Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology

Guo, Jun; Feng, Qiang; Chaemsaithong, P.; Appiah, Kubi; Sahota, Daljit Singh; Leung, Bo Wah; Chung, Jacqueline Pui Wah; Li, Tin‐Chiu; Poon, Liona C.

doi:10.1111/aogs.14618

Cited by 5 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Хронічний ендометрит відмічається в понад 40% пацієнток із непліддям [6,7]. У пацієнток із невдалими спробами екстракорпорального запліднення в анамнезі ця патологія є ключовим фактором невдалих повторних імплантацій ембріонів і самовільних переривань вагітності та відмічається у 30-60% випадків [4,5].…”

Section: оригінальні дослідженняunclassified

“…У пацієнток із невдалими спробами екстракорпорального запліднення в анамнезі ця патологія є ключовим фактором невдалих повторних імплантацій ембріонів і самовільних переривань вагітності та відмічається у 30-60% випадків [4,5]. Вона також верифікується в близько 72% гістологічних зразків біоптатів слизової оболонки матки в жінок із перенесеними в анамнезі інфекціями, що передаються статевим шляхом, та у 12-68% жінок із трубно-перитонеальними формами непліддя [6,17]. Також висока частота цього захворювання (від 33% до 87%) спостерігається в пацієнток зі звичним невиношуванням вагітності [8][9][10].…”

Section: оригінальні дослідженняunclassified

See 1 more Smart Citation

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

View full text Add to dashboard Cite

The incidence of chronic endometritis is more than twice higher the prevalence of other clinical forms of intrauterine pathology, leading to infertility, unsuccessful attempts of in vitro fertilization and spontaneous abortion. There is a lack of data on the alteration of pro- and anti-inflammatory cytokine production in chronic endometritis and their role in the subsequent development of miscarriage. Purpose - to investigate the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as well as the anti-inflammatory cytokine interleukin 10 (IL-10) in cervical mucus of women with chronic endometritis and to assess the impact of the developed comprehensive preconception treatment on normalizing cytokine disorders in these women. Materials and methods. The levels of pro-inflammatory cytokines TNF-α and INF-γ, as well as the anti-inflammatory cytokine IL-10, were determined using the enzyme-linked immunosorbent assay method in the cervical mucus of 426 women with chronic endometritis who were planning pregnancy. Among them, 168 patients (the Group I) received preconception comprehensive treatment, which included broad-spectrum antibacterial agents (azithromycin), hormonal estrogen-progestin therapy (Femoston 2/10) and L-arginine. The remaining 258 women (the Group II) did not receive treatment for chronic endometritis at the preconception stage. The control group consisted of 30 healthy individuals. Data analysis was performed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the mean (m). The Student’s t-test was applied, and probabilities were determined using the statistical program «STATISTICA» (StatSoft Inc., USA). Results. In the cervical mucus of women with chronic endometritis, an increase in the levels of pro-inflammatory cytokines INF-γ by 2.8 times (p<0.001) and TNF-α by 2 times (p<0.001) was detected, along with a 2-fold decrease in the concentration of the anti-inflammatory cytokine IL-10 (p<0.001). The shift in the cytokine balance towards pro-inflammatory cytokines is associated with a high frequency of miscarriage in these women. After the treatment of chronic endometritis, women had a 2.6 times lower level of INF-γ (p<0.05), a 2 times lower level of TNF-α (p<0.01), and a 1.7 times higher level of IL-10 (p<0.05) compared to untreated patients. Conclusions. Women with chronic endometritis experience a cytokine imbalance, characterized by an excessive increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Women with chronic endometritis who are planning pregnancy require comprehensive preconception treatment, which includes the administration of azithromycin, femoston 2/10 and L-arginine in addition to traditional preconception folate prophylaxis. This treatment, by promoting improved conditions for implantation, leads to a 15% increase in the pregnancy rate and a 1.9-fold reduction in the frequency of spontaneous abortion. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

show abstract

Section: оригінальні дослідженняunclassified

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

View full text Add to dashboard Cite

show abstract

“…The development of CE is associated with a number of pathological processes that significantly affect the functional state of the uterine mucosa, thereby creating unfavorable conditions for the onset of pregnancy [4,5]. These are primarily related to destructive changes in endometrial cells that occur during prolonged infl ammation [6], impaired microcirculation in the basin of the uterine spiral arteries [4], inadequate transformation of the uterine mucosa during the menstrual cycle [4][5][6][7], as well as a decrease in the synthesis of α2-microglobulin of fertility (also known as glycodelin-A) [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous studies, a decrease in the level of fer tility α2-microglobulin (glycodelin-A) was demonstrated in women with CE both in the preconception stage and during the first weeks of pregnancy [2,7]. Adequate synthesis levels create favorable conditions for implantation and embryonic development [8,9], as well as ensure adequate progression of trophoblast invasion into the uterine spiral arteries, which is a necessary step in the formation of adequate feto-maternal blood fl ow [10,11]. The processes of trophoblast invasion into the spiral arteries of the uterus are crucial for the entire process of pregnancy, and their disruption leads to the development of serious obstetric pathologies (such as pregnancy loss, pre-eclampsia, intrauterine growth restriction, placental abruption) [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

Likhachov,

Taranovska

2023

Neonatol. hìr. perinat. med.

View full text Add to dashboard Cite

Few data regarding the levels of TNF-α, INF-γ and IL-10 in the cervical mucus of pregnant women with the past medicalhistory of chronic endometritis have been found. The abovementioned cytokines have the impact on the course of pregnancy as well as the processes of trophoblast invasion into the spiral arteries of the uterus. Deviations in their levels at the early stages of pregnancy may be associated with the development of preeclampsia at later stages.Purpose: to assess the levels of TNF, INF-γ and cytokine IL-10 in the cervical mucus of pregnant women with a past medicalhistory of chronic endometritis. Additionally, the study aims to determine their role in the development of preeclampsia andevaluate the eff ectiveness of comprehensive preconception treatment in preventing cytokine imbalance and the occurrence of gestational complications.Method and Materials. 135 pregnant women with the past medical history of chronic endometritis have been supervisedduring their pregnancy and received preconception treatment (Group I), as well as 168 women, whose pregnancy occurred in the presence of untreated chronic endometritis (Group II). The control group (CG) involved 20 healthy women. Preconception treatment included the administration of azithromycin, hormonal therapy with Femoston- Comb 2/10, and L-arginine aspartate in combination with folate prophylaxis. During the study, the principles of patient- centered care were followed in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the International Recommendations of the Helsinki Declaration on Human Rights, the Convention on Human Rights and Biomedicine of the Council of Europe, the Laws of Ukraine, the Orders of the Ministry of Health of Ukraine and the requirements of the Ethical Code of the Ukrainian physician. The cytokine (TNF-α, INFγ, IL-10) analysis in the cervical mucus was performed at 5-, 17-18 and 32 weeks of pregnancy, using the enzyme- linked immunosorbent assay method with corresponding standard commercial reagent kits from the «Vector BEST» company. The obtained data were processed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the means (m). Student’s t-test was used for assessment and the likelihood ratio was calculated using the «STATISTICA» software (StatSoft Inc., USA).The paper is an excerpt from the initiative scientifi c research project of the Department of Obstetrics and Gynecology No.2 at Poltava State Medical University, entitled «Optimization of approaches to the management of pregnancy in women at high risk of obstetric and perinatal pathology» (State registration number 0122U201228, duration:10.2022-09.2027).Results. In pregnant women with a past medical history of chronic endometritis an increase in the levels of INF-γ in cervicalmucus by 2.1 times at 5-6 weeks (p<0.001), by 2.4 times at 17-18 weeks (p<0.001) and by 1.7 times at 32 weeks of pregnancy(p<0.001) compared to corresponding levels of this cytokine in healthy pregnant women, has been detected. Similarly, TNF-αwas by 4.3 times greater at 5-6 weeks of pregnancy compared to the values in the control group (p<0.001), by 3.3 times greater at 17-18 weeks of pregnancy (p<0.001) and by 4.4 times at 32 weeks of pregnancy (p<0.001). All pregnant women with a past medical history of chronic endometritis who had levels of INF-γ in the cervical mucus greater than 66.4 pg/ml and/or levels of TNF-α greater than 90.9 pg/ml at 5-6 weeks of pregnancy subsequently manifested preeclampsia (OR 2.01; 95 % CI [1.1-7.12]; p<0.05 and OR 1.8; 95 % CI [1.2-6.29]; p<0.05 respectively). The level of IL-10 in their cervical mucus was by 4 times higher than the control values at 5-6 weeks of pregnancy (p<0.0001); by 3.1 times higher at 17-18 weeks of pregnancy (p<0.0001) and by 3 times higher at 32 weeks of pregnancy (p<0.0001). This compensates for the increase in pro-infl ammatory cytokines, allowing the TNF-α/IL-10 ratio to remain at a level characteristic of healthy women throughout pregnancy. In treated women, the concentration of INF-γ is by 1.8 times lower than in untreated patients at 5-6 weeks of pregnancy (p<0.0001), by 2.1 times at 17-18 weeks of pregnancy (p<0.0001), and by 1.4 times at 32 weeks of pregnancy (p<0.0001). Similarly, TNF-α in cervical mucus was found to be lower by 3.6 times (p<0.01), 2.6 times (p<0.0001), and 4 times (p<0.001) respectively, in the specifi ed terms. This helps to avoid excessive production of the anti-infl ammatory cytokine IL-10.Conclusions. In women who got pregnant with untreated chronic endometritis, an increased production of cytokines INF-γand TNF-α at the early stages of pregnancy has been established. Comprehensive pregravidar treatment of chronic endometritis allows for the normalization of levels of anti-infl ammatory cytokines INF-γ and TNF-α at the beginning of gestation, which creates conditions for preventing the development of preeclampsia. This leads to a 1.9 times reduction in the frequency of this complication (OR 2.3; 95 % CI [1.25-4.31]; p<0.05), a 1.8 times decrease in the frequency of severe forms of preeclampsia (OR 4.64; 95 % CI [1.23-17.48]; p<0.05) and a delay in the average onset of its manifestations by 4.9 weeks (p<0.0001).

show abstract

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology

Nguyen‐Hoang,

Chaemsaithong,

et al. 2024

Intl J Gynecology & Obste

View full text Add to dashboard Cite

ObjectivesTo compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), placental growth factor (PlGF), and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large‐for‐gestational‐age (LGA) fetus, and uncomplicated ART pregnancies.MethodsThis was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6–6+3, 11–13+6, 20–24+6, 30–34+6, and 35–37+6 weeks for the measurement of MAP, UtA‐PI, PlGF, and sFlt‐1. A linear mixed‐effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation.ResultsThirty‐three (23.1%) and fifty‐five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs −0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (−0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11–13+6 to 30–34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA‐PI MoM and log10 sFlt‐1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (−0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20–24+6 and 35–37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA‐PI, and sFlt‐1 between GDM ± LGA and uncomplicated groups during pregnancy.ConclusionOur study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

show abstract

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology

Cited by 5 publications

References 38 publications

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology

Contact Info

Product

Resources

About