Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles (original) (raw)
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Fertility and Sterility, 1999
To study the effect of controlled ovarian hyperstimulation and the ovarian response on several features of endometrial morphology simultaneously. Prospective controlled study. Academic infertility center. Twenty-five oocyte donors undergoing COH and 10 ovulatory controls. Endometrial biopsies during the luteal phase and measurement of serum E2 and progesterone levels on days 12, 13, and 18-20. Endometrial morphology as judged by histologic dating, pinopode expression, and estrogen and progesterone receptor content. Controlled ovarian hyperstimulation caused the early expression of endometrial features as judged by histologic dating criteria, estrogen and progesterone receptor expression, and the timing of pinopode expression in many of the subjects. A significant correlation within subjects with regard to their particular result on any one measure (e.g., histologic examination) and the others (e.g., estrogen and progesterone receptors, pinopodes) was observed. Those with higher levels of progesterone the day after hCG administration exhibited the most prematurity of morphologic features. Many controlled ovarian hyperstimulation cycles are associated with synchronous early expression of the expected pattern of histologic features, estrogen and progesterone receptors, and pinopodes. The most predictive feature of this premature expression was the level of progesterone the day after hCG administration.
The presence of pinopodes in the human endometrium does not delineate the implantation window
Fertility and Sterility, 2007
Objective: To assess pinopode formation in human endometrium during the luteal phase of the menstrual cycle and in the first trimester of pregnancy. Design: Prospective clinical study. Setting: Outpatient infertility clinics and outpatient family planning clinic. Patient(s): Thirty-two regularly cycling infertile women, 15 regularly cycling fertile women, 9 women receiving elective termination of pregnancy, and 1 woman receiving GnRH agonist and hormone therapy addback. Intervention(s): Endometrial tissue was collected by suction pipelle and examined by scanning electron microscopy for pinopode formation. Main Outcome Measure(s): Endometrial tissue was scored (0, 1, 2, 3, or 4) depending on the percentage of the surface covered in pinopodes (from 0% to Ͼ20% of 100 fields).
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...
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.
The endometrium in stimulated cycles for IVF
Human Reproduction Update, 2003
Ovarian stimulation for IVF is known to affect luteal phase function. The endometrium in IVF cycles is thus subject to an altered endocrinological environment and to a possible direct effect of the ovarian stimulation therapy. Factors in¯uencing the endometrial receptivity in such cycles are poorly understood. Studies comparing the endometrium in IVF cycles with natural cycles as controls have shown premature secretory changes in the post-ovulatory and early luteal phase of IVF cycles, followed by a large proportion of dyssynchronous glandular and stromal differentiation in the mid-luteal phase. These ®ndings suggest a profound modi®cation of luteal endometrial development in stimulated cycles. This hypothesis is further supported by the demonstration of a modi®ed endometrial steroid receptor regulation and a profound antiproliferative effect in IVF cycles. The time of maximal endometrial receptivity is de®ned as the implantation window and is characterized by the expression of various endometrial products, among which pinopodes, integrins and leukaemia inhibitory factor are best described. Premature expression of pinopodes and integrins are in line with the observation of precocious luteal transformation following ovarian stimulation, although the clinical relevance with respect to the establishment of a clinical pregnancy awaits further validation. Studies exploring the endometrium within the cycle of embryo transfer have shown a deleterious effect of severe peri-ovulatory maturation advancement exceeding 3 days, as no clinical pregnancies were obtained in this condition. Further unravelling of molecules involved in the implantation mechanism is needed for a better comprehension of the link between altered endometrial development and receptivity in IVF cycles.
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.
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.
Reproductive Health, 2015
Background: To compare the expression of receptivity markers in epithelial and stromal cells in the endometrium of ovulatory women and infertile with hypothalamic pituitary dysfunction (HPD), untreated or treated with clomiphene citrate (CC), or with recombinant follicle stimulating hormone (rFSH). Methods: Twelve control ovulatory and 32 anovulatory women, 22 of whom received ovulation induction with CC (n = 12) or rFSH (n = 10). Endometrial biopsies were obtained during the mid-secretory phase. Hormonal secretion was measured by chemiluminescence immunoassay, endometrial dating and cellular expression and distribution of receptivity proteins were evaluated by quantitative immunohistochemistry. Results: CC or rFSH treatments, modified the expression of epithelial receptivity markers, such as Glycodelin A, beta-catenin, CD166/ALCAM and IGF-1R, but not in stromal markers. Also, a change in their cell distribution was observed. Conclusions: Treatment of infertile women with HPD modified the expression and distribution of receptivity markers in the mid-secretory phase of the endometrium in epithelial but not stromal cells, which can help to explain changes in the receptivity of the endometrium during treatments and suggest an important role of these cells in the receptivity window.
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.
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...