Table I.
Characterization of transcriptomic studies evaluating uterine disorders. A) Clinical characterization of participants and study designs.
| GEO ID (Study name) | UD | Diagnostic and Sub-classification of the studied uterine disorder | Cycle type | Cycle phase dating method | N° Samples per cycle phase | Age | BMI |
|---|---|---|---|---|---|---|---|
| GSE6364 (Burney 2007) | EU | Laparoscopy proven, surgically documented and histologically validated. Subtype: Ovaric, peritoneal, rectovaginal. Stage: III–IV (rAF) (The American Fertility Society) | Natural; Regular; 3 months without hormonal treatment | 4 blind histopathologists (Noyes et al., 1975). | PF (n = 11), ESE (n = 9), MSE (n = 17) |
D: 22–44. C: N/A |
N/A |
| GSE23339 (Hawkins 2011) | EC | Surgical pathology reports. Subtype: Ovaric. | Regular; 30 days without hormonal treatment | Last menstrual period confirmed by pathology | PF (n = 12), S (n = 2) |
D : 20–43. C : 39–48 |
N/A |
| EU | Laparoscopy proven. Subtype: Ovaric, peritoneal, pelvic, vaginal, rectovaginal. Stage: I–II (n = 16), III–IV (n = 37) (rAF) (American Society for Reproductive Medicine, 1997) | 3 months without hormonal treatment | 2 pathologists (Noyes et al., 1975), confirmed by serum estradiol and P4 levels and corroborated by 2 independent bioinformatics methods: clustering in unsupervised whole-transcriptome principal component analysis and cycle phase assignment classifier analysis |
PF (n = 34), ESE (n = 15), MSE (n = 32) PF (n = 23), ESE (n = 7), MSE (n = 12), LSE (n = 1). |
E : 20–48. UF : 40–50. C : 23–40. |
N/A | |
| UF | Participants’ operative and pathology reports | N/A | |||||
| RIF |
≥ 3 failed IVF/ICSI or ≥10 good quality transferred embryos without pregnancy after IVF/ICSI. P: Previous implantations: 0–1. Embryo implantations: 3–12. Embryos replaced: 3–1. C: Previous implantations: 1. Embryo implantations: 1–7, 18. Embryos replaced: 1–8, 30. |
Natural. Regular (25–35 days), 30 days without hormonal treatment | Urinary LH ovulation predictor kit | LH + 5 (n = 8), LH + 6 (n = 27), LH + 7 (n = 70), LH + 8 (n = 10). | D: 27–38 C: 26–39 |
D: 19–37 C: 19–53 |
|
| RIF |
≥ 2 IVF cycles/ET with good quality embryos without previous conception (Polanski et al., 2014) |
Controlled ovarian stimulation | Days from first administration of hCG | hCG + 6 (n = 13), hCG + 7 (n = 5) |
D : 27–40 C : 21–30 |
N/A | |
| RPL | ≥ 3 1st trimester losses | Natural. 3 months without hormonal treatment | LH surge | LH + 6 (n = 3), LH + 7 (n = 5), LH + 8 (n = 6), LH + 9 (n = 4), LH + 10 (n = 2). | D: 31–40 C: 31–44 | D: 22–32 C: 18–33 |
| A) Clinical characterisation of participants and study designs. | |||||
|---|---|---|---|---|---|
| GEO ID (Study name) | Ethnicity | N° Cases and Controls (D) (C) | N° Evaluated Genes | Platform | Ref. |
| GSE6364 (Burney 2007) |
D: Caucasian (n = 13), Asian (n = 4), Black (n = 1), Asian Indian (n = 1), unknown (n = 2). C: N/A |
(21) (16) | 19 361 | hgu133plus2 Affymetrix | (Burney et al., 2007) |
| GSE23339 (Hawkins 2011) |
D: Latina (n = 5), Caucasian (n = 2). C: Latina (n = 5), African American (n = 2) |
(7) (7) | 24 613 | Illumina human-6 v2.0 expression beadchip | (Hawkins et al., 2011) |
|
E: Caucasian (n = 38), Asian (n = 4), Black (n = 1), Asian Indian (n = 1), Hispanic (n = 1), unknown (n = 8). UF: Caucasian (n = 11), Asian (n = 1), Black (n = 3). C: Caucasian (n = 19), Asian (n = 4), Black (n = 3), Hispanic (n = 1), unknown (n = 1) |
(53) (28) | 19 361 | hgu133plus2 Affymetrix | (Tamaresis et al., 2014) | |
| (15) (28) | 19 361 | ||||
| N/A | (43) (72) | 21 773 | Agilent G2565BA Scanner | (Koot et al., 2016) | |
| Indian | (10) (8) | 31 426 | Illumina Human HT-12 V4.0 expression beadchip | (Pathare et al., 2017) | |
| N/A | (10) (10) | 21 332 | Illumina HiSeq 2000 | (Lucas et al., 2016) | |
| B) Comparison between case and control groups in relation to the menstrual cycle phase of endometrial biopsy collection. | ||||
|---|---|---|---|---|
| Study | UD | N.° Samples per cycle phase |
Fisher P-value | |
| Cases | Controls | |||
| Burney 2007 |
EU |
PF (n = 6), ESE (n = 6), MSE (n = 9) |
PF (n = 5), ESE (n = 3), MSE (n = 8) |
00.834 |
| Hawkins 2011 | EC | PF (n = 6), S (n = 1) | PF (n = 6), S (n = 1) | 1 |
| Tamaresis 2014 | EU | PF (n = 18), ESE (n = 11), MSE (n = 24). | PF (n = 16), ESE (n = 4), MSE (n = 8) | 0.150 |
| UF | PF (n = 7), ESE (n = 3), MSE (n = 4), LSE (n = 1) | PF (n = 16), ESE (n = 4), MSE (n = 8) | 0.618 | |
| Koot 2016 | RIF | LH + 5 (n = 2), LH + 6 (n = 13), LH + 7 (n = 26), LH + 8 (n = 2) | LH + 5 (n = 6), LH + 6 (n = 14), LH + 7 (n = 44), LH + 8 (n = 8) | 0.398 |
| Pathare 2017 | RIF | hCG + 6 (n = 8), hCG + 7 (n = 2) | hCG + 6 (n = 5), hCG + 7 (n = 3) | 0.608 |
| Lucas et al., 2016 | RPL | LH + 6 (n = 2), LH + 7 (n = 1), LH + 8 (n = 3), LH + 9 (n = 2), LH + 10 (n = 2) | LH + 6 (n = 1), LH + 7 (n = 4), LH + 8 (n = 3), LH + 9 (n = 2) | 0.529 |
(A) Clinical characterisation of participants and study designs. The GEO identifier, study name given in this work, uterine disorder and clinical information about participants including diagnostic method and sub-classification of patients belonging to the case group, cycle type, endometrial dating method, cycle phase in which the endometrial biopsies were collected along with number of samples collected at each menstrual cycle phase, age, BMI, ethnicity and number of samples for both case and control groups are presented for each study. The transcriptomic platform used to measure gene expression and the publication in which data were initially employed are also presented together with the number of evaluated genes. Tamaresis 2014 includes samples from both endometriosis and uterine fibroid patients along with controls. N/A, not available. D, patients belonging to the case the control group. GEO ID, Gene Expression Omnibus identifier. UD, uterine disorder. BMI, body mass index. RIF, recurrent implantation failure. RPL, recurrent pregnancy loss. EU, eutopic endometriosis. EC, ectopic endometriosis. UF, uterine fibroids. rAF, revised American Fertility Society classification system. LH, luteinizing hormone. AMH, anti-müllerian hormone. ET, embryo transfer. FSH, follicle-stimulating hormone. PF, proliferative. ESE, early secretory. MSE, mid-secretory. LSE, late secretory. S, secretory. ICSI, intracytoplasmic sperm injection. IVF, in vitro fertilisation. PCOS, polycystic ovary syndrome. (B) For each study, the number of samples collected at each stage of the menstrual cycle is indicated independently for cases and controls, together with the two-sided Fisher’s exact test P-value obtained after evaluating whether the proportion of samples collected at each endometrial stage significantly differed between groups.