Original Study Laparoscopically Assisted Neovaginoplasty in Vaginal Agenesis: A Long-Term Outcome Study in 240 Patients € nfisch PhD 1, Katharina Rall MD 1, Melanie C. Schickner MD 1, Gianmaria Barresi MD 1, Birgitt Scho Markus Wallwiener MD 2, Christian W. Wallwiener MD 1, Diethelm Wallwiener MD 1, Sara Y. Brucker MD 1,* 1 2
€ bingen University Hospital, Calwerstr. 7, 72076 Tu € bingen, Germany Department of Obstetrics and Gynecology, Tu Department of Obstetrics and Gynecology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany
a b s t r a c t Study Objective: To assess the long-term outcome of an optimized minimally invasive neovaginoplasty technique in vaginal agenesis. Design: Combined retrospective and prospective study. Setting: University hospital. Participants: 240 patients with congenital vaginal agenesis. Interventions: Patients with an indication for neovagina creation underwent laparoscopically assisted neovaginoplasty involving vaginoabdominal blunt perforation and intracorporeal traction using tension threads and an abdominally positioned extracorporeal traction device. Main Outcome Measures: Long-term anatomic success, functional success compared with similar-aged controls, long-term complications, and incidence of human papilloma virus (HPV) infections. Results: During median follow-up for 16 (range 11-141) months, mean functional neovaginal length remained stable at 9.5 cm in all patients, including those who had no sexual intercourse and had stopped wearing the vaginal dummy. Median dummy wearing time was 8.6 months. Time to epithelialization depended on the time of onset and frequency of sexual intercourse. At long-term follow-up, median total Female Sexual Function Index score was 30.0, comparable with similar-aged controls. No common long-term complications occurred. Four patients required cauterization of granulation tissue. 7/240 (2.9%) patients were HPV-positive with low- to high-grade squamous intraepithelial lesions, 3 patients reverting to HPV-negative status at long-term follow-up. Conclusions: Our technique creates a neovagina of adequate size and secretory capacity for normal coitus, requiring no prolonged dilation postoperatively, even in the absence of sexual intercourse. The procedure is fast, effective and minimally traumatic, has a very low longterm complication rate and provides very satisfactory long-term functional results. € llerian aplasia, Mayer-Rokitansky-Ku € ster-Hauser (MRKH) syndrome, Laparoscopic Key Words: Vaginal aplasia, Uterovaginal agenesis, Mu creation of neovagina
Introduction
The creation of a functional neovagina that enables the patient to have sexual intercourse and provides adequate cosmesis while minimizing short and long-term morbidity is currently considered the primary therapeutic goal in patients with congenital vaginal agenesis, which is most € ster-Hauser commonly caused by Mayer-Rokitansky-Ku (MRKH) syndrome.1,2 In addition to nonsurgical progressive dilation, a number of surgical methods of neovagina creation have been developed over the past decades. There is, however, no firm general consensus among providers as to which method best creates a neovagina of adequate length and width with an anatomically correct axis, ensures first-time success with low morbidity and surgical complication rates, and requires no exogenous lubrication or continued postoperative The authors indicate no conflicts of interest. * Address correspondence to: Sara Y. Brucker, MD, Department of Obstetrics and € bingen University Hospital, Calwerstr. 7, 72076 Tu € bingen, Germany; Gynecology, Tu Phone: þ49 (0) 7071 29-80791; fax: þ49 (0) 7071 29-4663 E-mail address: [email protected] (S.Y. Brucker).
dilation.1,3,4 In the US and in the United Kingdom, surgical neovaginoplasty is primarily considered an option for patients who are unsuccessful with dilation therapy or prefer surgery after full discussion of the available surgical options and their risks and benefits.1,5 Our Centre for Rare Female Genital Malformations developed and optimized a laparoscopically assisted technique that creates a neovagina in a standardized, controlled manner by vaginoabdominal blunt perforation and traction exerted by a device positioned on the abdomen.6-8 We subsequently demonstrated in 101 patients that this technique produced better functional results with fewer complications than the standard laparoscopic Vecchietti procedure involving dissection of the vesicorectal space.9 Based on the substantial body of prospective and retrospective data collected at our institution between 1998 and 2011, the present study was conducted to assess our neovaginoplasty technique with regard to intermediate and long-term outcome. We aimed to demonstrate that our technique provides adequate anatomic and functional results in terms of stable length over time and sexual function comparable with an age-matched, anatomically normal
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general population sample. We also aimed to show that the procedure is well tolerated and not associated with longterm complications or increased health risks. We focused on 3 aspects: (1) the optimal frequency and duration of wearing a vaginal dummy postoperatively and the role of sexual intercourse and/or wearing a dummy in maintaining the neovagina and accelerating epithelialization, (2) sexual satisfaction compared with age-matched, general-population peers as well as overall patient satisfaction with surgery and outcome, and (3) potential long-term complications, including vaginal prolapse, malignancies, and granulation tissue, and the incidence of sexually transmitted infections, especially human papilloma virus (HPV), in view of the associated risk of vaginal cancer.
Estrogen-containing cream was used to facilitate insertion of the dummy and accelerate epithelialization.8 Study Assessments and Parameters Study Visits
Clinical follow-up examinations were carried out at 1, 3 and 6 months, and at $11 months for long-term follow-up. Each follow-up visit included: general gynecologic and standardized vaginal examinations by 1 of the 2 main investigators (K.R., S.Y.B.); recording of any neovaginoplastyrelated signs or symptoms; vaginal cytology (Pap smear), and, in the presence of pathology, an HPV test, assessment of neovaginal epithelialization, and microbiologic testing. Neovaginal Parameters
Materials and Methods Study Design and Patients
The present study was a combined analysis of prospectively collected questionnaire data and retrospective data from existing patient records and was approved by the € bingen. Included in Ethics Committee of the University of Tu the analysis were all 240 consecutive patients who presented to us with primary amenorrhea, were diagnosed with vaginal agenesis and underwent neovaginoplasty using our laparoscopically assisted technique at our institution between August 1998 and September 2011. In total, 223/240 (93.3%) patients had MRKH syndrome with a normal 46,XX female karyotype while 15/240 (6.3%) had a 46,XY karyotype and were diagnosed with complete androgen insensitivity syndrome (CAIS) and 1 patient was diagnosed with 47,XYY. Karyotype was unknown in the remaining patient. Mean age at surgery ( SD) was 20.5 ( 5.6) (median 18.7, range 14.5-49.7) years.
Treatment
After comprehensive diagnostic testing and detailed explanation of the treatment options, patients with a confirmed indication for our technique of laparoscopically assisted neovaginoplasty underwent surgery as previously described in detail.8-10 In brief, targeted blunt perforation was performed under laparoscopic guidance from the vagina to the abdomen, through the rectovesical septum, without dissecting the vesicorectal space. Using a curved thread guide, 2 tension threads were subperitoneally fed in a cranial direction and subsequently fixated in a traction device positioned on the patient's abdomen. The 2 other ends of these threads were connected to the rounded-top, that is, proximal, segment (“olive”) of a pluggable segmented dummy. After surgery, the tension threads were tightened daily under epidural anesthesia, the resulting continuous dilation pressure on the vaginal dimple creating a neovagina in about 4-5 days. The tension threads, traction device, and segmented dummy were then removed. To maintain neovaginal length and width, prevent tissue adhesions and stimulate epithelialization, the patient had to wear a vaginal dummy for several weeks postoperatively.
Anatomic length of the neovagina was determined by digital palpation without pressure, functional length by applying maximal pressure. Anatomic success was defined as a functional neovaginal length of $6 cm and easy introduction of 2 fingers.11 Functional success was considered achieved when the patient reported satisfactory sexual intercourse. Long-term Anatomic Success
This was defined as stable functional length $ 6 cm in the long term of $11 months in the presence or absence of continued dilation or sexual intercourse. To determine the optimal frequency and duration of wearing a vaginal dummy and evaluate the role of sexual intercourse in maintaining the achieved neovaginal length and creating a normal vaginal epithelium, patients were asked to complete a purpose-designed questionnaire at the follow-up visits. Long-term Functional Success
This was defined as having achieved successful, satisfactory coitus as reported on the purpose-designed followup questionnaire. To obtain more detailed information and enable comparison with other groups, sexual function was additionally assessed using the German version of Rosen's Female Sexual Function Index (FSFI-d) questionnaire in a subgroup of patients who had already been in a stable relationship before undergoing surgery (subgroup inclusion criterion). FSFI scores were determined according to published formulas.12,13 To determine whether the FSFI scores in neovaginoplasty patients differed from those in similaraged general-population peers we used data from 1 of our previous studies for comparison.14 Long-term Complications
To investigate the incidence of clinically significant longterm postoperative complications, patient evaluation at the follow-up visits also included assessment for neovaginal prolapse, presence of any dysplasia or malignancy, granulation tissue, loss of neovaginal length and STDs, specifically HPV infections. Data Collection and Analysis
For data collection, patients completed a comprehensive, purpose-designed, standardized questionnaire. Medical
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Table 1 Changes in Neovaginal Parameters over Time Parameter Anatomic length (cm) Mean SD Median; range Functional length (cm) Mean SD Median; range Anatomic width (fingers) Mean SD Median; range Functional width (fingers) Mean SD Median; range Mean epithelialization (%)* In all patients In patients still wearing vaginal dummy In patients no longer wearing vaginal dummy In patients with SI In patients without SI
1 Month
3 Months
6 Months
$ 11 Months (Long-term)
9.2 1.3 9.5; 5.0-12.0
9.3 1.5 10.0; 5.0-12.0
8.8 1.7 9.0; 4.0-14.0
8.0 1.7 8.0; 6.0-12.0
10.5 1.4 11.0; 6.0-15.0
10.7 1.4 11.0; 7.0-15.0
10.3 1.6 10.0; 4.5-14.0
9.5 1.5 10.0; 6.0-13.0
1.4 0.4 1.5; 1.0-3.0
1.4 0.4 1.5; 1.0-2.5
1.3 0.3 1.5; 1.0-2.0
1.3 0.3 1.5; 1.0-2.0
2.0 0.4 2.0; 1.0-4.0
2.0 0.3 2.0; 1.0-3.5
1.9 0.2 2.0; 1.0-3.5
1.9 0.3 2.0; 1.5-4.0
34 34 d 42 32
55 55 d 58 51
72 69 91 76 67
93 87 99 95 88
SI, sexual intercourse. Data given are based on different group sizes as not all results were available for all visits and all patients. * Percentage of the full length of the neovagina that was epithelialized.
records were evaluated by the investigators for information relevant to the study. The FSFI questionnaire was completed by a subgroup of the long-term follow-up patients (all of them need to have a stable relationship already preoperatively) preoperatively, after 6 months and at the long-term follow-up visit. Data were collected using Excel 2003 (Microsoft Corporation, Redmond, WA) and statistical analysis was done with the software R, version 2.12.1 (http://www.r-project. org). Results are reported as means and standard deviations (SD) or medians and ranges, as appropriate, and numbers and percentages. Continuous data are presented graphically as box plots. Differences between groups were assessed by the Wilcoxon rank-sum test or the Fisher exact test, as appropriate. Relationships between variables were estimated by Spearman rank correlation coefficient. Since the times during which patients wore a dummy were censored, the median wearing time was estimated using a Kaplan-Meier plot. All tests were carried out at a significance level of .05.
had stopped wearing a dummy (data shown are running averages of ten consecutive values (k 5 10)). Notably, as shown in Fig. 1, B, the absence of sexual intercourse also did not affect maintenance of the originally achieved anatomic or functional neovaginal lengths.
Results Duration of Follow-up
Long-term data covering a follow-up period $11 months were obtained for 153 of the 240 study patients with a median follow-up time of 16 (range: 11-141) months. Long-term Anatomic Success
Table 1 summarizes the results for neovaginal length and width over the follow-up period. It shows that a neovaginal functional length of $ 6 cm, the requirement for long-term anatomic success, had been achieved in all patients at the long-term follow-up examination. Fig. 1, A, shows that the surgically achieved neovaginal functional length remained stable over time in the long-term follow-up ($ 11 months) group, even in those patients who
Fig. 1. A, Long-term stability of neovaginal functional length in patients who had stopped wearing the vaginal dummy at the long-term assessment ($11 months after surgery). Running means (k 5 10) of functional length (cm) by time of follow-up (months after surgery). B, Box plots of anatomic and functional neovaginal lengths (white and grey boxes) in patients without and with sexual intercourse (left and right boxes of the respective color) at 1, 3, 6, and $11 (long-term) months after surgery.
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Fig. 2. Kaplan-Meier analysis of the postoperative period during which a vaginal dummy was worn. Half of the patients were still wearing a dummy at 12 months after surgery, the median wearing time. Vertical lines indicate censoring.
Analysis of patients who had not had sexual intercourse and were no longer wearing the dummy when they presented for their long-term visit (median 22.4 mo) revealed that neovaginal length remained stable even without wearing the dummy and without having sexual intercourse. In these patients, mean (SD) functional length at the longterm visit was 8.8 1.7 cm. Duration of Wearing a Dummy
In the postsurgical situation it is important to know how long patients need to, and should be advised to, wear a vaginal dummy to maintain neovaginal length and achieve complete epithelialization, and whether wearing a dummy or having sexual intercourse speeds up complete epithelialization of the neovagina. The Kaplan-Meier plot in Fig. 2 shows that the overall median postoperative wearing period was 12 months (95% confidence interval 9-16 months). Those patients who completely stopped wearing a dummy before their long-term visit wore it for a median duration of 8.6 months after surgery. Epithelialization
At each visit, epithelialization of the neovagina was assessed and recommended dummy wearing time adjusted on an individual basis depending on the extent to which epithelialization was found to have progressed. We therefore analyzed the average wearing time required to achieve complete epithelialization and examined whether the length of this period depended on the patient having regular sexual intercourse. As shown in Table 1, epithelialization increased from a mean of 34% of the neovaginal length at 1 month after surgery to 93% at the long-term assessment. In our experience, epithelialization appeared to occur more slowly in patients who wore the vaginal dummy 24 hours/day for more than 3 months compared with patients who gradually began reducing daily wearing time after 3 months and stopped wearing the dummy after about 6 months, as recommended and advised to do. Our data also
suggest that sexual intercourse had a positive effect on achieving complete epithelialization of the neovagina since patients who had started having sexual intercourse showed a greater extent of epithelialization at earlier visits than did those who abstained from penetrative intercourse. Analysis of the mean values for epithelialization at 6 and $11 months after surgery as summarized in Table 1 indicates that complete epithelialization along the entire length of the neovagina occurred significantly (P ! .001) faster in patients who were no longer wearing the vaginal dummy compared with those still wearing the dummy (91% vs 69% at 6 months and 99% vs 87% at $11 months). We also analyzed the effects of the long-term wearing of a dummy and sexual activity on epithelialization. At the long-term follow-up visit, 92% of the patients who had stopped wearing the dummy had a completely epithelialized neovagina whereas only 55% of those still wearing the dummy showed complete epithelialization (P ! .0001). Similarly, complete epithelialization at the long-term visit was observed in a significantly larger proportion (80%) of patients who had started having sexual intercourse than in patients who had not had penetrative sex (54%; P 5 .002). Long-term Functional Success
Sexual function, the experienced quality of sexual intercourse and the quality of sexual life were analyzed using a purpose-designed questionnaire and the FSFI. Our patients reported great satisfaction with the surgical result, as evidenced by a median score (range) of 10.0 points (3-10) on a scale from 1 (very dissatisfied) to 10 (very satisfied) and by the fact that 96.2% of respondents stated they would recommend the operation to others. At the long-term visit, 110/148 (74.3%) patients reported having had vaginal intercourse postoperatively, the first coitus having taken place at a median (range) of 16 (3-147) weeks after surgery and a median frequency (range) of 2 (05) times per week. Asked about general satisfaction with sexual function, patients reported great satisfaction with the length of the vagina (median score 8.5 on a 10-point scale) and with the quality of sexual intercourse (median score 8). The standardized FSFI questionnaire was used to evaluate quality of sexual life. The mean total score was 20.9 preoperatively, increasing to 24.9 at 6 months and 29.1 at the long-term follow-up. The difference between the preoperative and the long-term score was statistically significant (P 5 .004, paired test). Table 2 presents the long-term FSFI scores of 76 questionnaire responders from a subgroup of 80 patients from our study who had been in a stable relationship before surgery in comparison with control group scores from the original study by Rosen et al.12 As the FSFI, strictly speaking, covers the 4 weeks preceding questionnaire completion, the table also compares the subgroup of 55 patients who had sexual intercourse during the last 4 weeks before the long-term assessment with a similar-aged general-population control group (72% vs 78.8% younger than 25 years) of German female medical students.14 The total scores were very similar between our patients and the comparison
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Table 2 Long-term Female Sexual Function Index (FSFI) Scores in Our Neovaginoplasty Patients Who Had Sexual Intercourse after Surgery Compared with Scores Found in 2 General Population Samples FSFI
Mean SD Desire Arousal Lubrication Orgasm Satisfaction Pain Total score
Rosen et al12,* n 5 131 (Controls Only)
This Study n 5 55 (SI, last 4weeks)
Wallwiener et al14 n 5 1057 (SI, last 4weeks)
Median (range)
Mean SD
Median (range)
Median (range)
3.6 5.1 5.7 4.8 5.6 4.8 30.0
4.1 5.0 5.6 5.1 5.1 5.7 30.5
4.2 5.4 6.0 5.2 5.6 5.6 30.0
3.6 5.1 5.7 4.8 5.2 5.2 28.6
This Study n 5 76 (All Patients)
3.8 4.2 4.6 3.9 5.1 4.1 29.1
1.2 2.0 2.1 2.2 1.2 2.3 4.7
(1.2-6.0) (0.0-6.0) (0.0-6.0) (0.0-6.0) (1.2-6.0) (0.0-6.0) (7.2-36.0)
1.1 1.1 1.0 1.3 1.2 1.1 5.3
(1.2-6.0) (3.0-6.0) (3.6-6.0) (1.2-60) (1.2-6.0) (2.4-6.0) (20.4-36.0)
(1.2-6.0) (1.2-6.0) (1.2-6.0) (0.8-6.0) (1.2-6.0) (1.2-6.0) (9.5-36.0)
SI, sexual intercourse. * For comparability, scores were multiplied by a weighting factor.
samples. There were no statistically significant differences between our patients' FSFI scores and those reported by Rosen et al.12 Especially the similar-aged groups also did not differ significantly, the score even being slightly higher in the patient group. Applying the cut-off score of 26.55 according to Wiegel et al,15 only 27% of our patients were at risk for sexual dysfunction compared with 32.4% in the general-population sample studied by Wallwiener et al.14
Long-term Complications and Incidence of STDs
The present study also focused on the following longterm complications: vaginal prolapse, malignancy, excessive granulation tissue, loss of vaginal length, and STDs, particularly HPV infections. Vaginal prolapse and malignancies did not occur in any of our patients. Temporary formation of excessive granulation tissue was seen in 7 patients, all of whom had never had sexual intercourse and were still wearing a dummy 24 h/day when they presented for the long-term follow-up visit at $11 months although patients were instructed to reduce wearing time rapidly after surgery. Of these 7 patients, 4 required removal of the tissue by cauterization and treatment with cortisone cream, whereas 3 required only cortisone. Subsequently all 7 patients showed normal epithelial development again. In addition, 4 patients showed relevant decreases in neovaginal length below the functional length of 6 cm before long-term follow-up. These patients had failed to wear a dummy postoperatively. An increase in neovaginal length was achieved by self-dilation in 2 of these patients whereas the other 2 underwent repeat surgery with the same technique. All 4 patients achieved a successful functional length of $ 6 cm at the long-term follow-up. Pap smears revealed low- to high-grade squamous intraepithelial lesions associated with HPV in 7/240 (2.9%) patients before long-term follow-up, one of whom was diagnosed with a vaginal intraepithelial neoplasia grade 2 (VAIN-2) lesion at long-term follow-up. All these patients had started having sexual intercourse by 3 months after surgery. The 3 patients who tested HPV-positive at the 3- or 6-month visit were no longer HPV-positive and had normal Pap smears at $11 months whereas the other 4 patients remained HPV-positive. For the VAIN-2 patient, laser therapy was the treatment of choice.
Discussion Main Findings
Our study combined clinical data from patient records and data on sexual function and patient satisfaction with surgery collected via validated questionnaires. We demonstrated that our laparoscopically assisted neovaginoplasty technique achieved 98% long-term anatomic success in terms of functional neovaginal length $ 6 cm remaining stable over a follow-up period of up to 141 months. Moreover, even if patients never had sexual intercourse and stopped wearing the dummy after 8.6 months on average, neovaginal length remained stable at 8.8 ( 1.7) cm, allowing sexual intercourse even years after surgery (mean follow-up in this group was 22.4 months) without the need for continued postoperative dilation. Taken together, our findings evidence that neovaginal length remained stable over time even in the absence of penetrative sexual activity and that long-term wearing of the vaginal dummy did not have a significant increasing effect on neovaginal length, indicating that long-term dilation is unnecessary. First coitus as a measure of functional success took place at a median of 16 weeks. Moreover, FSFI assessment preoperatively and at the long-term follow-up visit demonstrated long-term sexual satisfaction as indicated by a score as high as that reported by Rosen et al12 and slightly, though not significantly, higher than that found by Wallwiener et al in a general-population sample of similar age.14 We observed no major complications even after up to 141 months after surgery in patients operated as early as 1998 whilst self-dilation is known to be associated with complications such as prolapse16-20 and urinary incontinence.21 HPV infections occurred in 7/240 (2.9%) of our patients before long-term follow-up, of whom 1 had a VAIN-2 lesion, confirming recent findings by Frega et al.22 As patients undergoing our operation develop a completely normal vaginal epithelium9 they can be expected to have the same prevalence of HPV infection as their peers in the general population. This underscores that the need for routine Papanicolaou testing is the same as in the general population, not least because squamous cell carcinoma has been reported after a Vecchietti procedure.23
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We also saw granulation tissue in 7/153 (4.6%) patients still wearing the dummy 24 h/day at $ 11 months. On the other hand, shorter dummy wearing time and starting to have sexual intercourse moderately soon after surgery significantly accelerated complete epithelialization. Zhou et al24 recently reported neovaginal vault granulation which healed after trimming in 34/182 (18.7%) patients after vaginoplasty using pelvic peritoneum. By contrast, we were able to treat our patients with cortisone cream or by cauterization. In light of these findings we now strongly advise patients not to wear the dummy too often and for too long. Strengths and Limitations
The present study is the first report of our long-term neovaginoplasty results. Our prospective and retrospective data were collected from the sizeable group of 240 patients diagnosed with MRKH or CAIS-related vaginal agenesis and treated using our previously described laparoscopically assisted neovaginoplasty technique6,7,9,10 at our institution during 1998-2011. This technique is considerably less invasive than the standard laparoscopic Vecchietti procedure as it dispenses with dissection of the vesicorectal space, using instruments that received approval from the United States Food and Drug Administration in 2010. Potential limitations of the study include the following. A preselection bias may have been introduced because although all patients were offered self-dilation most patients either refused to try, or were unsuccessful with, progressive dilation. In addition, there may be an element of surgeon comfort and experience with certain techniques in the choice of procedure.25 General Interpretation
The following considerations led us to discuss our longterm results in the context of nonsurgical self-dilation. In 2006 and 2013, the American College of Obstetricians and Gynecologists (ACOG) endorsed nonsurgical neovagina creation as the method of first choice.1,26 However, no comprehensive comparative studies have since been conducted to address the anatomic, functional and psychological outcomes of alternative, surgical approaches. Therefore, it appears reasonable to compare the long-term results of nonsurgical neovagina creation with those obtained with the least invasive surgical method available, that is, that which comes closest to the ideal proposed by ACOG1,26 and others27,28 in terms of creating a vagina in the correct axis and of adequate size and secretory capacity to allow intercourse without requiring continued postoperative dilation. On balance, techniques of neovagina creation based on, or modified from, the Vecchietti procedure have clear advantages over other surgical procedures in that they create a neovagina with a normal anatomy, histomorphology and functionality.9,11,29-32 Moreover, such traction-based techniques require no extraneous tissues such as skin, peritoneum or intestine, dispense with plastic surgery that causes visible external scars33 and achieve a satisfactory functional result in a short time.31
Obviously, the success of nonsurgical treatment depends on the patient's self-discipline and perseverance, her motivation and her ability to manage the physical and psychological strain associated with this method.34 Two recent studies have investigated nonsurgical success rates.21,25 Gargollo et al reported 12% treatment failure due to noncompliance and an achievement of functional success at a median of 18.7 months in 18/64 sexually active patients.25 Edmonds et al studied 245 patients who started self-dilation during an average 3 days of instruction in hospital.21 These authors reported a success rate of about 95%, with 13/245 (5.3%) patients not completing the treatment program, but remained somewhat vague as to the time this required. Additionally they noted that after a substantial period without dilation or intercourse some women needed to resort to dilation again to regain the original result and that some women required lubricants for sexual satisfaction. Thus, apart from being a lengthy procedure, Frank's method of progressive dilation35 often does not provide sufficient long-term stability in neovaginal length if dilation is discontinued. In principle, we share the preference for less invasive approaches and offer all our patients the alternative of selfdilation. However, in our experience, patients nowadays are usually well informed at first presentation and often expressly wish to undergo surgical neovaginoplasty. We also share the opinion that neovagina creation, be it surgical or by dilation, is elective and best performed in emotionally mature patients who can be involved in the decision making process.1,26 At our institution, we therefore pursue a multidisciplinary approach with preoperative and postoperative evaluations by a team of specialized psychologists, as do others.21,36 The motivation for reconstruction has meanwhile become much more strongly based on the patient's desire to appear and feel a normal woman, not only anatomically25 € bus but also in terms of being “ready” for sexual activity. Mo et al37 found an impressive increase in self-confidence in 61% of women after surgical neovaginoplasty. In our experience, the typical patient profile has clearly shifted in recent years from the woman aged over 18 years and living in a committed relationship (cf. the ACOG guidelines1,26) to the post-pubertal patient without a steady partner but with a radically changed female self-perception. In our patients, the age of emotional maturity has clearly dropped to 18 years and below; before 2007 median age (range) at first presentation was 19.0 (14.5-40.7) years and has since dropped to 18.2 (15.0-19.7) years. With this trend the demands on the outcome of surgery have also changed; patients tend to opt for immediate surgical correction rather than having to diligently perform self-dilation for prolonged periods and constantly deal emotionally with their chronic condition. We therefore consider it particularly important to have demonstrated that our optimized minimally invasive technique creates a neovagina of stable length even in the absence of sexual intercourse or the wearing of a dummy and, in contrast to progressive dilation, does not require the patient to start over again after a period of abstinence.
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Conclusion
A favorable safety, tolerability and efficacy profile combined with the speed of results and reduction of psychological strain merits particular consideration of this laparoscopically assisted neovaginoplasty technique as a first-line therapeutic option. A standardized and internationally certified surgical procedure with regulatoryapproved equipment and a structured training program could advance the international acceptance and success of our technique. Controlled trials directly comparing the nonsurgical approach with our laparoscopically assisted surgical procedure are currently lacking. Nonetheless, our findings strongly suggest that this technique can be considered the method of choice in patients with vaginal agenesis seeking surgical treatment. Finally, though our technique has been refined and experience with it has accrued, it remains a complex endoscopic procedure that should be performed only by experienced surgeons at high-volume centres.9 Moreover, the management of patients with vaginal agenesis unquestionably requires a multidisciplinary approach, whether definitive treatment is surgical or nonsurgical.21 Acknowledgments
We gratefully acknowledge all patients who participated in our study and thank all hospital staff members who were involved in the care of our patients. References 1. Committee on Adolescent Health Care: Committee opinion: no. 562: mullerian agenesis: diagnosis, management, and treatment. Obstet Gynecol 2013; 121: 1134 2. Routh JC, Laufer MR, Cannon GM Jr, et al: Management strategies for Mayer-Rokitansky-Kuster-Hauser related vaginal agenesis: a cost-effectiveness analysis. J Urol 2010; 184:2116 3. Miller RJ, Breech LL: Surgical correction of vaginal anomalies. Clin Obstet Gynecol 2008; 51:223 4. Rall K, Wallwiener D, Brucker S: Laparoscopic-assisted methods for neovaginoplasty. Sex Reprod Menopause 2010; 8:15 5. Nakhal RS, Creighton SM: Management of vaginal agenesis. J Pediatr Adolesc Gynecol 2012; 25:352 6. Brucker S, Aydeniz B, Gegusch M, et al: Improvement of endoscopically assisted neovagina: new application instruments and traction device. Gynecol Surg 2004; 1:133 7. Brucker S, Zubke W, Wallwiener D, et al: [Perfecting the laparoscopic-assisted creation of a neovagina with new application instruments and a new traction device]. Geburtshilfe Frauenheilkd 2004; 64:70 8. Brucker SY, Rall K, Wallwiener D: Laparoscopically assisted neovaginoplasty. In: Nezhat's video-assisted and robotic-assisted laparoscopy and hysteroscopy. In: Nezhat C, Nezhat FR, Nezhat C, editors, (4th ed.). Cambridge, Cambridge University Press, 2013, pp 426 9. Brucker SY, Gegusch M, Zubke W, et al: Neovagina creation in vaginal agenesis: development of a new laparoscopic Vecchietti-based procedure and optimized instruments in a prospective comparative interventional study in 101 patients. Fertil Steril 2008; 90:1940 10. Wallwiener D, Becker S, Beckmann MW, et al, editors. Atlas of Gynecologic Surgery, (4th ed.).. Stuttgart, Thieme, 2014, pp 459e466
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11. Barnhart KT, Izquierdo A, Pretorius ES, et al: Baseline dimensions of the human vagina. Hum Reprod 2006; 21:1618 12. Rosen R, Brown C, Heiman J, et al: The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther 2000; 26:191 13. Berner MM, Kriston L, Zahradnik HP, et al: Validity and Reliability of the German Female Sexual Function Index (FSFI-d). [Article in German] Geburtshilfe Frauenheilkd 2004; 64:293 14. Wallwiener CW, Wallwiener LM, Seeger H, et al: Prevalence of sexual dysfunction and impact of contraception in female German medical students. J Sex Med 2010; 7:2139 15. Wiegel M, Meston C, Rosen R: The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther 2005; 31:1 16. Burns E, Naim M, Badawy SZ: Mullerian agenesis with vaginal vault prolapse following mechanically created neovagina. J Pediatr Adolesc Gynecol 2012; 25:e75 17. Calcagno M, Pastore M, Bellati F, et al: Early prolapse of a neovagina created with self-dilatation and treated with sacrospinous ligament suspension in a € ster-Hauser syndrome: a case report. Fertil patient with Mayer-Rokitansky-Ku Steril 2010; 93:267.e1 18. Christopoulos P, Cutner A, Vashisht A, et al: Laparoscopic sacrocolpopexy to treat prolapse of the neovagina created by vaginal dilation in Rokitansky syndrome. J Pediatr Adolesc Gynecol 2011; 24:e33 19. Peters WA 3rd, Uhlir JK: Prolapse of a neovagina created by self-dilatation. Obstet Gynecol 1990; 76:904 20. Schaffer J, Fabricant C, Carr BR: Vaginal vault prolapse after nonsurgical and € llerian agenesis. Obstet Gynecol 2002; 99:947 surgical treatment of Mu € ster-Hauser 21. Edmonds DK, Rose GL, Lipton MG, et al: Mayer-Rokitansky-Ku syndrome: a review of 245 consecutive cases managed by a multidisciplinary approach with vaginal dilators. Fertil Steril 2012; 97:686 22. Frega A, Scirpa P, Sopracordevole F, et al: Impact of human papillomavirus infection on the neovaginal and vulval tissues of women who underwent surgical treatment for Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 2011; 96:969 23. Liebrich C, Reinecke-Luthge A, Kuhnle H, et al: Squamous cell carcinoma in neovagina at Mayer-Rokitansky-Kuster-Hauser-syndrome. [Article in German] Zentralbl Gynakol 2006; 128:271 24. Zhou JH, Sun J, Yang CB, et al: Long-term outcomes of transvestibular vaginoplasty with pelvic peritoneum in 182 patients with Rokitansky's syndrome. Fertil Steril 2010; 94:2281 25. Gargollo PC, Cannon GM Jr, Diamond DA, et al: Should progressive perineal dilation be considered first line therapy for vaginal agenesis? J Urol 1882; 2009(4 Suppl):182 26. ACOG Committee on Adolescent Health Care: ACOG Committee Opinion No. 355: Vaginal agenesis: diagnosis, management, and routine care. Obstet Gynecol 2006; 108:1605 27. Templeman CL, Lam AM, Hertweck SP: Surgical management of vaginal agenesis. Obstet Gynecol Surv 1999; 54:583 28. Laufer MR: Congenital absence of the vagina: in search of the perfect solution. When, and by what technique, should a vagina be created? Curr Opin Obstet Gynecol 2002; 14:441 e G, Brun JL, Trouette H, et al: Cytologic findings in a neovagina 29. Belleanne created with Vecchietti's technique for treating vaginal aplasia. Acta Cytol 1998; 42:945 € lbl H, Janisch H: [Morphologic and functional long-term results 30. Hanzal E, Ko after Vecchietti operation for the formation of a neovagina]. [Article in German] Geburtshilfe Frauenheilkd 1991; 51:563 31. Fedele L, Bianchi S, Frontino G, et al: The laparoscopic Vecchietti's modified technique in Rokitansky syndrome: anatomic, functional, and sexual long-term results. Am J Obstet Gynecol 2008; 198:377.e1 32. Fedele L, Bianchi S, Berlanda N, et al: Neovaginal mucosa after Vecchietti's laparoscopic operation for Rokitansky syndrome: structural and ultrastructural study. Am J Obstet Gynecol 2006; 195:56 € ster-Hauser 33. Vecchietti G: Creation of an artificial vagina in Rokitansky-Ku syndrome. [Article in Italian] Attual Ostet Ginecol 1965; 11:131 34. Makinoda S, Nishiya M, Sogame M, et al: Non-grafting method of vaginal construction for patients of vaginal agenesis without functioning uterus € ster syndrome). Int Surg 1996; 81:385 (Mayer-Rokitansky-Ku 35. Frank RT: The formation of an artificial vagina without operation. Am J Obstet Gynecol 1938; 35:1045 36. Nadarajah S, Quek J, Rose GL, et al: Sexual function in women treated with dilators for vaginal agenesis. J Pediatr Adolesc Gynecol 2005; 18:39 €bus VJ, Kortenhorn K, Kreienberg R, et al: Long-term results after operative 37. Mo correction of vaginal aplasia. Am J Obstet Gynecol 1996; 175:617
€ bingen University Hospital, Calwerstr. 7, 72076 Tu € bingen, Germany Department of Obstetrics and Gynecology, Tu Department of Obstetrics and Gynecology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany
a b s t r a c t Study Objective: To assess the long-term outcome of an optimized minimally invasive neovaginoplasty technique in vaginal agenesis. Design: Combined retrospective and prospective study. Setting: University hospital. Participants: 240 patients with congenital vaginal agenesis. Interventions: Patients with an indication for neovagina creation underwent laparoscopically assisted neovaginoplasty involving vaginoabdominal blunt perforation and intracorporeal traction using tension threads and an abdominally positioned extracorporeal traction device. Main Outcome Measures: Long-term anatomic success, functional success compared with similar-aged controls, long-term complications, and incidence of human papilloma virus (HPV) infections. Results: During median follow-up for 16 (range 11-141) months, mean functional neovaginal length remained stable at 9.5 cm in all patients, including those who had no sexual intercourse and had stopped wearing the vaginal dummy. Median dummy wearing time was 8.6 months. Time to epithelialization depended on the time of onset and frequency of sexual intercourse. At long-term follow-up, median total Female Sexual Function Index score was 30.0, comparable with similar-aged controls. No common long-term complications occurred. Four patients required cauterization of granulation tissue. 7/240 (2.9%) patients were HPV-positive with low- to high-grade squamous intraepithelial lesions, 3 patients reverting to HPV-negative status at long-term follow-up. Conclusions: Our technique creates a neovagina of adequate size and secretory capacity for normal coitus, requiring no prolonged dilation postoperatively, even in the absence of sexual intercourse. The procedure is fast, effective and minimally traumatic, has a very low longterm complication rate and provides very satisfactory long-term functional results. € llerian aplasia, Mayer-Rokitansky-Ku € ster-Hauser (MRKH) syndrome, Laparoscopic Key Words: Vaginal aplasia, Uterovaginal agenesis, Mu creation of neovagina
Introduction
The creation of a functional neovagina that enables the patient to have sexual intercourse and provides adequate cosmesis while minimizing short and long-term morbidity is currently considered the primary therapeutic goal in patients with congenital vaginal agenesis, which is most € ster-Hauser commonly caused by Mayer-Rokitansky-Ku (MRKH) syndrome.1,2 In addition to nonsurgical progressive dilation, a number of surgical methods of neovagina creation have been developed over the past decades. There is, however, no firm general consensus among providers as to which method best creates a neovagina of adequate length and width with an anatomically correct axis, ensures first-time success with low morbidity and surgical complication rates, and requires no exogenous lubrication or continued postoperative The authors indicate no conflicts of interest. * Address correspondence to: Sara Y. Brucker, MD, Department of Obstetrics and € bingen University Hospital, Calwerstr. 7, 72076 Tu € bingen, Germany; Gynecology, Tu Phone: þ49 (0) 7071 29-80791; fax: þ49 (0) 7071 29-4663 E-mail address: [email protected] (S.Y. Brucker).
dilation.1,3,4 In the US and in the United Kingdom, surgical neovaginoplasty is primarily considered an option for patients who are unsuccessful with dilation therapy or prefer surgery after full discussion of the available surgical options and their risks and benefits.1,5 Our Centre for Rare Female Genital Malformations developed and optimized a laparoscopically assisted technique that creates a neovagina in a standardized, controlled manner by vaginoabdominal blunt perforation and traction exerted by a device positioned on the abdomen.6-8 We subsequently demonstrated in 101 patients that this technique produced better functional results with fewer complications than the standard laparoscopic Vecchietti procedure involving dissection of the vesicorectal space.9 Based on the substantial body of prospective and retrospective data collected at our institution between 1998 and 2011, the present study was conducted to assess our neovaginoplasty technique with regard to intermediate and long-term outcome. We aimed to demonstrate that our technique provides adequate anatomic and functional results in terms of stable length over time and sexual function comparable with an age-matched, anatomically normal
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general population sample. We also aimed to show that the procedure is well tolerated and not associated with longterm complications or increased health risks. We focused on 3 aspects: (1) the optimal frequency and duration of wearing a vaginal dummy postoperatively and the role of sexual intercourse and/or wearing a dummy in maintaining the neovagina and accelerating epithelialization, (2) sexual satisfaction compared with age-matched, general-population peers as well as overall patient satisfaction with surgery and outcome, and (3) potential long-term complications, including vaginal prolapse, malignancies, and granulation tissue, and the incidence of sexually transmitted infections, especially human papilloma virus (HPV), in view of the associated risk of vaginal cancer.
Estrogen-containing cream was used to facilitate insertion of the dummy and accelerate epithelialization.8 Study Assessments and Parameters Study Visits
Clinical follow-up examinations were carried out at 1, 3 and 6 months, and at $11 months for long-term follow-up. Each follow-up visit included: general gynecologic and standardized vaginal examinations by 1 of the 2 main investigators (K.R., S.Y.B.); recording of any neovaginoplastyrelated signs or symptoms; vaginal cytology (Pap smear), and, in the presence of pathology, an HPV test, assessment of neovaginal epithelialization, and microbiologic testing. Neovaginal Parameters
Materials and Methods Study Design and Patients
The present study was a combined analysis of prospectively collected questionnaire data and retrospective data from existing patient records and was approved by the € bingen. Included in Ethics Committee of the University of Tu the analysis were all 240 consecutive patients who presented to us with primary amenorrhea, were diagnosed with vaginal agenesis and underwent neovaginoplasty using our laparoscopically assisted technique at our institution between August 1998 and September 2011. In total, 223/240 (93.3%) patients had MRKH syndrome with a normal 46,XX female karyotype while 15/240 (6.3%) had a 46,XY karyotype and were diagnosed with complete androgen insensitivity syndrome (CAIS) and 1 patient was diagnosed with 47,XYY. Karyotype was unknown in the remaining patient. Mean age at surgery ( SD) was 20.5 ( 5.6) (median 18.7, range 14.5-49.7) years.
Treatment
After comprehensive diagnostic testing and detailed explanation of the treatment options, patients with a confirmed indication for our technique of laparoscopically assisted neovaginoplasty underwent surgery as previously described in detail.8-10 In brief, targeted blunt perforation was performed under laparoscopic guidance from the vagina to the abdomen, through the rectovesical septum, without dissecting the vesicorectal space. Using a curved thread guide, 2 tension threads were subperitoneally fed in a cranial direction and subsequently fixated in a traction device positioned on the patient's abdomen. The 2 other ends of these threads were connected to the rounded-top, that is, proximal, segment (“olive”) of a pluggable segmented dummy. After surgery, the tension threads were tightened daily under epidural anesthesia, the resulting continuous dilation pressure on the vaginal dimple creating a neovagina in about 4-5 days. The tension threads, traction device, and segmented dummy were then removed. To maintain neovaginal length and width, prevent tissue adhesions and stimulate epithelialization, the patient had to wear a vaginal dummy for several weeks postoperatively.
Anatomic length of the neovagina was determined by digital palpation without pressure, functional length by applying maximal pressure. Anatomic success was defined as a functional neovaginal length of $6 cm and easy introduction of 2 fingers.11 Functional success was considered achieved when the patient reported satisfactory sexual intercourse. Long-term Anatomic Success
This was defined as stable functional length $ 6 cm in the long term of $11 months in the presence or absence of continued dilation or sexual intercourse. To determine the optimal frequency and duration of wearing a vaginal dummy and evaluate the role of sexual intercourse in maintaining the achieved neovaginal length and creating a normal vaginal epithelium, patients were asked to complete a purpose-designed questionnaire at the follow-up visits. Long-term Functional Success
This was defined as having achieved successful, satisfactory coitus as reported on the purpose-designed followup questionnaire. To obtain more detailed information and enable comparison with other groups, sexual function was additionally assessed using the German version of Rosen's Female Sexual Function Index (FSFI-d) questionnaire in a subgroup of patients who had already been in a stable relationship before undergoing surgery (subgroup inclusion criterion). FSFI scores were determined according to published formulas.12,13 To determine whether the FSFI scores in neovaginoplasty patients differed from those in similaraged general-population peers we used data from 1 of our previous studies for comparison.14 Long-term Complications
To investigate the incidence of clinically significant longterm postoperative complications, patient evaluation at the follow-up visits also included assessment for neovaginal prolapse, presence of any dysplasia or malignancy, granulation tissue, loss of neovaginal length and STDs, specifically HPV infections. Data Collection and Analysis
For data collection, patients completed a comprehensive, purpose-designed, standardized questionnaire. Medical
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Table 1 Changes in Neovaginal Parameters over Time Parameter Anatomic length (cm) Mean SD Median; range Functional length (cm) Mean SD Median; range Anatomic width (fingers) Mean SD Median; range Functional width (fingers) Mean SD Median; range Mean epithelialization (%)* In all patients In patients still wearing vaginal dummy In patients no longer wearing vaginal dummy In patients with SI In patients without SI
1 Month
3 Months
6 Months
$ 11 Months (Long-term)
9.2 1.3 9.5; 5.0-12.0
9.3 1.5 10.0; 5.0-12.0
8.8 1.7 9.0; 4.0-14.0
8.0 1.7 8.0; 6.0-12.0
10.5 1.4 11.0; 6.0-15.0
10.7 1.4 11.0; 7.0-15.0
10.3 1.6 10.0; 4.5-14.0
9.5 1.5 10.0; 6.0-13.0
1.4 0.4 1.5; 1.0-3.0
1.4 0.4 1.5; 1.0-2.5
1.3 0.3 1.5; 1.0-2.0
1.3 0.3 1.5; 1.0-2.0
2.0 0.4 2.0; 1.0-4.0
2.0 0.3 2.0; 1.0-3.5
1.9 0.2 2.0; 1.0-3.5
1.9 0.3 2.0; 1.5-4.0
34 34 d 42 32
55 55 d 58 51
72 69 91 76 67
93 87 99 95 88
SI, sexual intercourse. Data given are based on different group sizes as not all results were available for all visits and all patients. * Percentage of the full length of the neovagina that was epithelialized.
records were evaluated by the investigators for information relevant to the study. The FSFI questionnaire was completed by a subgroup of the long-term follow-up patients (all of them need to have a stable relationship already preoperatively) preoperatively, after 6 months and at the long-term follow-up visit. Data were collected using Excel 2003 (Microsoft Corporation, Redmond, WA) and statistical analysis was done with the software R, version 2.12.1 (http://www.r-project. org). Results are reported as means and standard deviations (SD) or medians and ranges, as appropriate, and numbers and percentages. Continuous data are presented graphically as box plots. Differences between groups were assessed by the Wilcoxon rank-sum test or the Fisher exact test, as appropriate. Relationships between variables were estimated by Spearman rank correlation coefficient. Since the times during which patients wore a dummy were censored, the median wearing time was estimated using a Kaplan-Meier plot. All tests were carried out at a significance level of .05.
had stopped wearing a dummy (data shown are running averages of ten consecutive values (k 5 10)). Notably, as shown in Fig. 1, B, the absence of sexual intercourse also did not affect maintenance of the originally achieved anatomic or functional neovaginal lengths.
Results Duration of Follow-up
Long-term data covering a follow-up period $11 months were obtained for 153 of the 240 study patients with a median follow-up time of 16 (range: 11-141) months. Long-term Anatomic Success
Table 1 summarizes the results for neovaginal length and width over the follow-up period. It shows that a neovaginal functional length of $ 6 cm, the requirement for long-term anatomic success, had been achieved in all patients at the long-term follow-up examination. Fig. 1, A, shows that the surgically achieved neovaginal functional length remained stable over time in the long-term follow-up ($ 11 months) group, even in those patients who
Fig. 1. A, Long-term stability of neovaginal functional length in patients who had stopped wearing the vaginal dummy at the long-term assessment ($11 months after surgery). Running means (k 5 10) of functional length (cm) by time of follow-up (months after surgery). B, Box plots of anatomic and functional neovaginal lengths (white and grey boxes) in patients without and with sexual intercourse (left and right boxes of the respective color) at 1, 3, 6, and $11 (long-term) months after surgery.
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Fig. 2. Kaplan-Meier analysis of the postoperative period during which a vaginal dummy was worn. Half of the patients were still wearing a dummy at 12 months after surgery, the median wearing time. Vertical lines indicate censoring.
Analysis of patients who had not had sexual intercourse and were no longer wearing the dummy when they presented for their long-term visit (median 22.4 mo) revealed that neovaginal length remained stable even without wearing the dummy and without having sexual intercourse. In these patients, mean (SD) functional length at the longterm visit was 8.8 1.7 cm. Duration of Wearing a Dummy
In the postsurgical situation it is important to know how long patients need to, and should be advised to, wear a vaginal dummy to maintain neovaginal length and achieve complete epithelialization, and whether wearing a dummy or having sexual intercourse speeds up complete epithelialization of the neovagina. The Kaplan-Meier plot in Fig. 2 shows that the overall median postoperative wearing period was 12 months (95% confidence interval 9-16 months). Those patients who completely stopped wearing a dummy before their long-term visit wore it for a median duration of 8.6 months after surgery. Epithelialization
At each visit, epithelialization of the neovagina was assessed and recommended dummy wearing time adjusted on an individual basis depending on the extent to which epithelialization was found to have progressed. We therefore analyzed the average wearing time required to achieve complete epithelialization and examined whether the length of this period depended on the patient having regular sexual intercourse. As shown in Table 1, epithelialization increased from a mean of 34% of the neovaginal length at 1 month after surgery to 93% at the long-term assessment. In our experience, epithelialization appeared to occur more slowly in patients who wore the vaginal dummy 24 hours/day for more than 3 months compared with patients who gradually began reducing daily wearing time after 3 months and stopped wearing the dummy after about 6 months, as recommended and advised to do. Our data also
suggest that sexual intercourse had a positive effect on achieving complete epithelialization of the neovagina since patients who had started having sexual intercourse showed a greater extent of epithelialization at earlier visits than did those who abstained from penetrative intercourse. Analysis of the mean values for epithelialization at 6 and $11 months after surgery as summarized in Table 1 indicates that complete epithelialization along the entire length of the neovagina occurred significantly (P ! .001) faster in patients who were no longer wearing the vaginal dummy compared with those still wearing the dummy (91% vs 69% at 6 months and 99% vs 87% at $11 months). We also analyzed the effects of the long-term wearing of a dummy and sexual activity on epithelialization. At the long-term follow-up visit, 92% of the patients who had stopped wearing the dummy had a completely epithelialized neovagina whereas only 55% of those still wearing the dummy showed complete epithelialization (P ! .0001). Similarly, complete epithelialization at the long-term visit was observed in a significantly larger proportion (80%) of patients who had started having sexual intercourse than in patients who had not had penetrative sex (54%; P 5 .002). Long-term Functional Success
Sexual function, the experienced quality of sexual intercourse and the quality of sexual life were analyzed using a purpose-designed questionnaire and the FSFI. Our patients reported great satisfaction with the surgical result, as evidenced by a median score (range) of 10.0 points (3-10) on a scale from 1 (very dissatisfied) to 10 (very satisfied) and by the fact that 96.2% of respondents stated they would recommend the operation to others. At the long-term visit, 110/148 (74.3%) patients reported having had vaginal intercourse postoperatively, the first coitus having taken place at a median (range) of 16 (3-147) weeks after surgery and a median frequency (range) of 2 (05) times per week. Asked about general satisfaction with sexual function, patients reported great satisfaction with the length of the vagina (median score 8.5 on a 10-point scale) and with the quality of sexual intercourse (median score 8). The standardized FSFI questionnaire was used to evaluate quality of sexual life. The mean total score was 20.9 preoperatively, increasing to 24.9 at 6 months and 29.1 at the long-term follow-up. The difference between the preoperative and the long-term score was statistically significant (P 5 .004, paired test). Table 2 presents the long-term FSFI scores of 76 questionnaire responders from a subgroup of 80 patients from our study who had been in a stable relationship before surgery in comparison with control group scores from the original study by Rosen et al.12 As the FSFI, strictly speaking, covers the 4 weeks preceding questionnaire completion, the table also compares the subgroup of 55 patients who had sexual intercourse during the last 4 weeks before the long-term assessment with a similar-aged general-population control group (72% vs 78.8% younger than 25 years) of German female medical students.14 The total scores were very similar between our patients and the comparison
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Table 2 Long-term Female Sexual Function Index (FSFI) Scores in Our Neovaginoplasty Patients Who Had Sexual Intercourse after Surgery Compared with Scores Found in 2 General Population Samples FSFI
Mean SD Desire Arousal Lubrication Orgasm Satisfaction Pain Total score
Rosen et al12,* n 5 131 (Controls Only)
This Study n 5 55 (SI, last 4weeks)
Wallwiener et al14 n 5 1057 (SI, last 4weeks)
Median (range)
Mean SD
Median (range)
Median (range)
3.6 5.1 5.7 4.8 5.6 4.8 30.0
4.1 5.0 5.6 5.1 5.1 5.7 30.5
4.2 5.4 6.0 5.2 5.6 5.6 30.0
3.6 5.1 5.7 4.8 5.2 5.2 28.6
This Study n 5 76 (All Patients)
3.8 4.2 4.6 3.9 5.1 4.1 29.1
1.2 2.0 2.1 2.2 1.2 2.3 4.7
(1.2-6.0) (0.0-6.0) (0.0-6.0) (0.0-6.0) (1.2-6.0) (0.0-6.0) (7.2-36.0)
1.1 1.1 1.0 1.3 1.2 1.1 5.3
(1.2-6.0) (3.0-6.0) (3.6-6.0) (1.2-60) (1.2-6.0) (2.4-6.0) (20.4-36.0)
(1.2-6.0) (1.2-6.0) (1.2-6.0) (0.8-6.0) (1.2-6.0) (1.2-6.0) (9.5-36.0)
SI, sexual intercourse. * For comparability, scores were multiplied by a weighting factor.
samples. There were no statistically significant differences between our patients' FSFI scores and those reported by Rosen et al.12 Especially the similar-aged groups also did not differ significantly, the score even being slightly higher in the patient group. Applying the cut-off score of 26.55 according to Wiegel et al,15 only 27% of our patients were at risk for sexual dysfunction compared with 32.4% in the general-population sample studied by Wallwiener et al.14
Long-term Complications and Incidence of STDs
The present study also focused on the following longterm complications: vaginal prolapse, malignancy, excessive granulation tissue, loss of vaginal length, and STDs, particularly HPV infections. Vaginal prolapse and malignancies did not occur in any of our patients. Temporary formation of excessive granulation tissue was seen in 7 patients, all of whom had never had sexual intercourse and were still wearing a dummy 24 h/day when they presented for the long-term follow-up visit at $11 months although patients were instructed to reduce wearing time rapidly after surgery. Of these 7 patients, 4 required removal of the tissue by cauterization and treatment with cortisone cream, whereas 3 required only cortisone. Subsequently all 7 patients showed normal epithelial development again. In addition, 4 patients showed relevant decreases in neovaginal length below the functional length of 6 cm before long-term follow-up. These patients had failed to wear a dummy postoperatively. An increase in neovaginal length was achieved by self-dilation in 2 of these patients whereas the other 2 underwent repeat surgery with the same technique. All 4 patients achieved a successful functional length of $ 6 cm at the long-term follow-up. Pap smears revealed low- to high-grade squamous intraepithelial lesions associated with HPV in 7/240 (2.9%) patients before long-term follow-up, one of whom was diagnosed with a vaginal intraepithelial neoplasia grade 2 (VAIN-2) lesion at long-term follow-up. All these patients had started having sexual intercourse by 3 months after surgery. The 3 patients who tested HPV-positive at the 3- or 6-month visit were no longer HPV-positive and had normal Pap smears at $11 months whereas the other 4 patients remained HPV-positive. For the VAIN-2 patient, laser therapy was the treatment of choice.
Discussion Main Findings
Our study combined clinical data from patient records and data on sexual function and patient satisfaction with surgery collected via validated questionnaires. We demonstrated that our laparoscopically assisted neovaginoplasty technique achieved 98% long-term anatomic success in terms of functional neovaginal length $ 6 cm remaining stable over a follow-up period of up to 141 months. Moreover, even if patients never had sexual intercourse and stopped wearing the dummy after 8.6 months on average, neovaginal length remained stable at 8.8 ( 1.7) cm, allowing sexual intercourse even years after surgery (mean follow-up in this group was 22.4 months) without the need for continued postoperative dilation. Taken together, our findings evidence that neovaginal length remained stable over time even in the absence of penetrative sexual activity and that long-term wearing of the vaginal dummy did not have a significant increasing effect on neovaginal length, indicating that long-term dilation is unnecessary. First coitus as a measure of functional success took place at a median of 16 weeks. Moreover, FSFI assessment preoperatively and at the long-term follow-up visit demonstrated long-term sexual satisfaction as indicated by a score as high as that reported by Rosen et al12 and slightly, though not significantly, higher than that found by Wallwiener et al in a general-population sample of similar age.14 We observed no major complications even after up to 141 months after surgery in patients operated as early as 1998 whilst self-dilation is known to be associated with complications such as prolapse16-20 and urinary incontinence.21 HPV infections occurred in 7/240 (2.9%) of our patients before long-term follow-up, of whom 1 had a VAIN-2 lesion, confirming recent findings by Frega et al.22 As patients undergoing our operation develop a completely normal vaginal epithelium9 they can be expected to have the same prevalence of HPV infection as their peers in the general population. This underscores that the need for routine Papanicolaou testing is the same as in the general population, not least because squamous cell carcinoma has been reported after a Vecchietti procedure.23
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We also saw granulation tissue in 7/153 (4.6%) patients still wearing the dummy 24 h/day at $ 11 months. On the other hand, shorter dummy wearing time and starting to have sexual intercourse moderately soon after surgery significantly accelerated complete epithelialization. Zhou et al24 recently reported neovaginal vault granulation which healed after trimming in 34/182 (18.7%) patients after vaginoplasty using pelvic peritoneum. By contrast, we were able to treat our patients with cortisone cream or by cauterization. In light of these findings we now strongly advise patients not to wear the dummy too often and for too long. Strengths and Limitations
The present study is the first report of our long-term neovaginoplasty results. Our prospective and retrospective data were collected from the sizeable group of 240 patients diagnosed with MRKH or CAIS-related vaginal agenesis and treated using our previously described laparoscopically assisted neovaginoplasty technique6,7,9,10 at our institution during 1998-2011. This technique is considerably less invasive than the standard laparoscopic Vecchietti procedure as it dispenses with dissection of the vesicorectal space, using instruments that received approval from the United States Food and Drug Administration in 2010. Potential limitations of the study include the following. A preselection bias may have been introduced because although all patients were offered self-dilation most patients either refused to try, or were unsuccessful with, progressive dilation. In addition, there may be an element of surgeon comfort and experience with certain techniques in the choice of procedure.25 General Interpretation
The following considerations led us to discuss our longterm results in the context of nonsurgical self-dilation. In 2006 and 2013, the American College of Obstetricians and Gynecologists (ACOG) endorsed nonsurgical neovagina creation as the method of first choice.1,26 However, no comprehensive comparative studies have since been conducted to address the anatomic, functional and psychological outcomes of alternative, surgical approaches. Therefore, it appears reasonable to compare the long-term results of nonsurgical neovagina creation with those obtained with the least invasive surgical method available, that is, that which comes closest to the ideal proposed by ACOG1,26 and others27,28 in terms of creating a vagina in the correct axis and of adequate size and secretory capacity to allow intercourse without requiring continued postoperative dilation. On balance, techniques of neovagina creation based on, or modified from, the Vecchietti procedure have clear advantages over other surgical procedures in that they create a neovagina with a normal anatomy, histomorphology and functionality.9,11,29-32 Moreover, such traction-based techniques require no extraneous tissues such as skin, peritoneum or intestine, dispense with plastic surgery that causes visible external scars33 and achieve a satisfactory functional result in a short time.31
Obviously, the success of nonsurgical treatment depends on the patient's self-discipline and perseverance, her motivation and her ability to manage the physical and psychological strain associated with this method.34 Two recent studies have investigated nonsurgical success rates.21,25 Gargollo et al reported 12% treatment failure due to noncompliance and an achievement of functional success at a median of 18.7 months in 18/64 sexually active patients.25 Edmonds et al studied 245 patients who started self-dilation during an average 3 days of instruction in hospital.21 These authors reported a success rate of about 95%, with 13/245 (5.3%) patients not completing the treatment program, but remained somewhat vague as to the time this required. Additionally they noted that after a substantial period without dilation or intercourse some women needed to resort to dilation again to regain the original result and that some women required lubricants for sexual satisfaction. Thus, apart from being a lengthy procedure, Frank's method of progressive dilation35 often does not provide sufficient long-term stability in neovaginal length if dilation is discontinued. In principle, we share the preference for less invasive approaches and offer all our patients the alternative of selfdilation. However, in our experience, patients nowadays are usually well informed at first presentation and often expressly wish to undergo surgical neovaginoplasty. We also share the opinion that neovagina creation, be it surgical or by dilation, is elective and best performed in emotionally mature patients who can be involved in the decision making process.1,26 At our institution, we therefore pursue a multidisciplinary approach with preoperative and postoperative evaluations by a team of specialized psychologists, as do others.21,36 The motivation for reconstruction has meanwhile become much more strongly based on the patient's desire to appear and feel a normal woman, not only anatomically25 € bus but also in terms of being “ready” for sexual activity. Mo et al37 found an impressive increase in self-confidence in 61% of women after surgical neovaginoplasty. In our experience, the typical patient profile has clearly shifted in recent years from the woman aged over 18 years and living in a committed relationship (cf. the ACOG guidelines1,26) to the post-pubertal patient without a steady partner but with a radically changed female self-perception. In our patients, the age of emotional maturity has clearly dropped to 18 years and below; before 2007 median age (range) at first presentation was 19.0 (14.5-40.7) years and has since dropped to 18.2 (15.0-19.7) years. With this trend the demands on the outcome of surgery have also changed; patients tend to opt for immediate surgical correction rather than having to diligently perform self-dilation for prolonged periods and constantly deal emotionally with their chronic condition. We therefore consider it particularly important to have demonstrated that our optimized minimally invasive technique creates a neovagina of stable length even in the absence of sexual intercourse or the wearing of a dummy and, in contrast to progressive dilation, does not require the patient to start over again after a period of abstinence.
K. Rall et al. / J Pediatr Adolesc Gynecol 27 (2014) 379e385
Conclusion
A favorable safety, tolerability and efficacy profile combined with the speed of results and reduction of psychological strain merits particular consideration of this laparoscopically assisted neovaginoplasty technique as a first-line therapeutic option. A standardized and internationally certified surgical procedure with regulatoryapproved equipment and a structured training program could advance the international acceptance and success of our technique. Controlled trials directly comparing the nonsurgical approach with our laparoscopically assisted surgical procedure are currently lacking. Nonetheless, our findings strongly suggest that this technique can be considered the method of choice in patients with vaginal agenesis seeking surgical treatment. Finally, though our technique has been refined and experience with it has accrued, it remains a complex endoscopic procedure that should be performed only by experienced surgeons at high-volume centres.9 Moreover, the management of patients with vaginal agenesis unquestionably requires a multidisciplinary approach, whether definitive treatment is surgical or nonsurgical.21 Acknowledgments
We gratefully acknowledge all patients who participated in our study and thank all hospital staff members who were involved in the care of our patients. References 1. Committee on Adolescent Health Care: Committee opinion: no. 562: mullerian agenesis: diagnosis, management, and treatment. Obstet Gynecol 2013; 121: 1134 2. Routh JC, Laufer MR, Cannon GM Jr, et al: Management strategies for Mayer-Rokitansky-Kuster-Hauser related vaginal agenesis: a cost-effectiveness analysis. J Urol 2010; 184:2116 3. Miller RJ, Breech LL: Surgical correction of vaginal anomalies. Clin Obstet Gynecol 2008; 51:223 4. Rall K, Wallwiener D, Brucker S: Laparoscopic-assisted methods for neovaginoplasty. Sex Reprod Menopause 2010; 8:15 5. Nakhal RS, Creighton SM: Management of vaginal agenesis. J Pediatr Adolesc Gynecol 2012; 25:352 6. Brucker S, Aydeniz B, Gegusch M, et al: Improvement of endoscopically assisted neovagina: new application instruments and traction device. Gynecol Surg 2004; 1:133 7. Brucker S, Zubke W, Wallwiener D, et al: [Perfecting the laparoscopic-assisted creation of a neovagina with new application instruments and a new traction device]. Geburtshilfe Frauenheilkd 2004; 64:70 8. Brucker SY, Rall K, Wallwiener D: Laparoscopically assisted neovaginoplasty. In: Nezhat's video-assisted and robotic-assisted laparoscopy and hysteroscopy. In: Nezhat C, Nezhat FR, Nezhat C, editors, (4th ed.). Cambridge, Cambridge University Press, 2013, pp 426 9. Brucker SY, Gegusch M, Zubke W, et al: Neovagina creation in vaginal agenesis: development of a new laparoscopic Vecchietti-based procedure and optimized instruments in a prospective comparative interventional study in 101 patients. Fertil Steril 2008; 90:1940 10. Wallwiener D, Becker S, Beckmann MW, et al, editors. Atlas of Gynecologic Surgery, (4th ed.).. Stuttgart, Thieme, 2014, pp 459e466
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