Funda CEVHER, İlknur SELVİ, Cengiz KARAKAYA, Mehmet ERDEM, Erhan DEMİRDAĞ, Ahmet ERDEM

Comparison of frozen-thawed embryo transfer protocols in patients with previous cycle cancellation due to uterine peristalsis: a pilot study

Background/aim: To investigate the optimal protocol for frozen-thawed embryo transfer (FET) cycles in patients who previously had a cycle cancellation due to uterine peristalsis (UP). Materials and methods: Thirty-four patients with previous embryo transfer (ET) cancellation due to UP during artificial cycle (AC) were included retrospectively. In the proceeding cycle, endometrium was prepared with AC (n: 23) in AC-FET group or with stimulated cycle that contains letrozole (L) (n: 11) in L-FET group. Intravenous bolus dose of 6.75 mg atosiban (Tractocile; Ferring Pharmaceuticals, Switzerland) injection was performed to all patients of AC-FET group due to UP ≥ 4/min on the planned ET day of proceeding cycle. Atosiban was not used in L-FET group. Primary outcome was live birth rate (LBR) per ET. Secondary outcomes were clinical pregnancy rate (CPR) per ET, implantation rate (IR), cycle cancellation rate. Results: The baseline characteristics such as age, body mass index, antral follicle count, duration of infertility, and the number of prior in vitro fertilization attempts of each group were similar. The IR, CPR per ET, LBR per ET, CPR per cycle and LBR per cycle were significantly higher; cycle cancellation rates were significantly lower in L-FET group as compared to the AC-FET group. Conclusion: Endometrial preparation with letrozole significantly improves CPR and LBR in FET cycles of patients with previous cycle cancellations due to UP.Key words: Uterine peristalsis, frozen-thawed cycle, embryo transfer, letrozole, atosiban

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1. Yarali H, Polat M, Mumusoglu S, Yarali I, Bozdag G. Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis. Journal of Assisted Reproduction and Genetics 2016; 33 (10): 1287-1304. doi: 10.1007/s10815-016-0787-0
2. D’Angelo A. Ovarian hyperstimulation syndrome prevention strategies: cryopreservation of all embryos. Seminars in Reproductive Medicine 2010; 28 (6): 513-518. doi: 10.1055/s0030-1265679
3. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Human Reproduction Update 2003; 9 (6): 515-522. doi: 10.1093/humupd/dmg045
4. Bahadur G, Homburg R, Bosmans JE, Huirne JAF, Hinstridge P et al. Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles. British Medical Journal Open 2020; 10 (3): e034566. doi: 10.1136/bmjopen-2019-034566
5. Sztachelska M, Ponikwicka-Tyszko D, Sokolowska G, Anisimowicz S, Czerniecki J et al. Oxytocin antagonism reverses the effects of high oestrogen levels and oxytocin on decidualization and cyclooxygenase activity in endometrial tissues. Reproductive Biomedicine Online 2019; 39 (5): 737- 744. doi: 10.1016/j.rbmo.2019.06.002
6. Li SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY et al. Letrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer. Archives of Gynecology and Obstetrics 2014; 289 (3): 687-693. doi: 10.1007/s00404-013-3044-0
7. Long Y, Liang R, Zhang J, Fang F, Cheng C et al. Identification and characterization of uterine micro-peristalsis in women undergoing in vitro fertilization and embryo transfer via dynamic ultrasound features. Archives of Gynecology and Obstetrics 2019; 300 (6): 1729-1739. doi: 10.1007/s00404-019- 05327-1
8. He Y, Wu H, He X, Xing Q, Zhou P et al. Application of atosiban in frozen-thawed cycle patients with different times of embryo transfers. Gynecological Endocrinology: the Official Journal of the International Society of Gynecological Endocrinology 2016; 32 (10): 811-815. doi: 10.1080/09513590.2016.1180680
9. Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reproductive Biology and Endocrinology 2018; 16 (1): 121. doi: 10.1186/s12958-018-0414-2
10. Chien LW, Au HK, Chen PL, Xiao J, Tzeng CR. Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Fertility and Sterility 2002; 78 (2): 245-251.
11. Wang L, Qiao J, Li R, Zhen X, Liu Z. Role of endometrial blood flow assessment with color Doppler energy in predicting pregnancy outcome of IVF-ET cycles. Reproductive Biology and Endocrinology 2010; 8: 122. doi: 10.1186/1477-7827-8- 122
12. Sardana D, Upadhyay AJ, Deepika K, Pranesh GT, Rao KA. Correlation of subendometrial-endometrial blood flow assessment by two-dimensional power Doppler with pregnancy outcome in frozen-thawed embryo transfer cycles. Journal of Human Reproductive Sciences 2014; 7 (2): 130-135. doi: 10.4103/0974-1208.138872
13. Kunz G, Leyendecker G. Uterine peristaltic activity during the menstrual cycle: characterization, regulation, function and dysfunction. Reproductive Biomedicine Online 2002; 4 Suppl 3: 5-9. doi: 10.1016/s1472-6483(12)60108-4
14. Orisaka M, Kurokawa T, Shukunami K, Orisaka S, Fukuda MT et al. A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2007; 135 (1): 111-115. doi: 10.1016/j. ejogrb.2006.07.040
15. Zhu L, Che HS, Xiao L, Li YP. Uterine peristalsis before embryo transfer affects the chance of clinical pregnancy in fresh and frozen-thawed embryo transfer cycles. Human Reproduction. 2014; 29 (6): 1238-1243. doi: 10.1093/humrep/deu058
16. de Ziegler D, Andersen CY, Stanczyk FZ, Ayoubi JM. Endocrine mechanisms and assay issues in premature progesterone elevation in assisted reproductive technology. Fertility and Sterility 2018; 109 (4): 571-576. doi: 10.1016/j. fertnstert.2018.02.137
17. Joo BS, Park SH, An BM, Kim KS, Moon SE et al. Serum estradiol levels during controlled ovarian hyperstimulation influence the pregnancy outcome of in vitro fertilization in a concentration-dependent manner. Fertility and Sterility 2010; 93 (2): 442-446. doi: 10.1016/j.fertnstert.2009.02.066
18. Ullah K, Rahman TU, Pan HT, Guo MX, Dong XY et al. Serum estradiol levels in controlled ovarian stimulation directly affect the endometrium. Journal of Molecular Endocrinology 2017; 59(2): 105-119. doi: 10.1530/JME-17-0036
19. Valbuena D, Martin J, de Pablo JL, Remohi J, Pellicer A et al. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertility and Sterility 2001; 76 (5): 962-968. doi: 10.1016/s0015- 0282(01)02018-0
20. Pierzynski P. Oxytocin and vasopressin V(1A) receptors as new therapeutic targets in assisted reproduction. Reproductive Biomedicine Online 2011; 22 (1): 9-16. doi: 10.1016/j. rbmo.2010.09.015
21. Steinwall M, Hansson S, Bossmar T, Larsson I, Pilka R et al. Oxytocin mRNA content in the endometrium of non-pregnant women. British Journal of Obstetrics and Gynaecology: an International Journal of Obstetrics and Gynaecology 2004; 111 (3): 266-270. doi: 10.1111/j.1471-0528.2004.00049.x
22. Huang QY, Rong MH, Lan AH, Lin XM, Lin XG et al. The impact of atosiban on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A metaanalysis. Public Library of Science One 2017; 12 (4): e0175501. doi: 10.1371/journal.pone.0175501
23. Brouard R, Bossmar T, Fournie-Lloret D, Chassard D, Akerlund M. Effect of SR49059, an orally active V1a vasopressin receptor antagonist, in the prevention of dysmenorrhoea. British Journal of Obstetrics and Gynaecology: an International Journal of Obstetrics and Gynaecology 2000; 107 (5): 614-619. doi: 10.1111/j.1471-0528.2000.tb13302.x
24. Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J et al. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused nonpregnant uteri. Molecular Human Reproduction 2004; 10 (5): 339-346. doi: 10.1093/molehr/gah039
25. Fanchin R, Ayoubi JM, Righini C, Olivennes F, Schonauer LM et al. Uterine contractility decreases at the time of blastocyst transfers. Human Reproduction 2001; 16 (6): 1115-1119. doi: 10.1093/humrep/16.6.1115
26. Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D et al. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Human Reproduction 1998; 13 (7): 1968-1974. doi: 10.1093/ humrep/13.7.1968
27. Kuijsters NPM, Methorst WG, Kortenhorst MSQ, Rabotti C, Mischi M et al. Uterine peristalsis and fertility: current knowledge and future perspectives: a review and metaanalysis. Reproductive Biomedicine Online 2017; 35 (1): 50-71. doi: 10.1016/j.rbmo.2017.03.019
28. Groenewoud ER, Cantineau AE, 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. Human Reproduction Update 2013; 19 (5): 458-470. doi: 10.1093/humupd/dmt030
29. Zhang J, Liu H, Wang Y, Mao X, Chen Q et al. Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome. Fertility and Sterility 2019; 112 (2): 371-377. doi: 10.1016/j.fertnstert.2019.04.014
30. Wallace KL, Johnson V, Sopelak V, Hines R. Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome. Fertility and Sterility 2011; 96 (4): 1051-1056. doi: 10.1016/j.fertnstert.2011.07.1092
31. Yu J, Ma Y, Wu Z, Li Y, Tang L et al. Endometrial preparation protocol of the frozen-thawed embryo transfer in patients with polycystic ovary syndrome. Archives of Gynecology and Obstetrics 2015; 291 (1): 201-211. doi: 10.1007/s00404-014- 3396-0
32. Narayan R, Goswamy R. Subendometrial-myometrial contractility in conception and non-conception embryo transfer cycles. Ultrasound in Obstetrics & Gynecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 1994; 4 (6): 499-504. doi: 10.1046/j.1469-0705.1994.04060499.x
33. Ledee-Bataille N, Lapree-Delage G, Taupin JL, Dubanchet S, Frydman R et al. Concentration of leukaemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation. Human Reproduction 2002; 17 (1): 213-218. doi: 10.1093/humrep/17.1.213
34. Ozkan ZS, Deveci D, Kumbak B, Simsek M, Ilhan F et al. What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility? Journal of Reproductive Immunology 2014; 103: 53-58. doi: 10.1016/j.jri.2013.11.002
35. Özkan ZS, Deveci D, Akpolat N, İlhan F, Şimşek M et al. The impact of plasma SOCS3 levels and endometrial leukocytes on unexplained infertility. Turkish Journal of Medical Sciences 2018; 48 (3): 509-516. doi: 10.3906/sag-1707-103
36. Fanchin R, Ayoubi JM. Uterine dynamics: impact on the human reproduction process. Reproductive Biomedicine Online 2009; 18 Suppl 2: 57-62. doi: 10.1016/s1472-6483(10)60450-6
37. Ng EH, Li RH, Chen L, Lan VT, Tuong HM et al. A randomized double blind comparison of atosiban in patients undergoing IVF treatment. Human Reproduction 2014; 29 (12): 2687- 2694. doi: 10.1093/humrep/deu263
38. Yuan C, Song H, Fan L, Su S, Dong B. The effect of atosiban on patients with difficult embryo transfers undergoing in vitro fertilization-embryo transfer. Reproductive Sciences 2019; 26 (12): 1613-1617. doi: 10.1177/1933719119831791
39. Ayoubi JM, Epiney M, Brioschi PA, Fanchin R, Chardonnens D et al. Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles. Fertility and Sterility 2003; 79 (5): 1101- 1105. doi: 10.1016/s0015-0282(03)00179-1
40. Zhu L, Li Y, Xu A. Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women. Human Reproduction 2012; 27 (9): 2684-2689. doi: 10.1093/ humrep/des257
41. European Atosiban Study G. The oxytocin antagonist atosiban versus the beta-agonist terbutaline in the treatment of preterm labor. A randomized, double-blind, controlled study. Acta Obstetricia et Gynecologica Scandinavica 2001; 80 (5): 413- 422.
42. Pierzynski P, Gajda B, Smorag Z, Rasmussen AD, Kuczynski W. Effect of atosiban on rabbit embryo development and human sperm motility. Fertility and Sterility 2007; 87 (5): 1147-1152. doi: 10.1016/j.fertnstert.2006.08.089
43. Pierzynski P, Reinheimer TM, Kuczynski W. Oxytocin antagonists may improve infertility treatment. Fertility and Sterility 2007; 88 (1): 213 e19-22. doi: 10.1016/j. fertnstert.2006.09.017
44. Moraloglu O, Tonguc E, Var T, Zeyrek T, Batioglu S. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF. Reproductive Biomedicine Online 2010; 21 (3): 338-343. doi: 10.1016/j.rbmo.2010.04.009
45. Lan VT, Khang VN, Nhu GH, Tuong HM. Atosiban improves implantation and pregnancy rates in patients with repeated implantation failure. Reproductive Biomedicine Online 2012; 25 (3): 254-260. doi: 10.1016/j.rbmo.2012.05.014
46. Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA et al. Endometrial receptivity defects during IVF cycles with and without letrozole. Human Reproduction 2012; 27 (3): 881-888. doi: 10.1093/humrep/der452
47. Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Human Reproduction 2004; 19 (2): 352-356. doi: 10.1093/humrep/deh075
48. Hu YJ, Chen YZ, Zhu YM, Huang HF. Letrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study. Clinical Endocrinology 2014; 80 (2): 283-289. doi: 10.1111/cen.12280
49. Samsami A, Ghasmpour L, Davoodi S, Moradi Alamdarloo S, Rahmati J et al. Frozen embryo transfer: Endometrial preparation by letrozole versus hormone replacement cycle: A randomized clinical trial. International Journal of Reproductive Biomedicine 2019; 17 (12): 915-922. doi: 10.18502/ijrm. v17i12.5793