Application of Increasing hCG Trigger Dose in Patients with Poor Ovarian Response

doi:10.12280/gjszjk.20210275

Abstract

Abstract:

Objective: To investigate whether increasing the trigger dose of human chorionic gonadotrophin (hCG) can improve the clinical outcome in patients with poor ovarian response who used gonadotropin releasing hormone agonist (GnRHa) long protocol in in vitro fertilization / intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycle. Methods: The clinical data of 409 patients with poor ovarian response were analyzed retrospectively in our reproductive medicine center from January 2018 to March 2021. According to the trigger dose of hCG, 409 patients were divided into two groups. The conventional dosage group used 6 500 U hCG for trigger (n=337), and the increased dose group (n=72) used hCG 10 000 U or hCG 2 000 U combined with the hCG 6 500 U for trigger. The number of oocytes, the rate of oocyte retrieval, MⅡ rate, 2PN rate, the number of transplantable embryos, the rumber of high-quality embryos, the clinical pregnancy rate, embryo implantation rate, abortion rate and OHSS incidence were compared between the two groups. Results: There were no significant differences in the number of oocytes, the rate of oocyte retrieval, MⅡ rate, 2PN rate, the number of transplantable embryos, the number of high-quality embryos and the rate of abortion between the two groups (all P>0.05). The clinical pregnancy rate (55.56% vs. 42.73%,P=0.047) and the embryo implantation rate（50.51% vs. 37.88%,P=0.021）of the increased dose group was significantly higher than those of the conventional dose group. OHSS was not found in both groups. Conclusions: For the poor ovarian response population, increasing the dose of hCG for trigger can increase embryo implantation rate and the clinical pregnancy rate of fresh cycle transplantation using GnRHa long protocol, which is relatively safe and feasible. This is a recommendable scheme for trigger.

Key words: Gonadotropin-releasing hormone, Chorionic gonadotropin, Fertilization in vitro, Embryo transfer, Ovary

SONG Yun-jie, ZHANG Yuan, XIA Xin-ru, XIA Meng, WU Wei, HUANG Jie, DIAO Fei-yang, MAO Yun-dong, LIU Jia-yin, ZHANG Ru-yang, MA Xiang. Application of Increasing hCG Trigger Dose in Patients with Poor Ovarian Response[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(6): 441-445.

Figures/Tables 6

References 19

[1]	Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of ′poor response′ to ovarian stimulation for in vitro fertilization: the Bologna criteria[J]. Hum Reprod, 2011, 26(7):1616-1624. doi: 10.1093/humrep/der092. doi: 10.1093/humrep/der092 URL
[2]	Drakopoulos P, Bardhi E, Boudry L, et al. Update on the management of poor ovarian response in IVF: the shift from Bologna criteria to the Poseidon concept[J]. Ther Adv Reprod Health, 2020, 14:2633494120941480. doi: 10.1177/2633494120941480. doi: 10.1177/2633494120941480
[3]	Giannelou P, Simopoulou M, Grigoriadis S, et al. The Conundrum of Poor Ovarian Response: From Diagnosis to Treatment[J]. Diagnostics (Basel), 2020, 10(9):687. doi: 10.3390/diagnostics10090687. doi: 10.3390/diagnostics10090687
[4]	The Eshre Guideline Group On Ovarian Stimulation, Bosch E, Broer S, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI [J]. Hum Reprod Open, 2020, 2020(2):hoaa009. doi: 10.1093/hropen/hoaa009. doi: 10.1093/hropen/hoaa009 URL
[5]	Lin MH, Wu FS, Hwu YM, et al. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve[J]. Reprod Biol Endocrinol, 2019, 17(1):7. doi: 10.1186/s12958-018-0451-x. doi: 10.1186/s12958-018-0451-x URL
[6]	Maged AM, Ragab MA, Shohayeb A, et al. Comparative study between single versus dual trigger for poor responders in GnRH-antagonist ICSI cycles: A randomized controlled study[J]. Int J Gynaecol Obstet, 2021, 152(3):395-400. doi: 10.1002/ijgo.13405. doi: 10.1002/ijgo.13405 URL
[7]	Sunkara SK, Coomarasamy A, Faris R, et al. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial[J]. Fertil Steril, 2014, 101(1):147-153. doi: 10.1016/j.fertnstert.2013.09.035. doi: 10.1016/j.fertnstert.2013.09.035 pmid: 24188873
[8]	Tsoumpou I, Muglu J, Gelbaya TA, et al. Symposium: Update on prediction and management of OHSS. Optimal dose of HCG for final oocyte maturation in IVF cycles: absence of evidence?[J]. Reprod Biomed Online, 2009, 19(1):52-58. doi: 10.1016/s1472-6483(10)60045-4. doi: 10.1016/s1472-6483(10)60045-4 pmid: 19573290
[9]	Revelli A, Carosso A, Grassi G, et al. Empty follicle syndrome revisited: definition, incidence, aetiology, early diagnosis and treatment[J]. Reprod Biomed Online, 2017, 35(2):132-138. doi: 10.1016/j.rbmo.2017.04.012. doi: 10.1016/j.rbmo.2017.04.012 URL
[10]	Borisova MA, Moiseenko DY, Smirnova OV. Human Chorionic Gonadotropin: Unknown about Known[J]. Fiziol Cheloveka, 2017, 43(1):97-110. pmid: 29509368
[11]	Abdalla HI, Ah-Moye M, Brinsden P, et al. The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program[J]. Fertil Steril, 1987, 48(6):958-963. doi: 10.1016/s0015-0282(16)59591-0. doi: 10.1016/s0015-0282(16)59591-0 pmid: 3119376
[12]	Lin H, Wang W, Li Y, et al. Triggering final oocyte maturation with reduced doses of hCG in IVF/ICSI: a prospective, randomized and controlled study[J]. Eur J Obstet Gynecol Reprod Biol, 2011, 159(1):143-147. doi: 10.1016/j.ejogrb.2011.07.009. doi: 10.1016/j.ejogrb.2011.07.009 URL
[13]	张希奇, 杨美琼. 不同剂量HCG控制性促排卵诱导卵泡成熟及对胚胎移植妊娠结局影响[J]. 中国计划生育学杂志, 2020, 28(12):2045-2048. doi: 10.3969/j.issn.1004-8189.2020.12.026. doi: 10.3969/j.issn.1004-8189.2020.12.026
[14]	Coleson MP, Sanchez NS, Ashley AK, et al. Human chorionic gonadotropin increases serum progesterone, number of corpora lutea and angiogenic factors in pregnant sheep[J]. Reproduction, 2015, 150(1):43-52. doi: 10.1530/REP-14-0632. doi: 10.1530/REP-14-0632 pmid: 25861798
[15]	Weissman A, Lurie S, Zalel Y, et al. Human chorionic gonadotropin: pharmacokinetics of subcutaneous administration[J]. Gynecol Endocrinol, 1996, 10(4):273-276. doi: 10.3109/09513599609012319. doi: 10.3109/09513599609012319 pmid: 8908528
[16]	Abbara A, Clarke SA, Dhillo WS. Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment[J]. Endocr Rev, 2018, 39(5):593-628. doi: 10.1210/er.2017-00236. doi: 10.1210/er.2017-00236 pmid: 29982525
[17]	Stouffer RL, Bishop CV, Bogan RL, et al. Endocrine and local control of the primate corpus luteum[J]. Reprod Biol, 2013, 13(4):259-271. doi: 10.1016/j.repbio.2013.08.002. doi: 10.1016/j.repbio.2013.08.002 pmid: 24287034
[18]	Sacchi S, Sena P, Degli Esposti C, et al. Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium[J]. J Assist Reprod Genet, 2018, 35(9):1703-1712. doi: 10.1007/s10815-018-1248-8. doi: 10.1007/s10815-018-1248-8 URL
[19]	Tsampalas M, Gridelet V, Berndt S, et al. Human chorionic gonadotropin: a hormone with immunological and angiogenic properties[J]. J Reprod Immunol, 2010, 85(1):93-98. doi: 10.1016/j.jri.2009.11.008. doi: 10.1016/j.jri.2009.11.008 pmid: 20227765

组别	n	IVF（n）	ICSI（n）	女方年龄（岁）	不孕时间（年）	BMI（kg/m²）	AFC（个）	bFSH（U/L）	AMH（ng/mL）
常规剂量组	337	275	62	32.50±4.45	2.00（1.00,4.00）	22.04±2.78	7.49±3.53	8.78（6.79,11.13）	0.84±0.28
增加剂量组	72	59	13	32.31±4.03	2.00（1.00,4.00）	22.15±3.00	6.38±2.97	9.10（6.44,11.34）	0.84±0.27
t或z				0.370	0.690	-0.300	2.810	0.003	0.210
P				0.714	0.406	0.768	0.006	0.958	0.830

组别	n	IVF（n）	ICSI（n）	女方年龄（岁）	不孕时间（年）	BMI（kg/m²）	AFC（个）	bFSH（U/L）	AMH（ng/mL）
常规剂量组	337	275	62	32.50±4.45	2.00（1.00,4.00）	22.04±2.78	7.49±3.53	8.78（6.79,11.13）	0.84±0.28
增加剂量组	72	59	13	32.31±4.03	2.00（1.00,4.00）	22.15±3.00	6.38±2.97	9.10（6.44,11.34）	0.84±0.27
t或z				0.370	0.690	-0.300	2.810	0.003	0.210
P				0.714	0.406	0.768	0.006	0.958	0.830

组别	n	促排卵方案		Gn启动剂量（U）	Gn使用总天数（d）	扳机日E₂ （pmol/L）	扳机日LH （U/L）	扳机日孕激素（nmol/L）	扳机日≥16 mm 卵泡数（个）	卵泡输出率（%）
组别	n	短效长方案	早卵泡期长方案	Gn启动剂量（U）	Gn使用总天数（d）	扳机日E₂ （pmol/L）	扳机日LH （U/L）	扳机日孕激素（nmol/L）	扳机日≥16 mm 卵泡数（个）	卵泡输出率（%）
常规剂量组	337	135（40.06）	202（59.94）	242.03±52.33	11.31±2.29	4 403.90（2742.70,6 492.20）	1.09（0.66,1.97）	2.74（1.92,3.99）	3.14±1.41	0.40（0.29,0.60）
增加剂量组	72	30（42.22）	42（57.78）	248.61±42.97	11.42±2.57	3 690.20（2 658.68,5 359.40）	1.06 （0.75,1.59）	2.83（1.90,3.67）	3.04±1.34	0.47（0.33,0.70）
t或χ²或z		0.01		-1.13	0.31	3.14	0.17	0.37	0.58	2.35
P		0.905		0.259	0.756	0.077	0.682	0.542	0.565	0.125

组别	n	促排卵方案		Gn启动剂量（U）	Gn使用总天数（d）	扳机日E₂ （pmol/L）	扳机日LH （U/L）	扳机日孕激素（nmol/L）	扳机日≥16 mm 卵泡数（个）	卵泡输出率（%）
组别	n	短效长方案	早卵泡期长方案	Gn启动剂量（U）	Gn使用总天数（d）	扳机日E₂ （pmol/L）	扳机日LH （U/L）	扳机日孕激素（nmol/L）	扳机日≥16 mm 卵泡数（个）	卵泡输出率（%）
常规剂量组	337	135（40.06）	202（59.94）	242.03±52.33	11.31±2.29	4 403.90（2742.70,6 492.20）	1.09（0.66,1.97）	2.74（1.92,3.99）	3.14±1.41	0.40（0.29,0.60）
增加剂量组	72	30（42.22）	42（57.78）	248.61±42.97	11.42±2.57	3 690.20（2 658.68,5 359.40）	1.06 （0.75,1.59）	2.83（1.90,3.67）	3.04±1.34	0.47（0.33,0.70）
t或χ²或z		0.01		-1.13	0.31	3.14	0.17	0.37	0.58	2.35
P		0.905		0.259	0.756	0.077	0.682	0.542	0.565	0.125

组别	n	穿刺卵泡数（个）	获卵数（个）	获卵率（%）	MⅡ率（%）	2PN率（%）	可移植胚胎数（个）	优质胚胎数（个）
常规剂量组	337	4.90±2.18	3.75±1.55	80.67±20.08	96.10±10.75	0.80 （0.60,1.00）	2.55±1.41	1.83±1.39
增加剂量组	72	4.53±1.89	3.60±1.47	84.81±26.86	94.17±10.62	0.83（0.57,1.00）	2.43±1.43	1.72±1.40
t或z		1.46	0.81	-1.24	0.58	0.16	0.62	0.62
P		0.147	0.419	0.219	0.572	0.69	0.535	0.539