Society for Reproductive Biology Founders' Lecture 2009. Preparing fertile soil: the importance of endometrial receptivity

2009 ◽  
Vol 21 (7) ◽  
pp. 923 ◽  
Author(s):  
Lois A. Salamonsen ◽  
Guiying Nie ◽  
Natalie J. Hannan ◽  
Evdokia Dimitriadis
Keyword(s):  
Reproductive Technologies ◽  
Endometrial Receptivity ◽  
Leukaemia Inhibitory Factor ◽  
Uterine Receptivity ◽  
Comprehensive Overview ◽  
Altered Expression ◽  
Molecular Events ◽  
Glandular Cells ◽  
Interleukin 11 ◽  
Secretory Capacity

The human endometrium is receptive for implantation of a blastocyst for only 4–5 days in each menstrual cycle. Failure of implantation is a major reason for infertility in women and the inability to achieve endometrial receptivity is responsible for much of the failure of reproductive technologies. Endometrial receptivity requires changes in the uterine luminal and glandular cells, particularly in terms of their secretory capacity and altered expression of adhesion molecules. In parallel with these changes, decidualisation (differentiation) of the endometrial stroma is initiated in women during the receptive phase, regardless of the presence of a blastocyst. Increased leucocyte numbers are also important. The microenvironments provided by the endometrium during the receptive phase and that support implantation are highly complex and constantly changing as implantation progresses. The present review provides a comprehensive overview of the cellular and molecular events of human implantation. It also summarises work from our laboratories emphasising the functional importance of proprotein convertase 6, along with key cytokines (interleukin-11, leukaemia inhibitory factor, activin A) and chemokines (including CX3CL1 and CCL14), during implantation. Of particular importance is how these mediators contribute to receptivity and how they are disturbed in infertile women. Factors that are critical for uterine receptivity may also be manipulated to provide new contraceptive strategies for women.

005. PREPARING FERTILE SOIL: THE IMPORTANCE OF ENDOMETRIAL RECEPTIVITY

2009 ◽  
Vol 21 (9) ◽  
pp. 4 ◽  
Author(s):  
L. A. Salamonsen
Keyword(s):  
Menstrual Cycle ◽  
Adhesion Molecules ◽  
Reproductive Technologies ◽  
Endometrial Receptivity ◽  
Present Review ◽  
Altered Expression ◽  
Endometrial Stroma ◽  
Infertile Women ◽  
Glandular Cells ◽  
Secretory Capacity

The human endometrium is receptive for implantation of a blastocyst, for only 4–5 days in each menstrual cycle. Failure of implantation is a major reason for infertility in women, and the inability to achieve endometrial receptivity is responsible for much of the failure of reproductive technologies. Endometrial receptivity requires alterations in the uterine luminal and glandular cells, particularly in terms of their secretory capacity and altered expression of adhesion molecules, along with decidualization of the endometrial stroma, which in women is initiated during the receptive phase, regardless of the presence of a blastocyst. Increased leukocyte numbers are also important. The microenvironments provided by the endometrium during the receptive phase and which support implantation are highly complex and constantly changing. The present review summarizes work from our laboratories and others, regarding these microenvironments, how they impact on receptivity and how they are disturbed in infertile women. Such microenvironments can also be manipulated to provide new contraceptive strategies for women.

Novel aspects of endometrial function: a biological sensor of embryo quality and driver of pregnancy success

2012 ◽  
Vol 24 (1) ◽  
pp. 68 ◽  
Author(s):  
Olivier Sandra ◽  
Nadéra Mansouri-Attia ◽  
Richard G. Lea
Keyword(s):  
Developmental Stages ◽  
Assisted Reproductive Technologies ◽  
Uterine Cavity ◽  
Reproductive Technologies ◽  
Biological Properties ◽  
Reproductive Capacity ◽  
Epigenetic Alterations ◽  
Uterine Receptivity ◽  
Blastocyst Development ◽  
Developmental Potential

Successful pregnancy depends on complex biological processes that are regulated temporally and spatially throughout gestation. The molecular basis of these processes have been examined in relation to gamete quality, early blastocyst development and placental function, and data have been generated showing perturbations of these developmental stages by environmental insults or embryo biotechnologies. The developmental period falling between the entry of the blastocyst into the uterine cavity to implantation has also been examined in terms of the biological function of the endometrium. Indeed several mechanisms underlying uterine receptivity, controlled by maternal factors, and the maternal recognition of pregnancy, requiring conceptus-produced signals, have been clarified. Nevertheless, recent data based on experimental perturbations have unveiled unexpected biological properties of the endometrium (sensor/driver) that make this tissue a dynamic and reactive entity. Persistent or transient modifications in organisation and functionality of the endometrium can dramatically affect pre-implantation embryo trajectory through epigenetic alterations with lasting consequences on later stages of pregnancy, including placentation, fetal development, pregnancy outcome and post-natal health. Developing diagnostic and prognostic tools based on endometrial factors may enable the assessment of maternal reproductive capacity and/or the developmental potential of the embryo, particularly when assisted reproductive technologies are applied.

scholarly journals Endometrial receptivity: the molecularmechanisms regulation of implantation

2013 ◽  
Vol 62 (2) ◽  
pp. 63-74 ◽  
Author(s):  
Yuliya Sergeyevna Krylova ◽  
Igor Moiseyevich Kvetnoy ◽  
Eduard Karpovich Aylamazyan
Keyword(s):  
Parameter Estimation ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Signaling Molecules ◽  
Endometrial Receptivity

Presents current views on endometrial receptivity and the molecular mechanisms regulation of implantation. Examines the signaling molecules as potential markers of parameter estimation window of implantation in assisted reproductive technologies.

scholarly journals Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

2019 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L. Young ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Seq ◽  
Uterine Receptivity ◽  
Normal Cycle ◽  
Estrogen Response ◽  
Molecular Events ◽  
History Of ◽  
And Function ◽  
Genomic Regions ◽  
Fertile Women

ABSTRACTContextPoor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.ObjectiveTo define PGR-regulated molecular mechanisms and epithelial roles in receptivity.DesignRNA-seq and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the WOI in endometrium of fertile women.SettingEndometrial biopsies from the proliferative and mid-secretory phases were analyzed.Patients or Other ParticipantsParticipants were fertile, reproductive aged (18-37) women with normal cycle length; and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.InterventionsThere were no interventions during this study.Main Outcome MeasuresHere we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle-dependently to regulate genes involved in uterine cell differentiation and function.Results653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, EMT, cell death, interleukin/STAT signaling, estrogen response, and MTORC1 response. Transcriptome of the epithelium identified 3,052 DEGs, of which 658 were uniquely regulated. Transcription factors IRF8 and MEF2C were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.ConclusionPGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.PrécisUsing a combination of RNA-seq and PGR ChIP-seq, novel signaling pathways and epithelial regulators were identified in the endometrium of fertile women during the window of implantation.

scholarly journals Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

2019 ◽  
Vol 105 (4) ◽  
pp. e1419-e1439 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L Young ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mammalian Target Of Rapamycin ◽  
Uterine Receptivity ◽  
Normal Cycle ◽  
Mesenchymal Transition ◽  
Estrogen Response ◽  
Molecular Events ◽  
And Function

Abstract Context Poor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility. Objective To define Progesterone Receptor (PGR)-regulated molecular mechanisms and epithelial roles in receptivity. Design RNA-sequencing and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the Window of implantation (WOI) in endometrium of fertile women. Setting Endometrial biopsies from the proliferative and mid-secretory phases were analyzed. Patients or Other Participants Participants were fertile, reproductive aged (18–37 years) women with normal cycle length, and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study. Interventions There were no interventions during this study. Main Outcome Measures Here we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle dependently to regulate genes involved in uterine cell differentiation and function. Results 653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, epithelial mesenchymal transition, cell death, interleukin/Signal Transducer And Activator Of Transcription (STAT) signaling, estrogen response, and Mammalian target of rapamycin complex 1 (MTORC1) response. Transcriptome of the epithelium identified 3052 differentially expressed genes, of which 658 were uniquely regulated. Transcription factors Interferon Regulatory Factor 8 (IRF8) and Myocyte Enhancer Factor 2C (MEF2C) were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized. Conclusion PGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.

Genes involved in implantation

2001 ◽  
Vol 13 (1) ◽  
pp. 41 ◽  
Author(s):  
Lois A. Salamonsen ◽  
Guiying Nie ◽  
Eva Dimitriadis ◽  
Lorraine Robb ◽  
Jock K. Findlay
Keyword(s):  
Calcium Binding ◽  
Embryo Implantation ◽  
Hostile Environment ◽  
Mouse Uterus ◽  
Suppressor Factor ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Human Fertility ◽  
Implantation Sites ◽  
Interleukin 11

The endometrium is normally a hostile environment for an embryo, except for a short phase in each reproductive cycle known as the ‘window of receptivity’. The precise molecular events involved in this transformation are not well understood. Application of state-of-the-art techniques of the 1990s has identified some of the genes involved, which are reviewed here. Mice with a null mutation in either the gene for leukemia inhibitory factor or the interleukin-11 receptor α chain are infertile, owing in both cases to a failure of embryo implantation. Both of these genes are expressed in the human endometrium with patterns suggesting a role in human fertility. The technique of RNA differential display has been applied to a comparison of the expression of genes at implantation sites v. inter-implantation sites in the mouse uterus on the first day of implantation, and has defined additional genes whose products may be important for this process. Among these are the calcium-binding protein D9K, the monoclonal non-specific suppressor factor β , and the splicing factor SC35. The major challenge is to determine whether manipulation of such genes can increase or decrease endometrial receptivity in humans.

scholarly journals Using Uterine Biophysical Profile as a Predictor of Endometrial Receptivity and Pregnancy in Stimulated IUI Cycles

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Rawaa Saad Hasan Abunayla ◽  
◽  
Lubna Amer Al-Anbari ◽  
Muayad S, Abood ◽  
Huda A. R. Hussaini ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Pulsatility Index ◽  
Uterine Artery ◽  
Assisted Reproductive Technologies ◽  
Intrauterine Insemination ◽  
Reproductive Technologies ◽  
Endometrial Receptivity ◽  
Infertile Women ◽  
Biophysical Profile ◽  
The Mean

Implantation failure and disorders of endometrial receptivity represent an essential cause of infertility; multiple parameters were needed to predict the uterine receptivity understanding that no sole parameter could predict the same. A score was termed as (Uterine Biophysical Profile) could be utilized as a predictor of endometrial receptivity. To evaluate the predictive potential of Uterine biophysical profile of both endometrial receptivity and pregnancy outcome in infertile women undergoing Intrauterine Insemination (IUI). The current cross-sectional study was conducted in the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies in Al Nahrain University, Baghdad, Iraq from the 1st of Oct. 2018 till 1st of May 2019 involving seventy women of infertile couples with the same inclusion and exclusion criteria. Uterine biophysical profile was evaluated using a doppler ultrasound examination and then a score was calculated and correlated to pregnancy outcome. The mean Uterine Artery Pulsatility Index (UAPI) was significantly lower in women with positive pregnancy in comparison to women with negative pregnancy, 2.10±0.19 versus 2.47±0.65, respectively (P=0.032). Moreover, no women with Pulsatility Index (PI) score (0) succeeded to get pregnant and the higher the score, the higher the rate of pregnancy (P=0.006). Furthermore, Spearman correlation showed significant positive correlation between positive pregnancy outcome and UAPI (r=0.365; P=0.002). The mean total score was significantly higher for pregnant women than in women with negative pregnancy, 18.27±1.33 versus 16.35±2.47, respectively (P=0.005). The cutoff value was >17 with an acceptable accuracy level of 74.2. The sensitivity of that cutoff vale was 80 % and the specificity was 65.5%. Uterine artery pulsatility index and total uterine biophysical score are the principal predictors of positive pregnancy outcomes in infertile women undergoing IUI.

P–254 The outcome of artificial reproductive technologies (ART) cycles with transfer of frozen-thawed blastocysts depending on whether expanded on day 5 or day 6

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Polumiskova ◽  
S Tevkin ◽  
M Shishimorova ◽  
T Jussubaliyeva
Keyword(s):  
Pregnancy Rate ◽  
Positive Outcome ◽  
Reproductive Technologies ◽  
Endometrial Receptivity ◽  
Ongoing Pregnancy ◽  
Miscarriage Rate ◽  
Ongoing Pregnancy Rate ◽  
Preimplantation Genetic Testing ◽  
Group A ◽  
Group B

Abstract Study question Is there a difference in ART cycle results after frozen embryo transfer (FET), depending on whether blastocysts were cryopreserved on day 5 or 6? Summary answer There’s no statistical difference in the clinical pregnancy rate (CPR), life birth rate (LBR), miscarriage rate (MR) between embryos frozen on day 5 and 6. What is known already Currently, opinions differ regarding this topic. Previous studies demonstrated no difference in ongoing pregnancy rates between embryos frozen on day 5 (group A) or day 6 (group B) after FET. However, metanalysis (2019) suggested higher CPR and LBR after transferring embryos from group A rather than group B. It has also been established that ovarian stimulation leads to endometrial changes that result in deleterious effects on the implantation window and endometrial receptivity. Consequently, fresh transfers were excluded. Due to hormonal priming of endometrial receptivity, the same pregnancy outcomes should be expected with frozen-thawed blastocysts (day 5 vs 6). Study design, size, duration Retrospective cohort study was conducted between January 2015 and December 2018 with selected group of patients under 40 years of age. Group A consisted of 2275 cryotransfers of blastocyst expanded on day 5; group B included 170 cryotransfers of blastocyst on day 6. Both groups had an average of 1,52 embryos transferred per patient. Participants/materials, setting, methods Embryos were vitrified and warmed with Cryotop method (Kitazato, BioPharma). Blastocysts were scored according to Gardner and Schoolcraft grading system. Only expanded on day or 6 blastocysts of excellent and good (AA, AB, BA, BB) quality were selected. The embryos were cultured in CSC medium (Irvine Scientific) for 2–4 hours prior intrauterine transfer. The cycles with donor gametes, surrogacy and preimplantation genetic testing (PGT) were excluded. Statistical validity was assessed by Pearson’s chi-squared test. Main results and the role of chance The rates of the CPR, the ongoing pregnancy rate (OPR) and the LBR between group A and B were 50,8% (1157/2275) vs 46,5% (79/170) (p = 0,26), 37,4% (852/2275) vs 37,0% (63/170) (p = 0,91), 36,5% (832/2275) vs 35,2% (60/170) (p = 0,73) respectively and no significant differences were found in each category. Moreover, similarly there were no significant differences in the miscarriage rate 26,0% (301/1157) and 21,5% (17/79) (p = 0,37) as well Limitations, reasons for caution The study is limited due to uneven distribution of patients in both groups and by a low number of participants. The grading of blastocysts’ quality is also subjected to a human factor. Wider implications of the findings: This study confirms that frozen-thawed blastocysts do not seem to exhibit a difference in the CPR, OPR, LBR and MR whether they were expanded on day 5 or day 6. The cryopreservation of day 6 blastocyst can increase the chances of the patient for the positive outcome. Trial registration number Not applicable

Sign in / Sign up

Export Citation Format

Share Document