The presence of pinopodes in the human endometrium does not delineate the implantation window (original) (raw)
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Medicina
Objective: To investigate morphological changes in the endometrial epithelial cells of patients with infertility problems. Materials and methods: Endometrial biopsies were obtained from 10 women who have undergone several unsuccessful in vitro fertilisation (IVF) procedures. Endometrial biopsies were performed between luteinizing hormone surge days LH+6 to +10 of the natural menstrual cycle. Each sample was divided into three parts, which were processed for histological, transmission (TEM), and scanning electron microscopy (SEM) investigations. Results: Histological investigations demonstrated significant alterations in the apical part of epithelial cells of one patient; in four patients, the gland maturity was low, not matching the cycle day, and thus a phase lag had developed. By TEM examination, we ascertained changes in secretory and ciliated cells in three patients (decreased amount or missing microvilli, irregular cilia in ciliated cells). SEM examination found pinopodes in fi...
Reproductive sciences (Thousand Oaks, Calif.), 2017
Endometriosis is frequently associated with infertility and it is believed that the impairment of endometrial receptivity may be one of the mechanisms involved in this condition. Pinopodes are endometrial cycle-dependent structures that seem to participate in embryo implantation, and alterations in their presence and/or morphology during the window of implantation could affect the endometrial receptivity and be involved in the disease-related infertility. However, the data on pinopodes in these women are scarce and inconclusive. This pilot study aimed to evaluate the cell pattern, including the presence and developmental stage of pinopodes, in eutopic endometrium of infertile patients with and without endometriosis during the window of implantation, using scanning electron microscopy (SEM). Endometrial biopsies were performed using a Pipelle catheter, and 12 samples classified in the window of implantation (6 infertile women with endometriosis and 6 infertile controls) were analyzed...
Fertility and Sterility, 2003
Objective: To assess the temporal and morphologic characteristics of pinopod expression on the surface of endometrium across the secretory phase, in LH-timed endometrial samples in normal, healthy women. Design: Prospective, randomized study. Setting: Academic teaching hospital. Patient(s): Sixty-eight healthy volunteers with proven fertility. Intervention(s): Urinary LH-timed endometrial and blood sampling was performed on each subject on a randomly selected day of the secretory phase. Main Outcome Measure(s): Histologic dating, assessment of pinopods using scanning electron microscopy, and comparison with serum P levels. Result(s): Eighty-six endometrial tissue samples obtained from 68 subjects were evaluated under scanning electron microscopy. Pinopods were first observed on luteal day 5, corresponding with the onset of the midluteal phase increase in serum P levels. Pinopods persisted for the entire duration of the secretory phase, but their morphology changed as the cycle advanced. Conclusion(s): The present findings demonstrate that pinopods are a characteristic feature of the mid to late secretory phase endometrial epithelium, exhibit cycle-dependent changes in morphology, and are most prominent during the putative implantation interval.
Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles
Human Reproduction, 1999
The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls. Up to four samples were taken from each woman at 24-72 h intervals between days 14 and 24, giving a total of 69 samples. The day of oocyte retrieval was designated day 14 in ovarian stimulation cycles and the day of luteinizing hormone surge was designated day 13 in natural cycles. Endometrial morphology and pinopode numbers were similar in both groups. Fully developed pinopodes appeared in only one sample per cycle, indicating their short life span. However, the cycle day these structures appeared varied up to 5 days between women and the distribution was as follows: day 18 (n⍧2), day 19 (n⍧7), day 20 (n⍧4), day 21 (n⍧3), day 22 (n⍧1) in ovarian stimulation cycles, and day 20 (n⍧2), day 21 (n⍧2), day 22 (n⍧3) in natural cycles. Furthermore, accelerated pinopode formation in ovarian stimulation cycles was positively correlated with day 13 progesterone. Our findings show that ovarian stimulation does not affect endometrial pinopode formation in terms of quantity and life span. The cycle days when pinopodes form are specific to the individual, being on average 1-2 days earlier in ovarian stimulation than in natural cycles. These changes in pinopode expression may reflect shifts in the window of receptivity, resulting in ovo-endometrial asynchrony and limiting implantation success in in-vitro fertilization.
Surface Morphology of the Human Endometrium: Basic and Clinical Aspects
Annals of the New York Academy of Sciences, 2006
The human endometrium is an extremely sensitive target for steroid hormones. During the menstrual cycle, this tissue undergoes dynamic changes that are reflected on the surface morphology of the epithelium and that can be followed by scanning electron microscopy. The morphologic changes peak at the midsecretory phase, with the formation of the so-called pinopodes. Increasing evidence suggests that these pinopodes are accurate markers for endometrial receptivity, and their detection may be of high clinical utility in the preparation of endometrium before embryo transfer. This article recapitulates published figures of endometrial ultrastructure and presents some unpublished data from ongoing studies.
Molecular Human Reproduction, 2002
Pinopodes have been suggested to be markers of uterine receptivity. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is expressed in increasing amounts in the secretory phase endometrium and is considered to be important for the human implantation process. The aim of this study was to investigate a possible co-existence of pinopodes and HB-EGF in the normal human endometrium. Endometrial biopsies were obtained from women with normal menstrual cycles. The biopsies were examined by scanning electron microscopy for the detection of pinopodes, by immunohistochemistry for the expression of HB-EGF protein, and by confocal microscopy to determine if HB-EGF was present on the surface of the pinopodes. The expression of HB-EGF in luminal and glandular epithelium was highest when fully developed pinopodes were present. Using confocal microscopy it was shown that HB-EGF was present both inside the luminal epithelial cells and on the surface of pinopodes. These findings suggest that HB-EGF might play a role in both the attachment and penetration steps in the human implantation process. Furthermore, the immunohistochemical staining demonstrates that HB-EGF can be used as a marker for the implantation window.
The effect of sperm activation on pinopod formation in endometrial epithelium
Journal of the Anatomical Society of India, 2016
Endometrial receptivity is crucial in implantation of the developing embryo in the endometrium and formation of the pregnancy. In this study, possible effect of sperm and uterine endometrial contact on formation of pinopod, an important element in morphological differentiation necessary for implantation, was investigated. Materials and methods: In this experimental study, 42 female Spraque-Dawley albino rats and 14 male Spraque-Dawley albino rats (total 56 rats) were used. Vasectomy was performed in half of the male rats. For each group, two distinct branches were formed with 21 females and 7 males: Group 1 (nonvasectomized) and Group 2 (vasectomized). Cases were sacrificed and evaluated every day from Day 1 to Day 3. Scanning electron microscopic (SEM) images were analyzed according to different stages of pinopod development on different days. Pinopods were classified as developing, developed and regressing pinopod. The average number of pinopods were calculated by counting the pinopods at four endometrial regions examined for each rat and total number was divided by 4. Same procedure was done for all rats in every group. Results were compared among the groups. For statistical analysis among the groups, *Independent Samples Test (Mean AE Std) and **Mann Whitney U Test (Median (25-75%)) were used. Results: The most important finding in SEM examination of uterus removed on the first day following mating from female rats that were copulated with non-vasectomy male rats which comprised the first group of the study was that heads of the sperms in the uterus were embedded in endometrial epithelium. Similarly, examination of the endometrium of uterus that were removed on postcoital second day revealed small number of developed pinopods (average 0.39) (P = 0.902). Examination was done by taking the developing pinopods within image area into account and number of developing pinopods in endometrium epithelium of the rats in first group (average 20.61) was higher than that of second group (average 12.86) (P < 0.001). Examination of endometrium of the uterus that were removed on third postcoital day revealed less number of developing pinopods in both groups. Examination of first group revealed an average of 1.21 developing pinopod, whereas the average number of developing pinopod in second group was 2.25 (P = 0.011). Examination based on the count of developed pinopods revealed that number of pinopods in first group (average 13.79) was higher than second group (average 8.96) (P < 0.001). Regressing pinopod images were observed in only endometrium that were taken on postcoital third day in the second group. Conclusion: In this study, it was clearly shown that sperms were entered into endometrial epithelium with their heads. It can be suggested that they might have a facilitating effect for pinopod formation by reacting with endometrial epithelium as a result of this invasion. It would be beneficial to demolish the other factors triggering pinopod formation to investigate whether presence of sperm alone in the uterus has an effect on pinopod formation.
Endometrial dating and determination of the window of implantation in healthy fertile women
Fertility and Sterility, 2000
To reassess endometrial morphological criteria of normality identifying the best morphological and molecular "implantation window" indicators in normal women. Design: Prospective clinical study. Setting: Assisted reproductive unit. Patient(s): Fourteen healthy volunteers. Intervention(s): Blood sampling for LH, E 2 , and progesterone (P4) determinations. Daily vaginal ultrasounds. Two endometrial biopsies per volunteer, 7 days apart, during luteal phase. Main Outcome Measure(s): Endometrial dating, pinopodes formation, immunohistochemical determination of integrins (␣v3, ␣41), leukemia inhibitory factor (LIF), interleukin-1 receptor type I (IL-1R tI), mouse ascites Golgi (MAG), the transmembrane mucin (MUC-1), and P4 receptor expression.
Fertility and Sterility, 2003
Objective: To determine cell-type-specific expression of leukemia inhibitory factor (LIF) and LIF receptor (LIFR) proteins relative to formation of pinopodes in human endometrial samples. Design: Prospective clinical study. Setting: Hospital-based unit for reproductive health and university-affiliated reproductive research laboratories. Patient(s): Twenty-six healthy fertile women with normal menstrual cycles. Main Outcome Measure(s): Routine blood and urine samples were obtained, and vaginal ultrasonography and endometrial biopsy were performed. Pinopode formation and expression of LIF and LIFR were examined in endometrial samples. Result(s): Samples obtained during LH days 6 through 9 had pinopodes at different developmental stages. Both surface and glandular epithelial cells expressed maximal levels of LIF and LIFR protein, in biopsy samples showed fully developed pinopodes. Immunostaining of LIF was more intense in the glandular epithelium, whereas immunostaining of LIFR was most intense in the surface epithelium. Before and after the appearance of pinopodes, LIF and LIFR immunostaining was less intense or faint. Stromal endometrial cells showed faint LIF accumulation. Conclusion(s): The simultaneous positive spatial and temporal expression of pinopodes and LIF and LIFR proteins in endometrial samples from healthy women suggests that both molecular and structural cell changes are important in the initiation of human blastocyst implantation. (Fertil Steril 2003;79(Suppl 1):808 -14.