scholarly journals Does dysbiotic endometrium affect blastocyst implantation in IVF patients?

2019 ◽  
Vol 36 (12) ◽  
pp. 2471-2479 ◽  
Author(s):  
Tomoko Hashimoto ◽  
Koichi Kyono

Abstract Purpose To analyze the pregnancy outcomes of IVF patients presenting eubiotic or dysbiotic endometrium at the time of embryo transfer and to analyze what bacterial profiles are suitable for embryo implantation. Methods Ninety-nine IVF patients under 40 years old undergoing vitrified-warmed blastocyst transfer in HRT cycle had concurrent endometrial microbiome analysis. Samples from the endometrium were taken from the participants at the time of mock transfer; the bacterial profiles at genus level and percentage of lactobacilli in the endometrium of the patients were analyzed. Results Thirty-one cases (31.3%) had dysbiotic endometrium. The background profiles, pregnancy rates per transfer (52.9% vs 54.8%), and miscarriage rates (11.1% vs 5.9%) were comparable between patients with eubiotic or dysbiotic endometrium. Major bacterial genera other than Lactobacillus detected in the dysbiotic endometrium were Atopobium, Gardnerella, and Streptococcus. Some patients achieved ongoing pregnancies with 0% Lactobacillus in the endometrium. The endometrial bacterial profiles of pregnant cases with dysbiotic endometrium were comparable with those of non-pregnant cases. Conclusion Analyzing microbiota at the species-level resolution may be necessary for identifying the true pathogenic bacteria of the endometrium and avoiding over-intervention against non-Lactobacillus microbiota. Further studies are necessary for analyzing the mechanism of how the pathogenic bacteria affect embryo implantation.

2021 ◽  
pp. 1-7
Author(s):  
Yuta Kasahara ◽  
Tomoko Hashimoto ◽  
Ryo Yokomizo ◽  
Yuya Takeshige ◽  
Koki Yoshinaga ◽  
...  

Background:The clinical value of personalized embryo transfer (pET) guided by the endometrial receptivity analysis (ERA) tests for recurrent implantation failure (RIF) cases is still unclear. The aim of this study is to clarify the efficacy of ERA leading to personalization of the day of embryo transfer (ET) in RIF patients. Methods: A retrospective study was performed for 94 patients with RIF who underwent ERA between July 2015 and December 2019. Pregnancy outcomes in a previous vitrified-warmed blastocyst transfer (previous VBT) and a personalized vitrified-warmed blastocyst transfer (pVBT) in identical patients were compared. The details of each pVBT were further analyzed between patients in a non-displaced group, which indicated “receptive” cases in ERA results and those who were in the displaced group, which indicated “non-receptive” cases. Results:When the pregnancy rate, both per patient and per transfer cycle, of previous VBT and pVBT were compared, a significant increase in pVBT was observed between the two methods (5.3% vs. 62.8%, 4.4% vs. 47.9%, respectively). The pregnancy rates, implantation rates, and clinical pregnancy rates of the first pVBT were significantly higher in the displaced group than the non-displaced group. The cumulative ongoing pregnancy rate of the displaced group tended to be higher compared to that of the non-displaced group in the first pVBT, although the difference was not statistically significant (51.0% vs. 31.1%, [Formula: see text] = 0.06). Conclusions:Our study demonstrates that pVBT guided by ERA tests may improve pregnancy outcomes in RIF patients whose window of implantation (WOI) is displaced, and its effect may be more pronounced at the first pVBT. The displacement of WOI may be considered to be one of the causes of RIF, and its adjustment may contribute to the improvement of pregnancy outcomes in RIF patients.


1999 ◽  
Vol 84 (8) ◽  
pp. 2638-2646
Author(s):  
Carlos Simón ◽  
Amparo Mercader ◽  
Juan Garcia-Velasco ◽  
George Nikas ◽  
Carlos Moreno ◽  
...  

We have developed a coculture system with autologous human endometrial epithelial cells (AEEC) that retained many features of human endometrial epithelium. Implantation failure (IF; >3 previous cycles failed with 3–4 good quality embryos transferred) is a distressing condition in which 2-day embryo transfer repetition is the routine option. The objective of this study was to investigate the basics and to evaluate prospectively the clinical value of embryo coculture on AEEC and blastocyst transfer with their own oocytes [in vitro fertilization (IVF) patients] or with donated oocytes (oocyte donation patients) compared to a routine day 2 embryo transfer for patients with IF. Scanning electron microscopy and mouse embryo assays demonstrate that EEC from fertile and IF patients were morphologically and functionally similar; similar findings were observed in EEC obtained from fresh or frozen endometria. Clinically, 168 IVF cycles were performed in 127 patients with 3.8 ± 0.2 previously failed cycles, and 80 cycles were performed in 57 patients undergoing oocyte donation with 3.0 ± 0.2 previously failed cycles. Twenty IVF patients and 15 ovum donation patients with 3 previously failed cycles in whom a 2-day embryo transfer was performed were used as controls. In 88% of ovum donation cycles, at least 2 blastocysts were available for transfer, with 60.1% blastocyst formation; 2.2 ± 0.1 blastocysts were transferred/cycle, and 36 pregnancies (determined by fetal cardiac activity) were obtained (32.7% implantation and 54.5% pregnancy rates). In 168 IVF cycles, 8.1 ± 0.2 embryos/cycle started coculture, resulting in 49.2% blastocyst formation; 2.3 ± 0.2 blastocysts were transferred/cycle, and 29 clinical pregnancies were obtained (11.8% implantation and 20.2% pregnancy rates). Fifteen cycles were canceled (9%). In oocyte donation patients with IF undergoing 2-day embryo transfer, implantation and pregnancy rates were significantly lower (4.5% and 13.3%; P < 0.01) than with coculture; however, in IVF patients with IF, results with day 2 transfer (10.7% and 35%) were similar to those with coculture. The present study demonstrates that coculture of human embryos with AEEC and blastocyst transfer is safe, ethical, and effective and constitutes a new approach to improve implantation in patients with IF undergoing ovum donation, but not in IVF patients.


2020 ◽  
Author(s):  
Yanhong Wu ◽  
Chang Liu ◽  
Chaochao Sheng ◽  
Haitao Xi ◽  
Yanghua Fu ◽  
...  

Abstract Background:Previous studies have shown that in young women, single blastocyst transfer can achieve satisfactory pregnancy results, but there are few studies on the difference between fresh and frozen-thawed single blastocyst transfer. In this retrospective analysis, the purpose of this study was to compare the pregnancy outcomes of young patients who received fresh or frozen-thawed single blastocyst transfer, so as to provide further clinical strategies for single blastocyst transfer.Methods: A retrospective analysis of patients aged ≤35 years old undergoing single blastocyst transfer was performed from January 2018 to December 2018 in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University. A total of 901 patients were involved and were divided into two groups according to the type of transfer cycle, 693 of which were in the fresh embryo transfer cycle (group A) and 208 of which were in the frozen-thawed embryo transfer cycle (group B). The laboratory and pregnancy outcomes were compared between the groups. Results:The number of oocytes retrieved in group B was significantly more than in group A ( P<0.05). The early miscarriage rate in group B was higher than in group A, with significant difference(P<0.05). There were no significant differences in other basic conditions and obstetric pregnancy outcomes between the two groups.Conclusions:Favorable pregnancy outcomes could be obtained in both fresh and frozen-thawed single blastocyst transfer in young patients without increasing the birth defect rate. For patients with risk factors of OHSS such as more oocyte retrieval, ovarian hyper-response, or risk factors of ectopic pregnancy such tubal infertility and the history of ectopic pregnancy, frozen-thawed single blastocyst transfer could be highly recommended in clinical practice. However, since the early miscarriage rate is higher in frozen-thawed embryo transfer group, further research is needed to figure out the cause and possible solutions.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Alvarez ◽  
A Racca ◽  
S García ◽  
F Martínez ◽  
I González-Foruria ◽  
...  

Abstract Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pregnancy rates in embryo transfer-under hormonal replacement therapy (ET-HRT) in patient with Progesterone (P)<10.6 ng/mL? Summary answer Reduced P on the β-hCG day is associated with lower pregnancy-rates and higher miscarriage-rate. PS from the same day showed significant increase of reproductive outcomes. What is known already Up until now, in ART, very little has been done to understand whether the P intake should be personalized during the luteal phase. Most recent studies on the topic showed that low P levels on the day of ET-HRT or on the day before are associated with decreased pregnancy rates; however, when low P values are supplemented from the day before embryo-transfer (ET), similar results to cases with adequate P are reported. Nevertheless, little is known about the association between low P level, on the day of β-hCG (P- β-hCG) and PS from this day in ET-HRT, and pregnancy outcomes. Study design, size, duration This is a single centre, cohort, retrospective study conducted at a university-affiliated fertility centre between January 2018 and June 2020 where PS took place from the day of positive β-hCG determination when P < 10.6 ng/mL. In total 789 ET-HRT cycles were analysed of which 239 were performed in both fresh and frozen heterologous ET-HRT (het-ET), 336 in homologous ET-HRT (hom-FET) and 214 in euploid ET-HRT (eu-FET) after preimplantation genetic testing for aneuploidies IVF cycles (PGT-A). Participants/materials, setting, methods Women undergoing ET-HRT with normal P (>10.6ng/mL) on the day before ET were screened for P on the day of β-hCG. All women received vaginal P 200 mg/8 hours for the second part of HRT. PS was performed by adding P to the HRT when P- β-hCG was considered low (<10.6 ng/mL). Primary outcome: ongoing-pregnancy-rate (OPR); secondary outcome: miscarriage-rate (MR). Both were evaluated by considering PS on the day of β-hCG as a categorical variable. Main results and the role of chance Patients characteristics were comparable between groups (het-ET, hom-FET and eu-FET) although significantly lower body mass index was found when P- β-hCG>10.6 ng/mL compared to the subgroup with P- β-hCG<10.6 ng/mL and no PS (p = 0.012). Overall clinical pregnancy rate was 52.1% with no-significant differences between groups (48.5% in het-ET, 52.9% in hom-FET and 54.7% in eu-FET). P- β-hCG was considered as adequate in 75.7% (311/411) ET-HRT with positive β-hCG and low in 24.3% (100/411), with no differences between groups. In case of positive β-hCG and P- β-hCG >10.6 ng/mL, OPR was 83.6% and MR was 16.4%, with no-significant differences between groups. Among the 100 low P- β-hCG, 80 ET-HRT received PS. In this subgroup OPR was 96.2% and MR was 3.8%, with no-significant differences between groups. In 20 out of 100 ET with P- β-hCG <10.6 ng/mL, no PS was added for different reasons. This group showed the lowest OPR (30%) and the highest MR (70%), again with no between-group differences according to het-ET, hom-FET or eu-FET. Miscarriage rate was significantly higher (p < 0.001) when P- β-hCG was <10.6 ng/mL and no PS was added to HRT compared to P- β-hCG <10.6 ng/mL but with PS, and also compared to the P- β-hCG >10.6 ng/mL group. Limitations, reasons for caution The main limitation of the study is due to its retrospective nature and the small sample of patients with P- β-hCG<10.6 ng/mL that was not supplemented. Furthermore, the cut-off of P- β-hCG was arbitrarily decided upon previous studies, and lastly different routes of administration were considered for the PS. Wider implications of the findings: The results of this study showed that individualization of Progesterone supplementation in ET-HRT may be a crucial turn point in order to increase the pregnancy rates and decrease the miscarriage rates. An adequate PS should be considered in case of low P- β-hCG levels for both het-ET, hom-FET and eu-FET. Trial registration number Not applicable


2016 ◽  
Vol 113 (50) ◽  
pp. E8079-E8088 ◽  
Author(s):  
Jia Yuan ◽  
Jeeyeon Cha ◽  
Wenbo Deng ◽  
Amanda Bartos ◽  
Xiaofei Sun ◽  
...  

Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo–uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations directed from the primary lumen toward the AM domain. The morphological orientation of crypts in rodent uteri was recognized more than a century ago, but the mechanism remained unknown. Here we provide evidence that planar cell polarity (PCP) signaling orchestrates directed epithelial evaginations to form crypts for implantation in mice. Uterine deletion of Vang-like protein 2, but not Vang-like protein 1, conferred aberrant PCP signaling, misdirected epithelial evaginations, defective crypt formation, and blastocyst attachment, leading to severely compromised pregnancy outcomes. The study reveals a previously unrecognized role for PCP in executing spatial cues for crypt formation and implantation. Because PCP is an evolutionarily conserved phenomenon, our study is likely to inspire implantation studies of this signaling pathway in humans and other species.


2020 ◽  
Vol 26 ◽  
Author(s):  
Hui-na Zhang ◽  
Jun-zhao Zhao ◽  
Yi-lu Chen ◽  
Ying-fen Ying ◽  
Xiao-sheng Lu ◽  
...  

Reproduction ◽  
2001 ◽  
pp. 151-154 ◽  
Author(s):  
M Elli ◽  
B Gaffuri ◽  
A Frigerio ◽  
M Zanardelli ◽  
D Covini ◽  
...  

Embryo implantation is a critical step in both cows and humans. The use of ibuprofen lysinate to enhance implantation has been investigated in cattle with the specific aim of improving pregnancy rates after embryo transfer. In this study, heifers (n = 100) were assigned randomly to one of two groups: one group was treated i.m. with 5 mg ibuprofen lysinate kg(-1) body weight 1 h before embryo transfer and a control group received vehicle only. A single embryo was transferred into each recipient cow. There was a significant difference in the number of pregnancies after embryo transfer between cows in the treated (41 of 50; 82%) and control (28 of 50; 56%) groups (P < 0.05). These data indicate that ibuprofen lysinate may be an effective adjunctive treatment for assisted reproduction in cattle. Further studies are needed to clarify whether this effect is associated with the reduction of cyclooxygenase enzyme isoforms during embryo transfer or whether other mechanisms are involved.


2018 ◽  
Vol 103 (7) ◽  
pp. 2735-2742 ◽  
Author(s):  
Daimin Wei ◽  
Yunhai Yu ◽  
Mei Sun ◽  
Yuhua Shi ◽  
Yun Sun ◽  
...  

Abstract Context Supraphysiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer. Women with polycystic ovary syndrome (PCOS), who usually overrespond to ovarian stimulation, have a better live birth rate after frozen embryo transfer (FET) than after fresh embryo transfer; however, ovulatory women do not. Objective To evaluate whether the discrepancy in live birth rate after fresh embryo transfer vs FET between these two populations is due to the variation in ovarian response (i.e., peak estradiol level or oocyte number). Design, Setting, Patients, Intervention(s), and Main Outcome Measure(s) This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS and 2157 ovulatory women were randomly assigned to undergo fresh or FET. The primary outcome was live birth. Results Compared with fresh embryo transfer, FET resulted in a higher live birth rate (51.9% vs 40.7%; OR, 1.57; 95% CI, 1.22 to 2.03) in PCOS women with peak estradiol level &gt;3000pg/mL but not in those with estradiol level ≤3000 pg/mL. In women with PCOS who have ≥16 oocytes, FET yielded a higher live birth rate (54.8% vs 42.1%; OR, 1.67; 95% CI, 1.20 to 2.31), but this was not seen in those with &lt;16 oocytes. In ovulatory women, pregnancy outcomes were similar after fresh embryo transfer and FET in all subgroups. Conclusions Supraphysiological estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS but not in ovulatory women.


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