Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in “freeze-all” approach

Figures & data

Table 1. Classification of mild, moderate and severe OHSS according to Golan’s system [24].

Mild	Clinical features
	Grade 1	Abdominal distension and discomfort
	Grade 2	Features of Grade 1 plus nausea/vomiting and/or diarrhea. Ovaries enlarged to 5–12 cm.
Moderate
	Grade 3	Features of mild OHSS plus ultrasonic evidence of ascites.
Severe
	Grade 4	Features of moderate OHSS plus clinical evidence of ascites and/or hydrothorax (or breathing difficulties). Paracentesis due to OHSS symptoms.
	Grade 5	All of the above plus change in blood volume, increased blood viscosity due to hemoconcentration, coagulation abnormalities, and diminished renal perfusion and function. Hospitalization due to OHSS symptoms.

OHSS, ovarian hyperstimulation syndrome.

Table 2. Baseline characteristics of all women who received a GnRH agonist trigger.

	All high responders* N = 77	High responders* with OHSS N = 17	High responders without OHSS N = 60
Age (years)	32.3 ± 3.5	32.8 ± 3.4	32.1 ± 3.5
Body weight (kg)	58.4 ± 10.2	61.7 ± 11.8	57.5 ± 9.6
BMI (kg/m^2)	21.9 ± 3.2	23.4 ± 3.2	21.5 ± 3.1
Race (n, (%))
White	45 (58.4%)	8 (47.1%)	37 (61.7%)
Asian	31 (40.3%)	8 (47.1%)	23 (38.3%)
Black or African	1 (1.3%)	1 (5.9%)	–
Infertility history
Duration of infertility (months)	37.4 ± 32.0	30.0 ± 9.7	39.5 ± 35.7
Primary infertility	57 (74.0%)	13 (76.5%)	44 (73.3%)
Reason for infertility
Unexplained infertility	22 (28.6%)	5 (29.4%)	17 (28.3%)
Tubal infertility	18 (23.4%)	3 (17.6%)	15 (25.0%)
Male factor	36 (46.8%)	8 (47.1%)	28 (46.7%)
Endometriosis stage I/II	1 (1.3%)	1 (5.9%)	–
Ovarian volume (cm^3)	6.7 ± 2.9	6.4 ± 2.7	6.8 ± 2.9
AFC	21.5 ± 9.2	17.9 ± 7.9	22.5 ± 9.4
Endocrine profile
AMH (pmol/l)	42.4 ± 20.7	40.9 ± 24.7	42.8 ± 19.7
FSH (IU/l)	6.3 ± 1.6	6.1 ± 1.8	6.3 ± 1.5
LH (IU/l)	5.2 ± 2.6	4.1 ± 1.5	5.5 ± 2.7
Estradiol (pmol/l)	167.0 ± 75.3	157.9 ± 51.7	169.6 ± 81.0
Progesterone (nmol/l)	2.1 ± 2.5	1.6 ± 0.9	2.2 ± 2.7
Inhibin B (ng/l)	102.3 ± 36.6	110.0 ± 31.3	100.2 ± 37.8

*High responders had 25–35 follicles with diameter ≥12 mm at day of triggering and had opted to receive a GnRH agonist trigger and freeze all embryos.

AFC, antral follicle count; AMH, anti-Müllerian hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinising hormone; OHSS, ovarian hyperstimulation syndrome.

Figure 1. Probability of OHSS vs E₂ per follicle with diameter ≥ 12 mm at end of ovarian stimulation E_2, estradiol, OHSS, ovarian stimulation.

Table 3. Ovarian stimulations in high responders triggered with a GnRH agonist.

	All high responders* N = 77	High responders with early OHSS N = 17	High responders without OHSS N = 60
Duration of stimulation (days)	9.5 ± 1.6	9.3 ± 1.1	9.5 ± 1.7
Number of follicles at EOS
≥12 mm	26.5 ± 4.4	25.2 ± 4.9	26.9 ± 4.3
≥17 mm	8.8 ± 4.7	8.2 ± 5.8	9.0 ± 4.3
Hormones at EOS
E2 (pmol/l) E2/follicle ≥12 mm	17,159 ± 9,757 662 ± 389	19,558 ± 9,549 819 ± 469	16,479 ± 9,787 617 ± 355
Progesterone (nmol/l)	5.1 ± 2.7	5.3 ± 2.2	5.1 ± 2.9
Inhibin B (ng/l)	2477.1 ± 894.5	2626.7 ± 822.9	2437.2 ± 915.0
Inhibin A (ng/l)	905.6 ± 429.5	1021.8 ± 433.5	872.6 ± 426.2
Number of oocytes retrieved
Mean ± SD	23.1 ± 9.1	23.9 ± 8.9	22.9 ± 9.2
Median [IQR]	22.0 [16.0–30.0]	24.0 [17.0–31.0]	22.0 [16.0–30.0]
Range (min–max)	2–44	10–41	2–44

*High responders had 25–35 follicles with diameter ≥12 mm at day of triggering and had opted to receive a GnRH agonist trigger and freeze all embryos.

E_2, estradiol; EOS, end of stimulation; GnRH, gonadotropin-releasing hormone; IQR, interquartile range; OHSS, ovarian hyperstimulation syndrome, SD, standard deviation.

Table 4. Characteristics and symptoms of each woman with early OHSS following GnRH agonist triggering.

Subject number	Patient and stimulation characteristics						Signs and symptoms of OHSS				Other
	Age (yrs)	Body weight (kg)	AMH (pmol/L)	Number of follicles ≥12 mm	Serum estradiol (pmol/L)	Oocytes	Abdominal Distension/ Discomfort	Enlarged ovaries (cm)	Nausea (N) Vomiting (V) Diarrhea (D)	Ultrasonic evidence of ascites (cm^2)	Duration (days)	Related Medication
Spain-1	33	60.2	25.4	29	17,745	33	Yes	–	–	–	9	–
UK-1	38	77.3	73.6	29	13,382	35	Yes	–	–	–	6	–
Czech-1	34	62.4	119.0	30	32,871	41	Yes	5.5 × 7.0	–	–	10	LMWH, A, C, HES, RS
Russia-1	39	73.9	15.0	19a	6466	10	Yes	–	–	16	8	HES
Italy-1	39	72.2	36.5	25	4201	12	Yes	6.5 × 5.3	–	9.8	9	–
Italy-2	29	73.9	29.8	30	12,736	12	Yes	5 × 6	–	–	10	–
Denmark-1	32	90.3	31.8	26	9351	20	Yes	6.1 × 5.4	N + D	2.1	13	–
Brazil-1	32	47.1	24.0	20a	20,515	27	–	6.0 × 8.5	–	12	7	C
Brazil-2	33	55.5	46.2	28	25,057	32	Yes	6.2 × 6.4	N	4.0	10	C
Japan-1	27	53.1	19.7	27	12,747	24	Yes	5 × 5	N	–	15	–
Japan-2	32	52.8	46.2	27	26,944	21	Yes	5.6 × 4.7	–	–	8	C
Japan-3	33	56.8	24.4	18a	24,040	17	Yes	6.2 × 5.3	–	–	12	C
Japan-4	31	58.0	34.5	15a	23,326	16	Yes	–	–	8.4	10	C
Japan-5	34	56.4	40.0	19a	34,281	22	Yes	4.7 × 5.2	–	1.2	10	C
China-1	32	57.7	57.4	30	36,000	27	Yes	6.3 × 5.0	–	4.2	21	L
China-2	32	53.2	41.3	27	18,532	26	Yes	7.2 × 6.1	–	6.4	19	L
China-3	28	47.6	30.9	29	14,299	31	Yes	7.2 × 7.3	–	5.4	14	–

^aCriteria for triggering with GnRH agonist not met.

LMWH, Low Molecular Weight Heparin; A, albumin; C = cabergoline; HES, hydroxyethyl starch; RS, ringer solution; L, letrozole.

Golan A, Ron-el R, Herman A, et al. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989; Jun44(6):430–440.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.