Evaluation of factors influencing pregnancy success rate in infertile women who underwent intracytoplasmic sperm injection (ICSI)

Abstract

Purpose: The aim of our study is to evaluate the factors affecting pregnancy success rate in infertile women who underwent intracytoplasmic sperm injection as an assisted reproductive technique. Materials and methods: Between January 2018 and December 2020, 325 cycles of 283 infertile patients who underwent intracytoplasmic sperm injection and a single fresh embryo transfer were included in the study. Age of patients, BMI, causes of infertility, number of collected oocytes and maturation rate, endometrial thickness on embryo transfer day, quality of embryo and transfer day were determined. In addition, anti-Müllerian Hormone, basal FSH, LH, estradiol (E2) levels and E2 and progesterone (P) levels on the day of Human Chorionic Gonadotropin (hCG) administration and pregnancy outcomes were evaluated. Results: Age of women (p=0.015), basal FSH level (p=0.005), AMH (p=0.002), number of oocytes obtained (p=0.003), number of MII oocytes (p=0.001), embryo quality (p<0.001) and embryo transfer rate on fifth day (p<0.0001) were found to be statistically significant in cycles resulting in a pregnancy (n:141) compared to nonsuccesful cycles (n:184). BMI (p=0.814), basal E2 level (p=0.411), E2 (p=0.056) and P (p=0.119) levels on hCG day, EMT (p=0.146) on ET day, oocyte maturation index (p=0.140) and total progressive motile sperm count (p=0.747) were not significantly different between the groups. When the effects of infertility causes on pregnancy succes rate were evaluated, there was no significant differences between the groups. Conclusion: The most important prognostic factors in predicting pregnancy success rate in infertile women who underwent ICSI are maternal age, embryo quality and transfer day.

Keywords

• Infertility
• Intracytoplasmic sperm injection
• embryo quality
• pregnancy

İntrasitoplazmik sperm enjeksiyonu (ICSI) uygulanan infertil kadınlarda gebelik başarısını etkileyen faktörlerin değerlendirilmesi

Öz

Amaç: Çalışmamızın amacı, yardımcı üreme tekniği olarak intrasitoplazmik sperm enjeksiyonu uygulanan infertil kadınlarda gebelik başarısını etkileyen faktörlerin değerlendirilmesidir. Gereç ve yöntem: Ocak 2018 ve Aralık 2020 tarihleri arasında, intrasitoplazmik sperm enjeksiyonu uygulanan, tek ve taze embriyo transferinin yapıldığı toplam 283 infertil hastaya ait 325 siklus çalışmaya dâhil edildi. Hastaların yaşı, vücut kitle indeksleri, infertilite nedenleri, kaç adet oosit toplandığı ve maturasyon oranı, embriyo transfer günü endometriyal kalınlık, embriyonun kalitesi ve kaçıncı gün transfer edildiği belirlendi. Ayrıca hastaların Anti-Müllerian Hormon (AMH), bazal FSH, LH, estradiol (E2) düzeyleri, Human Chorionic Gonadotropin (hCG) uygulandığı gün E2 ile progesteron (P) düzeyleri ve gebelik sonuçları değerlendirildi. Bulgular: Gebelik oluşan sikluslarda (n:141), oluşmayan sikluslara (n:184) kıyasla kadın yaşı (p=0,015), bazal FSH seviyesi (p=0,005), AMH (p=0,002), elde edilen oosit sayısı (p=0,003), MII oosit sayısı (p=0,001 ), embriyo kalitesi (p<0,001 ) ve 5. gün embriyo transfer oranı (p<0,0001 ) istatiksel olarak anlamlı bulundu. VKİ (p=0,814), bazal E2 seviyesi (p=0,411), hCG günü E2 (p=0,056) ve P seviyesi (p=0,119), ET günü EMK (p=0,146), oosit maturasyon indeksi (p=0,140) ve total pogressif motil sperm sayısı (p=0,747) açısından her iki grup arasında anlamlı bir farklılık gözlenmedi. İnfertilite nedenlerinin gebelik oluşumuna etkisi değerlendirildiğinde gruplar arasında anlamlı fark olmadığı izlendi. Sonuç: ICSI uygulanan infertil kadınlarda gebelik başarısını öngörmede en önemli prognostik faktörler maternal yaş, embriyo kalitesi ve transfer günüdür.

Anahtar Kelimeler

• İnfertilite
• İntrasitoplazmik sperm enjeksiyonu
• Embriyo kalitesi
• Gebelik

References

1. 1. Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978;2(8085):366. https://doi.org/10.1016/s0140-6736(78)92957-4
2. 2. Niederberger C, Pellicer A, Cohen J, et al. Forty years of IVF. Fertil Steril 2018;110:185-324.e5. https://doi.org/10.1016/j.fertnstert.2018.06.005
3. 3. Sunderam S, Kissin DM, Zhang Y, et al. Assisted reproductive technology surveillance - United States, 2016. MMWR Surveill Summ 2019;68:1-23 https://doi.org/10.15585/mmwr.ss6804a1
4. 4. Pinter B, da Silav MO, Bloemenkamp K, Fronteira I, Karro H. Assisted reproductive technologies in european union: findings of the reproductive health report, 2018. https://webgate.ec.europa.eu/chafea_pdb/assets/files/pdb/2007110/2007110_d12-01_en_ps.pdf. Erişim tarihi: 24/02/2021
5. 5. Pasqualini RS, Quintans CJ. Clinical practice of embryo transfer. Reprod Biomed Online. 2002;4:83-92. https://doi.org/10.1016/s1472-6483(10)61920-7
6. 6. Lessey BA, Young SL. What exactly is endometrial receptivity? Fertil Steril 2019;111:611-617. https://doi.org/10.1016/j.fertnstert.2019.02.009
7. 7. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on poor ovarian response definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011;26:1616-24. https://doi.org/10.1093/humrep/der092
8. 8. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010;16:231-45. https://doi.org/10.1093/humupd/dmp048

9. 9. Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril 2020;113:305-322. https://doi.org/10.1016/j.fertnstert.2019.10.014
10. 10. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 1999;11:307-11. https://doi.org/10.1097/00001703-199906000-00013
11. 11. Practice Committee of the American Society for Reproductive Medicine. Performing the embryo transfer: a guideline. Fertil Steril 2017;107:882-896. https://doi.org/10.1016/j.fertnstert.2017.01.025
12. 12. Erden M. Kadınlarda infertilite. In: Günalp GS, ed. Speroff klinik jinekolojik endokrinoloji ve infertilite, 9.baskı. Ankara: Güneş tıp kitabevleri, 2020;973-1027
13. 13. Muttukrishna S, McGarrigle H, Wakim R, Khadum I, Ranieri DM, Serhal P. Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology? BJOG 2005;112:1384-1390. https://doi.org/10.1111/j.1471-0528.2005.00670.x
14. 14. Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E. Relevance of anti-mullerian hormone measurement in a routine IVF program. Hum Reprod 2008;23:1359-1365. https://doi.org/10.1093/humrep/den108
15. 15. Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update 2006;12:685-718. https://doi.org/10.1093/humupd/dml034
16. 16. van Rooij IA, Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization. Fertil Steril 2003;79:482-488. https://doi.org/10.1016/s0015-0282(02)04839-2
17. 17. Ziebe S, Loft A, Petersen JH, et al. Embryo quality and developmental potential is compromised by age. Acta Obstet Gynecol Scand 2001;80:169-174. https://doi.org/10.1034/j.1600-0412.2001.080002169.x
18. 18. Hull MG, Fleming CF, Hughes AO, McDermott A. The age-related decline in female fecundity: a quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization. Fertil Steril 1996;65:783-790. https://doi.org/10.1016/s0015-0282(16)58214-4
19. 19. Farr SL, Schieve LA, Jamieson DJ. Pregnancy loss among pregnancies conceived through assisted reproductive technology, United States, 1999-2002. Am J Epidemiol. 2007;165:1380-1388. https://doi.org/10.1093/aje/kwm035
20. 20. Centers for disease control and prevention, American society for reproductive medicine society for assisted reproductive technology. 2010 assisted reproductive technology: fertility clinic success rates report. Atlanta (GA): CDC; 2012.http://www.cdc.gov/art/ART2010/PDFs/ART_2010_Clinic_Report-full.pdf. Erişim tarihi 28 Şubat 2021
21. 21. Scott L. Analysis of fertilization. Textbook of assisted reproductive techniques. Gardner DK, Weissman A, Howles CM, Shoham Z, ed. London, United Kingdom: Martin Dunitz Ltd, 2001;281-296
22. 22. Gardner DK, Sakkas D. Assessment of embryo viability: the ability to select a single embryo for transfer-a review. Placenta 2003;24:5-12. https://doi.org/10.1016/s0143-4004(03)00136-x
23. 23. Racowsky C, Combelles CM, Nureddin A, et al. Day 3 and day 5 morphological predictors of embryo viability. Reprod Biomed Online 2003;6:323-331. https://doi.org/10.1016/s1472-6483(10)61852-4
24. 24. Irani M, Reichman D, Robles A, et al. Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates. Fertil Steril 2017;107:664-670. https://doi.org/10.1016/j.fertnstert.2016.11.012
25. 25. Bakkensen JB, Brady P, Carusi D, Romanski P, Thomas AM, Racowsky C. Association between blastocyst morphology and pregnancy and perinatal outcomes following fresh and cryopreserved embryo transfer. J Assist Reprod Genet 2019;36:2315-2324. https://doi.org/10.1007/s10815-019-01580-0
26. 26. Milki AA, Hinckley MD, Fisch JD, Dasig D, Behr B. Comparison of blastocyst transfer with day 3 embryo transfer in similar patient populations. Fertil Steril 2000;73:126-129. https://doi.org/10.1016/s0015-0282(99)00485-9
27. 27. Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 2016;6:CD002118. https://doi.org/10.1002/14651858.CD002118.pub5
28. 28. Martins WP, Nastri CO, Rienzi L, van der Poel SZ, Gracia C, Racowsky C. Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes. Ultrasound Obstet Gynecol 2017;49:583-591. https://doi.org/10.1002/uog.17327
29. 29. Ahmadi F, Akhbari F, Zamani M, Ramezanali F, Cheraghi R. Value of endometrial echopattern at HCG administration day in predicting IVF outcome. Arch Iran Med 2017;20:101-104.
30. 30. Ghamdi A, Coskun S, Al-Hassan S, Al-Rejjal R, Awartani K. The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET) outcome. Reprod Biol Endocrinol 2008;6:37. https://doi.org/doi:10.1186/1477-7827-6-37
31. 31. Aydin T, Kara M, Nurettin T. Relationship between endometrial thickness and in vitro fertilization-intracytoplasmic sperm injection outcome. Int J Fertil Steril 2013;7:29-34.
32. 32. Dechaud H, Bessueille E, Bousquet PJ, Reyftmann L, Hamamah S, Hedon B. Optimal timing of ultrasonographic and doppler evaluation of uterine receptivity to implantation. Reprod Biomed Online 2008;16:368-375. https://doi.org/10.1016/s1472-6483(10)60598-6
33. 33. Inafuku K. Hysteroscopy in midluteal phase of human endometrium evaluation of functional aspect of the endometrium. Nihon Sanka Fujinka Gakkai Zasshi 1992;44:79-83.
34. 34. Li S, Pan P, Yao S, et al. Hysteroscopic appearence of midsecretory endometrium in relation to pinopodes expression and the reproductive outcome in infertile women. J Reprod Contracept 2010;21:17–26.
35. 35. Santi A, Felser R, Bersinger NA, Wunder DM, McKinnon B, Mueller DM. The hysteroscopic view of infertility: the mid-secretory endometrium and treatment success towards pregnancy. Gynecol Surg 2012;9:147–150. 36. Masamoto H, Nakama K, Kanazawa K. Hysteroscopic appearance of the mid-secretory endometrium: relationship to early phase pregnancy outcome after implantation. Hum Reprod 2000;15:2112-2118. https://doi.org/10.1093/humrep/15.10.2112
36. 37. Halperin R, Ron-El R, Golan A, et al. Uterine fluid human decidua-associated protein 200 and implantation after embryo transfer. Hum Reprod 1995;10:907-910. https://doi.org/10.1093/oxfordjournals.humrep.a136059
37. 38. Florio P, Bruni L, De Falco C, et al. Evaluation of endometrial urocortin secretion for prediction of pregnancy after intrauterine insemination. Clin Chem 2008;54:350–355.
38. 39. Florio P, Bruni L, Galleri L, et al. Evaluation of endometrial activin A secretion for prediction of pregnancy after intrauterine insemination. Fertil Steril 2010;93:2316–2320.
39. 40. Rahiminejad ME, Moaddab A, Ebrahimi M, et al. The relationship between some endometrial secretion cytokines and in vitro fertilization. Iran J Reprod Med 2015;13:557–562.
40. 41. Rahiminejad ME, Moaddab A, Ganji M, et al. Oxidative stress biomarkers in endometrial secretions: a comparison between successful and unsuccessful in vitro fertilization cycles. J Reprod Immunol 2016;116:70–75.
41. 42. Jin XY, Zhao LJ, Luo DH, et al. Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles. Hum Reprod 2017;32:2394-2403. https://doi.org/10.1093/humrep/dex312
42. 43. Mahajan N. Endometrial receptivity array: Clinical application. J Hum Reprod Sci 2015;8:121-129. https://doi.org/10.4103/0974-1208.165153
43. 44. Michimata T, Ogasawara MS, Tsuda H, et al. Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion. Am J Reprod Immunol 2002;47:196-202. https://doi.org/10.1034/j.1600-0897.2002.01048.x
44. 45. Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril 2013;100:818-824. https://doi.org/10.1016/j.fertnstert.2013.05.004
45. 46. Al-Ghamdi A, Coskun S, Al-Hassan S, Al-Rejjal R, Awartani K. The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET) outcome. Reprod Biol Endocrinol 2008;6:37. https://doi.org/10.1186/1477-7827-6-37
46. 47. Chen SL, Wu FR, Luo C, et al. Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study. Reprod Biol Endocrinol 2010;8:30. https://doi.org/10.1186/1477-7827-8-30
47. 48. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril 2007;87:53-59. https://doi.org/10.1016/j.fertnstert.2006.05.064
48. 49. Laasch C, Puscheck E. Cumulative embryo score, not endometrial thickness, is best for pregnancy prediction in IVF. J Assist Reprod Genet 2004;21:47-50. https://doi.org/10.1023/b:jarg.0000025937.43936.73
49. 50. Yoeli R, Ashkenazi J, Orvieto R, Shelef M, Kaplan B, Bar-Hava I. Significance of increased endometrial thickness in assisted reproduction technology treatments. J Assist Reprod Genet 2004;21:285-289. https://doi.org/10.1023/b:jarg.0000043701.22835.56
50. 51. Rashidi BH, Sadeghi M, Jafarabadi M, Tehrani, Nejad ES. Relationships between pregnancy rates following in vitro fertilization or intracytoplasmic sperm injection and endometrial thickness and pattern. Eur J Obstet Gynecol Reprod Biol 2005;120:179-184. https://doi.org/10.1016/j.ejogrb.2004.08.016
51. 52. Corbacioğlu A, Baysal B. Effects of endometrial thickness and echogenic pattern on assisted reproductive treatment outcome. Clin Exp Obstet Gynecol 2009;36:145-147.
52. 53. Holden EC, Dodge LE, Sneeringer R, Moragianni VA, Penzias AS, Hacker MR. Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women. Hum Fertil (Camb) 2018;21:288-293. https://doi.org/10.1080/14647273.2017.1334130
53. 54. Zhao J, Zhang Q, Wang Y, Li Y. Endometrial pattern, thickness and growth in predicting pregnancy outcome following 3319 IVF cycle. Reprod Biomed Online. 2014;29:291-298. https://doi.org/10.1016/j.rbmo.2014.05.011
54. 55. Gallos ID, Khairy M, Chu J, et al. Optimal endometrial thickness to maximize live births and minimize pregnancy losses: Analysis of 25,767 fresh embryo transfers. Reprod Biomed Online 2018;37:542-548. https://doi.org/10.1016/j.rbmo.2018.08.025
55. 56. Chan JM, Sukumar AI, Ramalingam M, Ranbir Singh SS, Abdullah MF. The impact of endometrial thickness (EMT) on the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective cohort analysis in Malaysia. Fertil Res Pract 2018;4:5. https://doi.org/10.1186/s40738-018-0050-8
56. 57. Tomic V, Kasum M, Vucic K. Impact of embryo quality and endometrial thickness on implantation in natural cycle IVF. Arch Gynecol Obstet 2020;301:1325-1330. https://doi.org/10.1007/s00404-020-05507-4
57. 58. Kasius A, Smit JG, Torrance HL, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update 2014;20:530-541. https://doi.org/10.1093/humupd/dmu011