For successful implantation, a high-quality embryo, receptive endometrium, and tight communication between the two are required. The lack of uterine contractions during embryo transfer is one of the characteristics that greatly affects endometrial receptivity. This is because it has been observed that ET may cause uterine contractions, which may be harmful to embryonic apposition and endometrial blood flow .The aim of this study was to assess how magnesium sulfate administration on the day of embryo transfer improve sub endometrial blood flow, endometrial receptivity, and increase implantation rate and clinical pregnancy rate . Eighty infertile women undergoing ART cycles participated in this prospective. Recombinant FSH (Gonal-F) was used in a controlled ovarian hyperstimulation technique. The first group A (n=40) got a 4gm infusion of magnesium sulfate, while the second placebo control group B (n=40) received 200ml of 5% glucose water as a placebo, respectively. While there were no significant changes in body mass index (BMI), endometrial thickness, number of transferred embryos, or embryo transfer day, significant variations were seen in patient mean age (p<0.001) and mean number of grades I embryo (P=0.003). It was significantly different after magnesium sulfate administration with the lowest value in magnesium sulfate group (P=0.024; P <0.001 and P <0.001 respectively). Implantation rate and clinical pregnancy rate both increased after drugs administration although it was non-significant (P= 0.106 and P= 0.348 respectively). It appears that magnesium sulfate injection before to embryo transfer can significantly increase sub endometrial vascularity and endometrial receptivity and improving implantation rate and clinical pregnancy rate non significantly in ICSI cycles by lowering uterine muscular
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 1 st of Oct. 2018 till 1 st 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.
E ndometrial thickness (ET) is one of the best predictors of implantation rate and pregnancy success rate because endometrial growth depends on hormones. Estrogen regulates the proliferative phase, endometrial proliferation induced by estrogen after menstruation is largely dependent on blood flow to the basal endometrium that produces progesterone receptors which are required for progesterone-regulated endometrial growth in the secretory process. To compare the effect of estradiol valerate vs. sildenafil citrate on endometrial receptivity and subsequent pregnancy outcome in unexplained infertility patients receiving letrozole for ovulation induction. Herein, 21 patients with unexplained infertility underwent ovulation induction by letrozole (2.5 mg). Patients were divided into 2 groups; group A (10 patients) were given sildenafil tablets vaginally (25 mg) four times daily and group B (11 patients) were treated with estradiol valerate tablet 2 mg/12 hours. Patients were evaluated by transvaginal ultrasonography (TVS) to determine endometrial thickness, pattern, size, and the number of the dominant follicles, serum assessment of Vascular Endothelial Growth Factor (VEGF) level at trigger day, and chemical pregnancy outcome 14 days later. Results showed that the endometrial thickness, patterns of the endometrium, VEGF, size of the dominant follicle at the trigger day, and pregnancy rates were not significantly different between the two groups. However, the difference in the number of the dominant follicles at trigger day was statistically significant which is more in the sildenafil treated group. The present study confirmed the findings of both Sildenafil and E 2 valerate to boost endometrial receptivity and pregnancy rate.
Background: Endometrial receptivity is defined as a temporary unique sequence of factors that make the endometrium receptive to the embryonic implantation. Histological evaluation, now considered to add little clinically significant information, should be replaced by functional assessment of endometrial receptivity. A large number of functional molecular mediators have been identified to date, including adhesion molecules. Thus, endometrial biopsy samples can be used to identify molecules associated with uterine receptivity to obtain a better insight into human embryo implantation. Objectives: To investigate E-cadherin expression in the endometrium throughout the menstrual cycle of fertile females. Patients, Materials and Methods: Under simple analgesia, fractional endometrial biopsies from anterior, posterior, fundal walls, and the cervix of (32) fertile females (age= 29.91± 5.9 year, parity= 3.6±2.1) were taken at different days of the menstrual cycle. The immunohistochemical (IHC) stained tissues were analyzed using computerized image analysis for measurement of PI of E-cadherin which is ratio of the number of stained cells to the number of total cells. PI were measured in three regions: stromal, membranous, and glandular epithelium. Results: E-cadherin expression in the endometrium is up-regulated in the proliferative phase and down-regulated in the secretory phase of the menstrual cycle. The PI of E-cadherin in the glandular epithelium of the anterior wall of the endometrium was significantly lower than that of posterior and fundal walls (P=0.027). The PI of E-cadherin in the endocervical epithelium was significantly higher than that in the anterior, posterior, and fundal walls of the endometrial cavity (P=0.004). Conclusion: E-cadherin might have a role in embryo implantation.
Pregnancy cannot develop without a coordinated stability between an invading trophoblast and a receptive maternal decidua. Both the maternal decidua and the trophoblast, which is embryonic, must incessantly regulate and change one another during the processes of implantation, trophoblast invasion, and placentation. The goal of this study was to determine whether intrauterine infusion of hCG at various doses on the day of ovum pick-up would affect endometrial receptivity markers, biochemical markers, and ICSI outcome. To this end, measurements of serum levels of TNF and IL-10, endometrial thickness using ultrasound, and sub-endometrial blood flow indices using Doppler ultrasound were used.Ninety infertile women were randomly assigned to one of three groups: the research group (n = 60) was given intrauterine administration of either 700 IU or 500 IU of hCG on the day of ova pickup. The control group (n = 30) without hCG. On cycle days 2- 3, a plasma hormone level assessment was performed on each patient.In the 700 hCG group, the pregnancy rate was statistically higher (53.3% and 40%in the 500IU group respectively) as compared with the control group C (26.7%), no significant difference in ICSI outcome between group A &B. The RI and PI were significantly lower in group A (700IU) compared to group B and C. The biochemical marker TNA and ratio of TNF/IL-10 also lower in group A confirming role of Hcg in enhancement of implantation. Intrauterine injection of hCG at day of ova pickup significantly improved the endometrial receptivity marker and this effect occur in dose dependent manner
Successful implantation needs a receptive endometrium, a functional and normal embryo at the stage of blastocyst developmental and a synchronized dialogue between embryonic tissues and maternal tissues. The current study was planned and conducted to investigate the potential role of vaginal pessary of hyaluronic acid on intracytoplasmic sperm injection (ICSI) outcome. This study included 63 infertile women (32 women as study group receiving hyaluronic acid and 31 control group) who were subjected to ovulation induction programs with gonadotropin releasing hormone (GnRH) antagonist protocols for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) procedures. Blood samples were taken by Vacutainer tubes and centrifuged according to the manufacturer’s instructions for the preparation of serum samples. Serum samples for Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) were obtained from each patient when the basal hormonal status was determined. The second time point is when the samples were obtained on the day of ova pickup, after that the G1 embryos will be transferred inside the uterine cavity. Then performance of endometrial receptivity parameters or patterns evaluation and patients were followed up to do pregnancy test after14 days after embryo transfer. On the day of human chorionic gonadotropin (hCG), there was no significant difference in mean serum Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) between hyaluronic acid group and reference group, respectively (p = 0.824). There was no significant difference in mean follicular fluid Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) between the hyaluronic acid group and reference group, 0.92 ±0.36 pg/ml versus 0.82 ±0.22 pg/ml, respectively (p = 0.223). Treatment with the hyaluronic acid resulted in non-significant increase in serum and follicular fluid Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), and this increment is not related to Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) improvement in local blood endometrial blood flow as reflected by reduction in resistive index and pulsatility index with eventual improvement in pregnancy outcome.
Granulocyte colony-stimulating factor (G-CSF), traditionally utilized in hematopoietic disorders, has garnered attention in reproductive medicine for its potential to enhance endometrial receptivity and improve pregnancy outcomes in assisted reproductive technology (ART). This study aimed to compare the effect of G-CSF administration via intrauterine infusion versus subcutaneous injection on pregnancy outcomes in infertile women undergoing IUI, 75 infertile women aged 18–40 years were enrolled and randomly assigned into three groups (n=25 each): Group 1 received 300 µg G-CSF via intrauterine infusion, Group 2 received 300 µg G-CSF via subcutaneous injection, and Group 3 served as the control with no G-CSF treatment. All participants underwent controlled ovarian stimulation followed by IUI. Endometrial thickness and sub-endometrial blood flow indices (PI, RI, V1/V2) were evaluated using Doppler ultrasound. Serum levels of TNF-α, IL-10, and VEGF were measured before and after G-CSF administration. Clinical pregnancy was confirmed by β-hCG testing two weeks after IUI and confirmation by transvaginal ultrasound. Both G-CSF intervention groups demonstrated significant improvements in sub-endometrial blood flow parameters compared to controls, with intrauterine infusion showing the most favorable Doppler indices (p<0.05). Additionally, intrauterine G-CSF administration resulted in upregulation of VEGF and IL-10 and a reduction in TNF-α levels, though differences did not reach statistical significance. Clinical pregnancy rates were higher in the intrauterine group compared to the subcutaneous and control groups, though differences did not reach statistical significance. Intrauterine infusion of G-CSF appears to offer superior benefits in enhancing endometrial receptivity, modulating inflammatory and angiogenic biomarkers, and improving pregnancy outcomes in IUI cycles compared to subcutaneous injection or no treatment. Further large-scale studies are warranted to validate these findings.
The crosstalk between a receptive endometrium and a functional blastocyst during human embryo implantation is crucial for conception. Because platelets rich plasma (PRP) with concentrated platelets 4-5 times higher than normal, when release of granules containing growth factors including VEGF, TGF, PDGF, IGF, and EGF, these factors involved for sub endometrial angiogenesis and endometrial receptivity. 44 women under the age of 40 were given antagonist ovarian stimulation treatments, the oocytes were harvested utilizing 2-D power doppler ultrasound guidance, then ICSI done for them. On the hCG day all had an intrauterine autologous PRP infusion. Power Doppler is utilized to measure endometrial thickness (EnT), pulsatility index (PI), and resistance index (RI) of sub endometrial arteries, as well as serum levels of VEGF and EGF were measured on the hCG day and ovum pickup (OPU). The ultrasound findings, on the hCG day compared to those of OPU in all women with intrauterine infused autologous PRP were highly significant (HS). The mean EnT, RI, PI, VEGF and EGF at OPU day was lower than that on hCG day in a HS manner, with (p < 0.001), (p < 0.001), (p=0.047), (p < 0.001), and (p<0.001) respectively. These characteristics were shown to be significantly and independently associated to intrauterine PRP infusion. After PRP injection, both growth factors serum levels (VEGF and EGF) increased, and ultrasonography sub-endometrial metrics such as EnT, RI, and PI changed as the thickness grew while vascular resistance decreased, and all considered as predictors of endometrial receptivity.
In recent years increasing evidence proposed that local immune cells at implantation site have largely contributed to embryo implantation. The intrauterine infusion of activated peripheral blood mononuclear cells culture 2 days before embryo transfer can enhance the implantation. One of the methods used to evaluate the endometrial receptivity is by assessing the sub endometrial blood flow. A total of 67 infertile women (30) women receives intrauterine non-invasive insemination of peripheral blood mononuclear cells (PBMC) culture 2 days before embryo transfer representing the PBMC test group, and (37) women without receiving any cell as Non-PBMC group. The cultured PBMC are administered into the uterine cavity of the patients. 2 days later, embryos are transferred into the uterine cavity. Endometrial thickness and sub-endometrial blood flow measurements are taken for all cases on trigger and embryo transfer days. On embryo transfer day there was no significant difference (p = 0.770) in mean endometrial thickness between the PBMC group and Non-PBMC group. There was a significant difference (p< 0.001) in the mean resistive index; the level being lower in the PBMC group. Moreover, there was a significant difference (p< 0.001) in the mean pulsatility index. Regarding all enrolled women, the pregnancy rate of 25.4 %, the rate was higher in the PBMC group in comparison with the Non-PBMC group, 43.3 % versus 10.8 %, respectively and the difference was significant (p = 0.002). The use of PBMC culture can improve sub-endometrial. Endometrial Receptivity, ICSI, Fresh Embryo Transfer, Peripheral
Failure to conceive may be deeply upsetting and stressful, eventually leading to social, physical, and psychological implications. This study aimed to evaluate the impact of dual trigger on endometrial receptivity and the role of uterine biophysical profile in estimating the conception rate in women with primary or secondary infertility. A comparative prospective randomized clinical study was conducted at the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies/ Al-Nahrain University, from October 2019 to April 2020. 90 infertile women who were attending the infertility diagnosis clinic of the institute was included in the study, receiving stimulated intrauterine insemination. Vaginal ultrasound was done for all women at the early and mid-follicular phase. The uterine scoring system for reproduction was assessed and total score of 20 was calculated and subsequently correlated to conception rate. A uterine scoring system for reproduction cut-off of 16 showed a sensitivity of 86.4% and a specificity of 75%. Patients with total score of 18, pulsatility index of lower than 1.79, and three or more endometrial contractions had the highest prevalence of successful pregnancy. Individual variables of endometrium (thickness, pattern, blood flow in zone 3, and myometrium features) had no statistical significance Applebaum's uterine score system for reproduction is a simple and non-invasive ultrasonic assessment. Low pulsatility index, endometrial contraction ≥3, and total score of 18 can point to the appropriate endometrial environment for implantation as well as the rate of conception.
In a perfect world, the peak of receptivity of the endometrial lining would occur simultaneously with the entry into the uterine cavity of a healthy blastocyst, which would then be able to adhere, attach, invade, and develop protected until the time of delivery. This would be the ideal scenario. The study was carried out on 200 infertile women who have thin , poorly vascularized endometrium, those patients were divided into five groups ; 40 patients in each group, group A received esterofem oral, group B received vagifem vaginal tablets, group C received sildenafil citrate gel, group D received pentoxifylline oral and group E received 4 grams of pentoxifylline vaginal gel. The endometrial thickness, vascularity zones, sub endometrial flow, and both uterine arteries resistance and pulsatility indices were assessed at the middle of the menstrual cycle (day 11–14) on a monthly basis for six cycles or until a positive pregnancy test was obtained. Pentoxifylline vaginal gel, pentoxifylline+ vitamin E capsule, and sildenafil vaginal gel have improved the vascularity indeces of endometrium and uterine arteries, while the vagifem and esterofem were less effective in terms of improving the vascularity indeces of endometrium and uterine arteries. The study also showed that 57.5% of women succeed to get pregnant after six months of receiving pentoxifylline vaginal gel, 35% of women succeed to get pregnant after six months of Pentoxifylline+vit E, while 22.5% of women succeed to get pregnant after six months of sildenafil, about 10% of women got pregnant after six months of vagifem, and finally 2.5% of women got pregnant after six months of receiving estrofem tablets. It was discovered that pentoxifylline vaginal gel, pentoxifylline tablet plus vitamin E capsule, and sildenafil vaginal gel were able to improve the vascularity index of the endometrium, the uterine arteries and endometrial thickness, and enhance the pregnancy rates in patients with thin poorly vascularized endometrium.
Despite many improvements in Assisted reproductive techniques during the last three decades, clinical pregnancy and live-birth rates still nearly 30–40% and 20–30%, respectively. To enhance endometrial receptivity many attempts done one of the endometrial scratching could provoke delay in endometrial maturation reforms asynchrony between endometrium and the concepts and indeed induce wound healing by producing a considerable raise in the local secretion of pro-inflammatory cytokines and growth factors like Heparin Binding Epidermal Growth Factor (HBEGF) and its receptors has role in mediate the receptivity, maturation, and decidualization of endometrium and facilitates the implantation and development of both placenta and embryo. All women were undergone IUI procedure. They divided into two groups. Intervention group who did endometrial scratching by using pipelle catheter in luteal phase of preceding cycle and another blood sample aspirated before scratch. Control group include women without intervention of endometrial scratch. Both groups underwent controlled ovarian stimulation, triggering of ovulation and another blood sample was aspirated at day of IUI to measure level of HBEGF. 14 days later with luteal support, BHCG test underwent in blood to check pregnancy. Higher pregnancy rate among patients with scratch group (5/20) 25% than non-interventional group (3/25)12%. These result showed that HBEGF level in scratch group (386.1±124.7) is significantly higher than control group (279±189.3) as P-value was (0.035). Moreover, the HBEGF level at day of IUI (455.67±157.34) and in pregnant (563.9±163.66) is significantly higher than before scratch in scratch group (279.0±124.67), (406.26±138.89), as P-values were (0.00007, 0.049) respectively. Intentional local damage to the endometrium is a cost–effective procedure can be used to enhance the uterine receptivity that may help to overcome implantation failure problem.
During the process of embryo development, endometrial receptivity is very important for the successful implantation of blastocysts. This research investigated the influence of endometrial thickness on the day of oocyte retrieval and fresh embryo transfer on pregnancy outcomes in Iraqi women who are undergoing intracytoplasmic sperm injection (ICSI). Women from Iraq are taking part in this investigation. Participating in in vitro fertilization (IVF) cycles with the use of ICSI was a group of 44 women who were diagnosed with polycystic ovarian syndrome (PCOS) and had unexplained infertility. During the phases of oocyte retrieval and embryo transfer, there were significant differences seen between the two groups (p-values of 0.003 and 0.049), respectively. There was a total of 44 individuals, and 31 of them had negative pregnancy test results. The remaining 13 persons had positive findings. These results illustrate the importance of endometrial thickness in influencing the effectiveness of assisted reproductive technologies in achieving pregnancies.