PubMed]
- Taylor AE, Whitney H, Hall JE, Martin K, Crowley WF Jr. Midcycle levels of sex steroids are sufficient to recreate the follicle-stimulating hormone but not the luteinizing hormone midcycle surge: evidence for the contribution of other ovarian factors to the surge in normal women. J Clin Endocrinol Metab. 1995;80(5):1541- 7. [Crossref] [PubMed]
- Fauser BC, de Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J, et al. En- docrine 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. [Crossref] [PubMed]
- Bosch E, Labarta E, Kolibianakis E, Rosen M, Meldrum D. Regimen of ovarian stimulation affects oocyte and therefore embryo quality. Fertil Steril. 2016;105(3):560-70. [Crossref] [PubMed]
- Schachter M, Friedler S, Ron-El R, Zimmerman AL, Strassburger D, Bern O, et al. Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) an- tagonist cycles by administering GnRH agonist before oocyte retrieval? A prospec- tive, randomized study. Fertil Steril. 2008 Oct;90(4):1087-93. [Crossref] [PubMed]
- Orvieto R. Triggering final follicular maturation: hCG, GnRH-agonist, or both, when and to whom? J Assist Reprod Genet. 2017;34(9):1231-2. [Crossref] [PubMed] [PMC]
- Mollaahmadi L, Keramat A, Ghiasi A, Hashemzadeh M. The relationship between semen parameters in processed and unprocessed semen with intrauterine insem- ination success rates. J Turk Ger Gynecol Assoc. 2019;20(1): 1-7. [Crossref] [PubMed] [PMC]
- Haahr T, Roque M, Esteves SC, Humaidan P. GnRH Agonist Trigger and LH Ac- tivity 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. [Crossref] [PubMed] [PMC]
- States U, Union S, Union TS. Introduction: Meeting the New Economic Challenge- Forging an American Dream for the Twenty-First Century. 2000;(10):1-14.
- Allahbadia GN. Intrauterine Insemination: Fundamentals Revisited. J Obstet Gy- naecol India. 2017;67(6):385-92. [Crossref] [PubMed] [PMC]
- Dale O, Tanbo T, Lunde O, Abyholm T. Ovulation induction with low-dose follicle- stimulating hormone in women with the polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1993;72(1):43-6. [Crossref] [PubMed]
- Tur R, Barri PN, Coroleu B, Buxaderas R, Martínez F, Balasch J. Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: ev- idence from a large series of 1878 consecutive pregnancies in a single centre. Hum Reprod. 2001;16(10):2124-9. [Crossref] [PubMed]
- Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Con- sensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23(3):462-77. [Crossref] [PubMed]
- Dickey RP, Taylor SN, Lu PY, Sartor BM, Rye PH, Pyrzak R. Risk factors for high- order multiple pregnancy and multiple birth after controlled ovarian hyperstimula- tion: results of 4,062 intrauterine insemination cycles. Fertil Steril. 2005;83(3):671-83. [Crossref] [PubMed]
- Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-45. [Crossref] [PubMed]
- Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predic- tive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril. 1988;49(1):112-7. [Crossref] [PubMed]
- Miralpeix E, Gonzalez-Comadran M, Sola I, et al. Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and metaanalysis. J Assist Reprod Genet. 2014;31(1):89-100. [Crossref] [PubMed] [PMC]
- Gonen Y, Balakier H, Powell W, et al. Use of gonadotropin-releasing hormone ag- onist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab. 1990;71(4):918-22. [Crossref] [PubMed]
- Kumar P, Sait SF. Luteinizing hormone and its dillema in ovulation induction. J Hum Reprod Sci. 2011;4(1):2-7 [Crossref] [PubMed] [PMC]
- Beck-Fruchter R, Weiss A, Lavee M, et al. Empty follicle syndrome: Successful treatment in a recurrent case and review of the literature. Hum Reprod. 2012;27(5):1357-1367. [Crossref] [PubMed]
- Griffin D, Feinn R, Engmann L, et al. Dual trigger with gonadotropin-releasing hor- mone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril. 2014;102(2):405-9. [Crossref] [PubMed]
- Beck-Fruchter R, Weiss A, Lavee M, et al. Empty follicle syndrome: Successful treatment in a recurrent case and review of the literature. Hum Reprod. 2012;27(5):1357-1367. [Crossref] [PubMed]
- Eftekhar M, Mojtahedi MF, Miraj S, et al. Final follicular maturation by administra- tion of GnRH agonist plus HCG versus HCG in normal responders in ART cycles: An RCT. Int J Reprod Biomed (Yazd, Iran). 2017;15(7):429-34. [Crossref] [PubMed]
- Le MT, Nguyen DN, Zolton J, et al. GnRH agonist versus hCG trigger in ovulation induction with intrauterine insemination: A randomized controlled trial. Int J En- docrinol. 2019;2019. [Crossref] [PubMed] [PMC]
- Sasaki K, Norwitz ER. Gonadotropin-releasing hormone/gonadotropin-releasing hormone receptor signaling in the placenta. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):401-8. [Crossref] [PubMed]
- Liu J, Cao B, Li Y, et al. GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts. Reprod Biol Endocrinol. 2010;8:5. [Crossref] [PubMed] [PMC]
- Liu J, MacCalman CD, Wang YL, et al. Promotion of human trophoblasts invasion by gonadotropin-releasing hormone (GnRH) I and GnRH II via distinct signaling pathways. Mol Endocrinol. 2009;23(7):1014-21. [Crossref] [PubMed] [PMC]
- Lainas GT, Lainas TG, Sfontouris IA, et al. Is oocyte maturation rate associated with triptorelin dose used for triggering final oocyte maturation in patients at high risk for severe ovarian hyperstimulation syndrome. Hum Reprod. 2019;34(9):1770-7. [Crossref] [PubMed]
- Gülekli B, Göde F, Sertkaya Z, et al. Gonadotropin-releasing hormone agonist trig- gering is effective, even at a low dose, for final oocyte maturation in ART cycles: Case series. J Turkish Ger Gynecol Assoc. 2015;16(1):35-40. [Crossref] [PubMed] [PMC]
- Yen SS, Llerena O, Little B, et al. Disappearance rates of endogenous luteinizing hormone and chorionic gonadotropin in man. J Clin Endocrinol Metab. 1968;28(12):1763-67 [Crossref] [PubMed]
- Cerrillo M, Rodríguez S, Mayoral M, et al. Differential regulation of VEGF after final oocyte maturation with GnRH agonist versus hCG: a rationale for OHSS reduc- tion. Fertil Steril. 2009;91(4 SUPPL.):1526-8. [Crossref] [PubMed]
- Babayof R, Margalioth EJ, Huleihel M, et al. Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective ran- domized trial. Hum Reprod. 2006;21(5):1260-5. [Crossref] [PubMed]
- Halim B, Lubis H. Dual trigger with gonadotropin-releasing hormone agonist and recombinant human chorionic gonadotropin improves the outcome of intrauterine insemination. Obstet Gynecol Science. 2022; 65(2): 207-14. [Crossref] [PubMed] [PMC]