[Management of tubal ectopic pregnancies with methotrexate : is it an effective treatment ?] / La prise en charge des grossesses extra-utérines tubaires par méthotrexate : un traitement efficace ?

Ectopic pregnancy is a gynecological emergency. The hCG level, the clinical presentation and the ultrasound remain the key steps for the diagnosis. The criteria tend to be more and more codified to decide on the optimal treatment, however, there is no consensus. The aim of this study was to evaluate the impact of applying a mathematical formula to predict the failure rate of metho-trexate for tubal ectopic pregnancy. A retrospective, monocentric study was conducted on a cohort of 193 patients for whom the formula could be calculated. Regarding our professional practice, the success rate of first-line metho-trexate is 93 %. It would increase to 96 % if the formula had been applied. The use of the formula would also reduce the rate of first-line surgery by 12 %.

La grossesse extra-utérine est une urgence gynécologique. Le taux d'hCG, la clinique et l'échographie restent les examens clé pour le diagnostic. Les critères tendent à être de plus en plus codifiés pour décider du traitement optimal. Cependant, il n'existe aucun consensus. Le but de cette étude était d'évaluer l'impact de l'application d'une formule mathématique permettant de prédire le taux d'échec du méthotrexate pour une grossesse extra-utérine tubaire. Une étude rétrospective et monocentrique a été menée sur une cohorte de 193 patientes pour lesquelles la formule a pu être calculée. Concernant notre pratique professionnelle, le taux de réussite du méthotrexate en 1ère intention est de 93 %. Il passerait à 96 % si la formule avait été appliquée. L'emploi de la formule permettrait également de diminuer de 12 % le taux de chirurgie réalisée en première intention.

Laparoscopic Isthmocele Repair: Efficacy and Benefits before and after Subsequent Cesarean Section.

OBJECTIVE: To evaluate the effect of laparoscopic isthmocele repair on isthmocele-related symptoms and/or fertility-related problems. The residual myometrial thickness before and after subsequent cesarean section was also evaluated. DESIGN: Retrospective, case series. SETTING: Public university hospital. POPULATION: Women with isthmocele (residual myometrium < 5 mm) complaining of abnormal uterine bleeding, chronic pelvic pain or secondary infertility not otherwise specified. METHODS: Women's complaints and the residual myometrium were assessed pre-operatively and at three to six months post-operatively. In patients who conceived after surgery, the latter was measured at least six months after delivery by cesarean section. MAIN OUTCOME MEASURES: Resolution of the main symptom three to six months after surgery and persistence of laparoscopic repair benefits after subsequent cesarean section were considered as primary outcome measures. RESULTS: Overall, 31 women underwent laparoscopic isthmocele repair. The success rates of the surgery as improvement of abnormal uterine bleeding, chronic pelvic pain and secondary infertility were 71.4% (10 of 14), 83.3% (10 of 12) and 83.3% (10 of 12), respectively. Mean residual myometrial thickness increased significantly from 1.77 mm pre-operatively to 6.67 mm, three to six months post-operatively. Mean myometrial thickness in patients who underwent subsequent cesarean section (N = 7) was 4.49 mm. In this sub-group, there was no significant difference between the mean myometrial thickness measured after the laparoscopic isthmocele repair and that measured after the subsequent cesarean section. None of these patients reported recurrence of their symptoms after delivery. CONCLUSION: Our findings suggest that the laparoscopic isthmocele excision and repair is an appropriate approach for the treatment of isthmocele-related symptoms when done by skilled laparoscopic surgeons. The benefit of this new surgical approach seems to persist even after a subsequent cesarean section. Further investigations and prospective studies are required to confirm this finding.

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application.

OBJECTIVE: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically. METHODS: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing. RESULTS: Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group. CONCLUSIONS: In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

Video Summary:http://links.lww.com/MENO/A672.

Morphological and Functional Changes in the Vagina following Critical Lifespan Events in the Ewe.

BACKGROUND/AIMS: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan. METHODS: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves. RESULTS: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries. CONCLUSION: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women.

First delivery and ovariectomy affect biomechanical and structural properties of the vagina in the ovine model.

INTRODUCTION AND HYPOTHESIS: Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina. METHODS: We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group). We also harvested mid-vaginal and distal vaginal tissue to determine smooth muscle contractility and passive biomechanical properties, for morphometric assessment of the vaginal wall layers, to determine collagen and elastin content, and for immunostaining for α-smooth muscle actin and estrogen receptor-α. RESULTS: There were no regional differences in the nulliparous vagina. One year after the first vaginal delivery, stiffness and contractility of the distal vagina were decreased, whereas the elastin content increased. The mid-vagina of ovariectomized sheep was stiff, and its epithelium was thin and lacked glycogen. HRT decreased the stiffness of the mid-vagina by 45% but had no measurable effect on contractility or elastin content, and increased epithelial thickness and glycogen content. HRT also increased the epithelial thickness and glycogen content of the distal vagina. At this location, there were no changes in morphology or stiffness. CONCLUSION: In sheep, life events including delivery and ovariectomy affect the biomechanical properties of the vagina in a region-specific way. Vaginal delivery mainly affects the distal region by decreasing stiffness and contractility. HRT can reverse the increase in stiffness of the mid-vagina observed after surgical induction of menopause. These observations are in line with scanty biomechanical measurements in comparable clinical specimens.

Long-term (8.5 years) analysis of the type and rate of reoperation after transvaginal mesh repair (Prolift®) in 349 patients.

OBJECTIVE: Polypropylene meshes have specific complications, and in 2016 the Food and Drug Administration required a Premarket Approval for their use in pelvic prolapse repair, as there was a lack of long-term data. Our objectives were to determine the long-term reoperation rates and type in our patients after transvaginal mesh repair and to study their risk factors. STUDY DESIGN: We were able to follow up with 349 patients from a single University Hospital, with phone calls, after a median time of 8,5 years. The 8.5-year reoperation rates were derived from Kaplan-Meier survival curves. RESULTS: Our global, long-term reoperation rate, including mesh complications, prolapse recurrence and urinary incontinence after a median follow-up of 8.5 years, was 14.5%. The mesh-related complication rate (including mesh exposures, infections, and retractions requiring surgery) was 4.3%, the urinary incontinence rate was 5.7%. The prolapse recurrence rate was 7.2%; mainly found with posterior mesh only (18.5% of reoperations). For total Prolift, the reoperation rate for prolapse recurrence was only 4%. Moreover, 867% of the patients who had an anterior Prolift only or a posterior Prolift only and who were re-operated for prolapse recurrence showed recurrence exclusively in another compartment. In bivariate analysis, only the posterior mesh type was significantly associated with prolapse recurrence versus total meshes. CONCLUSION: Despite their market withdrawal, the transvaginal meshes are a safe and efficient option for pelvic organ prolapse surgical management. Low rates of mesh complications can be achieved with cautious dissection and adequate training of surgeons.

A nonlinear-elastic constitutive model for soft connective tissue based on a histologic description: Application to female pelvic soft tissue.

To understand the mechanical behavior of soft tissues, two fields of science are essential: biomechanics and histology. Nonetheless, those two fields have not yet been studied together often enough to be unified by a comprehensive model. This study attempts to produce such model. Biomechanical uniaxial tension tests were performed on vaginal tissues from 7 patients undergoing surgery. In parallel, vaginal tissue from the same patients was histologically assessed to determine the elastic fiber ratio. These observations demonstrated a relationship between the stiffness of tissue and its elastin content. To extend this study, a mechanical model, based on an histologic description, was developed to quantitatively correlate the mechanical behavior of vaginal tissue to its elastic fiber content. A satisfactory single-parameter model was developed assuming that the mechanical behavior of collagen and elastin was the same for all patients and that tissues are only composed of collagen and elastin. This single-parameter model showed good correlation with experimental results. The single-parameter mechanical model described here, based on histological description, could be very useful in helping to understand and better describe soft tissues with a view to their characterization. The mechanical behavior of a tissue can thus be determined thanks to its elastin content without introducing too many unidentified parameters.

Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

INTRODUCTION AND HYPOTHESIS: The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C0) and high (C1) deformation rates. RESULTS: Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C0), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C0 and the elastin/collagen ratio (p = 0.048) in the lamina propria. However, at large strain levels (C1), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples. CONCLUSION: Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to analyze the histomorphometric properties of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: In 15 women undergoing surgery for POP, full-thickness biopsies were collected at two different sites of location from the anterior and/or posterior vaginal wall. Properties of the precervical area (POP-Q point C/D) were compared with the most distal portion of the vaginal wall (POP-Q point Ba/Bp) using histological staining and immunohistochemistry. The densities of total collagen fibers, elastic fibers, smooth muscle cells, and blood vessels were determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. RESULTS: The mean elastin density was significantly decreased in the lamina propria and muscularis layer of the vaginal wall from the most distal portion of the prolapsed vaginal wall compared with the precervical area. This difference was statistically significant in the lamina propria for both anterior (8.4 ± 1.2 and 12.1 ± 2.0, p = 0.048) and posterior (6.8 ± 0.5 and 10.1 ± 1.4, p = 0.040) locations, and in the muscularis for the anterior (5.2 ± 0.4 and 8.4 ± 1.2, p = 0.009) vaginal wall. There were no statistically significant differences in the mean densities of collagen fibers, smooth muscle cells or blood vessels between the two locations. CONCLUSIONS: In this study, we observed changes in elastin density in two different locations of the vaginal wall from women with POP. The histomorphometric properties of the vaginal wall can be variable from one place to another in the same patient. This result supports the existence of most vulnerable locations within the vaginal wall and the potential benefit of site-specific prolapse surgery.

Histology of the vaginal wall in women with pelvic organ prolapse: a literature review.

INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal wall and its possible involvement in the pathogenesis of pelvic organ prolapse. METHODS: Eligible studies were selected through a MEDLINE search covering January 1986 to December 2012. The research was limited to English-language publications. RESULTS: Investigations of changes in the vaginal tissue that occur in women with genital prolapse are currently still limited and produced contrary results. The heterogeneity of the patients and the control groups in terms of age, parity and hormonal status, of the localization of biopsies and the histological methods as well as the lack of validation of the quantification procedures do not allow clear and definitive conclusions to be drawn. CONCLUSIONS: This review shows that current knowledge of the histological changes observed in women with POP are inconclusive and relatively limited. More studies are needed in this specific field to better understand the mechanisms that lead to POP.

Biomechanical properties of human pelvic organs.

OBJECTIVE: To comparatively define the biomechanical characteristics of the pelvic organs (the vagina, bladder, and rectum), which are crucial for the maintenance of pelvic support. Despite minimal fundamental studies, meshes are increasingly implanted into the vesicovaginal and rectovaginal spaces to replace disrupted native tissues and to treat pelvic organ prolapse. However, the mechanical characteristics of these materials have not yet been compared with those of the "functional unit," the vagina, bladder, and rectum. METHODS: Samples from 5 fresh female cadavers without prolapse were collected. Uniaxial tension tests under monotonic and cyclic loading were performed and the stress-strain curves obtained. RESULTS: The biomechanical properties of the vaginal, bladder, and rectal tissues differed significantly. We were able to demonstrate a nonlinear relationship between the stress and strain and a visco-hyperelastic behavior with a Mullins effect of damage of the tissues examined. Comparable rigidity was found between the investigated tissues at low strains; however, at large strain levels, marked differences could be observed. The vagina was much more rigid and less extendible than the rectal tissue, which, in turn, was more rigid than the bladder tissue. The anterior and posterior vagina revealed a different stiffness, and the bladder tissue was anisotropic at large strain levels. CONCLUSION: Our results underline the pivotal role of the vaginal tissue for the maintenance of pelvic support. The observed differences with respect to tissue rigidity should have pronounced effects on the physiologic organ function, pointing to the necessity of a differentiated view on using the same prosthetic material for different anatomic locations.

Surgical intervention after transvaginal Prolift mesh repair: retrospective single-center study including 524 patients with 3 years' median follow-up.

OBJECTIVE: The aim of this study was to explore the nature and rate of surgical intervention after transvaginal Prolift mesh repair for pelvic organ prolapse. STUDY DESIGN: This was a retrospective study of all patients who underwent Prolift mesh repair between January 2005 and January 2009. Patient data were obtained from medical records, and patients were telephoned to check if they had surgery in other hospitals. RESULTS: A total of 600 consecutive patients were identified. Of these, 524 patients (87.3%) were included in the study, with a median follow-up duration of 38 months (range, 15-63). Global reoperation rate was 11.6%. Indications of intervention were surgery for urinary incontinence (6.9%), mesh-related complications (3.6%), or prolapse recurrence (3%). CONCLUSION: The global reoperation rate after transvaginal Prolift mesh repair was 11.6%, with urinary incontinence surgery being the most common indication. Rates of mesh complications and prolapse recurrence are relatively low in an experienced team.

Vagina, abdominal skin, and aponeurosis: do they have similar biomechanical properties?

INTRODUCTION AND HYPOTHESIS: despite minimal fundamental works, there is an increasing use of meshes in urogynecology. The concept is mainly based on experiences with abdominal wall surgery. We aimed to compare the biomechanical properties of vaginal tissue, abdominal aponeurosis, and skin. METHODS: samples from 11 fresh women cadavers without prolapse were collected. Uniaxial tension tests were performed and stress-strain curves were obtained. RESULTS: biomechanical properties of the vagina, aponeurosis, and skin differed significantly. The aponeurosis was much more rigid and less extendible than the vagina and skin. Vaginal tissue was less rigid but more extendible than skin. There was no difference between the vagina and skin at low strains (p = 0.341), but a highly significant difference at large strains (p = 0.005). CONCLUSIONS: skin and aponeurosis are not suited to predict vaginal tissue biomechanics. We should be cautious when transferring experiences from abdominal wall surgery to vaginal reconstructive surgery.

Management of recurrent or persistent stress urinary incontinence after TVT-O by mesh readjustment.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate, retrospectively, the place of sub-urethral mesh readjustment when treating recurrent stress urinary incontinence (SUI) after TVT-O. METHODS: Between August 2006 and August 2008, eight patients had recurrent or persistent SUI. They were treated surgically by tightening the pre-implanted sling. RESULTS: Medium delay between first surgery and mesh adjustment was 6 months. One patient needed a second TVT-O for rupture of the pre-implanted mesh during adjustment. Among the seven patients who underwent a mesh readjustment, three were cured, three improved, there was one failure. Mean follow-up was 25 months. CONCLUSIONS: The sub-urethral mesh readjustment is a simple and safe procedure for patients with recurrent SIU after TVT-O procedure. Success rates are high, surgery minimally invasive but long-term follow-up is needed to evaluate efficiency.