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. 2022 Sep 18;12(9):2250. doi: 10.3390/diagnostics12092250
Authors and Year Study Design, Country, and Period of Enrollment Participants and Main Inclusion Criteria IVF-ET Cycle Methods Diagnostic Criteria of CE Groups Outcomes
Cicinelli et al. 2015 [4] Retrospective study
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Italy
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January 2009–June 2012
106 RIF patients undergoing IVF-ET cycle
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-Unexplained infertility
-Age < 40 years
-At least 6 good quality embryos transferred in ≥3 previous IVF/ICSI cycles
-Normal karyotype
-FSH on day 3 ≤10 mUI/mL
-BMI ≤ 30 kg/m2
-No previous surgery for myoma and/or endometriosis
-No condition interfering with immune system
-No antiphospholipid syndrome or thrombophilic
condition
-No antisperm antibodies
-GnRH-ant with flexible or fixed scheme
-rFSH (175–225 IU/day)
-U-Hcg (10,000 UI) at follicle size 17 mm (≥2).
-Egg retrieval 34 h after ovulation induction
-≤3 embryos transferred (of which at least one with good quality) on day 3 of culture
-Luteal phase support with vaginal progesterone
-Diagnostic HSC
-EB
-HIS examination
-Endometrial culture
-Antibiotic therapy
(when appropriate)
-Control EB
-IVF cycle
1–5 plasma cells/HPF or discrete clusters of <20 plasma cells by CD138 staining Group A: patients with cured CE (n = 46)
Group B: patients with persistent CE (n = 15)
-Clinical pregnancy rate
-Ongoing pregnancy/live birth rate
-Miscarriage rate
Demirdag et al. 2021 [11] Retrospective study
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Turkey
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September 2016–December 2019
1164 patients undergoing IVF-ET cycle (232 RIF)
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-At least 4 good quality embryos transferred in ≥3 previous IVF/ICSI cycles
-Age < 40 years
-Normal karyotype
-Normal uterine cavity
-normal antiphospholipid
antibody testing
-no previous surgery for myoma and/or endometriosis
-no male factors infertility
- no autoimmune diseases, antiphospholipid antibody syndrome,
endocrinological disorders
Exogenous gonadotropins, rFSH alone or with hMG
- GnRH antagonist cetrorelix at follicle size ≥14 mm or E2 > 300 pg/mL
-rhCG (250 mcg) at follicle size 18 mm (≥2).
-Egg retrieval 36 h after ovulation induction
-1 to 2 top-quality embryos transferred on day 3 or 5
-Luteal phase support with vaginal progesterone
-EB
- HIS examination
-Antibiotic therapy (when appropriate)
-IVF cycle
≥1 plasma cell/HPF Group 1: patients with treated CE (n = 129)
Group 2: patients without CE (n = 103)
Group 3: patients undergoing the first IVF cycle (n = 932)
-Implantation rate
-Clinical pregnancy rate
-Live birth rate
Fan et al. 2019 [33] Retrospective study
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China
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December 2016–July 2018
141 patients undergoing 1 IVF-ET cycle
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-At least 2 high quality fresh embryos transferred in a previous IVF/ICSI cycle
-Age 20–38 years
BMI: 18–25 Kg/m2
- Normal uterine cavity
-no endometriosis, adenomyosis, hydrosalpinx, fibroids
- -EB
-HIS examination
--IVF cycle
Two methods:
≥1 plasma cell/section
or
≥1 plasma cell/mm2
Group 1: <1 CD138+(n = 97)
Group 2: ≥1 CD138+ (n = 44)
-Implantation rate
-Clinical pregnancy rate
Hirata et al. 2021 [32] Prospective study
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Japan
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June 2014–September 2017
53 patients undergoing IVF-ET cycle
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-Age <41 years
-Normal uterine cavity
-Unexplained infertility
- No history of RIF or RPL
- No genetic disorders, endocrine diseases or autoimmune diseases
-GnRH-a or GnRH ant protocol
-oocyte retrieval and blastocyst freezing
-Single blastocyst transfer within 90 days of endometrial tissue sampling with a hormone replacement cycle
-Oocyte retrieval and blastocyst freezing
-Diagnostic HSC
-EB
-HIS examination
- single blastocyst transfer
Four different diagnostic criteria:
-≥1 plasma cell/10 HPFs
-≥2 plasma cell/10 HPFs
-≥3 plasma cell/10 HPFs
-≥4 plasma cell/10 HPFs
Based on the diagnostic criterion: (≥1; ≥2; ≥3, ≥4)
Group A: patients with CE (26; 19; 14; 11)
Group B: patients without CE (27; 34; 39; 42)
-Clinical pregnancy rate
-Live birth rate
-Miscarriage rate
Johnston-MacAnanny et al. 2010 [6] Prospective study
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USA
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2001–2007
518
RIF patients undergoing IVF-ET cycle
33 with an EB and 485 without an EB
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-At least 1 good quality embryos transferred in ≥2 previous IVF/ICSI cycles
-GnRH-a or GnRH ant protocol
-rFSH alone or with hMG
-U-Hcg (5000 or 10000 UI) at follicle size 17 mm (≥2).
-Egg retrieval 35 h after ovulation induction
-Luteal phase support with vaginal progesterone
-EB
-HIS examination
-Antibiotic therapy
(when appropriate)
-Control EB
-IVF cycle
≥1 plasma cell/HPF Group 1: patients with treated CE (n = 10)
Group 2: patients without CE (n = 23)
Group 3: RIF patients who did not have an EB (n = 485)
-Clinical pregnancy rate
-Ongoing pregnancy rate
Kitaya et al. 2017 [12] Prospective cohort study
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Japan
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November 2011–
July 2014
421 RIF patients undergoing up to three IVF-ET cycle
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-IVF failure with three
or more morphologically good cleavage-stage
embryos and/or
blastocysts transferred.
-No intrauterine pathology
- -Diagnostic HSC
-EB
-HIS examination
-Endometrial culture
-Antibiotic therapy
(when appropriate)
-Control EB
-IVF cycle
ESPDI ≥ 0.25 The endometrial stromal plasmacyte density index (ESPDI) was calculated as the sum of the stromal CD138+ cell counts divided by the number of the HPF evaluated. Group A: patients with cured CE (n = 116)
Group B: patients with persistent CE (n = 4)
Group C: patients without CE (n = 226)
Clinical pregnancy rate
-Ongoing pregnancy/live birth rate
-Miscarriage rate
Kuroda et al. 2020 [8] Cross sectional study
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Japan
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June 2018– February 2020
88 infertile women
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-No intrauterine pathology
-clomiphene
citrate or letrozole in combination with rFSH or hMG
-hCG 250 μg or nasal buserelin acetate spray 600 μg at follicle size ≥17 mm (≥2)
-Egg retrieval 35 h after ovulation induction
-Conventional IVF or ICSI
- All embryos were cryopreserved at blastocyst developmental
stage ≥4 in the Gardner classification using the
vitrification method
-endometrium prepared for ET via a hormone replacement cycle
-EB
-IHC staining
-ERA testing
-Antiobiotic therapy (when appropriate)
-Control EB
-IVF cycle
≥5 CD138+
plasma cells per 10 random stromal areas at ×400 magnification.
Group A: non CE patients (n = 33);
Group B: CE patients (n = 19)
at ERA testing;
Group C: cured-CE patients (n = 36)
-hCG positive rate
-Clinical pregnancy rate
-Miscarriage rate
-Ongoing pregnancy rate
Li et al. 2021 [9] Retrospective study
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China
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Between 2017 and 2018
716 infertile patients undergoing IVF-ET cycle
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- <45 years;
- endometrial scratching
- previous antibiotic treatment for CE
- - endometrial scratching
-EB
-HIS examination
-IVF
Six different diagnostic criteria
- 0 plasma cell/HPF in all of the 30 selected HPFs;
-1 plasma cell/hpfs in at least 1 out of 30 selected HPFs;
-2 plasma cell/HPFs in at least 1 out of 30 selected HPFs;
-3 plasma cell/HPFs in at least 1 out of 30 selected HPFs;
-4 plasma cell/HPFs in at least 1 out of 30 selected HPFs;
-≥5 plasma cell/HPFs in at least 1 out of 30 selected HPFs;
Group A: 0 CD138+/HPF in all of the 30 selected HPFs (n = 433);
Group B: 1 CD138+/HPF in at least 1 out of 30 selected HPFs (n = 178);
Group C: 2 CD138+/HPF in at least 1 out of 30 selected HPFs (n = 33);
Group D: 3 CD138+/HPF in at least 1 out of 30 selected HPFs (n = 18);
Group E: 4 CD138+/HPF in at least 1 out of 30 selected HPFs (n = 6);
Group F: ≥5 CD138+/HPF in at least 1 out of 30 selected HPFs (n = 38);
-Clinical pregnancy rate
-Live birth rate
-Miscarriage rate
Xiong et al. 2021 [10]
Retrospective study
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China
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June 2017–June 2018
640 infertile patients undergoing IVF-ET cycle
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-No antibiotic treatments before the hysteroscopy
- age < 40 years;
-Normal basal hormone
levels (FSH < 10 IU/L and E2 < 60 pg/mL);
-BMI < 30 Kg/m2;
-Normal parental peripheral karyotypes;
-Frozen embryo transfer cycles within 6 months after antibiotic treatment
- No RPL
- no primary ovarian insufficiency
- no previous surgery for myoma or endometriosis, - normal uterine cavity
-GnRH a or GnRH ant
protocol:
-rFSH or hMG
-GnRH a or GnRH ant
mild stimulation protocol:
oral clomiphene citrate 100mg/day + hMG from the fifth day
-hCG (10,000 IU) or recombinant
hCG (250 mg) when >3 follicles reached a
mean diameter of 18 mm;
- Oocyte retrieval was performed
36 h after hCG administration;
-Luteal phase support with intra-
muscular injection of progesterone (60 mg daily) or once daily
vaginal progesterone
combined with dydrogesterone
(10 mg 3 times a day).
-Diagnostic HSC
-EB
-HIS examination
-Antibiotic therapy (when appropriate)
-Control EB
-IVF cycle
≥1 plasma cell/HPF Group 1: patients with
CD138+/HPF = 0 (n = 88);
Group 2: patients with CD138+/HPF 1–4 with antibiotic treatment (n = 116);
Group 3: patients with CD138+/HPF 1–4 without antibiotic treatment (n = 199).
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Group 1: patients with CD138+/HPF 0–4 (n = 403);
Group 2: patients with cured CE (n = 211);
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Group 1: patients with CD138+/HPF 0–4 (n = 403);
Group 2: patients with persistent CE (n = 26);
-Implantation rate
-Clinical pregnancy rate
-Live birth rate
-Early pregnancy loss rate
-Cumulative live birth rate
Zhang et al. 2019 [34] Prospective cohort study
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China
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February 2015–June 2017
298 RIF patients undergoing 1 IVF-ET cycle
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-age < 35 years
-≥three failed IVF-ET cycles or ≥6 high-quality embryo transferred
-Normal uterine cavity
-Normal parental peripheral karyotype.
-rFSH (175–225 IU/day)
-U-Hcg (10,000 UI) at follicle size 17 mm (≥2)
-Egg retrieval 36 h after ovulation induction
-≤3 embryos transferred (of which at least one with good quality) on day 3 of culture
- Luteal phase support with intramuscular progesterone 60 mg daily
-Diagnostic HSC
-EB
- HIS examination
-intrauterine antibiotic therapy (when appropriate)
-Control EB
-IVF cycle
≥1 plasma cell/HPF Group 1: patients without CE (n = 126)
Group 2: patients with cured CE (n = 85)
Group 3: patients with persistent CE (n = 24)
-Implantation rate
-Clinical pregnancy rate
-Live birth rate
-Clinical loss rate
BMI: body mass index; CE: chronic endometritis; E2: estradiol; EB: endometrial biopsy; ERA testing: endometrial receptivity array testing; ET: embryo transfer; FSH: follicle-stimulating hormone; GnRH-a: GnRH agonist; GnRH-ant: gonadotropin releasing hormone antagonist; HIS: histology; hMG: human menopausal gonadotropin; HPF: high power fields; HSC: hysteroscopy; ICSI: intracytoplasmatic sperm injection; IU: international unit; IVF: in vitro fertilization; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; rFSH: recombinant FSH; r-Hcg: recombinant human chorionic gonadotropin; U-Hcg: urinary human chorionic gonadotropin.