Use of Triggers on in vitro Fertilization and Evaluation of Risk Factors for Sub-Optimal Maturation Rate

Matsumoto, Larissa; Yamakami, Lucas Yugo Shiguerhara; Turco, Edson Guimarães Lo; Benetti-Pinto, Cristina Laguna; Yela, Daniela Angerame

doi:10.1055/s-0041-1741455

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Revista Brasileira de Ginecologia e Obstetrícia

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Original Article • Rev. Bras. Ginecol. Obstet. 44 (04) • Apr 2022 • https://doi.org/10.1055/s-0041-1741455 copy

Use of Triggers on in vitro Fertilization and Evaluation of Risk Factors for Sub-Optimal Maturation Rate

Uso de gatilhos na fertilização in vitro e avaliação dos fatores de risco para taxa de maturação subótima

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To compare the oocyte maturation rate in the treatment of in vitro fertilization (IVF) in terms of the use of human chorionic gonadotropin (hCG), agonist gonadotropin-releasing hormone (GnRH) and dual trigger and to evaluate the associated risk factors for sub-optimal maturation rates.

Methods

A retrospective cohort study with 856 women who underwent IVF. They performed oocyte retrieval and were classified into 3 groups (1 - hCG, 2 - GnRHagonist, 3 - dual trigger). The primary outcome was maturation rate per trigger, and the secondary outcomes were the pregnancy rate per oocyte retrieval and the correlations between low maturation rate as well as the clinical and treatment characteristics of women.

Results

The maturation rate was 77% in group 1; 76% in group 2, and 83% in group 3 (p=0.003). Group 2 showed women with better ovarian reserve, greater number of oocytes collected, and more mature oocytes and embryos compared with the other groups (p<0.001). The cumulative clinical pregnancy rate was no different between the groups (p=0.755). Low ovarian reserve and low doses of follicle-stimulating hormone (FSH) administered during the stimulus were associated with a higher chance of null maturation rate.

Conclusion

The oocyte maturation rates and IVF results were similar in all groups. Low ovarian reserve is associated with the worst treatment results.

Keywords:
dual trigger; GnRH agonist; HCG in vitro fertilization; oocyte maturation

Variables	Total(n = 856)	HCG(n = 525)	Agonist GnRH (n = 271)	Double trigger(n = 60)	P*	P**
	Average ± SD	Average ± SD	Average ± SD	Average ± SD
Age (years)^{b, c}	35.93 ± 4.59	36.18 ± 4.56	34.97 ± 4.57	38.12 ± 3.83	< 0.001	—
Infertility period (months)^b	36.43 ± 34.24	38.18 ± 35.38	32.01 ± 32.99	40.37 ± 27.55	0.006	0.016
BMI (kg/m2)^{b, c}	25.33 ± 4.84	25.36 ± 4.40	25.87 ± 5.93	22.73 ± 4.80	0.029	0.028
Basal FSH (UI/L)^a	8.76 ± 8.09	9.31 ± 9.22	7.84 ± 6.18	8.14 ± 3.73	< 0.001	0.002
Basal LH (UI/L)	6.55 ± 6.43	6.76 ± 7.24	6.43 ± 5.26	5.34 ± 2.73	0.369	0.388
AMH (ng/ml)^a	1.39 ± 1.88	1.10 ± 1.70	2.12 ± 2.45	1.29 ± 1.00	0.033	0.042
AFC (unit)^{a, b, c}	11.63 ± 7.58	10.21 ± 6.30	15.00 ± 8.91	8.63 ± 6.06	< 0.001	< 0.001

Variables	Total(n = 856)	HCG(n = 525)	Agonist GnRH (n = 271)	Double trigger(n = 60)	P*	P**
	Average ± SD	Average ± SD	Average ± SD	Average ± SD
Stimulus (days)^{b, c}	10.82 ± 2.01	10.62 ± 2.00	10.94 ± 1.85	12.03 ± 2.27	< 0.001	< 0.001
FSH dosage (UI)^{b, c}	2,054.30 ± 653.77	2,043.30 ± 579.43	1,936.1 ± 685.38	2,682.10 ± 768.82	< 0.001	< 0.001
LH dosage (UI)^{b, c}	941.24 ± 572.44	922.20 ± 558.96	873.89 ± 503.65	1,391.10 ± 749.88	< 0.001	< 0.001
E2 trigger (pg/ml)^{a, b}	2,249.90 ± 2,979.0	1,676.70 ± 1,334.30	3,310.30 ± 4,462.60	1,455.20 ± 944.10	< 0.001	< 0.001
P2 trigger (ng/ml)^{b, c}	2.25 ± 6.75	1.01 ± 0.5	1.10 ± 1.80	3.66 ± 1.74	< 0.001	< 0.001
LH start (UI/L)	4.99 ± 1.65	5.12 ± 2.1	4.91 ± 5.24	4.31 ± 3.78	0.300	0.196
LH trigger (UI/L)	5.33 ± 3.28	6.2 ± 4.23	4.03V6.41	4.23 ± 5.30	0.159	0.189
Total follicles ^{a, b}	11.57 ± 7.23	9.71 ± 5.52	15.52 ± 8.80	9.97 ± 5.17	< 0.001	< 0.001
Follicles > 16mm ^{a, b}	5.16 ± 3.67	4.22 ± 2.82	7.08 ± 4.46	4.65 ± 2.83	< 0.001	< 0.001
Oocytes collected ^{a, b, c}	10.11 ± 7.82	8.46 ± 6.23	14.12 ± 9.37	6.72 ± 5.71	< 0.001	< 0.001
MII ^{a, b}	7.65 ± 5.96	6.32 ± 4.50	10.73 ± 7.39	5.43 ± 4.57	< 0.001	< 0.001
Maturation rate^b	0.77 ± 0.22	0.77 ± 0.24	0.76 ± 0.20	0.83 ± 0.17	0.035	0.161
2PN ^{a, b}	5.39 ± 4,07	4.62 ± 3.45	7.11 ± 4.69	4.57 ± 3.96	< 0.001	< 0.001
D3 Embryos ^{a, b}	5.29 ± 4.17	4.50 ± 3.52	6.99 ± 4.82	4.37 ± 3.98	< 0.001	< 0.001
Blastocysts ^{a, b}	2.01 ± 2.51	1.63 ± 2.08	2.80 ± 3.08	1.80 ± 2.41	< 0.001	< 0.001

Variables	HCG(n = 525)	Agonist GnRH(n = 271)	Double trigger(n = 60)	P*
	n/n total	n/n total	n/n total
Β-HCG	211/459–46%	106/217–49%	17/34–50%	0.755
Clinical pregnancy	194/456–43%	89/213–42%	16/34–47%	0.284
Twinning	50/211–24%	26/89–29%	42,401–13%	0.227
Miscarriage	39/455–09%	27/217–12%	12,510–12%	0.272

Variables	Categories	P-value	PR (CI 95%) *
Ages (years)	< 30 (ref.)	—	1.00 (—)
	30–39	0.847	1.04 (0.68–1.61)
	≥ 40	0.178	0.71 (0.42–1.17)
Infertility period (months)	—	0.101	1003 (0.999–1.007)
Low ovarian reserve	No (ref.)	—	1.00 (—)
	Yes	0.786	1.04 (0.80–1.34)
Group/Trigger	Double trigger (ref.)	—	1.00 (—)
	Agonist GnRH	0.499	1.23 (0.68–2.21)
	HCG	0.202	1.44 (0.82–2.54)
BMI (Kg/m2)	< 20	0.703	0.86 (0.39–1.88)
	20.0–24.9 (ref.)	—	1.00 (—)
	25.0–29.9	0.181	1.30 (0.89–1.90)
	≥ 30.0	0.053	1.53 (0.99–2.36)
LH trigger (UI)	< 1.00 (ref.)	—	1.00 (—)
	1.00–1.99	0.905	1.03 (0.66–1.59)
	2.00–3.79	0.419	0.83 (0.52–1.31)
	≥ 3.80	0.590	0.88 (0.56–1.39)
FSH dose (UI/L)	≥ 2,475 (ref.)	—	1.00 (—)
	2,025–2,474	0.390	1.16 (0.83–1.64)
	1,650–2,024	0.794	1.05 (0.72–1.53)
	< 1,650	0.096	1.35 (0.95–1.92)
LH dose (UI/L)	< 600 (ref.)	—	1.00 (—)
	600–884	0.268	0.82 (0.57–1.17)
	885–1,349	0.829	0.96 (0.67–1.38)
	≥ 1,350	0.923	0.98 (0.70–1.38)

Variables	Categories	P-value	Crude PR (CI 95%) *	Adjusted PR (CI 95%) *
Ages (years)	< 30 (ref.)	—	1.00 (—)
	30–39	0.128	4.68 (0.29–76.86)
	≥ 40	0.096	5.84 (0.34–100.90)
Infertility period (months)	—	0.411	0.993 (0.978–1.009)
Low ovarian reserve	No (ref.)	—	1.00 (—)	1.00(—)
	Yes	0.001	3.95 (1.70–9.15)	4.58 (1.77–11.90)
Group/Trigger	Double trigger (ref.)	—	1.00 (—)
	Agonist	0.215	3.28 (0.19–56.54)
	HCG	0.152	4.15 (0.25–67.97)
BMI (Kg/m2)	< 20	0.294	0.43 (0.03–7.22)
	20.0–24.9 (ref.)	—	1.00 (—)
	25.0–29.9	0.496	0.63 (0.17–2.38)
	≥ 30.0	0.857	1.13 (0.30–4.26)
LH trigger (UI)	< 1.00 (ref.)	—	1.00 (—)
	1.00–1.99	0.324	0.34 (0.0–8.31)
	2.00–3.79	0.224	3.90 (0.44–34.87)
	≥ 3.80	0.028	10.09 (1.29–78.81)
FSH dose (UI/L)	≥ 2,475 (ref.)	—	1.00 (—)	1.00 (—)
	2,025–2,474	0.187	4.25 (0.50–36.33)	5.78 (0.67–49.85)
	1,650–2,024	0.177	4.52 (0.51–40.46)	6.36 (0.71–57.25)
	< 1,650	0.008	15.83 (2.08–120.35)	16.03 (2.07–124.32)
LH dose (UI/L)	< 600	0.049	4.74 (1.01–22.30)
	600–884	0.257	2.58 (0.50–13.31)
	885–1,349	0.031	5.39 (1.16–24.92)
	≥ 1,350 (ref.)	—	1.00 (—)

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[1] Address for correspondence
Daniela Angerame Yela, Professor, Rua Alexander Fleming, 101, Cidade Universitária, 13083-881, Campinas, SP, Brazil (e-mail: yela@unicamp.br).