Investigating the impact of different strategies for endometrial preparation in frozen cycles considering normal responders undergoing IVF/ICSI cycles: a multicenter retrospective cohort study

Figures & data

Table 1. Descriptive characteristics of the study population [reported as total number (percentage) for counts]

		Estrogen administration		Progesterone administration				Endometrial preparation
	Total	Increasing	Stable	IM	Gel	Tabs	Combination	Natural, with P4	Natural, without P4	HRT, with GnRH	HRT, without GnRH
Cycles (Women)	456 (311)	55 (12)	397 (88)	1 (0.2)	38 (8.3)	366 (80.3)	50 (11)	14 (3.1)	61 (13.4)	159 (35.3)	221 (48)
• 1^st cycle	336	38 (11.6)	296 (88.1)	1 (0.3)	24 (6.2)	272 (85.1)	38 (8.3)	11 (3.3)	35 (11)	149 (44.3)	140 (41.4)
• 2^nd cycle	80	14 (7.3)	66 (90.2)	0 (0)	11 (13.4)	61 (72)	9 (11)	3 (3.7)	21 (25.6)	9 (11)	48 (58.5)
• 3^rd cycle	19	1 (5.3)	18 (94.7)	0 (0)	3 (15.8)	14 (73.7)	2 (10.5)	0 (0)	3 (15.8)	1 (5.3)	15 (78.9)
• >4^th cycle	6	0 (0)	6 (100)	0 (0)	0 (0)	6 (100)	0 (0)	0 (0)	1 (16.7)	0 (0)	5 (83.3)
Mean age (SD)	35.35 (4.6)	33.76 (2.5)	35.49 (4.4)**	44	36.5 (3.8)	35.4 (4.23)	33. 6 (4.22)*	36.14 (3.23)	35.82 (3.77)	36.03 (5.5)	34.57 (3.12)**
BMI 25–29.9 kg/m^2 (%)	256 (56.1)	13 (25.5)	248 (62.47)	0 (0)	22 (65.8)	204 (54.6)	36 (62)**	13 (92.9)	39 (59.02)	135 (77.3)	85 (38.4)
Subfertility type
•Tubal	-	6 (8.8)	62 (91.2)	0 (0)	5 (7.9)	43 (77.8)	8 (12.7)	1 (1.6)	15 (23.8)	3 (4.8)	43 (68.3)
•Male	-	30 (11.7)	223 (87.2)	0 (0)	18 (7)	219 (80.5)	32 (12.5)	11 (4.3)	28 (10.9)	120 (46.7)	98 (38.1)
•Male + Tubal	-	3 (11.1)	24 (88.9)	1 (3.7)	4 (14.8)	21 (77.8)	1 (3.7)	0 (0)	5 (18.5)	6 (22.2)	16 (59.3)
•Not otherwise explained	-	16 (18.2)	71 (80.7)	0 (0)	6 (6.8)	75 (85.2)	7 (8)	1 (1.1)	8 (9.1)	32 (36.4)	47 (53.4)
•PCOS	-	0 (0)	16 (100)	0 (0)	3 (18.8)	11 (68.8)	2 (12.5)	1 (6.3)	4 (25)	0 (0)	11 (68.7)
•Endometriosis	-	0 (0)	4 (100)	0 (0)	2 (50)	2 (50)	0 (0)	0 (0)	1 (25)	0 (0)	3 (75)
Basal FSH (IQR)	-	6.15 (1.82)	6.99 (4.78)*	NA	7.2 (2.63)	6.97 (4.91)	6.08 (1.52)	5.99 (1.83)	6.41 (1.76)	8.57 (9.59)	6.48 (2.19)
Basal LH (IQR)	-	6.43 (3.19)	7.27 (9.98)	3.7	7.02 (7.4)	7.08 (9.98)	7.21 (3.31)	4.50 (1.93)	6.33 (2.63)	11.1 (21.7)	6.50 (3.89)
Basal TSH (IQR)	-	2.06 (1.17)	2.10 (1.60)	2.12	1.66 (0.9)	2.06 (1.16)	2.75 (3.23)**	1.92 (0.78)	1.74 (1.03)	2 (0.96)	2.21 (1.74)
Positive hCG test (%)	120	6 (14.6)	110 (28.42)	0	9 (23.68)	100 (29.07)	9 (19.15)	2 (15.4)	8 (13.1)	69 (43.4)	39 (19.8) **
Clinical pregnancy at 7 weeks	90	4 (9.52)	84 (21.9)	0	7 (18.4)	77 (23.4)	3 (6.4)	0	4 (6.6)	62 (39.6)	24 (11.62) **
Live birth	74	1 (50)	71 (21.5)	0	4 (10.5)	66 (25.7)	1 (3.8)	0	4 (6.56)	58 (36.48)	9 (9.89) **
Twin pregnancy
•Yes	18	0 (0)	18 (100)	0 (0)	2 (11.1)	14 (77.8)	2 (11.1)	0 (0)	3 (16.7)	8 (44.4)	7 (38.9)
•No	437	3 (1)	434 (99)	0 (0)	30 (10.2)	241 (82)	23 (7.8)	10 (3.4)	57 (19.4)	151 (51.4)	76 (25.9)

In the BMI group row, percentages represent the number of women that were within the specified BMI range out of all women having undergone the specific intervention, for example 25.5% of women having undergone the increasing estrogen protocol had a BMI of 25–29.9. Women with BMI in the normal range were significantly more likely to be administered a stable estrogen protocol (62.47%) and less likely to undergo an HRT cycle without GnRH (41.1%). Differing values (Student’s t-test) are marked as follows. *: p < 0.05, **: p < 0.01, ***: p < 0.001. Differing values as indicated by pairwise comparisons (Wilcoxon test) are marked in bold. In the number of cycles and BMI groups, the figures do not add up to the complete number of women due to data missingness.

Table 2. Relative Risks for Exposures and Outcomes

Outcomes Exposures	POSITIVE HCG TEST	Clinical Pregnancy	Live Birth	Miscarriage
Estrogen Protocol	-	-	-	-
Increasing	-	Reference	-	-
Stable	0.44(0.18,1.07)	0.37(0.13,1.09)	1.72(0.15,19.26)	NA
Progesterone Protocol	-	-	-	-
Tabs	-	Reference	-	-
Gel	0.77(0.35,1.69)	0.75 (0.28,2.07)	0.93 (0.10, 1.04)	2.40 (0.77,7.50)
Combination	0.59(0.27,1.26)	0.19 (0.05,0.71)	0.10 (0.01, 0.80)	0.19 (0.05,0.71)
EndometrialPreparation	-	-	-	-
Group 4	-	Reference	-	-
Group 1	0.73 (0.15, 3.44)	NA	NA	NA
Group 2	0.61(0.27,1.38)	0.52 (0.17,1.61)	0.62 (0.18, 2.20)	0.50 (0.15,1.66)
Group 3	3.09(1.93,4.94)	5.22 (2.82,9.63)	5.87(2.44,14.14)	0.19(0.06,0.60)
EndometrialPreparation2	-	-	-	-
Group 4	-	Reference	-	-
Group 1 + 2	0.61(0.27,1.38)	0.52 (0.17,1.61)	0.62 (0.18, 2.13)	0.50 (0.15,1.66)
GROUP 3	3.09(1.93,4.94)	5.22(2.82,9.63)	5.87(2.44,14.14)	0.19(0.06,0.6

Table 3. Adjusted relative risks for exposures and outcomes

Outcomes / Exposures	Positive hCG test	Clinical pregnancy	Live birth	Miscarriage
Estrogen Protocol	-	-	-	-
Increasing	-	Reference	-	-
Stable	0.49 (0.19, 1.25)	0.39 (0.12, 1.30)	1.88 (0.10, 33.9)	NA
Progesterone protocol
Tabs	-	Reference	-	-
Gel	0.70 (0.30, 1.63)	0.83 (0.31, 2.25)	0.43 (0.13, 1.50)	0.80 (0.17, 3.64)
Combination	0.49 (0.22, 1.13)	0.18 (0.05, 0.71)	0.12 (0.01, 1.07)	1.95 (0.36, 10.49)
Endometrial Preparation	-	-	-	-
Group 4	-	Reference	-	-
Group 1	0.76 (0.15, 3.72)	NA	NA	NA
Group 2	0.63 (0.27, 1.46)	0.55 (0.18, 1.74)	0.67 (0.17, 2.61)	0.47 (0.14, 1.65)
Group 3	3.49 (1.98, 6.15)	5.64 (2.71, 11.8)	5.77 (2.25, 14.82)	0.26 (0.07, 0.95)
Endometrial preparation 2	-	-	-	-
Group 4		Reference
Group 1 + 2	0.65 (0.30, 1.42)	0.47 (0.15, 1.47)	0.54 (0.54, 0.56)	0.42 (0.12, 1.45)
Group 3	3.47 (1.97, 6.11)	5.78 (2.75, 12.14)	5.68 (5.63, 5.73)	0.26 (0.07, 0.98)

Multivariable Logistic Regression Models, with mixed effects, were used to adjust for the confounders of age, BMI and type of infertility.