Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

Setti, Amanda Souza; Braga, Daniela Paes de Almeida Ferreira; Iaconelli Júnior, Assumpto; Borges Júnior, Edson

doi:10.1055/s-0041-1736306

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev. Bras. Ginecol. Obstet. 43 (10) • Oct 2021 • https://doi.org/10.1055/s-0041-1736306 copy

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

Melhorando a taxa de implantação no 2° ciclo de ICSI através do estímulo ovariano com FSH e LH no regime com antagonista do GnRH

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle.

Methods

For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups.

Results

Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group.

Conclusion

Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Keywords:
follicle-stimulating hormone; intracytoplasmic sperm injection implantation; luteinizing hormone; ovarian stimulation

Variables	rFSH group (n = 114)	rFSH + rLH group (n = 114)	p-value
Female age	37.19 ± 0.35	37.89 ± 0.35	0.160
Male age	39.23 ± 0.63	39.96 ± 0.64	0.416
BMI	24.88 ± 0.42	24.68 ± 0.42	0.740
FSH dose (IU)	2826.92 ± 199.67	2693.64 ± 198.79	0.636
LH dose (IU)	0.0	1346.82 ± 34.50	NA
Estradiol level (pg/mL)	1151.73 ± 194.34	1909.11 ± 194.34	0.006
Cycles triggered with GnRHa	9/114 (7.9)	10/114 (8.8)	0.811
Follicles (n)	9.99 ± 0.70	10.38 ± 0.70	0.695
Retrieved oocytes (n)	6.37 ± 0.49	7.30 ± 0.49	0.185
Oocyte yield (%)	63.41 ± 2.24	69.78 ± 2.24	0.045
MII oocyte rate (%)	67.72 ± 2.53	71.48 ± 2.52	0.293
Fertilization rate (%)	77.33 ± 2.41	73.02 ± 2.37	0.202
Normal cleavage speed rate (%)	67.16 ± 3.16	73.07 ± 3.11	0.182
D3 high –quality embryos rate (%)	34.13 ± 4.37	47.71 ± 4.40	0.029
Blastocyst development rate (%)	36.72 ± 6.68	42.68 ± 5.73	0.499
Frozen embryos (n)	2.21 ± 0.61	3.05 ± 0.57	0.308
Endometrial thickness (mm)	10.32 ± 0.27	10.71 ± 0.25	0.288
Embryos transferred (n)	2.08 ± 0.09	2.04 ± 0.09	0.759
Cycles with embryo transfer (%)	70/114 (61.4)	69/114 (60.5)	0.892
Implantation rate (%)	18.57 ± 0.52	26.47 ± 0.62	< 0.001
Pregnancy rate (%)	15/70 (21.4)	20/69 (29.0)	0.303
Miscarriage rate (%)	5/15 (33.0)	1/20 (5.0)	0.031
OHSS rate (%)	3/114 (2.6)	6/114 (5.3)	0.308

Variable	rFSH group (n = 25)	rFSH + rLH group (n = 25)	p-value
Female age	32.00 ± 0.48	32.05 ± 0.54	0.942
Male age	36.26 ± 1.39	36.31 ± 1.66	0.981
BMI	25.54 ± 0.98	24.58 ± 1.03	0.500
FSH dose (IU)	2521.50 ± 138.76	2471.05 ± 159.17	0.811
LH dose (IU)	0.0	1235.53 ± 401.07	NA
Estradiol level (pg/mL)	1085.05 ± 399.49	1916.20 ± 357.31	0.322
Cycles triggered with GnRHa	1/25 (4.0)	2/25 (8.0)	0.551
Follicles (n)	12.12 ± 1.49	13.74 ± 1.71	0.475
Retrieved oocytes (n)	8.12 ± 1.09	9.84 ± 1.25	0.298
Oocyte yield (%)	70.98 ± 4.49	75.54 ± 5.16	0.505
MII oocyte rate (%)	68.08 ± 4.75	67.36 ± 5.44	0.920
Fertilization rate (%)	81.08 ± 4.47	72.83 ± 5.2	0.229
Normal cleavage speed rate (%)	71.79 ± 5.13	75.32 ± 5.97	0.654
D3 high-quality embryos rate (%)	42.97 ± 9.99	40.41 ± 12.24	0.871
Blastocyst development rate (%)	41.60 ± 12.12	47.44 ± 11.06	0.859
Frozen embryos (n)	1.50 ± 0.56	2.83 ± 0.64	0.118
Endometrial thickness (mm)	10.30 ± 0.59	10.87 ± 0.66	0.520
Embryos transferred (n)	2.33 ± 0.14	2.07 ± 0.17	0.223
Cycles with embryo transfer (%)	21/25 (84.0)	18/25 (72.00)	0.409
Implantation rate (%)	21.43 ± 1.01	38.46 ± 1.72	< 0.001
Pregnancy rate (%)	6/21 (28.57)	9/18 (50.00)	0.197
Miscarriage rate (%)	2/6 (33.33)	0/9 (0.0)	0.083
OHSS rate (%)	0/25 (0.0)	1/25 (4.0)	0.999

Variable	rFSH group (n = 89)	rFSH + rLH group (n = 89)	p-value
Female age	38.65 ± 0.29	39.06 ± 0.28	0.303
Male age	40.10 ± 0.68	40.67 ± 0.66	0.549
BMI	24.70 ± 0.47	24.70 ± 0.45	0.995
FSH dose (IU)	2913.69 ± 248.86	2738.16 ± 2369.51	0.611
LH dose (IU)	0.0	1369.08 ± 359.66	NA
Estradiol level (pg/mL)	1161.80 ± 215.94	1966.55 ± 220.13	0.009
Cycles triggered with GnRHa	8/89 (9.0)	8/89 (9.0)	> 0.999
Follicles (n)	9.39 ± 0.77	9.71 ± 0.75	0.772
Retrieved oocytes (n)	5.88 ± 0.54	6.79 ± 0.53	0.227
Oocyte yield (%)	61.28 ± 2.54	68.62 ± 2.46	0.038
MII oocyte rate (%)	67.61 ± 2.95	72.33 ± 2.83	0.248
Fertilization rate (%)	76.20 ± 2.81	73.06 ± 2.65	0.417
Normal cleavage speed rate (%)	65.72 ± 3.78	72.65 ± 3.57	0.184
D3 high-quality embryos rate (%)	32.01 ± 4.83	48.81 ± 4.69	0.013
Blastocyst development rate (%)	39.06 ± 7.34	45.10 ± 6.24	0.531
Frozen embryos (n)	2.42 ± 0.75	3.09 ± 0.67	0.508
Endometrial thickness (mm)	10.33 ± 0.30	10.68 ± 0.26	0.386
Embryos transferred (n)	1.98 ± 0.11	2.04 ± 0.10	0.712
Cycles with embryo transfer (%)	49/89 (55.06)	51/89 (57.30)	0.698
Implantation rate (%)	17.35 ± 0.60	23.64 ± 0.66	< 0.001
Pregnancy rate (%)	9/49 (18.37)	12/51 (23.53)	0.508
Miscarriage rate (%)	3/9 (33.33)	1/12 (8.33)	0.140
OHSS rate (%)	3/89 (3.4)	5/89 (5.6)	0.469

Variable	rFSH group (n = 51)	rFSH + rLH group (n = 51)	p-value
Female age	38.37 ± 0.54	38.93 ± 0.58	0.481
Male age	39.90 ± 0.89	39.97 ± 0.98	0.959
BMI	25.11 ± 0.45	24.23 ± 0.50	0.194
FSH dose (IU)	3051.60 ± 456.34	2536.05 ± 492.09	0.442
LH dose (IU)	0.0	1268.02 ± 442.97	NA
Estradiol level (pg/mL)	596.24 ± 101.87	725.51 ± 111.24	0.391
Cycles triggered with GnRHa	0/51 (0.0)	0/51 (0.0)	> 0.999
Follicles (n)	4.65 ± 0.30	4.33 ± 0.33	0.472
Retrieved oocytes (n)	2.29 ± 0.16	2.47 ± 0.18	0.481
Oocyte yield (%)	56.82 ± 1.31	63.29 ± 1.34	0.001
MII oocyte rate (%)	69.87 ± 1.34	78 + 12 ± 1.56	< 0.001
Fertilization rate (%)	79.46 ± 1.68	81.0 ± 1.8	0.533
Normal cleavage speed rate (%)	62.5 ± 1.08	75.83	< 0.001
D3 high-quality embryos rate (%)	32.47 ± 6.44	49.14 ± 7.32	0.087
Blastocyst development rate (%)	32.81 ± 7.23	33.20 ± 6.41	0.967
Frozen embryos (n)	0.71 ± 0.17	0.69 ± 0.19	0.957
Endometrial thickness (mm)	10.22 ± 0.45	10.10 ± 0.50	0.861
Embryos transferred (n)	1.68 ± 0.12	1.68 ± 0.13	0.992
Cycles with embryo transfer (%)	25/51 (49.02)	26/51 (50.98)	0.836
Implantation rate (%)	10.00 ± 0.63	20.45 ± 0.96	< 0.001
Pregnancy rate (%)	3/25 (12.00)	6/26 (23.08)	0.332
Miscarriage rate (%)	3/3 (100)	0/6 (0.0)	< 0.001
OHSS rate (%)	0/51 (0.0)	0/51 (0.0)	0.999

Variable	rFSH group (n = 63)	rFSH + rLH group (n = 63)	p-value
Female age	36.24 ± 0.44	37.27 ± 0.42	0.092
Male age	38.78 ± 0.86	39.95 ± 0.83	0.322
BMI	24.68 ± 0.66	24.94 ± 0.60	0.770
FSH dose (IU)	2648.61 ± 75.42	2789.08 ± 71.04	0.175
LH dose (IU)	0.0	1394.54 ± 308.62	NA
Estradiol level (pg/mL)	1725.74 ± 303.65	2788.37 ± 281.12	0.010
Cycles triggered with GnRHa	9/63 (14.3)	10/63 (15.9)	0.803
Follicles (n)	14.32 ± 0.91	14.04 ± 0.86	0.826
Retrieved oocytes (n)	9.67 ± 0.61	10.23 ± 0.57	0.503
Oocyte yield (%)	75.37 ± 1.99	82.69 ± 1.78	0.006
MII oocyte rate (%)	73.33 ± 1.43	71.8 ± 1.69	0.489
Fertilization rate (%)	78.31 ± 2.65	72.40 ± 2.51	0.105
Normal cleavage speed rate (%)	70.02 ± 3.16	72.54 ± 3.00	0.565
D3 high-quality embryos rate (%)	35.80 ± 5.96	46.78 ± 5.45	0.174
Blastocyst development rate (%)	41.79 ± 11.63	53.29 ± 9.59	0.445
Frozen embryos (n)	3.71 ± 0.99	4.23 ± 0.80	0.680
Endometrial thickness (mm)	10.40 ± 0.33	10.98 ± 0.27	0.182
Embryos transferred (n)	2.29 ± 0.107	2.21 ± 108	0.603
Cycles with embryo transfer (%)	45/63 (71.43)	42/63 (66.67)	0.513
Implantation rate (%)	23.33 ± 0.72	29.35 ± 0.80	< 0.001
Pregnancy rate (%)	12/43 (27.91)	13/42 (30.95)	0.579
Miscarriage rate (%)	2/12 (16.67)	1/13 (7.69)	0.425
OHSS rate (%)	3/63 (4.76)	6/63 (9.52)	0.299

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[1] Address for correspondence Amanda Setti, M.Sc., Av. Brigadeiro Luis Antonio, 4545, 01401-002, São Paulo, SP, Brazil (e-mail: amanda@sapientiae.org.br).