Glycoforms of [alpha]-2-macroglobulin in uterine fluid, are altered during the menstrual cycle, and differ between fertile and infertile women

2014 ◽  
Author(s):  
Tracey A. Edgell ◽  
Harriet Fitzgerald ◽  
Lois Salamonsen
2010 ◽  
Vol 22 (9) ◽  
pp. 73
Author(s):  
N. Hannan ◽  
P. Paiva ◽  
K. L. Meehan ◽  
C. Hincks ◽  
L. J. F. Rombauts ◽  
...  

Embryo implantation requires synchronized dialogue between a receptive endometrium and an activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle there is increased glandular secretion into the uterine lumen. These secretions contain important mediators that modulate the endometrium and support the conceptus during implantation. Analysis of the composition of uterine fluid across the menstrual cycle and in fertile and infertile women will, therefore, provide new insights into uterine receptivity. We hypothesized that multiplex platform analysis of human uterine lavages would identify soluble mediators important for the establishment of pregnancy in humans. Lavages were collected (by flushing the uterine cavity with 5mL of saline) from fertile and infertile women during the MS phase and from fertile women during the mid-proliferative (MP) phase of the menstrual cycle. Comparison of lavages from the three cohorts was performed using quantitative MilliplexTM Luminex® cytokine/chemokine assays containing 42-analytes. Luminex analysis detected a number of cytokines in uterine fluid, revealing 8 soluble mediators previously unknown in the endometrium and present in human uterine fluid including, PDGF-AA, TNFβ, sIL-2Rα, Flt-3 ligand, sCD40L, IL-7, IFNα2 and GRO. Furthermore comparison of the three cohorts revealed VEGF levels were significantly higher in the fertile (MS) fluid when compared to infertile. Functional studies demonstrated that rhVEGF treatment significantly increased the adhesive properties in cells present at the maternal-fetal interface. These findings suggest VEGF plays a role in regulating embryo implantation. Furthermore identifying the soluble mediators in uterine fluid may provide potential markers of endometrial receptivity, insight into the unique microenvironment essential for pregnancy and a profile of maternal factors that influence the implanting blastocyst.


2017 ◽  
Vol 1 (28) ◽  
pp. 661-670
Author(s):  
NASSER NAFAA ABRAHEM ◽  
SAAD HASSAN DREIJ ◽  
Mahdi Saber Al-Deresawi

This study aimed to determine the relationship of  thyroid hormone disturbance and prolactin over production to impact on the menstrual irregularities anovulation .This  study were carried out in Al-Karama teaching hospital and  included (47) primary infertile women, (30 ) of them were with hypothyroidism , the patients aged between (18-40). This study extended from February to June  2017. The hormonal assay of TSH, FT3, FT4 ,FSH , LH and PRL that revealed  :- There were high  significantly (p < 0.01) increased in TSH concentrations , significantly (p < 0.05) decreased in levels of FT3 and  FT4.Gonadotropins hormones recorded significantly ( p <0.05) decreased in levels of FSH and non significantly increased in levels of LH. Prolactin concentrations that obtained revealed to significantly (p < 0.05) increased in patients with hypothyroidism . This study reported there were (70%) of hypothyroidism patients with menstrual disturbance. We concluded , that hypothyroidism and Hyperprolactinemia commonly related and synergized to menstrual irregularities and ovulatory failure. 


2009 ◽  
Vol 21 (9) ◽  
pp. 4 ◽  
Author(s):  
L. A. Salamonsen

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.


2015 ◽  
Vol 8 (4) ◽  
pp. 244 ◽  
Author(s):  
Azra Azmoodeh ◽  
Mansoureh Pejman Manesh ◽  
Firouzeh Akbari Asbagh ◽  
Azizeh Ghaseminejad ◽  
Zeinab Hamzehgardeshi

<p><strong>BACKGROUND: </strong>Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG<strong> </strong>and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes.</p> <p><strong>METHODS:</strong> The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups.<strong> </strong>For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18–23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38–40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured,<strong> </strong>a<strong> </strong>third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome.</p> <p><strong>RESULTS: </strong>There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p &lt; 0.001). The results of our multivariate logistic regression indicate that size 18–19.9 mm leads to the complete LUF  less than ≥22 mm [AOR: 0.25, P = 0.005], and  in size 20– 21.9 mm  as well [AOR: 0.17, P = 0.002].</p> <p><strong>CONCLUSION: </strong>Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.<strong></strong></p>


2018 ◽  
Vol 25 (07) ◽  
pp. 1089-1093
Author(s):  
Sabeen Nasir ◽  
Muhammad Mumtaz Khan ◽  
Naveed Sharif ◽  
Sadaf Alam ◽  
Sara Ziaullah ◽  
...  

Background: In histopathology, inter-observer variability is frequently encounterleading to diagnostic dilemma. Endometrial biopsies are one of them where multiple factorsincluding hormonal influences make the interpretation difficult. The aim of the article was tofind the interobserver variability level between two consultants on endometrial biopsies byapplying kappa and ICC analysis. Study Design: Prospective study. Setting: Department ofPathology Peshawar Medical College Peshawar from Health Care Centre, University Town,Peshawar. Period: March to August 2013. Methods: This study consisted of 102 endometrialbiopsies of infertile women on 22nd or 23rd day of menstrual cycle. All cases were examined bytwo consultants separately and formed their opinions independent of each other according toNoye’s criteria. Their opinions were categorized as those in agreement, with minor disagreementand with major difference in opinion. Results: Agreement of opinion was established only in 34(33.3%) cases. There was disagreement in 68 (66.7%) of cases. Out of these 68 cases, 46 (68%)belonged to the category of major conflicting opinion. In case of minor conflicting opinion,there was difference in specific day of the phase of menstrual cycle. The Kappa coefficient andICC statistics was performed which gave the overall results as fair agreement. Conclusion:The main cause of disagreement was difficulty in applying the criteria for effects of hormonalinfluences on endometrial biopsies leading to subjective interpretation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Hutchison ◽  
T T Truong ◽  
T A Egell ◽  
L A Salamonsen ◽  
D K Gardner ◽  
...  

Abstract text Globally, 39% of the adult population is overweight or obese, with the prevalence of obesity following an upward trajectory over the recent decades (WHO). Up to 30% of women of reproductive age in Western countries are obese before conception, and obese women experience higher rates of infertility and pregnancy complications than lean women; however, the mechanisms underpinning obesity-related infertility are poorly understood. Advanced Glycation Endproducts (AGEs) are a proinflammatory modification of proteins exposed to sugars, formed through the Maillard reaction. AGEs are elevated four-fold in the uterine fluid of obese, infertile women, compared to lean. AGEs equimolar to those in the obese microenvironment negatively impact the functions of endometrial epithelial and stromal cells, and adhesion and invasion of trophoblast cells, reducing the potential for successful maternal-fetal interactions (Antoniotti et al., 2018). This research further investigated preimplantation embryo development and endometrial cell functions in the presence of AGEs equimolar to those in obese uterine fluid. Altered local environments in very early life can set offspring up for a lifetime of health or disease (DoHAD); thus, uterine AGEs may contribute to the prevalence of non-communicable disease in children of obese parents. Preimplantation mouse embryos were cultured in vitro with AGEs equimolar with uterine fluid concentrations from lean and obese women, and their development and implantation potential assessed. “Obese” AGEs did not impact the proportion of embryos reaching blastocyst stage by day 4, but significantly reduced the proportion of blastocysts hatching by day 5 (P &lt; 0.01). AGEs equimolar with the obese uterine environment detrimentally impacted trophectoderm formation and function: reduced trophectoderm cell number (P &lt; 0.01), reduced outgrowth on fibronectin (indicative of reduced implantation potential, (P &lt; 0.01), but did not increase cell apoptosis (TUNEL assay). RAGE antagonism, but neither metformin nor antioxidants, improved trophectoderm cell number. Thus, obesity-associated AGEs link obesity and reduced fertility through poor placentation potential of embryos (Hutchison et al, 2020). Endometrial epithelial cell function was examined in the presence of lean and obese concentrations of AGEs. Obese AGEs significantly reduced the rate of proliferation (xCelligence real time cell analysis) of the endometrial epithelial cell line ECC-1 versus lean AGEs (P = 0.04). Antioxidants successfully restored the rate of proliferation in the presence of obese AGEs (P = 0.7 versus lean AGEs). Subsequently, human endometrial epithelial organoid culture was utilised as a more physiologically relevant experimental paradigm. When cultured as organoids, primary endometrial epithelial cells were functionally responsive to obesity-associated AGEs, expressing both RAGE and TLR4. The morphology of organoids in culture was not impacted by the presence of obese AGEs versus lean; however, the proliferation of epithelial cells retrieved from organoid culture was altered by obese AGEs versus lean. Obese AGEs also increased the secretion of proinflammatory CXCL16 versus vehicle control (P = 0.04) while increased secretion of other proinflammatory cytokines and chemokines including TNFa approached significance in the presence of obese AGEs. As the inflammatory milieu is altered in the uterine fluid of infertile women, elevated AGEs may promote an infertile endometrial inflammatory environment. AGEs link obesity and reduced fertility, being detrimental to preimplantation embryo development and endometrial cell function when present at concentrations equal to those in obese uterine fluid. Antioxidants and RAGE antagonism provide beneficial effects to cell function in the presence of obesity-associated AGEs. This research provides evidence supporting AGEs as a factor contributing to obesity related infertility, and as an emerging frontier for reproductive health. Clinically, reduction of uterine AGEs may improve fertility for obese couples wishing to conceive. Antoniotti et al (2018). Hum Rep. 33(4), 654-665. PMID: 29471449 Hutchison et al (2020). RBMO. 41(5), 757-766. PMID: 32972872


2021 ◽  
pp. 7-9
Author(s):  
Anshu Anshu ◽  
Usha Kumari ◽  
Debarshi Jana

Background: Infertility in polycystic ovary syndrome (PCOS) is one of the leading causes of anovulatory infertility. Ovulation induction is indicated for the management of anovulatory infertility in PCOS and for augmentation of ovulation in ovulatory infertility, in unexplained infertility. The aim of this retrospective study was to compare and determine the efcacy of letrozole administration in infertile women with PCOS to that of infertile women without PCOS by transvaginal sonography. This Methods: study was done at Obstetrics and Gynaecology Department of JLNMCH, Bhagalpur, Bihar from January to December 2020. Fifty six infertile women including 16 diagnosed as having PCOS and 40 infertile women with regular menstrual cycle (non-PCOS) were included in this study. Patients were treated with letrozole 7.5 mg/day from day 2-6 of the menstrual cycle. Subjects were monitored once during the days 11 to 14 of the cycle by transvaginal ultrasound. Main outcome measures were number of ovulatory follicles, dominant follicle diameter and endometrial thickness. Letrozole as an ovulation inducing drug was found equally effective in t Results: erms of follicular recruitment, follicular maturation and endometrial development both in PCOS and non-PCOS women, as there was no signicant difference regarding mature follicular development and endometrial response between the two study groups. Association of endometrial response particularly with follicular diameter 18 mm or more among the study groups revealed no statistically signicant difference. In conclusion, our results indicate that the Conclusion: effect of letrozole on endometrial thickness and follicular development in patients of anovulatory PCOS did not signicantly differ compared to non-PCOS infertile women.


2016 ◽  
Vol 5 (1) ◽  
pp. 43-48
Author(s):  
Manoj Bhattarai

Background Ultrasonography is the first line imaging modality for evaluation of ovaries, monitoring ovarian follicular development and detecting ovulation in infertile women; thus plays a significant role in infertility management. This study was undertaken to evaluate the pattern of ovarian follicular growth and to predict and detect ovulation in infertile women by transvaginal sonography in eastern region of Nepal.Material and Methods Hospital based prospective cross-sectional study on 100 infertile patients referred for ultrasonographic monitoring of ovarian follicle was conducted over duration of 26 months. Serial transvaginal sonography of the patients was performed using standard procedure daily from day 10 of menstrual cycle till detection of ovulation. Identification of ovarian dominant follicle, monitoring of dominant follicle development and detection of ovulation was assessed in relation to the day of menstrual cycle.Results Increase in mean diameter of the dominant follicle was seen in serial ultrasound scan till ovulation, which occurred in all cases by day 16 of menstrual cycle. The average daily follicular growth rate ± SD from day 10 of menstrual cycle till detection of ovulation was 2.2 ± 0.2 mm per day and the mean diameter ± SD of dominant follicle on the day prior to ovulation was 21.4 ± 2.8 mm (range: 17.2 – 26.3 mm).Conclusion Transvaginal sonography is an excellent method for monitoring of ovarian follicular development and shows a linear increase in mean diameter of dominant follicle from day 10 of menstrual cycle till detection of ovulation.Journal of Nobel Medical CollegeVolume 5, Number 1, Issue 8, January-July 2016, 43-48


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