Pubococcygeal Line Versus H-line as MR Defecography Reference for Bladder Descent.

INTRODUCTION AND HYPOTHESIS: Magnetic resonance defecography imaging techniques have been used widely to study pelvic floor function and diagnose pelvic organ prolapse (POP). The aim of this study was to investigate the diagnostic accuracy of the H-line to detect bladder descent compared with the current landmark, the pubococcygeal line (PCL). METHODS: In this retrospective cohort study, patients who underwent MR defecography in our medical center and were diagnosed with moderate to severe cystocele by radiological measurements were recruited. One rest image and one maximum evacuation image for each subject were used for the following measurements: bladder base perpendicular distance from the genital hiatus (GH), indicative of clinically significant bladder descent, PCL as the current radiological reference line, and the H-line, or minimal levator hiatus line, indicative of pelvic floor muscle and connective tissue support. Subjects were categorized as having clinically significant cystocele if the "bladder base" reached within 1 cm or lower of the GH (stage II or higher cystocele). A comparison was performed to assess differences and predictive capabilities of the reference lines relative to the GH measure. RESULTS: Seventy subjects were included, 30 with clinically significant bladder descent based on distance to GH. Women with bladder descent were older (64.0 ± 11.8 vs 51.2 ± 15.6, p < 0.001), had increased parity (3 [1-7] vs 2 [0-5], p = 0.009), and had a bladder that descended lower than the H-line at rest (1.9 ± 0.5 vs 2.2 ± 0.4, p = 0.003) and evacuation (-2.4 ± 1.6 vs -0.7 ± 1.1, p < 0.001). Multivariate regression analysis confirmed that age, length of the H-line at evacuation, the perpendicular distances between the H-line and the lowest bladder point at rest, and the PCL to the lowest bladder point at evacuation significantly correlated with bladder descent. Receiver operating characteristic analysis was used to identify a measurement threshold to diagnose clinically significant cystocele for both measurements, bladder base to the H-line: -1.2 (80.0, 72.5) area under the curve (AUC) 0.82, and bladder base PCL: -3.3 (77.8, 79.5) AUC 0.86. CONCLUSION: Our data support the application of using the minimal levator hiatus plane and specifically the H-line as a reliable landmark to diagnose bladder descent using MR defecography imaging.

Primary Vaginal Carcinoma Arising on Cystocele Mimicking Vulvar Cancer.

BACKGROUND: Primary vaginal carcinoma is a rare gynaecological tumour representing 1%-3% of all gynaecologic cancers. Several studies report increased vaginal cancer risk associated with genital prolapse following the occurrence of inflammatory lesions or decubitus ulcers. CASE: We report the rare case of an 82-year-old woman with primary squamous cell carcinoma arising from vaginal wall prolapse. Vaginal carcinoma was suspected during gynaecological examination for vulvar bleeding. A wide local excision was performed and pathologic examination revealed a primary squamous cell carcinoma of the vagina. CONCLUSION: Persistent genital prolapse may be at risk for vaginal carcinoma, and cytological and a colposcopic assessments are essential to identify patients who require diagnostic biopsy.

Functional pelvic floor anatomy in Nepali women attending a general gynaecology clinic.

INTRODUCTION AND HYPOTHESIS: Limited existing evidence suggests that there is a high prevalence of female pelvic organ prolapse (POP) amongst Nepali women. However, to date, no comprehensive assessment of pelvic floor functional anatomy has been undertaken in this population. Our study aimed to determine functional pelvic floor anatomy in Nepali women attending a general gynaecology clinic. METHODS: One hundred and twenty-nine consecutive women attending the clinic were offered an interview, clinical examination [International Continence Society Pelvic Organ Prolapse Quantification system (ICS/POP-Q)] and 4D translabial ultrasound (TLUS). Most presented with general gynaecological complaints. Five were excluded due to previous pelvic surgery, leaving 124. RESULTS: A POP-Q exam was possible in 123 women, of whom 29 (24%) were diagnosed with a significant cystocele, 50 (41%) significant uterine prolapse and seven (6%) significant posterior compartment prolapse. Evaluation of 4D TLUS data sets was possible in 120 women, of whom 25 (21%) had a significant cystocele, 45 (38%) significant uterine prolapse and ten (8%) significant descent of the rectal ampulla. In 13 cases, there was a rectocele with a mean depth of 14 (10-28) mm. Of 114 women in whom uterine position could be determined, 68 (60%) had a retroverted uterus associated with significant uterine prolapse (P 0.038). CONCLUSIONS: POP is common in Nepali women attending a general gynaecology clinic, with a high prevalence of uterine prolapse (40%). Uterine retroversion was seen in 60% and was associated with uterine prolapse. Patterns of POP in Nepal seem to be different from patterns observed in Western populations.

The long and short of it: anterior vaginal wall length before and after anterior repair.

INTRODUCTION AND HYPOTHESIS: Anterior vaginal wall length (AVL) is on average 6.1 ± 1.3 cm in women with normal support and lengthened in women with cystocele. We hypothesize that AVL is reduced after anterior repair and that women with larger cystoceles will have greater reduction in AVL. METHODS: Demographic, clinical, and surgical data were collected for women undergoing hysterectomy and anterior repair in whom intraoperative vaginal wall measurements had been made between November 2009 and April 2014. In the operating room, AVL was defined preoperatively as the distance from the hymenal ring to the anterior cervicovaginal junction at the hysterectomy incision site, and postoperatively, from the hymenal ring to the same location on the anterior cuff. During the anterior repair the fibromuscular tissues were plicated using an interrupted technique. RESULTS: Measurements were available for 40 women. Average age was 61.7 ± 10 years, median parity was 2.5 and median preoperative Pelvic Organ Prolapse Quantification System (POP-Q) point Ba was 3 cm distal to the hymen. On average, AVL was reduced after surgery by 2.5 cm. Mean postoperative AVL was similar to mean AVL in women with normal pelvic support (6.4 ± 0.8 cm vs 6.1 ± 1.3 cm, p = 0.15). Longer preoperative AVLs had greater AVL change (R (2) = 0.78, p = <0.0001). CONCLUSIONS: In women undergoing anterior repair, mean AVL was reduced by 28 % and returned to the normal range after surgery. These data highlight a rarely discussed effect of anterior repair, which is restoration of normal anterior vaginal wall length.

Transvaginal single-incision mesh reconstruction for recurrent or advanced anterior vaginal wall prolapse.

AIMS: Single-incision transvaginal mesh for reconstruction of Level I and II prolapses in women with recurrent or advanced prolapse. We evaluated functional, anatomical, sonomorphological and quality-of-life outcome. METHODS: Data were collected retrospectively for preoperative parameters and at follow-up visits. Anatomical cure was assessed with vaginal examination using the ICS-POP-Q system; introital-ultrasound scan for postvoidal residual and description of mesh characteristics was performed. We applied a visual analogue scale (VAS) and the German Pelvic Floor Questionnaire to assess quality-of-life. RESULTS: Seventy women with cystocele (III: 61.3%/IV: 16%), all post-hysterectomy and in majority (81.4%) after previous cystocele repair, were operated using a single-incision transvaginal technique. Overall anatomical success rate was 95.7% with significant improvement in quality-of-life (p < 0.0001). Mesh erosion occurred in 5.7%, one patient presented symptomatic vaginal vault prolapse. Postvoidal residual declined significantly (58 vs. 2.9%). Sonographic mesh length was 55.7% of implanted mesh with a wide range of mesh position, but no signs of mesh dislocation. There was no de novo dyspareunia reported, one case of preoperative existing dyspareunia worsened. No severe adverse event was observed. CONCLUSIONS: We hereby present a trial of a high-risk group of patients requiring reconstruction of anterior and apical vaginal wall in mostly recurrent prolapse situation. Our data support the hypothesis of improved anatomical and functional results and less mesh shrinkage caused by the single-incision technique with fixation in sacrospinous ligament in combination with modification in mesh quality compared to former multi-incision techniques.

The length of anterior vaginal wall exposed to external pressure on maximal straining MRI: relationship to urogenital hiatus diameter, and apical and bladder location.

INTRODUCTION AND HYPOTHESIS: In cystoceles, the distal anterior vaginal wall (AVW) bulges out through the introitus and is no longer in contact with the posterior vaginal wall or perineal body, exposing the pressure differential between intra-abdominal pressure and atmospheric pressure. The goal of this study is to quantify the length of the exposed vaginal wall length and to investigate its relationship with other factors associated with the AVW support, such as most dependent bladder location, apical location, and hiatus diameter, demonstrating its key role in cystocele formation. METHODS: Fifty women were selected to represent a full spectrum of AVW support. Each underwent supine, dynamic MR imaging. Most dependent bladder location and apical location were measured relative to the average normal position on the mid-sagittal plane using the Pelvic Inclination Correction System . The length of the exposed AVW and the hiatus diameter were measured as well. The relationship between exposed AVW and most dependent bladder location, apical location, and hiatus diameter were examined. RESULTS: A bilinear relationship has been observed between exposed vaginal wall length and most dependent bladder location (R(2) = 0.91, P < 0.001). When the bladder descents up to the inflection point (about 4.4 cm away from its normal position), there is little change in the exposed AVW length. With further descent, the exposed vaginal wall length increases significantly, with a 2 cm increase in exposed AVW length for every additional 1 cm of drop bladder location. A similar but weaker bilinear relationship exists between exposed AVW and apical location. Exposed vaginal wall length is also highly correlated with hiatus diameter (R(2) = 0.85, P < 0.001). CONCLUSION: A bilinear relationship exists between exposed vaginal wall length and most dependent bladder location and apical location. It is when the bladder descent is beyond the inflection point that exposed vaginal wall length increases significantly.

Use of a preventive sling surgery for the simultaneous correction of latent stress urinary incontinence during the cystocele repair: two year follow-up.

AIM: The aim of this paper was to assess the feasibility and utility of adding a preventive trans obturatory tape (TOT) during the same intervention for anterior prolapse repair, in patients with masked urinary incontinence and massive cystocele. METHODS: A retrospective trial was conducted in a Tertiary care University Hospital. Ninety-nine women with a massive cystocele (Ba ≥2 cm of pelvic organ prolapse quantification) and an occult stress urinary incontinence were recruited from 2004 to 2010: 53 women were subjected to an anterior fascial reconstruction alone while 46 underwent the same intervention with the addition of TOT. Patients were also asked to rate their overall quality of life, using the International Consultation on Incontinence Modular Questionnaire-Lower Urinary Tract Symptoms Quality Of Life (ICIQ-LUTSqol). All patients were assessed at one, six, twelve and twenty-four months of follow-up. Statistical analysis was performed with SPSS 15.0 software; SPSS inc., Chicago IL, USA was performed using the Chi-square test with Fisher's post-hoc correction. RESULTS: At 24 month follow-up the rate of appearance of stress urinary incontinence at the urogynecological examination, was higher in the group without TOT (81% vs. 19%, P=0.004). In terms of overall quality of life, significantly higher rates of satisfaction have been reported by the group treated with additional TOT (P=0.006). CONCLUSION: The addition of TOT during the anterior prolapse correction seems to give a greater durability to the correction, resulting, in the long term, in a lower rate of urinary symptoms onset (first latency) and in a better quality of life compared to the traditional anterior colporrhaphy alone.

3D analysis of cystoceles using magnetic resonance imaging assessing midline, paravaginal, and apical defects.

INTRODUCTION AND HYPOTHESIS: This study assesses relative contributions of "midline defects" (widening of the vagina) and "paravaginal defects" (separation of the lateral vagina from the pelvic sidewall). METHODS: Ten women with anterior predominant prolapse and ten with normal support underwent pelvic MR imaging. 3-D models of the anterior vaginal wall (AVW) were generated to determine locations of the lateral AVW margin, vaginal width, and apical position. RESULTS: The lateral AVW margin was farther from its normal position in cases than controls throughout most of the vaginal length, most pronounced midvagina (effect sizes, 2.2-2.8). Vaginal widths differed in the midvagina with an effect size of 1.0. Strong correlations between apical and paravaginal support were evident in mid- and upper vagina (r = 0.77-0.93). CONCLUSIONS: Changes in lateral AVW location were considerably greater than changes in vaginal width in cases vs controls, both in number of sites affected and effect sizes. These "paravaginal defects" are highly correlated with apical descent.

Single-incision vaginal approach to treat cystocele and vault prolapse with an anterior wall mesh anchored apically to the sacrospinous ligaments.

INTRODUCTION AND HYPOTHESIS: The safety and early efficacy of a new technique to treat cystocele and/or concomitant apical prolapse through a single vaginal incision with a lightweight mesh anchored apically bilaterally to the sacrospinous ligaments is reported. METHODS: Women with anterior compartment and/or apical prolapse ≥ stage II underwent repair through a single anterior vaginal wall incision with the Anterior Elevate System (AES). The technique utilizes a lightweight (24 g/m(2)) type I mesh anchored to the sacrospinous ligaments via two mesh arms with small self-fixating tips. The bladder neck portion of the graft is anchored to the obturator internus with similar self-fixating tips. The apical portion of the graft is adjustable to vaginal length prior to locking in place. Outcome measures included prolapse degree at last follow-up visit, intra/post-operative complications, and QOL assessments. RESULTS: Sixty patients were implanted with average follow-up of 13.4 months (range 3-24 months). Mean pre-op Ba was +2.04 ± 1.3 and C -2.7 ± 2.9. Average blood loss was 47 cc and average hospital stay was 23 h. Sixty-two percent of patients had concomitant sling for SUI. Mean post-op Ba is -2.45 ± 0.9 and C -8.3 ± 0.9. There was no statistical difference in pre- to post-op TVL. Objective cure rate at current follow-up is 91.7% (≤ stage 1). To date, there have been no mesh extrusions. No patients have reported significant buttock or leg pain. No patients have required surgical revision for any reason. CONCLUSION: The AES is a minimally invasive technique to treat anterior compartment and/or apical prolapse through a single vaginal incision. Initial results show the procedure to be safe and early efficacy is promising. Longer-term follow-up is ongoing.

Accuracy of assessing Pelvic Organ Prolapse Quantification points using dynamic 2D transperineal ultrasound in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: We determined the relationship between clinical assessment of female pelvic organ prolapse (POP) using the validated Pelvic Organ Prolapse Quantification (POP-Q) and dynamic 2D transperineal ultrasound (TPUS). METHODS: Women attending the urogynecology clinics between July and October 2009 were recruited. Prolapse was assessed using the POP-Q. Points Ba, Bp and C (anterior, posterior and middle compartments, respectively) were measured. TPUS was performed at maximum Valsalva by another clinician. As the TPUS probe compresses the prolapse that extends beyond the hymen, these women were excluded. A reference line was drawn parallel to the inferoposterior margin of the pubic symphysis, perpendicular to which the leading edge of descent was measured. The offset measured from the curved array of the probe to the reference line was added to the prolapse quantification on ultrasound (US) scan to make it objectively comparable with the POP-Q reference of the hymen. Points Ba, Bp and C on POP-Q were then compared with points of maximum descent achieved on TPUS. RESULTS: One hundred and fifty-eight women had a POP-Q and TPUS; 20 scans (12.6 %) were not analysable, and 41 women had prolapse beyond the hymen. Ninety-seven women were thus analysed. The correlation between 2D TPUS (with/without the addition of the offset) and POP-Q was statistically significant (p value <0.0001) for all three compartments. The proportion of correct predictions was 59.6 %, 61.5 % and 32.6 % for bladder, bowel and middle-compartment prolapse, respectively. CONCLUSION: These findings suggest that the accuracy of pelvic floor US staging is limited and that clinical assessment remains the gold standard.

Encephalocystocele - uncommon diagnosis in prenatal medicine.

Encephalocystocele is a developmental malformation characterized by brain herniation accompanied with extracranial cystic protrusion of the ventricular system. This nosological unit is often overlooked and insufficiently classified merely as encephalocele. Herein, two exceptionally clear cases of the parieto-occipital cranioschisis with encephalocystocele and congenital hydrocephalus of the lateral ventricles are documented with 2-dimensional/3-dimensional sonographic images and the corresponding MRI findings. In both cases, prenatal diagnosis was confirmed by autopsy.

Cellular proliferation in female pelvic organ prolapse: a pilot study.

PURPOSE: To assess cell proliferation in pelvic organ prolapse (POP). METHODS: Tissue samples of the anterior vaginal wall and uterosacral ligaments (USLs) were obtained from eight women with combined anterior vaginal wall and uterine prolapse and from eight women without POP in a standardized fashion. Immunohistochemistry against Ki-67 was used to assess cell proliferation in vaginal and USL biopsies. RESULTS: There were no significant differences in age, parity, menopausal status or hormone replacement therapy between the two groups. The POP-Q stage of uterine and anterior vaginal wall prolapse was significantly higher in the group of women with prolapse compared to the group without prolapse [median (range) 3 (3-4) vs. 0 (0), <0.01]. There was no significant difference between Ki-67 expressions in women with or without prolapse. CONCLUSION: There were no significant differences in cell proliferation between samples from women with or without POP.

Modified extensive anterior vaginal wall repair for cystocoele.

We describe a new transvaginal technique for cystocoele repair. We prospectively evaluated patients with moderate and high-grade cystocoele who underwent repair with the new transvaginal repair between 2000 and June 2009. Preoperative evaluation included history and physical examination using the Pelvic Organ Prolapse Quantification, urine culture, residual urine measurement, urodinamycs and cystoscopy. We performed the repair in 76 patients with a mean age of 65.24 years (range, 36 to 84 years), wit anatomical cure in 72 (95%) patients. Four (5%) patients had recurrent cystocoele, 3 (4%) patients claimed residual sensory urgency and 4 (5%) stress urinary incontinence (SUI) after the operation. The operation is safe, simple, and provides good anatomic results with minimal complications.

Perineal approach to vascular anatomy during transobturator cystocele repair.

OBJECTIVE: To evaluate the risk of vascular injury during transobturator approach of cystocele repair. DESIGN: Dissection of the obturator area by perineal approach was performed after placement of mesh needles used for cystocele mesh repair. SETTING: Surgery school of Paris. POPULATION OR SAMPLE: Twenty obturator regions in ten fresh female cadavers. METHODS: Transperineal dissection of the obturator area was conducted in ten fresh female anatomic subjects after inserting anterior Prolift needles. MAIN OUTCOME MEASURES: The vascular anatomy of the obturator region was mapped. Distances between needles and vascular structures of the obturator area were measured three times and averaged for each side. RESULTS: The anterior cannula-equipped needle perforated the gracilis and the adductor brevis muscles. The mean (SD) distance to the anterior obturator vessels was 21.2 (1.6) mm on the right side and 20.4 (1.5) mm on the left. The posterior needle perforated the adductor magnus. Its distance to the posterior division of the obturator vessels was 1.8 (1.0) mm on the right side and 1.1 (0.9) mm on the left. CONCLUSIONS: During mesh cystocele repair by transobturator approach, the posterior obturator vessels division seems at risk of injury during the posterior needle insertion.

Dynamic MR imaging of the pelvic floor: a pictorial review.

Pelvic floor dysfunctions involving some or all pelvic viscera are complex conditions that occur frequently and primarily affect adult women. Because abnormalities of the three pelvic compartments are frequently associated, a complete survey of the entire pelvis is necessary for optimal patient management, especially before surgical correction is attempted. With the increasing use of magnetic resonance (MR) imaging in assessing functional disorders of the pelvic floor, familiarity with normal imaging findings and features of pathologic conditions are important for radiologists. Dynamic MR imaging of the pelvic floor is an excellent tool for assessing functional disorders of the pelvic floor such as pelvic organ prolapse, outlet obstruction, and incontinence. Findings reported at dynamic MR imaging of the pelvic floor are valuable for selecting patients who are candidates for surgical treatment and for choosing the appropriate surgical approach. This pictorial essay reviews MR imaging findings of pelvic organ prolapse, fecal incontinence, and obstructed defecation. Supplemental material available at http://radiographics.rsnajnls.org/cgi/content/full/e35v1/DC1.

Prolapse worsens with age, doesn't it?

BACKGROUND: Female pelvic organ prolapse is common and generally thought to worsen over time. This assumption has recently become less plausible, as the author and others have been able to show that mild to moderate pelvic organ descent is common in young, nulligravid women. AIMS: To investigate the relationship between age and pelvic organ prolapse. METHODS: The records of 1110 women seen for interview, clinical examination, urodynamics and ultrasound were evaluated in a retrospective study. Data were analysed to investigate the relationship between patient age at presentation and pelvic organ descent on clinical examination and ultrasound imaging. RESULTS: After removal of 139 datasets of women with previous incontinence or prolapse surgery, 971 datasets remained. Mean age was 54 years (17-90), mean vaginal parity was 2.4 (0-12), with 31% complaining of prolapse. We found weak complex relationships between age and cystocele/rectocele staging, with a positive correlation to menopause and a negative relationship thereafter. This was confirmed on imaging findings, with regression showing an almost parabolic fitted line plot for cystocele and rectocele, but a near-linear curve for uterine prolapse. In nulliparous women, the positive relationship between age and cystocele in premenopausal women was still significant (P = 0.028), indicating that it is not explained by the confounding effect of child bearing. CONCLUSIONS: Ageing seems to play a complex role in the aetiology and pathogenesis of pelvic organ prolapse. Our results contradict epidemiological studies showing age to be a major risk factor for pelvic reconstructive surgery and pelvic organ prolapse.

[Transobturator subvesical mesh: Tolerance and mild-term results. A prospective study]. / La prothèse sous-vésicale transobturatrice: tolérance et résultats à moyen terme Etude prospective à propos de 45cas.

AIM: To evaluate midterm results, tolerance and efficiency of interposition of a transobturator subvesical mesh for the repair of cystoceles. PATIENTS AND METHODS: We report the results of a total of 45 consecutive transobturator mesh fixation between March 1, 2005 and March 1, 2007. We used a transvaginal polypropylen tension-free mesh (Prolène, Ethicon, Johnson & Johnson, France) fixed through the obturator foramen. RESULTS: Before surgery, all patients had cystocele of more or equal than grade II, according to Baden and Walker classification. Five had grade II cystocele (11%), 36 had grade III (80%) and four grade IV (9%). Thirty-nine women had associated median and/or posterior prolapse (86%). Eleven women had urinary incontinence (24%). The procedure was performed in all cases. Duration of a cystocele cure procedure was 25minutes+/-3.2 (12-32). Mean follow-up was 18 months+/-4.2 (13-29). Vaginal erosion ratio was 6%. There was no mesh infection. The objective success rate was 93%. The satisfaction index was 70%. CONCLUSION: Transobturator mesh is a safe and efficient method for anterior segment prolapse repair. This procedure is simple, mini-invasive, reproducible and efficient with low morbidity and good tolerance.

Cystocoele and sensory urgency--our experience.

Sensory urgency appears mostly in patients with a specific or non specific cystitis, interstitial cystitis, intravesical foreign bodies, bladder carcinoma and carcinoma of the prostate, infravesical obstruction, estrogen deficiency and in some neurologic and psychiatric diseases. The aim of this study was to analyze and explain the relation between vaginal vault prolapse and sensory urgency. Clinical courses of 64 patients with cystocoele, which between 1999 and January 2006 have been treated on the Clinic of urology, University Hospital, Rijeka, Croatia, were analyzed retrospectively. On physical examination, using the International Society for Continence staging system we found that 4 (0.6%) had grade II, 29 (45.3%) had grade III, and 31 (48.4%) had grade IV cystocoele. Forty-seven (73.4%) women had urgency, for minimally 6 months to many years before the vaginal vault prolapse manifestation. In all but 3 (4.6%) an extended anterior vaginal colporaphy has been done, with only 1 (1.6%) recurrence of cystocele. It seems that sensory urgency may in fact be a predictor of cystocele.

[Laparoscopic repair of urogenital prolapse without paravaginal repair: medium-term anatomical results]. / Cure de prolapsus urogénital par voie coelioscopique sans réparation paravaginale: résultats anatomiques à moyen terme.

OBJECTIVE: To evaluate the medium-term anatomical results of laparoscopic repair of urogenital prolapse by sacral colpopexy without associated paravaginal repair (PVR). MATERIAL AND METHODS: The medical records of 97 patients operated in a single centre between 1997 and 2005 by laparoscopic sacral colpopexy without PVR were retrospectively reviewed. The primary endpoint for evaluation of the functional results was anatomical relapse, defined by the appearance of prolapse greater than or equal to grade 2 according to the Baden and Walker classification. RESULTS: Eighty two patients were reviewed with a mean follow-up of 14.3 months (range: 1-62.9). Nine patients (11%) presented an anatomical relapse with a mean follow-up of 26 months [range : 6-63]. One early relapse (< 6 months) was due to avulsion of the posterior tape and 8 late relapses presented with cystocele or isolated distal rectocele. CONCLUSION: Laparoscopic sacral colpopexy allows good anatomical correction, especially of cystocele.

Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial.

Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.