scholarly journals The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Meryam Cheloufi ◽  
Alaa Kazhalawi ◽  
Anne Pinton ◽  
Mona Rahmati ◽  
Lucie Chevrier ◽  
...  
Keyword(s):  
Live Birth ◽  
Pregnancy Loss ◽  
Embryo Implantation ◽  
Live Birth Rate ◽  
Endometrial Biopsy ◽  
Three Dimension ◽  
Uterine Receptivity ◽  
Hormonal Stimulation ◽  
Personalized Care ◽  
Immune Profiling

IntroductionThe endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.MethodsThis is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.ResultsUterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).ConclusionOur study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

scholarly journals Live Birth Rate of Fresh Embryo Transfer with GnRH Agonist Long Protocol is Higher Than Frozen Embryo Transfer

2020 ◽  
Author(s):  
Xiaoyan Ding ◽  
Jingwei Yang ◽  
Lan Li ◽  
Na Yang ◽  
Ling Lan ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Implantation Rate ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Fresh Embryo Transfer ◽  
Long Protocol

Abstract Background: Along with progress in embryo cryopreservation, especially in vitrification has made freeze all strategy more acceptable. Some studies found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer（ET）in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. But there were no reports about live birth rate differences between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to analyze whether patients benefit from freeze all strategy in GnRH-a protocol from real-world data.Methods: This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.Results: A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between two groups, except BMI. After controlling for a broad range of potential confounders (including age, infertility duration, BMI, AMH, no. of oocytes retrieved and no. of available embryos), multivariate logistic regression analysis demonstrated that there was no significant difference in terms of clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P>0.05). However, the implantation rate and live birth rate of fresh ET group were significantly higher than FET group (P<0.001 and P=0.012, respectively).Conclusion: Compared to FET, fresh ET following GnRH-a long protocol could lead to higher implantation rate and live birth rate in infertile patients underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.

P-377 Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H Yoshihara ◽  
M Sugiura-Ogasawara ◽  
T Kitaori ◽  
S Goto
Keyword(s):  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Recurrent Pregnancy Loss ◽  
Live Birth Rate ◽  
Negative Group ◽  
Birth Rates ◽  
Positive Group ◽  
Live Birth Rates ◽  
Uterine Anomaly

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2 % (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62 % (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1 40 dilution, the subsequent live birth rates were 71.34 % (219/307) for the ANA-positive group and 70.67 % (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707-1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41 % (219/237) for the ANA-positive group and 92.04 % (347/377) for the ANA-negative group (0.951, 0.517-1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62 % (22/26) for the ANA-positive group, and 70.47 % (544/772) for the ANA-negative group (0.434, 0.148-1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number not applicable

scholarly journals Association of a family history of autoimmune disease with time to pregnancy, pregnancy loss, and live birth rate

2017 ◽  
Vol 108 (3) ◽  
pp. e34
Author(s):  
T.C. Plowden ◽  
M.T. Connell ◽  
P. Mendola ◽  
K. Kim ◽  
C. Nobles ◽  
...  
Keyword(s):  
Family History ◽  
Autoimmune Disease ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Time To Pregnancy ◽  
History Of

Uterine immune profiling for increasing live birth rate: A one-to-one matched cohort study

2017 ◽  
Vol 119 ◽  
pp. 23-30 ◽  
Author(s):  
Nathalie Lédée ◽  
Laura Prat-Ellenberg ◽  
Lucie Chevrier ◽  
Richard Balet ◽  
Cynthia Simon ◽  
...  
Keyword(s):  
Cohort Study ◽  
Live Birth ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
One To One ◽  
Immune Profiling

scholarly journals Gram-Negative Bacterial LPS Induced Poor Uterine Receptivity and Implantation Failure in Mouse: Alterations in IL-1β Expression in the Preimplantation Embryo and Uterine Horns

2005 ◽  
Vol 13 (3) ◽  
pp. 125-133 ◽  
Author(s):  
Kaushik Deb ◽  
Madan Mohan Chaturvedi ◽  
Yogesh Kumar Jaiswal
Keyword(s):  
Cross Sections ◽  
Pregnancy Loss ◽  
Embryo Implantation ◽  
Preimplantation Embryos ◽  
Soluble Form ◽  
Implantation Failure ◽  
Perinatal Complications ◽  
Uterine Receptivity ◽  
Gram Negative ◽  
Blastocyst Implantation

Genito-urinary tract or systemic infections of the gram-negative bacteria in pregnant women, causes abortions, preterm labor, and several other perinatal complications. LPS is the most potent antigenic component of the gram-negative bacterial cell wall and is known to modulate the expression of various proinflammatory cytokines. Here we investigate the role of the soluble form of IL-1 i.e., IL-1β in the ‘minimum dose’ of LPS induced pregnancy loss in mice. Uterine cross-sections on each day of the preimplantation period of pregnancy were examined histopathologically for finding out LPS induced changes in the uterine preparation for embryo implantation. The expression of IL-1β in the various stages of the preimplantation period of pregnancy was studied by RT-PCR in the embryos and the uterine horns of the LPS treated and normal pregnant mice. We found that LPS significantly alters the proliferation of the glandular epithelium, luminal epithelium and stroma during the preimplantation period. We also found large infiltration of macrophages into the uterine horns of the LPS treated animals. The level and pattern of IL-1β expression in the preimplantation embryos and uterine horns were also altered in LPS treated animals. These observations indicate that LPS can alter the uterine preparation for blastocyst implantation, which could be due to the change in the IL-1β expression in the uterine horns. However, a change in the expression pattern of IL-1β in the preimplantation embryos underlines the significance of this molecule in LPS induced pregnancy loss or implantation failure in mouse.

Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure

2019 ◽  
Vol 34 (12) ◽  
pp. 2340-2348 ◽  
Author(s):  
Takeshi Sato ◽  
Mayumi Sugiura-Ogasawara ◽  
Fumiko Ozawa ◽  
Toshiyuki Yamamoto ◽  
Takema Kato ◽  
...  
Keyword(s):  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Recurrent Pregnancy Loss ◽  
Live Birth Rate ◽  
Not Given ◽  
Recurrent Implantation Failure ◽  
Miscarriage Rate ◽  
Preimplantation Genetic Testing ◽  
Biochemical Pregnancy

Abstract STUDY QUESTION Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? SUMMARY ANSWER PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. WHAT IS KNOWN ALREADY PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40–50% and 5–25% in patients with RPL, respectively. STUDY DESIGN, SIZE, DURATION A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35–36, 37–38, 39–40 or 41–42 years) were selected for PGT-A groups. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. MAIN RESULT AND THE ROLE OF CHANCE There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16–13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28–10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02–0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03–0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. LIMITATIONS, REASONS FOR CAUTION The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. WIDER IMPLICATION OF THE FINDINGS A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A

scholarly journals Comparison of PGS2.0 versus conventional embryo morphology evaluation for patients with recurrent pregnancy loss: a study protocol for a multicentre randomised trial

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e036252
Author(s):  
Caixia Lei ◽  
Yilun Sui ◽  
Jiangfeng Ye ◽  
Yao Lu ◽  
Ji Xi ◽  
...  
Keyword(s):  
Live Birth ◽  
Pregnancy Loss ◽  
Scientific Evidence ◽  
Randomised Trial ◽  
Live Birth Rate ◽  
Preimplantation Genetic Screening ◽  
Multivariate Logistic Regression Model ◽  
Embryo Morphology ◽  
Routine Practice

IntroductionPregnancy loss (PL) is an adverse life event, and there is no proven effective treatment for recurrent PL (RPL). Preimplantation genetic screening (PGS) can be performed to reduce the risks of PL; however, there is still no solid scientific evidence that PGS improves outcomes for couples experiencing RPL. Comprehensive chromosome screening (PGS2.0) has become a routine practice in in vitro fertilisation (IVF) clinics. Previous studies based on PGS1.0 with a focus on RPL couples where the female is of advanced maternal age have reported contradictory results. Hence, a multicentre randomised trial is needed to provide evidence for the clinical benefits of PGS2.0 treatment for RPL couples.Methods and analysisOverall, 268 RPL couples undergoing IVF cycles will be enrolled. Couples will be randomised according to a unique grouping number generated by a random digital software into (1) PGS2.0 group and (2) non-PGS (conventional embryo morphology evaluation) group. This study aims to investigate whether the live birth rate (LBR) per initiated cycle after PGS2.0 is superior to the LBR per initiated cycle after conventional embryo evaluation (non-PGS group). Live birth will be defined as a live baby born after a gestation period of >28 weeks, with a birth weight of more than 1000 g. A multivariate logistic regression model will be used to adjust for confounding factors.Ethics and disseminationEthical approval has been granted by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University and the participating hospitals. Written informed consent will be obtained from each couple before any study procedure is performed. Data from this study will be stored in the Research Electronic Data Capture. The results of this trial will be presented and published via peer-reviewed publications and presentations at international conferences.Trial registration numberNCT03214185; Pre-results.

scholarly journals Endometrial inflammation and effect on implantation improvement and pregnancy outcome

Reproduction ◽  
2012 ◽  
Vol 144 (6) ◽  
pp. 661-668 ◽  
Author(s):  
I Granot ◽  
Y Gnainsky ◽  
N Dekel
Keyword(s):  
Inflammatory Response ◽  
Pregnancy Outcome ◽  
Immune Cells ◽  
Embryo Implantation ◽  
Substantial Improvement ◽  
Subsequent Pregnancy ◽  
Endometrial Biopsy ◽  
Implantation Failure ◽  
Uterine Receptivity ◽  
Major Barrier

Implantation failure, which is presently the major barrier in human fertility, is attributed, in many cases, to the failure of the uterus to acquire receptivity. The transition into a receptive uterus includes cellular changes in the endometrium and the modulated expression of different cytokines, growth factors, transcription factors, and prostaglandins. These molecules partake in the generation of an inflammatory response followed by the recruitment of immune cells. These cells have shown to be involved in the maternal immune tolerance toward the implanted embryo as well as in the maternal–fetus interaction during pregnancy. Most of the accumulated evidence indicates that embryo implantation is associated with an active Th1 inflammatory response while a Th2-humoral inflammation is required for pregnancy maintenance. Yet, recent findings suggest that a Th1 inflammatory response is also necessary for the acquisition of uterine receptivity. This notion was originally suggested by reports from our and other clinical centers worldwide that IVF patients with repeated implantation failure subjected to endometrial biopsy exhibit a substantial improvement in their chances to conceive. These findings, followed by the demonstration of an elevated pro-inflammatory cytokine/chemokine expression, as well as an increased abundance of immune cells, in the endometrium of these patients, raised the idea that acquisition of uterine receptivity is closely associated with an inflammatory response. This review summarizes the molecular and biochemical evidence that confirm this notion and proposes a mechanism by which injury-induced inflammation improves uterine receptivity and the subsequent pregnancy outcome.

scholarly journals Fertility outcomes in women after controlled ovarian stimulation with gonadotropin releasing hormone agonist long protocol: fresh versus frozen embryo transfer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyan Ding ◽  
Jingwei Yang ◽  
Lan Li ◽  
Na Yang ◽  
Ling Lan ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Implantation Rate ◽  
Live Birth Rate ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Long Protocol

Abstract Background Along with progress in embryo cryopreservation, especially the vitrification, freeze all strategy has become more acceptable than ever. Some studies have found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer(ET)in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. However from our literature research, there have been no reports about live birth rate comparison between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to retrospectively investigate whether patients benefit from freeze all strategy in GnRH-a protocol using real-world data. Methods This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate. Results A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between fresh ET and FET groups, except BMI. After controlling for a broad range of potential confounders including age, infertility duration, BMI, AMH, number of oocytes retrieved and of available embryos, multivariate logistic regression analysis demonstrated that there was no significant difference in clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P > 0.05). However, the implantation rate and live birth rate in fresh ET group were significantly higher than FET group (P < 0.001 and P = 0.012, respectively). Conclusions Under GnRH-a long protocol, compared to FET, fresh ET was associated with higher implantation rate and live birth rate in infertile patients that underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.

Sign in / Sign up

Export Citation Format

Share Document