The natural cycle protocol of endometrial preparation for frozen embryo transfer decreases the miscarriage rate in women with recurrent pregnancy loss

Figures & data

Table 1. Baseline characteristics of patients between two endometrial preparation protocols.

Characteristics	HRT (n = 797)	NC (n = 111)	Z	p Value
Women’s age (years)
At oocyte retrieve	33.82 ± 5.23	33.83 ± 5.14		.989
At embryo’s transfer	34.35 ± 5.24	34.17 ± 5.13		.739
Women’s BMI (kg/m^2)	22.73 ± 2.90	22.43 ± 2.68		.309
Infertility duration (months)	23.04 ± 22.8	23.64 ± 29.52		.821
Number of previous FET cycles (n)	1 (1, 7)a	1 (1, 4)a	−2.895	.004
Number of previous miscarriages (n)	2 (2, 7)a	2 (2, 5)a	−0.678	.497
Type of recurrent pregnancy loss				.163
Primary	77.2 (615/797)	71.2 (79/111)
Secondary	22.8 182/797)	28.8 (32/111)
Cause of recurrent pregnancy loss				.352
Explained	62.1 (495/797)	66.7 (74/111)
Unexplained	37.9 (302/797)	33.3 (37/111)
Abnormal parental karyotype rate (%)	2.89 (23/797)	2.70 (3/111)		.914
Abnormal uterus rate (%)	12.6 (100/797)	13.5 (15/111)		.774
Antiphospholipid antibody positive rate (%)	3.1 (25/797)	3.6 (4/111)		.793
Abnormal protein S rate (%)	2.0 (16/797)	2.7 (3/111)		.632
Abnormal protein C rate (%)	1.9 (15/797)	1.8 (2/111)		.953
Rate of hypothyroidism (%)	16.1 (128/797)	15.3 (17/111)		.841
Rate of hyperthyroidism (%)	1.9 (15/797)	2.7 (3/111)		.561
Previous miscarriage type (n)				.073
Miscarriage after spontaneous	89.1 (710/797)	94.6 (105/111)
Miscarriage after IVF	10.9 (87/797)	5.4 (6/111)
Abnormal karyotype in previous miscarriage tissue (%)	11.4 (91/797)	14.4 (16/111)		.359
Basal AFC (n)	11.56 ± 6.43	9.28 ± 5.63		<.001
Fertilization type (%)				.471
IVF	62.1 (495/797)	58.6 (65/111)
ICSI	37.9 (302/797)	41.4 (46/111)
Protocol in fresh cycle (%)				.180
Agonist	47.9 (382/797)	38.7 (43/111)
Antagonist	40.4 (322/797)	48.6 (54/111)
Minimal ovarian stimulation	11.7 (93/797)	12.6 (14/111)

HRT: hormone replacement therapy; NC: natural cycles; BMI: body mass index; FET: frozen embryo transfer; AFC: antral follicle count; IVF: in vitro fertilization; ICSI: intracytoplasmic sperm injection.

^a These numbers mean the median and range.

Table 2. Clinical outcomes of patients between two endometrial preparation protocols.

Clinical outcomes	HRT (n = 797)	NC (n = 111)	Z	p Value
Number of oocytes retrieved (n)	10.90 ± 6.80	8.98 ± 5.81		.005
Endometrial thickness on the day of P administration (mm)	9.35 ± 1.77	10.35 ± 2.04		<.001
Number of embryos transferred (n)	1 (1, 3)a	1 (1, 2)a	−1.564	.118
Number of good quality embryos transferred (n)	1 (0, 2)a	1 (0, 2)a	−1.859	.063
Type of embryos transferred (%)				.788
Cleavage stage	34.6 (276/797)	33.3 (37/111)
Blastocyst stage	65.4 (521/797)	66.7 (74/111)
Implantation rate (%)	42.5 (477/1122)	46.9 (69/147)		.308
Clinical pregnancy rate (%)	53.3 (425/797)	57.7 (64/111)		.568
Biochemical pregnancy rate (%)	64.2 (512/797)	65.8 (73/111)		.753
Miscarriage rate (%)	29.4 (125/425)	17.2 (11/64)		.042
Ectopic rate (%)	0.9 (4/425)	1.6 (1/64)		.645
Preterm birth rate (%)	12.2 (52/425)	7.81 (5/64)		.304
Live birth rate (%)	37.0 (295/797)^b	46.9 (52/111)		.046

^aThese numbers mean the median and range.

^b One patient in HRT group induced labor because of fetus malformation at 29 weeks.

Table 3. Univariate analysis for the miscarriage rate.

Univariate	Statistics	OR (95% CI)	p Value
Women’s age (age)
At oocyte retrieve	33.82 ± 0.17	1.089 (1.040, 1.140)	<.001
At embryo transfer	34.33 ± 0.17	1.098 (1.049, 1.151)	<.001
Women’s BMI (kg/m^2)	22.69 ± 0.10	1.001 (0.935, 1.071)	.981
Number of previous FET cycles (n)	1.58 ± 0.03	1.122 (0.920, 1.369)	.256
Number of previous miscarriages (n)	2.52 ± 0.03	1.106 (0.865, 1.414)	.420
Basal AFC (n)	11.28 ± 0.21	1.000 (0.969, 1.032)	.981
Number of oocytes retrieved (n)	10.67 ± 0.22	0.990 (0.961, 1.020)	.517
Endometrial thickness on the day of P administration (mm)	9.47 ± 0.06	0.909 (0.808, 1.024)	.117
Number of good quality embryos transferred (n)	0.75 ± 0.02	0.934 (0.658, 1.325)	.700

Table 4. Relationship between endometrial preparation protocols and the miscarriage rate.

	Crude model		Adjusted model I		Adjusted model II
Endometrial preparation	β (95% CI)	p Value	β (95% CI)	p Value	β (95% CI)	p Value
NC	Reference
HRT	2.008 (1.015, 3.971)	.045	2.004 (1.003, 4.003)	.049	2.194 (1.071, 4.497)	.032

Data availability statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.