A prospective evaluation of the effect of salpingectomy on endometrial receptivity in cases of women with communicating hydrosalpinges.

BACKGROUND: We aimed to assess whether salpingectomy in women with communicating hydrosalpinges influenced endometrial receptivity. METHODS: The inclusion criteria were: women with communicating hydrosalpinges, absence of other confounding infertility factors and aged <40 years. Patients were scheduled for laparoscopy during the putative window of implantation (cycle days 19-21). In patients in whom salpingectomy was decided upon due to the severity of tubal disease (n = 10), an intra-operative endometrial biopsy was performed. Post-treatment endometrial sampling was done between day 19-21 of the fourth consecutive cycle. Pre-treatment and post-treatment samples were assessed by both conventional histologic criteria and alpha(v)beta3 integrin immunostaining, where histological score (HSCORE) was used for quantification. RESULTS: Despite normal histological maturation assessed by conventional criteria, 8/10 hydrosalpinx cases yielded an epithelial HSCORE of <0.7, which was below the accepted threshold. Following salpingectomy, luminal endometrial epithelium demonstrated a significantly increased alpha(v)beta3 integrin expression (Wilcoxon's signed rank test, P = 0.017). Although the mean HSCORE for glandular epithelia improved, it failed to reach statistical significance. Ultrasound visible hydrosalpinges (n = 5) and non-visible cases (n = 5) were also compared. However, neither the pre-treatment integrin expression, nor the postoperative improvement were significantly different between these groups. CONCLUSIONS: We conclude that the surgical treatment of communicating hydrosalpinges may improve endometrial receptivity as assessed by alpha(v)beta3 integrin expression. Women with hydrosalpinges may undergo endometrial evaluation by the molecular markers of implantation, such as alpha(v)beta3 integrin. This evaluation may be decisive in determining the optimal management of cases, and may also be used to assess the efficacy of the treatment. The expression of the implantation markers should be correlated with implantation and clinical pregnancy rates in IVF-embryo transfer programs.     

A quantitative evaluation of alpha1, alpha4, alphaV and beta3 endometrial integrins of fertile and unexplained infertile women during the menstrual cycle. A flow cytometric appraisal.

The expression of integrin molecules alpha1beta1, alpha4beta1 and alphaVbeta3 within endometrial tissue has been proposed as a marker of uterine receptivity during the implantation window. The present investigation examines by flow cytometric analysis the concentrations of alpha1, alpha4, alphaV and beta3 integrin subunits in endometrial stromal (ESC) and epithelial cells (EEC) in two groups of women throughout the menstrual cycle: normal fertile women (n = 27) and women with unexplained infertility (n = 26). Integrin concentrations in endometrial cells were calculated in relative fluorescence units against a negative cellular control. The assessment of integrin subunits detected the protein in ESC and EEC from the late proliferative to the late secretory phase. In both groups of women, the alpha1 was the highest integrin expressed in ESC and EEC throughout the menstrual cycle. All women exhibited low concentrations of alpha4-EEC at the time of the implantation window. Infertile women expressed lower concentrations of the alpha4-ESC during the proliferative and early secretory phase while lower concentrations of the alpha1-ESC were seen during the late secretory phase. Interestingly, the infertile women expressed lower concentrations of beta3-EEC in the early, mid-secretory and late secretory phases (P < 0.05). Infertile women also expressed lower concentrations of alpha1-EEC and alphaV-EEC during the late secretory phase (P < 0.05). It can be concluded that the quantitative determination of beta3-EEC by flow cytometry confirmed its potential feature as a marker of endometrial receptivity at the time of the implantation window. In addition, the defective expression of the alpha1-ESC found in the late secretory phase might be associated with the poor fertility outcome of women with unexplained infertility.     

Integrin expression in normal and out-of-phase endometria

Integrins have recently been proposed as having a major role in endometrial receptivity. Different patterns of integrin expression have been described during the normal endometrial cycle, and the co- expression of several integrins, mainly alpha1, alpha4 and beta3 has been considered as specific to the 'window of implantation'. In the present study 55 infertile patients underwent two endometrial biopsies during a single menstrual cycle. An early biopsy was done on postovulatory days 6-8, and a late biopsy was performed on postovulatory days 10 to 12. Histological dating as well as immunohistochemical evaluation of alpha1, alpha4, beta1, beta3, beta5, alpha(v)beta3 integrin expression and oestrogen and progesterone receptors were determined in all endometrial biopsies. Oestradiol and progesterone serum concentrations in serum were evaluated on the same days of the endometrial samplings. Nine out of the 55 midluteal biopsies (16.4%) showed out-of-phase endometria, but all biopsies were in phase in the late luteal phase. Differences in integrin expression between in- and out-of-phase biopsies were observed only for alpha(v)beta3 integrin glandular expression during the midluteal phase. Alpha(v)beta3 integrin glandular expression was found in all late luteal phase biopsies. Alpha(v)beta3 expression was closely correlated with histological maturation of the endometrium appearing suddenly at postovulatory day 6-7 and being expressed by all endometria dated as postovulatory day > or = 8, irrespective of midluteal endometrial biopsies being in phase or out of phase. No differences in integrin expression were detected between patients with or without endometriosis or between patients who became spontaneously pregnant and those who did not. In conclusion, further studies are necessary before patterns of integrin expression may offer an alternative to predict uterine receptivity and implantation potential.      

The effect of antiprogestin on integrin expression in human endometrium: an immunohistochemical study

Integrins are cell surface receptors for the extracellular matrix and connect extracellular cell adhesion proteins to cytoskeletal components. Several investigators have recently described the expression of different integrins in the human endometrium as markers of receptivity. In the present study we investigated the effect of various doses of the antiprogestin mifepristone on the endometrial expression of integrins during the implantation phase. Endometrial biopsies from healthy fertile women were obtained in the midluteal phase. The study included one control and one, two or three treatment cycles. In treatment cycles either 2.5 (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly, 0.5 mg daily (n = 5), or 200 mg as a single dose administered on day 2 after the luteinizing hormone surge (day LH + 2; n = 8). By using polyclonal antibodies against integrin alpha(v)beta3, subunit beta3 and subunit alpha4 we found reduced immunostaining for alpha4 and beta3 subunit in glandular epithelium after treatment with mifepristone while alpha(v)beta3, expression appeared to be unaffected. No differences between treatment groups were noted. This study demonstrates that treatment with mifepristone interferes with integrin distribution during the implantation window. This may imply that the contraceptive effect of mifepristone is primarily due to impaired endometrial receptivity. However, since no effect was shown on the distribution of the vitronectin receptor, this integrin might be regulated differently by other factors such as cytokines.      

Endometrial vascular and glandular expression of integrin alpha(v)beta3 in women with and without endometriosis

The integrin alpha(v)beta3 functions in both cell-cell and cell- extracellular matrix adhesion, and has reported roles in platelet aggregation, immune function, tissue repair, tumour invasion, angiogenesis and uterine receptivity. The aim of this study was to use immunohistochemistry to describe the vascular and glandular expression of integrin alpha(v)beta3 in formalin fixed, paraffin embedded endometrium obtained from women with (n = 29) and without (n = 24) endometriosis. The results showed a significant increase in the percentage of vessels expressing alpha(v)beta3 in the endometrium of women with endometriosis compared with controls (P = 0.0001). This difference was more pronounced in the secretory phase (P = 0.001) than the proliferative phase (P = 0.016). There was no correlation between vascular alpha(v)beta3 expression and the endothelial cell proliferation index (P > 0.05). Vascular sprouts were not observed in any of the 53 endometrial tissues obtained from women with or without endometriosis throughout the menstrual cycle. Results from semi- quantitative scoring of gland immunostaining showed that neither controls (P = 0.3329) nor the endometriosis group (P = 0.2260) had any significant changes in terms of alpha(v)beta3 expression between the different stages of the menstrual cycle. There was also no difference in glandular alpha(v)beta3 expression between women with and without endometriosis (P = 0.4302). These results provide evidence for increased endometrial angiogenesis in women with endometriosis compared with controls, and suggest that glandular expression of alpha(v)beta3 is not related to uterine receptivity per se.      

Removal of hydrosalpinges increases endometrial leukaemia inhibitory factor (LIF) expression at the time of the implantation window

BACKGROUND: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation. METHODS: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry. RESULTS: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells. CONCLUSIONS: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.     

Hydrosalpinges adversely affect implantation in donor oocyte cycles

Hydrosalpinges have been associated with poor in-vitro fertilization (IVF) outcome in some, but not all, studies, perhaps through endometrial effects. To determine whether hydrosalpinges affect IVF outcome via endometrial factors alone, we analysed the results of recipients of donor oocytes with hydrosalpinges, thereby controlling for confounding variables, while isolating the intrauterine environment. We retrospectively analysed 110 patients who underwent 121 donor oocyte cycles in a university-based assisted reproduction programme. Thirteen cycles involving recipients (n = 10) with hydrosalpinges were compared to 108 cycles involving recipients (n = 100) without hydrosalpinges. Pregnancy, implantation, miscarriage, and ectopic pregnancy rates were compared between women with and without hydrosalpinges. There were no significant differences between the hydrosalpinx and no hydrosalpinx groups with respect to donor age, recipient age, or number or grade of embryos transferred. Patients with a hydrosalpinx had significantly lower embryo implantation rates (7.1 versus 19.3%, P < 0.05) and significantly higher miscarriage (75.0 versus 14.9%, P < 0.05) and ectopic pregnancy rates (33.3 versus 0.0%, P < 0.05) than normal controls. We conclude that the presence of a hydrosalpinx adversely affects early pregnancy events by altering the intrauterine environment.     

Distribution of integrin cell adhesion molecules in endometrial cancer.

Integrins are ubiquitous cell adhesion molecules that are involved in maintaining normal tissue morphology and have been implicated in the behavior of certain malignancies. We examined the expression of nine integrin subunits in 38 endometrial adenocarcinomas using immunohistochemistry. The pattern of integrin expression in the cancers was compared with that seen in the endometrium of 20 normal cycling women and 7 postmenopausal women. Integrin expression was correlated with grade, stage, nodal status, depth of invasion, steroid receptor status, and histological pattern. In endometrial cancers there was an inverse relationship between the number of integrins expressed and histological grade (P = 0.011). Of the normally expressed, constitutive endometrial epithelial integrin subunits (alpha 2, alpha 3, alpha 6, and beta 4), the least frequently seen in the cancers was the alpha 3 subunit (44.7%) and the most frequently found was alpha 6 (81.6%). The alpha 5 beta 1 integrin, a fibronectin receptor normally found only on endometrial stromal cells, was seen in 17.8% of cases of these epithelial cancers. In addition, a significant association was found between the loss of the alpha 2 beta 1 integrin and the presence of lymph node metastases (P < 0.001). These data suggest that a decline in integrin expression occurs more frequently in poorly differentiated endometrial cancers and that the loss of specific integrins may be associated with metastatic nodal spread.     

Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice

BACKGROUND: The impact of different ovarian stimulation (OS) protocols on endometrial receptivity remains controversial. In this study, the effects of different OS on the expression of endometrial integrin beta3 subunit and leukaemia-inhibitory factor (LIF) during the implantation window and the implantation rate in mice were investigated. METHODS: Three OS protocols were used, involving either pregnant mare's serum gonadotrophin (PMSG) alone, PMSG plus GnRH agonist or PMSG plus GnRH antagonist. Uterus samples were collected at 48 h after OS or ovulation and were detected with immunohistochemistry, Western blot and RT-PCR analyses. Normal embryos at gestation day 4 were transferred into the uteri of mice in the control and OS groups. RESULTS: All OS groups showed a significant decrease in the expression of both the endometrial integrin beta3 subunit and LIF during the implantation window and the implantation rate. Among the three OS groups, GnRH agonist-treated mice showed a higher endometrial integrin beta3 subunit and LIF expression and a higher implantation rate. No significant difference was found in the measured indices between the GnRH antagonist and PMSG groups. CONCLUSIONS: OS may inhibit the expression of endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the endometrial physiological secretion and improve uterine receptivity.     

Endometrial markers of uterine receptivity utilizing the donor oocyte model

BACKGROUND: Ethical constraints limit the ability to study peri-implantation phase human endometrium. In this study, the donor oocyte model was used to study candidate endometrial markers of uterine receptivity. METHODS: Archived, paraffin-embedded tissue obtained by endometrial biopsy during cycle days 21-23 of patients undergoing 'mock' hormonal treatment cycles were evaluated by standard histological criteria and immunohistochemical staining for alpha v beta 3 integrin and glycodelin. All of these patients (n = 101) had undergone a donor oocyte embryo transfer cycle utilizing the exact same hormonal protocol. RESULTS: Histological evaluation revealed 62 (61.3%) in-phase, 34 (33.7%) dyssynchronous, 2 (2.0%) immature and 3 (3.0%) advanced endometria. The clinical outcomes of patients with either in-phase or dyssynchronous endometria were similar. Very strong correlations were noted between endometrial glandular dating and either alpha v beta 3 integrin or glycodelin immunostaining intensity (P < 0.001 for both). Glycodelin and alpha v beta 3 integrin immunostaining intensities were also highly correlated with each other (P < 0.001). CONCLUSIONS: Throughout the time period corresponding to the putative window of maximal endometrial receptivity (cycle days 21-23) a dynamic process was observed in exogenous hormonal replacement cycles characterized by a rapid histological advancement of endometrial glandular elements as well as progressive alpha v beta 3 integrin and glycodelin expression.     

Clomiphene citrate does not affect the secretion of alpha3, alphaV and beta1 integrin molecules during the implantation window in patients with unexplained infertility.

BACKGROUND: The expression of integrin molecules on the endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of beta1, alpha3 and alphaV integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. METHODS: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. RESULTS: Staining of alpha(v) but not beta1 and alpha3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 +/- 0.12 versus 2.21 +/- 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. CONCLUSIONS: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of alpha(v), beta1 and alpha3 integrin molecules, which might play a role in implantation, was not affected.     

Expression of integrin receptors on peripheral lymphocytes: correlation with endometrial receptivity

PROBLEM: To investigate the expression of integrin (ITG) cell adhesion molecules on peripheral blood lymphocytes (PBL) and their correlation with endometrial cell ITG expression in fertile and infertile women during peak uterine receptive period (day 19/20). METHOD OF STUDY: Surface marker expression and quantification of alpha6, alpha4 and beta3 ITG subunits was done by immunohistochemistry, indirect immunofluroscence and cell-enzyme-linked immunosorbent assay methods using endometrial cells and PBL obtained from fertile and infertile (unexplained infertility) women. RESULTS: The expression of ITGs was significantly (P<0.001) decreased in the endometrial cells of infertile women compared to normal fertile women. These results correlated well with the data obtained using PBL-ITG expression. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, the expression of alpha4 and beta3-ITG subunits on PBL may be used as clinical markers to assess endometrial receptivity in infertile women. Moreover, frequent blood sampling is advantageous over repeated endometrial biopsies as the former approach is easier, non-traumatic and avoids intra-uterine infections.     

The influence of hydrosalpinx on IVF and embryo transfer: a review

Several retrospective studies have shown an impaired outcomeof IVF in the presence of hydrosalpinx. The retrospective datahave been compiled and presented in meta-analyses, demonstratinga reduction by half in the probability of achieving a pregnancyin the presence of hydrosalpinx and a doubled rate of spontaneousabortion. The main theories trying to explain the underlyingmechanisms have focused on potential embryotoxic propertiesof the fluid or impaired endometrial receptivity to implantation.Several mouse studies have suggested an embryotoxic effect ofthe hydrosalpingeal fluid, a finding which is not supportedin studies on human embryos. It is believed that the fluid exertsa detrimental effect on the endometrium by altering the receptivityor simply by causing a mechanical hindrance for implantation.Different treatment options would then be tubal ligation, salpingostomy,aspiration of hydrosalpinx fluid or salpingectomy. The effectof aspiration has been studied in a few retrospective trialswith contradictory results. Treatment with salpingectomy hasentered into clinical practice without proper evidence for itsbenefit. Concerns have also been raised about the potentialhazard of surgical intervention to ovarian circulation and function.A randomized controlled trial on salpingectomy prior to IVFhas now been conducted as a multicentre study in Scandinavia.Laparoscopic salpingectomy prior to IVF was shown to be beneficialin patients with large hydrosalpinges that were visible on ultrasound,a result which supports the theory of the fluid being involvedin the impaired implantation process.     

Endometrial integrin expression in women undergoing IVF and ICSI: a comparison of the two groups and fertile controls

BACKGROUND: Integrins are thought to play a vital role in implantation. Three integrins in particular (alpha(4)beta(1), alpha(v)beta(3) and alpha(1)beta(1)) are all present during the implantation window. Defects in their expression have been linked to tubal disease, unexplained infertility and endometriosis. Hence, a reduced endometrial integrin expression would be expected in women attending for IVF due to these causes of infertility when compared with those with male factor infertility attending for ICSI. METHODS: Women attending for IVF (n = 25) and ICSI (n = 25) treatment were recruited, and timed endometrial biopsies were taken during the 'implantation window' (cycle day 20-24). A group of fertile women (n = 15) attending for sterilization was used as controls. RESULTS: There was no significant difference in integrin expression between patients undergoing IVF or ICSI. Neither did these groups differ from the control group. CONCLUSIONS: The endometrium in patients undergoing ICSI treatment is sometimes thought to be more receptive, as the infertility might be due to a male factor. This study shows that there is no significant difference in integrin expression between patients attending for IVF or ICSI and the control group. These data add to the increasing uncertainty about the clinical value of assessing the endometrium with only one marker, in this case integrins.     

Investigation and treatment of repeated implantation failure following IVF-ET

Pregnancy rate following one cycle of IVF and ET can be as high as 60%. But even in the very successful units, some couples fail repeatedly. The causes for repeated implantation failure (RIF) may be because of reduced endometrial receptivity, embryonic defects or multifactorial causes. Various uterine pathologies, such as thin endometrium, altered expression of adhesive molecules and immunological factors, may decrease endometrial receptivity, whereas genetic abnormalities of the male or female, sperm defects, embryonic aneuploidy or zona hardening are among the embryonic reasons for failure of implantation. Endometriosis and hydrosalpinges may adversely influence both. In this mini review, we discuss the suggested methods for evaluation and treatment of RIF: repeated hysteroscopy, myomectomy, endometrial stimulation, immunotherapy, preimplantation genetic screening (PGS), assisted hatching, zygote intra-Fallopian transfer (ZIFT), co-culture, blastocyst transfer, cytoplasmic transfer, tailoring stimulation protocols and salpingectomy for hydrosalpinges.     

3Development of an in vitro model for human embryo implantation and progesterone regulation

Aim:  Develop an in vitro 3D-model for human embryo implantation on receptive endometrial construct.
Material and Methods:  Three-dimensional in vitro endometrial construct (n=12) was developed by culturing isolated human endometrial stromal cells in collagen matrix overlaid with epithelial cells. After priming hormonally, human blastocysts were placed and cultured in alpha-medium. Attachment of embryo was confirmed using cytokeratin-7 and expression of endometrial receptivity markers using immunohistochemistry. Antiprogestin mifepristone was used to test implantation and receptivity.
Results:  Embryos attached to receptive endometrial construct . Epithelial and stromal cells of endometrial construct expressed ER-α, ER-β, PR-(A+B), PR-B, VEGF, LIF, IL-1beta and COX-2. Epithelial cells expressed AR, integrinα_Vβ₃ and MUC1. Mifepristone inhibited blastocyst attachment, up-regulated epithelial ER-β, PR-B; down regulated stromal VEGF, MUC1 and integrin α_Vβ₃ as observed in vivo .
Conclusion:  An in vitro human embryo implantation model, regulated by progesterone was developed and tested. This could be further used to understand molecular basis of human embryo implantation .     

alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase endometria of fertile and infertile women

BACKGROUND: There is scanty and contradictory information regarding the comparison of traditional histological dating criteria of the endometrium with the expression of the new markers of endometrial receptivity such as alphavbeta3 integrin and pinopods. Also, definite data with respect to the potential correlation existing between these different new markers in defining the putative window of implantation are lacking. METHODS: The temporal relationship between alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase endometrial biopsies from normal healthy women (n = 12) and infertile patients (n = 36) was investigated. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. Estradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling. RESULTS: No statistically significant difference regarding alphavbeta3 integrin expression, pinopod formation, and hormone concentrations was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase. Although a coordinate high level of expression of alphavbeta3 integrin and pinopod on postovulatory days 7-8 was observed, there was an evident lack of temporal co-expression of these markers over the luteal phase in the endometrial samples investigated. CONCLUSIONS: There is a clear dissociation in the temporal expression of the most cited markers postulated to frame the window of implantation. The functional significance (if any) of these new markers remains to be established.     

Immunolocalization of integrins and fibronectin in tubal pregnancy

Integrins are a large family of cell adhesion molecules that serve as receptors involved in cell-to-cell and cell-to-matrix interactions during implantation. We studied immunohistochemical staining of integrins (alpha 3, alpha V, beta 1, and alpha 2 beta 1) and fibronectin in ectopic tubal pregnancy. Thirty fallopian tube samples with ectopic pregnancies and five normal tubal segments were obtained during ligation operations; the latter specimens served as controls in the study. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against alpha 3, beta 1, alpha V, and alpha 2 beta 1 integrins and fibronectin, using the avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare staining intensities. In the control samples, immunostaining of all integrins was found in a single layer of tall columnar epithelial cells, the lamina propria (Lp) and the muscular layer. Fibronectin staining was detected in the Lp and the muscular layer. Staining intensities of alpha 3 and beta 1 integrins and fibronectin were increased in the normal part of fallopian tubes with ectopic pregnancies. Staining of beta 1 integrin was more intense than staining of alpha 3 and fibronectin, whereas there was no difference in alpha V and alpha 2 beta 1 integrin expression between normal tubal tissue in the ectopic pregnancy group and control tubal tissue. In the tubal pregnancy group at the site of implantation, staining intensity of alpha 3 and beta 1 integrins and fibronectin was strong in decidual cells, supporting tissue and placental villi, whereas alpha V and alpha 2 beta 1 staining was mild. We concluded that integrins, especially beta 1 and alpha 3, and fibronectin may play a role in progression of tubal implantation. Although the role of integrins has not yet been clearly defined, these molecules may function as markers of normal and abnormal states of receptivity. We like to suggest that integrins and fibronectin, which are needed in utero implantation, are expressed in tubal tissues during ectopic pregnancy and are involved in ectopic implantation.     

Only hydrosalpinges visible on ultrasound are associated with reduced implantation and pregnancy rates after in-vitro fertilization

A retrospective analysis of clinical and laboratory data was made of all in-vitro fertilization (IVF) patients with tubal pathology who had their first ever embryo transfer cycle between January 1st, 1992 and September 1st, 1996. The aim of the study was to determine the effect of the presence of a hydrosalpinx, whether or not visible by ultrasound, on pregnancy, multiple pregnancy and implantation rates in our patient population. The IVF success rate was also analysed by calculating cumulative ongoing pregnancy rates of the same patient group using the lifetime table approach. In the presence of an ultrasound-visible hydrosalpinx, rates of pregnancy and multiple pregnancy appeared reduced, but the differences were not significant. The rates of implantation, clinical implantation and ongoing implantation were significantly lower in the presence of an ultrasound- visible hydrosalpinx (odds ratios 0.33-0.46, C.I. 0.21-0.96). The cumulative chance of achieving an ongoing pregnancy after one or more IVF cycles was significantly reduced in the presence of an ultrasound- visible hydrosalpinx (relative hazard 0.36, C.I. 0.22-0.59). In the presence of a hydrosalpinx not visible by ultrasound the IVF outcome was not reduced. This retrospective study confirms that patients with hydrosalpinges have an impaired IVF outcome. Unique to this study and previously unobserved is the finding that there is a subgroup of patients with hydrosalpinges, those with ultrasound-visible hydrosalpinges, which is exclusively responsible for this impaired outcome.