Human Reproduction Update, Vol.20, No.5 pp. 775–801, 2014 Advanced Access publication on June 3, 2014 doi:10.1093/humupd/dmu024

An update on surgical and non-surgical treatments for

Nina Callens1, Griet De Cuypere2, Petra De Sutter3, Stan Monstrey4, Steven Weyers3, Piet Hoebeke5, and Martine Cools1,* 1Department of Paediatric Endocrinology, University Hospital Ghent and Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 2Department of Sexology and Gender Problems, University Hospital Ghent and Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 3Department of and , University Hospital Ghent and Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 4Department of Plastic , University Hospital Ghent and Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 5Department of Urology, University Hospital Ghent and Ghent University, De Pintelaan 185, 9000 Ghent, Belgium

*Corresponding address. Tel: +32-9-332-47-28; Fax: +32-9-332-38-75; E-mail: [email protected] Submitted on March 11, 2014; resubmitted on April 24, 2014; accepted on May 1, 2014

table of contents ...... † Introduction Differential diagnosis Compromised womanhood Reproductive challenges † Plethora of vaginal reconstruction methods techniques Vaginal dilation techniques To dilate or not to dilate? † Methods: outcome studies under scrutiny † Practice informing theory Comprehensive synopsis of main outcomes Quest for the optimal vaginoplasty technique Effectiveness of vaginal dilation as first-line technique: a time-honoured practice? Pitfalls in treatment success † Theory informing practice Recommended treatment algorithm in women with vaginal hypoplasia New ideas from old concepts: vaginal dilation treatment in clinical practice † Remaining questions and future perspectives

background: In women with vaginal hypoplasia, such as in Mayer–Rokitansky–Ku¨ster–Hauser syndrome (MRKH) and in Complete Androgen Insensitivity Syndrome (CAIS), surgical vaginoplasty and non-surgical self-dilation treatments are available to lengthen the and facilitate , but the best treatment remains controversial. Vaginal dilation has been recommended as a first-line treatment, because of its less invasive character and high success rate. However, the exploration of factors associated with compliance and long-term outcome is incomplete, including whether psychological counselling needs to be embedded in treatment to maximize efficacy. It is not known if failed vaginal dilation therapy jeopardizes further surgical success outcomes, especially because in a number of these procedures ongoing vaginal dilationis required.Inaddition, if surgeryis needed,thereis alackofevidence toinform physicians regarding the optimum surgical technique to use. Also, it is unclear whether maintenance dilation therapy in case of sexual inactivity is crucial to ensure functional success. methods: In view of this ongoing debate, we performed a search of all published literature (English language only) restricted to the management of vaginal hypoplasia in patients with MRKH or CAIS from 1898 to March 2013 using Pubmed, Cochrane Library and Web of Science. Of the 6700 articles initially identified, a total of 190 studies are analysed. More specifically, by establishing the risk/efficacy profile

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(vaginal capacity, complications and long-term durability in terms of sexual function) of the different surgical and non-surgical reconstruction tech- niques, we evaluate if vaginal dilation proposed as the first-line technique is justified based on the evidence. results: When anatomical success was defined as a length of ≥7 cm and functional success as coitus, all vaginoplasty techniques yielded sig- nificantly higher success rates (.90 versus 75% after vaginal dilation), irrespective of underlying diagnosis or start vaginal length. When functional success was defined as ‘satisfaction with sex’, including non-genital sex, differences disappeared. Failed dilation therapy does not preclude ana- tomical (nor functional) success if vaginoplasty afterwards is necessary. Traction vaginoplasty seems to have the highest anatomical (99%) and functional success rates (96%), whereas both split- and full-thickness skin graft procedures and intestinal procedures have the lowest successful outcomes (83–95%). Overall, rates were significantly lower within the vaginal dilation groups when compared with the different vaginoplasty techniques. Although no randomized control data exist regarding maintenance dilation, the available evidence suggests that contin- ued dilation is needed to maintain patency in periods of coital inactivity. Despite the expectancy that the probability of further positive outcomes is maximized with psychological counselling, this could not be confirmed. conclusions: As the medical literature lacks high-quality comparative outcome studies and prospective, longitudinal studies are scarce, no evidence-based treatment guidelines can be provided. However, because of the physically low complication rate and an overall success chance of 75%, vaginal dilation as first choice treatment seems to be justified. Overall, the laparoscopic Vecchietti procedure, becoming more and more available in specialized centres, is considered an appropriate surgical option in patients who are poorly compliant and failed dilation therapy, or for those who do not want to start with vaginal dilation therapy. Future approaches need to raise a wider range of psychosexually oriented questions, elucidate the relationship between vaginal depth and satisfactory outcomes and gain additional experience concerning the format of acceptable and efficient psychological care.

Key words: vaginal hypoplasia / vaginal reconstruction / vaginal dilation / vaginoplasty / sexual function

Introduction imbalance. However, the aetiology of MRKH still remains unclear (Morcel et al., 2007). It is apparent that the clinical management of congenital disorders of sex The differential diagnosis of MRKH mainly includes 46,XY DSD, spe- development (DSD)—in which anatomical, gonadal or chromosomal cifically androgen insensitivity syndrome in which the lack of a functional sex is atypical—has been in a state of great flux, debate and controversy androgen receptor results in phenotypically normal female external geni- during the last decade (Zucker, 2002; Hughes et al., 2006). Advances in talia (Quigley et al., 1995). These women have testes, absent Mu¨llerian medical knowledge and understanding of psychosexual development, as structures and a blind short vaginal pouch due to the action of anti- well as an increased emphasis on the rights and autonomy of the individ- Mu¨llerian hormone (Sarpel et al., 2005; Hurme et al., 2009). Estimated ual, have all contributed to discussion about the role and efficacy of incidences vary according to the population studied, ranging from 1 in medical intervention (Dreger, 1998; Preves, 1998; Carmichael and 41 000–120 000 (Quigley et al., 1995; Minto, 2004). In addition, Alderson, 2004; Creighton, 2004; Liao, 2006a, b). Clinical practices vaginal hypoplasia can be associated with disorders of testosterone bio- developed to promote psychosexual wellbeingremainthe subject of crit- synthesis or other rare complex conditions affecting the urinary and ical review (Dreger, 2006). gastrointestinal tracts, such as cloacal and anorectal anomalies (Michala et al., 2007). In pubertal females, differential diagnosis can be made by assessing serum testosterone levels and karyotype analysis. Differential diagnosis Conventional transabdominal, transinguinal or transrectal ultrasonog- Patients with DSD requiring vaginal reconstruction, because of vaginal raphy, 3D ultrasonography and magnetic resonance imaging can be hypoplasia or aplasia, typically present with primary in ado- used toevaluatethe absence of the and vagina and can in individual lescence with an otherwise normal growth and development (Nakhal cases be helpful in definitively characterizing (reproductive) anatomy and Creighton, 2012). The most commonly involved condition is Mu¨ller- (American College of Obstetricians and Gynecologists (ACOG), 2013; ian agenesis or Mayer–Rokitansky–Ku¨ster–Hauser syndrome (MRKH), Hall-Craggs et al., 2013; Grimbizis et al., 2013). occurring in 1 in 4000–5000 females (Rall et al., 2010; Nakhal and Creighton, 2012). Women with MRKH have a XX karyotype and normal functioning , but an absent or rudimentary uterus and Compromised womanhood and a short vagina resulting from failed embryonic development Besides correct diagnosis of the underlying condition and evaluation for of the Mu¨llerian duct (Nakhal and Creighton, 2012). The syndrome associated congenital anomalies, an important step in the effective (i.e. vaginal hypoplasia) may be isolated (typical form, type I) but it is medical management is psychosocial counselling before any treatment more frequently associated with malformations of the ovaries and/or or intervention (ACOG, 2013). These conditions have devastating impli- renal system (atypical form, type II) and to a lesser extent systemic cations for fertility and sexual intercourse and affected women may ex- defects [Malformations Urinary, Cardiac and Skeletal (MURCS), Type perience variable levels of distress, connected to the perception of III] (Oppelt et al., 2006). In familial cases, the syndrome appears to be having a compromised womanhood and characterized by the fear of transmitted as an autosomal dominant trait with incomplete penetrance being devalued by others (Hecker and McGuire, 1977; Alderson et al., and variable expressivity, which suggests the involvement of either muta- 2004). Sensitive pacing of information is recommended in order to tions in a major developmental gene or a limited chromosomal allow young women and their family to make informed decisions about Review of surgery and dilation for vaginal hypoplasia 777 different treatment modes and a realistic adaptation to living with this limited reproductive potential for becoming a biological parent and may condition (ACOG, 2013). help them further deal with the diagnosis and its implications. In women with 46,XY karyotypes, gonadal management requires add- itional attention, with the approach varying depending on the underlying Reproductive challenges DSD and its manifestation. As a general rule, Y chromosome bearing The route has long been the sole option of family choice in mal-developed gonads that remain within the will function women with these conditions. With the advent of IVF 20 years ago, poorly from a reproductive standpoint and are at high risk for malignancy assisted reproduction technology (ART) and gestational carriers have (Cools et al., 2006). In women with complete androgen insensitivity syn- also provided fertility options in women with an ovarian reserve, such drome (CAIS), retention of gonads through puberty is acceptable in as in cases of MRKH (Edmonds, 2013). The frequent ectopic position terms of tumour risk, thus spontaneous puberty can be experienced. Al- of ovaries in these women (40%) is important to take into account for though the riskof malignancyin CAIS, especiallyatan adult age,isnot pre- egg harvesting, as they may not be amenable to transvaginal collection cisely known, it is significantly lower than in cases with dysgenetic gonads (Hall-Craggs et al., 2013). A number of small series have reported clinical (Cools et al., 2006, 2011). Recent reports challenge the need to perform rates of 17–37% (Petrozza et al., 1997; Beski et al., 2000; gonadectomy in CAIS women at all, since there have been anecdotal Brinsden, 2002; Raziel et al., 2012), with similar rates in women with reports of loss of libido following gonadectomy, concerns about long- type I and II MRKH, although the former needed fewer ampoules of term hormonal replacement and even the potential of the gonads har- gonadotrophin for stimulation and had a higher number of follicles, bouring viable germ cells that could be used for procreation with oocytes and cleaving embryos (Raziel et al., 2012). future advanced technology (Deans et al., 2012). However, as a rule, a Although many females with MRKH have complete aplasia of all (near-)complete germ cell loss has been observed in adult CAIS Mu¨llerian structures (Class U5/C4/V4 ESHRE/ESGE Classification; gonads (Cools et al., 2005; Kaprova-Pleskacova et al., 2013). In addition, Grimbizis et al., 2013), 47–84% have uterine remnants, either bi- or optimal modalities of surveillance and screening intervals for gonadal unilateralrudimentary horns with cavity(Class U5a),or uterine remnants tumours remain to be defined (Cools et al., 2014). without cavity (Class U5b; Oppelt et al., 2012; Grimbizis et al., 2013). The presence of a horn with cavity containing functional (2–7%) is clinically important, because it is combined with cyclic pain Plethora of vaginal and/or haemato-cavity, necessitating treatment (ACOG, 2013). Con- reconstruction methods servative surgical management remains controversial and the possibility Sexually experienced patients may present with natural dilation of the of conception after such an operation poses a unique therapeutic chal- vaginal dimple and occasionally require no additional treatment. Enlarge- lenge (Deffarges et al., 2001). Total laparoscopic resection of the ment procedures for vaginal hypoplasia in non-sexually experienced uterine remnants is typically recommended, but successful women include surgical vaginoplasty and non-surgical dilation therapy have been achieved by uterine and cervical reconstruction, creation of (Deans et al., 2010). Tables I and II, and Fig. 1 provide an overview of a neovagina and placement of an uterovaginal conduit (or vaginal– the variety of techniques and their main advantages and disadvantages uterine fistula tract; Hampton et al., 1990; Thijssen et al., 1990; Deffarges (based on Ismail et al., 2006; Michala et al., 2007; Schober, 2007; et al., 2001; Grimbizis et al., 2004; Doyle and Laufer, 2009). Although the Thomas and Brock, 2007; Gargollo et al., 2009; Deans et al., 2010; overall success rate of these reconstructive proceduresis 60% (Grimbizis Ozkan et al., 2011). et al., 2004), they are frequently complicated by fibrotic stenosis, recur- rent obstruction and sepsis (Rock et al., 1995; Casey and Laufer, 1997), making , as well as the use of ART and a gestational carrier Vaginoplasty techniques currently a safer option. Dupuytren (1817, see Dupuytren, 1835) and later Amussat (Amussat, As most women without functional uteri still feel very strongly about 1835) are frequently mentioned as being the first proponents of surgical being pregnant (Edmonds, 2013) and encouraged by the results of correction, which involved creating a perineal pouch between bladder uterine auto- and allotransplantation and experiments resulting from off- and with strong digital pressure and then packing the cavity spring from a transplanted uterus in animals (Ramirez et al., 2011; Wran- with linen (Minto and Creighton, 2003). Wharton (1938) and Counsellor ning et al., 2011), the role of human uterine transplantation has been (1948) subsequently refined this technique by using a mould covered further investigated in the last decade (Bra¨nnstro¨m, 2013). Since the with a rubber sheath to hold the perineal pouch open, which allowed first unsuccessful attempt in 2000 (Fageeh et al., 2002), at least nine spontaneous epithelization to take place (Wharton, 1938; Counsellor, verified transplants of a uterus have been carried out (Del Priore and 1948). It became quickly clear that the mould had to be used for several Gudipudi, 2014), but have yet to result in a viable pregnancy and delivery hours every day to reduce vaginal strictures due to scar formation. Per- of a healthy near-term baby. Most notably, the transplant reported from manent dilation to prevent stenosis of the neovagina (3–6 months or Turkey around 2012 sustained a transferred embryo until 9 weeks longer) was further insisted upon by Banister and McIndoe (1938). They (Erman Akar et al.,2013). The need for the use of immunosuppressive popularized a technique, first pioneered by Abbe (1898), in which split- agents and their teratogenic potential for fetal growth remains a major thickness skin grafts taken from the anterior surface of the thigh or issue, and has an ethical dimension as the risk-benefit ratio in this type of buttock were inserted over the mould, after dissection of a space surgery is different from life-saving forms of organ transplantation between rectum and bladder (Abbe, 1898; McIndoe, 1950). There (Brosensetal.,2013;Caplan,2013).Until furthersuccessfuldevelopments were problems with fistula formation secondary to the use of the mould in the field, the discussion on ART and gestational carriers is appropriate and the need for lubrication as the skin graft tended to be rather dry (Mac- and should allow these young women with MRKH to understand their Dougall and Creighton, 2004). Numerous modifications of the mould 778 Callens et al.

Table I Vaginal reconstruction methods.

Non-surgical 1. Simple pressure (Frank, 1938) 2. Pressure from a bicycle stool (Ingram, 1981) 3. Regular coitus (Serment et al., 1969) Surgical 1. Surgical creation of a neovaginal space between bladder and rectum 1.1 Simple reconstruction with insertion of form, without grafting (Wharton, 1938; Counsellor, 1948) 1.2 Simple reconstruction with insertion of inlay graft over form (a) Split-thickness skin graft (Abbe, 1898; Banister and McIndoe, 1938) (b) Full-thickness skin graft and Flap vaginoplasty Simple and thigh flaps (Graves, 1921) Tubed pedicle flap from thigh (Frank and Geist, 1927) Pedicled bladder flap (Krzeski and Borkowski, 1983) Gracilis myocutaneous flaps (McCraw et al., 1976) and transpelvic rectus abdominis myocutaneous flaps (Tobin and Day, 1988): † Perineal artery axial flap of Hagerty (Hagerty et al., 1988) † Pudendal thigh flap vaginoplasty (Singapore flap; Wee and Joseph, 1989; Woods et al., 1992) † Free flap graft from scapula (Johnson et al., 1991) † Vulvoperineal fasciocutaneous flap (the Malaga flap; Giraldo et al., 1996) (c) Allogenic tissue: Amnion (Brindeau, 1934), epidermal sheets (Carranza-Lira et al., 1999) (d) Peritoneum (Davydov, 1969; Rothman, 1972) (e) Artificial grafts: Interceed barriers (Jackson and Rosenblatt, 1994), silicone membrane with incorporation of recombinant fibroblast growth factor (Noguchi et al., 2004) (f) Tissue expanders (Lilford et al., 1988) (g) Autologous in vitro-cultured vaginal tissue (Panici et al., 2007), autologous buccal mucosa (Lin et al., 2003) 2. Bowel vaginoplasty 2.1 Ileum (Baldwin, 1904), sigmoid colon (Ruge, 1914) or caecum and ascending colon (Kun, 1972) 2.2 Rectum (Popoff, 1910) 2.3 Free jejunal autograft (Emiroglu et al., 1996) 3. Vulvavaginoplasty (Williams, 1964) 4. Surgical traction 4.1 Vecchietti procedure (Vecchietti, 1965) 4.2 Balloon vaginoplasty (El Saman et al., 2007; Darwish, 2010)

material (soft, semi-rigid or rigid) or shape, and improvements in post- where an external pouch is created by suturing the labia majora to form operative care have been suggested to reduce the incidence of complica- a short vertical ‘vagina’, which can despite its unnatural axis be further tions (Golditch, 1968; Ulfelder, 1968; Khanna and Khanna, 1982). expanded through use or intercourse (Williams, 1964).Mostof However, marked scarring at the donor site and vaginal stenosis or con- these techniques can suffer from visible scars and keloid formation, and tracture, particularly at its distal end, remains a problem. lack of vaginal lubrication and regrowth in the neovagina, which can The problem of contraction of the vagina post-operatively was thought become stenosed (Ismail et al.,2006). In addition, a risk of squamous to be avoided with skin flap vaginoplasty and the use of full-thickness skin cell carcinoma has been reported (Creighton, 2004). grafts from labia minora or thighs, first described by Graves in 1921, with In an attempt to overcome some of the disadvantages of the skin graft disappointing results (Graves, 1921; Frank and Geist, 1927; Falls, 1940; techniques, a variety of other tissues have been used to line new . MacDougall and Creighton, 2004). The technique was modified by Bhon- In 1934, Brindeau described a novel approach using chemically pro- sale and Sheares wholined the posterior wallofthe rectovesical cavitywith cessed and sterilized freeze-dried human amniotic membranes that are a single skin flap dissected from the vaginal dimple, retaining its attachment considered immunologically inert and thus have low risk of graft rejection at the perineum (Bhonsale, 1956). Fortunoff utilized a U-shaped skin flap (Brindeau, 1934). It has the advantage that no graft site is required, (Fortunoff et al., 1964). Other skin flaps used included rotated buttock thereby leaving no external scars for the patient to have to tolerate. flaps (Hendren and Donahoe, 1980), and myocutaneous flaps, involving However, it is important that the use of this material is properly governed the gracilis muscle, a vulvobulbocavernosus myocutaneous graft (Hatch, and that donors are suitably screened for transmittable diseases 1984) and rectus abdominis muscle, which also have been used with (Ashworth et al., 1986). Various other authors have reported on the success in vaginal deficiencies following neoplasms or traumas (McCraw use of artificial or biological materials, including buccal mucosa (Lin et al.,1976; Tobin and Day, 1988). Pudendal thigh flaps (Wee and et al., 2003), artificial dermis (atelocollagen sponge) and with use of Joseph, 1989), free flap graft from the scapula (Johnson et al.,1991; basic fibroblast growth factor to accelerate epithelization (Noguchi Hockel, 2003) and vulvoperineal fasciocutaneous flaps (Giraldo et al., et al., 2004), oxidized cellulose (Sharma et al., 2007), and autologous 1996) have been used as well. Williams preferred vulvavaginoplasty, in vitro-cultured vaginal tissue (Panici et al., 2007). Pedunculated Review of surgery and dilation for vaginal hypoplasia 779

Table II Advantages and disadvantages of different vaginal reconstruction methods.

Technique Advantages Disadvantages ...... 1. Dilation method (Frank/Ingram) Non-invasive Motivated and mature patients required (low compliance) No hospitalization Time-consuming Psychological advantage of the subject being in Discomfort and constant reminder of difference control Awkward sitting on an Ingram stool Preserves vaginal tissue Manual fatigue, boring and unability to create enough perineal pressure Cost–effective, inexpensive (Frank) Minimal morbidity and complications Limited success in younger patients (,18 years) After failed treatment, the option still exists to Long-term dilation needed proceed to surgical neovaginal creation Poor results with skin dimple Increased risk of vaginal 2. Vecchietti procedure Preserves vaginal tissue Pain and therefore need for strong analgesia during daily tightening Laparoscopic approach minimally invasive Post-operative self-dilation required No excessive mucus production or vaginal Significant potential complications because of the limited stenosis retrovesicorectal space into which the traction threads need to be placed Pliable tissue required (not recommended in the presence of scars from previous reconstructive ) Increased risk of vaginal prolapse 3. Intestinal vaginoplasty (sigmoid Lubricated segment with reliable blood supply Requires laparotomy and bowel anastomosis colon, ileum, jejenum) Grows with the patient (advantageous for Prolapse 3–8% younger children) Excessive discharge No scarring Complication rate of 16–26% (post-operative ileus, bowel obstruction, No dilation needed diversion, ulcerative colitis, adenocarcinoma) Low rate of stricture Can be performed with previous extensive surgery 4. Davydov procedure Suitable for women who had previous pelvic Decreased lubrication (peritoneum) surgery Potential for bladder and rectum injury Lack of granulation tissue Potential infections and prolapse No scar formation Post-operative dilation needed

5. McIndoe procedure Vaginal approach avoids laparotomy Post-operative dilation needed (split-thickness skin grafts) No bowel anastomosis High rate of graft contracture and neovaginal stenosis High rate of graft take Disfiguring scar at the donor site Low rate of prolapse Potential of graft infection Lack of lubrication Risk for squamous cell carcinoma Complication rate up to 14% Mcindoe (modified) Reduction of the occurrence of chronic Risk of allograft rejection Allogenic tissue granulation tissue Risk of transmission of infectious diseases Autologous vaginal mucosa No donor site scarring Morbidity connected with the removal of the mucosa No stenosis Long time needed for the meshed vagina to colonize the entire No vaginal dryness neovagina 6. Full-thickness skin grafts Good pelvic support following exenteration High rate of prolapse and flap loss (gracilis) Myocutaneous/fasciocutaneous Can be done at time of exenteration Skin appendages flaps Good blood supply, low infection rate Deficient lubrication Pudendal thigh flap Flap incision incorporated into laparotomy site Disfiguring scar at the donor site Labia minora flaps Pedicled tissue form better than free-tissue, Wound site infection Malaga flap because no dilation required Hair regrowth in the neovagina Singapore flap No skin graft with pudendal thigh flaps Scapula flap 7. Williams Vulvavaginoplasty (flaps Simple surgery Hair bearing skin from labia majora) Non-invasive Sexual contact is difficult due to angle of the external vagina Insufficient vaginal depth, no feeling of penetration Wound opening, haematoma, trauma infection 780 Callens et al.

Figure 1 Vaginal reconstruction techniques. Different vaginal reconstruction techniques. (A) Vecchietti technique: pressure is applied on the vaginal dimple by an acrylic olive connected by threads that pass through the potential neovaginal space, are guided preperitoneally along the abdominal wall and exit via the anterior abdominal wall where they are connected to a traction device. The threads are tightened daily. (B) Williams’ procedure: the Labia majora are used to line an external pouch formed by a U-shaped perineal incision. (C) Bowel vaginoplasty: a short segment of bowel (ileum or sigmoid colon) is isolated. The mesentery of the bowel segment is extensively dissected upwards in order to connect this neovagina with minimal tension. (D) McIndoe procedure: split-thickness skin grafts are obtained from the thighs or buttocks and adapted around a mould to line the dissected space between rectum and bladder. (E) Davydov procedure: A transverse incision is made below the ; peritoneum is dissected off the rectum, bladder and side wall of the pelvis using fingers, and developing a space; the canal is tightly packed and an incision is made in the peritoneum over the pack; stay sutures in the peritoneum are used to pull a tube of peritoneum towards the perineum; the edges of the peritoneal tube are sutured to the skin of the introitus and the abdominal end of the tube is closed. (F) Vaginal dilation techniques: Frank vaginal of different sizes increasing in length and width, and the Ingram stool method whereby patients are instructed to sit on bicycle seat-shaped stool for short periods with a vaginal dilator held in position in or at the vaginal opening to stretch the vaginal tissue.

bladder wall flap (Krzeski and Borkowski, 1983) and peritoneum from attachment of the peritoneum to the created introitus and finally the Douglas pouch (i.e. Davydov procedure) have been used in a com- closure of the neovaginal vault with purse-string suture (Davydov, bined abdominoperineal approach (Davydov, 1969; Rothman, 1972). 1969; Davydov and Zhvitiashvili, 1974; Ward et al., 1998). The Davydov developed a three-stage operation involving dissection of the claimed advantage of this technique by the authors is the lack of granula- rectovesical space with abdominal mobilization of the peritoneum, tion and scar formation. The procedure was modified to a laparoscopic Review of surgery and dilation for vaginal hypoplasia 781 approach, having the advantages of less bleeding and post-operative pain inward into the introital region (Frank, 1938; Lee, 2006). Interestingly, in addition to shorter hospital stay, faster recovery and better cosmetic for almost 40 years this technique was only infrequently used, although outcome (Soong et al., 1996). These merits are specifically important in his series and the majority of case reports suggested that this approach adolescent patients in whom cosmesis may be very important and a was one of promise (Holmes and Williams, 1940; Steinmetz, 1940; faster recovery would allow for earlier return to school (Pandis et al., Campbell, 1941; Marshall, 1944; TeLinde, 1946; Williams, 1957). In 2009). 1981, Ingram modified the technique based on presumed inconve- The use of bowel segments, reported as early as 1892 by Sneguireff, niences of Frank’s method, such as sheer fatigue of the hands and has gained enormous popularity for vaginal reconstruction in DSD and fingers, the need to squat, and the inability to perform other productive is also widely used following for (Minto and activities during the procedure. He inserted dilators into the saddle of a Creighton, 2003). Because of the high morbidity and mortality rates bicycle stool and had the patients sit astride this to gently create perineal when ileum segments were first used by Baldwin in 1904, the technique pressure (Ingram, 1981). The seat was later modified by Lee (2006) and was largely abandoned until 1961, when the use of a sigmoid loop was Lankford and Haefner (2008). described (Baldwin, 1904; Popoff, 1910) and later the use of cecum and jejenum (Kun, 1972; Emiroglu et al., 1996). A laparoscopic approach To dilate or not to dilate? has been carried out since 1996 (Ohashi et al., 1996), but the procedure Non-surgical vaginal dilation has been put forward by ACOG in 2002 as a is still most frequently performed through a laparotomy. Overall, the first choice treatment, because it is a patient-driven technique that is easy main advantages of this operation are said to be the lack of shrink- to perform, cost–effective and safe (Gargollo et al., 2009; Routh et al., age—with no long-term vaginal dilation needed—and the natural lubri- 2010; ACOG, 2013). Meanwhile, the concept of surgery for DSD con- cation provided by the mucous production that obviates the need for ditions became increasingly controversial and led to a call in some quar- artificial lubricants and decreases the risk of dyspareunia (Gatti et al., ters for a moratorium on genital surgery as long as long-term data are 2010). Greatest concerns surrounding this operation are bleeding or unavailable (Schober, 1998; Creighton, 2004). Successful neovaginal cre- copious and smelly vaginal discharge, which also may mask adenocarcin- ation by dilation obviates the need for major surgery in most patients, oma (Creighton, 2004; Davies et al., 2005). Diversion colitis may also while those not achieving adequate vaginal length with dilation can still occur, possibly due to a lack of short-chain fatty acids normally present undergo vaginoplasty as a second-line intervention. It is expected that in colonic contents and required for mucosal integrity, but is less of a only 85% of women will achieve a functional vagina without a surgical ap- problem with ileum than with colon segments (Minto and Creighton, proach (Edmonds, 2000). Reasons for failure, however, need further 2003). clarification. Moreover, it is not known if failed vaginal dilation therapy Finally, other surgical techniques are based on passive traction rather jeopardizes further surgical success outcomes, especially because in a than dilation. In 1965, Vecchietti proposed a device permitting an number of these procedures ongoing vaginal dilation is required. In add- upwards traction on the retrohymenal fovea by an acrylic olive and the ition, if surgery is needed, there is a lack of evidence to inform physicians creation of a neovaginal space in 1 week, this without the use of extrane- regarding the optimum surgical technique to use. Also, the extent to ous tissue (Vecchietti, 1965, 1979). The laparoscopic adaptation pro- which psychological interventions are needed to maximize treatment posed in 1992 offers enhanced speed and ease (Gauwerky et al., success needs to be further elucidated. In view of this ongoing debate 1992). The complication rate including bladder and rectal wall injury is and in order to provide a comprehensive, non-biased reference tool, reported to be low (Fedele et al., 2008b). However, a more common the available literature on the various approaches to vaginal reconstruc- drawback for this procedure is the pain resulting from the sustained trac- tion is reviewed below. The anatomical outcomes, referring to vaginal tion which necessitates a hospital stay throughout the whole traction capacity, and functional outcomes, referring to sexual activity levels process (Deanset al., 2010). Balloon vaginoplasty is based on the same and successful coital or non-coital sexual activities, of the current techni- principle, however, traction and dilation of the vaginal dimple is ques reported hitherto are discussed. exerted by a with an inflated balloon (El Saman et al., 2007; Darwish, 2010). The authors claim that the main advantage of this technique is the neovaginal width, which can be manipulated accord- Methods: outcome studies under ing to balloon distension. scrutiny A search of all published literature restricted to the management of Vaginal dilation techniques vaginal hypoplasia in patients with MRKH or CAIS since 1898 up to Because there is pliable perineal skin between the urethra and anus in March 2013 was conducted using Pubmed, Cochrane Library, Web of women with vaginal hypoplasia, coitus has been shown to lead to an in- Science, as well as hand searches for relevant articles not initially identi- crease in vaginal depth and width (Masters and Johnson, 1966; Serment fied using the search parameters (MRKH, CAIS, vaginal agenesis, vaginal et al., 1969; D’Alberton and Santi, 1972; Moen, 2000). In young women hypoplasia/aplasia plus vaginoplasty,vaginal dilation, (non-)surgical man- with an understanding and cooperative partner, excellent results can be agement, neovagina, vaginal reconstruction). Studies were restricted to obtained with little intervention from medical professionals (Lappo¨hn, systematic reviews, RCTs, controlled clinical trials and observational 1995). When women do not have a partner or vaginal depth does not studies that provided data on surgical or non-surgical indications, ana- increase by coital dilation, supportive treatment with dilators has been tomical success, intraoperative and short- and long-term complications, proposed. and long-term sexual function and wellbeing if available. Single case Frank described in 1938 the use of Pyrex tubes of gradually increasing reports, non-English manuscripts, and manuscripts solely on patients sizes (0.8, 1.5 and 2.0 cm in diameter) to force the mucous membrane born with ambiguous genitalia (e.g. congenital adrenal hyperplasia) or 782 Callens et al. associated urogenital (including lower urinary or anorectal) anomalies 223, 229). Tables III–VI summarize the outcomes of the various surgical were excluded. and non-surgical proceduresand influencing factors regarding anatomical Approximately 6700 articles were identified, of which 190 articles and functional success, clarified for each of the studies. were included. The studies were carried out across all continents. In the majorityof the studies, no information wasprovided on the indication for the particular treatment offered, there was no blinding of either the Practice informing theory patients or the clinicians, with only one study having randomized care Establishing the risk/efficacy profile of the different surgical and non- (Cao et al., 2012). Because of the diverse range of details available surgical techniques, we evaluate if vaginal dilation, proposed as first-line with mixed information and follow-up, the use of the recommended technique is justified on an evidence base. methodology from the preferred reporting items from systematic reviewsand meta-analyses (PRISMA) checklistfor meta-analyses was un- Comprehensive synopsis of main outcomes fortunately not possible (Moher et al., 2009). We nevertheless Anatomical success and complications attempted to synthesize and dichotomize dataforanalysisusing statistical Anatomical success, referring to an adequately sized vagina, seems to be software. When different vaginal reconstruction regimens were separ- in most studies defined on the basis of two (related) parameters. The first ately discussed in the studies included, the results were separately is vaginal length, agreed upon to be at least 6 cm. The second is an handled (Supplementary data, Tables SI–SIII, references 13, 23, 33, absence of complications (and in particular contractures affecting 35, 41, 42, 44, 46, 49, 102, 108, 126, 164, 171, 194, 202, 204, 227, vaginal length, or scar formation), considered to be associated with acos- 268, 287, 311, 312, 328). For analysis purposes, the surgical options metically pleasing result (in the rule according to the clinician’s perspec- were divided into seven major types: (i) vaginoplasty without grafting tive). Reference values for normal vaginal length were previously (i.e. Wharton procedure) (11, 41, 46, 51, 111, 202, 206, 279, 286, described to be 7–13 cm (mean 9.25 + 1.56 cm; Lloyd et al., 2005). 314, 319); (ii) McIndoe procedures (7, 11, 12, 17, 35, 38, 41, 46, 60, Non-surgical vaginal dilation treatment has been shown to normalize 72, 97, 98, 102, 108, 120, 121, 126, 140, 153, 164, 171, 173, 174, vaginal length in at least 75% of women, irrespective of karyotype or 179, 186, 204, 211, 216, 243, 244, 259, 268, 275, 282, 283, 287, 291, underlying diagnosis. However, when anatomical success was defined 297, 300, 320, 327, 328); and modified procedures [amnion (10, 24, as a length of ≥7 cm, all vaginoplasty techniques yielded significantly 82, 114, 126, 171, 229, 235, 277), absorbable adhesion barrier (85, higher anatomical success rates (.90 versus 78% after vaginal dilation). 163, 230, 285) and buccal mucosa (196, 334, 335)]; (iii) skin flap proce- In contrast, intratreatment complication rates (i.e. rectal, urethral or dures, including myocutaneous/fasciocutaneous flaps (130), pudendal bladder injuries, haemorrhage), as well as short- and long-term post- thigh flaps (3, 225), full-thickness skin grafts from groins/buttock (4, operative complication rates [in the short-term: Infection (including 101, 295), labia minora flaps (22, 110, 158, 254, 256, 308) or a mix of ), haematoma, anastomotic leak; in the long-term skin flap techniques (304); (iv) Vulvavaginoplasty (i.e. Williams proced- prolapse, stenosis, stricture or contracture, scarring, vaginal discharge, ure) (46, 64, 108, 164, 239, 323, 324); (v) peritoneal vaginoplasty (i.e. bowel obstruction, granulation tissue, hair regrowth, rectovaginal or Davydov procedure) carried out laparatomically (75, 76, 222, 294, vesicovaginal fistulae, graft necrosis] were significantly lower within the 315) or laparoscopically (8, 23, 44, 70, 107, 129, 137, 197, 200, 289, vaginal dilation series when compared with the published surgical 336); (vi) bowel vaginoplasty with use of sigmoid colon, cecum or series. Main complications in the vaginal dilation group were urinary com- ileum (14, 35, 36, 39, 41, 44, 46, 49, 53, 69, 81, 92, 109, 118, 119, plaints and infrequent pain and bleeding (≤1%). Similar complications 127, 132, 134 147, 148, 149, 159, 170, 176,199, 203, 207, 237, 238, and rates were found with use of traction vaginoplasty techniques, 240, 249, 257, 260, 263, 292, 302, 305, 307, 318, 332, 333, 335), with the exception of intraoperative bladder trauma (2%) being more jejenum (245, 274) or rectosigmoid (84, 188, 231) and (vii) Traction va- surgery-prone. Complications of the majority of surgical techniques in- ginoplasty, consisting of the Vecchietti technique (23, 26, 33, 34, 66,104, volving a dissection between the rectum and bladder were intraoperative 105, 112, 125, 128, 166, 172, 175, 183, 311, 312) or balloon traction (71, rectal or bladder perforation (1–4%) and short- and long-term urinary 93, 94). Five studies reportedthe outcomes of different vaginoplasty pro- tract infections (4–7%), vaginal strictures, contractures or stenosis cedures combined (13, 42, 194, 227, 309). Seventeen studies also spe- (4–9%), and vesicovaginal or rectovaginal fistulae (1–3%). In the case cifically mentioned the sexual long-term outcomes in women without of , extra complications included (partial) necrosis of the treatment (with or without coitus) (42, 68, 185, 194, 223, 257, 284, graft (1–3.5%) and hair growth in the neovagina (1–6%). Peritoneal va- 328) or after mixed treatment regimens (dilation, surgery, coitus or no ginoplasty yielded neovaginal granulation tissue (9%). Persistent dis- treatment) (54, 143, 168, 177, 185, 220, 228, 326). Lastly, vaginal dilation charge (3%) and vaginal prolapse (3%) were only apparent after bowel studies are reviewed (5, 13, 30, 42, 46, 49, 59, 91, 102, 116, 122, 160, vaginoplasty. In general, reported complications rates were higher in 161, 164, 185, 194, 202, 204, 215, 221, 227, 233, 265, 266, 268, 287, studies where previous treatment (surgery or dilation) had failed, and 311, 313, 325, 329) (Fig. 2). even higher after surgery as a first-line treatment compared with To assess diagnosis-related success rates, we included in a separate after dilation for most main complications associated with the respective analysis only studies in which the diagnosis of the participants was speci- techniques. fied as either 46,XX MRKH (n ¼ 151 studies) or 46,XY disorders of tes- tosterone biosynthesis or action (mainly CAIS) (n ¼ 22 studies) (10, 12, 42, 59, 93, 94, 102, 118, 121, 125, 127, 161, 173, 199, 220, 223, 229, Functional success 257, 309, 326, 328, 329), including nine studies in which there was a There is more variability regarding the definitions of functional success, mix of 46,XX and 46,XY, but differences between the two groups of although most seem to include the notion of ‘full genital performance women were separately discussed (10, 121, 125, 127, 161, 173, 199, during heterosexual intercourse as the essence of sexual functioning’ Review of surgery and dilation for vaginal hypoplasia 783

Figure 2 Literature review of the management of vaginal hypoplasia. *In some reviewed studies the outcomes of different treatment modalities were separately discussed and as such counted as separate studies. Note: See Supplementary data, Tables SI–SIII for numbered references. 784

Table III Summary of vaginal surgery studies.

Traction Intestinal vaginoplasty Peritoneal vaginoplasty Vulvavaginoplasty Skin flap Modified McIndoe McIndoe procedure Vaginoplasty without vaginoplasty vaginoplasty procedures grafts ...... N patients 837 912 393 286 171 154 1720 209 Diagnosis 98% MRKH 85% MRKH 98.5% MRKH 100 % MRKH 83% MRKH 96% MRKH 92% MRKH 88% MRKH 2% CAIS 8.3% AIS 1.5% MRKH or AIS 8% vaginal agenesis 2.6% AIS 4.3% AIS 1.5% AIS 6.7% other (e.g. CAH, mixed and small uterus 1.4% cervicovaginal 2.1% male or female 8% vaginal agenesis with GD) 4.5% trauma (e.g. agenesis pseudohermaphroditismb functioning uterus Note: Excluding (41; 46)a oncological 0.7% with 2.5% other (chromosomal resection) functional uterus anomalies, male 1% AIS 0.9% uterovaginal atresia )b 3.5% Note: Excluding (41; 97; Note: Excluding (41; 46; (mixed GD or 46; 275; 11; 186; 151)a 11)a CAH) Anatomical 99 95 92 97 91 96 83 93 success (%) Definition ≥6 cm, except ≥10 cm in Adequate or good anatomical ≥6 cm: 82% (114; 70; 129; Vagina of normal ≥7 cm: 100% (22; Normal epithelization of ≥7 cm: 89% (211; 300; No contractures: 91% (112) result with no contracture or 197; 107; 44) length and caliber, 110; 295; 4; 304) the vagina and ≥7 cm for 72; 102; 171; 174; 12) (319; 286; 51) shrinkage: 94%(207; 35; 41; 46; ≥8 cm : 100%(75; 294; 76; mean vaginal length of Sufficiently amnion procedures: 97% ≥8 cm: 92% (151; 173; Max 25% contracture of 132; 274; 36; 318; 149; 302; 200; 137) 12 cm (64) or spacious: 70–95% ≥6 cm for interceed 204) vaginal space’: 50% (46) 118; 249; 53; 14; 92; 49; 305) Complete epithelization of the between 7.5–9.5 cm (101; 158) procedures: 94% ≥10 cm: 83% (186; 243; ‘Normal’ vaginal depth’ Cosmetically pleasing: 96% neovagina: 100% (23) (239) Fine cosmetic ≥8 cm for buccal mucosa 7; 244) (≥7 cm) (206; 314; 279; (263; 81) No shrinkage: 100% (336) result with natural procedures: 100% Max 25% contracture: 202; 111): 96% .7 cm: 100% (69) (100%) angle: 100% (132; 82% (35; 41; 97;268; ‘Good/adequate’: 71.5% .10 cm: 100% (333) Not further specified: 97.5% 256; 3) 11;282) (11; 41) .12 cm 100% (119; 199; 39; (315; 289) No scar and ‘Normal’ vagina: 33– 84;238; 44) polypoid formation 100% (320; 164) .15 cm: 100% (245; 332; 335) or contracture ‘Good’ or ‘adequate’ Note: NR in (188; 292; 148; (308; 225; 254): result: 89% (108; 46; 38; 237; 134; 231; 240; 170; 307; 63–92% 17; 291; 297) 260; 176; 203; 257) Successful take of the graft: 96% (61; 153; 282; 120) Main Intraoperative Intraoperative Intraoperative Intraoperative Intraoperative Intraoperative Intraoperative Intraoperative intraoperative Rectal or bladder injury Rectal, urethral or bowel injury Rectal, urethral or bladder None None Hemorraghe: 1.3% Hemorrhage: ,1% Hemorrrhage: 1.9% complications: 1.8% ,1% injuries: 3.8% Rectal or bladder injury: Rectal perforation ,1% Bowel injury: ,1% proportion of Hemorrhage: ,1% Hemorraghe: 1% Hemorraghe: None 1.9% patients Note: Bladder perforation was more common in studies in which women had previous failed surgery (9 versus 1.6%), but not other complications Callens tal. et eiwo ugr n iainfrvgnlhypoplasia vaginal for dilation and surgery of Review Post-operative Post-operative Post-operative Post-operative Post-operative Post-operative Post-operative: Post-operative Infections: 2.1% Introital stenosis: 9.5% Neovaginal vault granulations: Woundopening: 3% Vaginal narrowing Urinary tract infections: Vaginal, urinary tract and Vaginal contractures or Vaginal synechiae ; Mucosal prolapse: 3.1% 8.7% Protruding : 1% and scar formation: 4.5% graft infections : 7.3% strictures: 8.6% Hematuria; Neccrosis: Vaginal discharge: 2.9% Strictures, stenosis or Haermatoma; 5.8% Strictures: 3.9% Strictures and Rectovaginal or Dehiscence; Fisttulae; Infection: 2.3% contracture: 5.1% infection: ,1% Hair growth: 5.8% Only in amnion group: contractures: 4.9% vesicovaginal fistulae: 3.3% Stenosis: ,1% Bowel obstruction: 1.2% Rectovaginal or vesicovaginal Note:No (Partial) necrosis of Rectal injury: 2% Fistulae: 2.4% Note: Complications were Haematoma; Diversion colitis; fistulae: 1% complications were the graft: 3.5% Labial inflammation: 3% Granulation tissue: 1% only reported in studies in Ileus, Fistulae; Abcess ,1% : 1% reported in studies in Fistulae: 2.3% Only in buccal mucosa Total or partial graft loss ; which a previous Note: Mortality due to bowel Urinary retention: 1% which women had Infection: 2.3% group: Hemorraghe: 9.5% Expulsion of the vaginal procedure (vaginoplasty or obstruction or heart failure Haematoma; Fever and abcess; previous failed dilation Note: No difference Note: Urinary tract stent; Urinary dilation) had failed, after occurred in n ¼ 5, in two older Persistent discharge; therapy in complications infections were higher in incontinence; keloid; both short-term (,6m) studies (35; 237). Intestinal Abdominal migration of mould rates was observed studies with previous vaginal discharge; and long-term follow-up obstruction only occurred in ,1% between the treatment (after failed condyloma; women who had had previous Note: In those studies in which different skin flap surgery 12.5%, after prolapse:,1% surgery. In studies in which previous surgery had failed, techniques (labia dilation 8 versus 3% after Note: Studies in which women had previous surgery, complications of stenosis, minora flaps, no previous treatment), women had failed surgery higher stenosis and discharge discharge and fistulae were gracilis but no differences were reported an equal amount complications (9 and 3%) were higher (respectively 9 versus 1, musculocutaneous found regarding strictures of strictures (5.4%) and reported, compared with 3 versus ,1% and 4 versus flaps, (respectively, 6.3% and fistulae (2–3%), but more studies without previous ,1%) fasciocutaneous 5.4%, versus 6.6%) urinary tract and vaginal surgery (4% and 1%). Prolapse flaps, pudendal infections (11 versus complications were the same thigh flaps, and full- 3.6%) compared with (3%) thickness skin graft) studies in which women Fistulae were only did not have surgery reported in studies before. In studies with with previous failed failed vaginal dilation surgery, before surgery, 3% of complications of strictures were reported, necrosis and vaginal and urinary tract narrowing were infections and fistulae also higher were present in (respectively 9 respectively 2 and 3.5% versus 1.6% and 4.5 versus 2.4%) Proportion of 0.4% (33; 34; 66) 3 % (35; 147; 302; 109; 53; 260; 1.5% Dilation under anesthesia 0% 1% (223) 0.6% (114) 3.7% (35; 318; 41; 97; 11% (11; 317; 111; 41) patients with 0.4% Additional dilation 148; 176; 238; 231; 84) for not complying with dilators 185; 108; 121; 102; 170; Note: the majority (77%) repeat under anesthesia (33) 1.2% Dilation under anesthesia (315; 129) 98; 38; 11; 7; 326) already had previous vaginoplasty (251; 49; 188) surgery Sexual activity 96% 70% 88% 93% 82% Note: with 81% (Amnion: 78% 83% 100% wide range: 0–33% Interceed: 97% Note: .75% sexually in (110; 130; 254) Buccal mucosa: 62%) active in all studies, except to .30 % (22; 295; in (320; 216; 97; 61; 121; 308; 4; 256) and 102; 173) 100% in (304; 225; 3) Functional 96% 90% 93% 95% 93% 97% (Amnion: 98%, 89.5% 96% success Interceed: 93%, Buccal mucosa: 88%) Continued 785 786 Table III Continued

Traction Intestinal vaginoplasty Peritoneal vaginoplasty Vulvavaginoplasty Skin flap Modified McIndoe McIndoe procedure Vaginoplasty without vaginoplasty vaginoplasty procedures grafts ...... Definition Satisfactory intercourse Satisfactory intercourse Satisfactory coitus: 89.7% (222; Satisfactory Satisfactory coitus: Pleasurable sexual Satisfactory sexual Satisfactory intercourse without dyspareunia: 96% without difficulties: 90%, (41; 76; 315; 289; 200; 107; 336; intercourse: 95% (108; 91% (22;130; 304; intercourse, without intercourse (no Satisfactory (322) Satisfaction with non- 46; 318; 200; 148; 302; 274; 137; 44; 23) 46; 239) 225; 3) dyspareunia and dyspareunia), without coital activities and 109; 188; 291; 134; 249; 53; 69; Normal heterosexual Intercourse without Adequate erotic lubrications problems, and partner complaints (164; pleasure: 100% (183; 34) 159; 176; 245; 335; 170; 332; relationships: 98% (75; 294) dyspareunia or vaginal sensation: 100% validated questionnaire 173) nor differences with Satisfying marriage or ‘very 49; 44; 333; 92) Same FSFI scores as controls: dryness : 94% (225; 254) scores comparable to a control group (259) good quality of sexual Married sex life: 100% (207) 90% (70; 129; 197; 23). Satisfactory Satisfactory sex life controls (85; 114). ‘Normal or successful sex relations’ (311; 112): 55– Satisfactorysexual activity: 85% Note: Only in one study results intercourse without (for both partners): life’: 100% (244; 153; 61; 100% (132; 36; 119; 127; 81;231; were 0% over thewhole line (8) partner complaints: 71–100% (295; 275; 282) ‘Satisfaction Significant increase of 307; 240; 39; 263; 84; 238; 86% (164) 308 4; 3) with sexual function: 67% penetration and 305) Normal libido and Married women: -100 (328; 17; 204) satisfaction scores for both orgasm: 100% (323; 100% (256) partners (94; 93): 100% 324) Post-operative A tendency of strictures Advised post-operative In (222; 19 197; 8; 107; 289; 44; In 8% (63; 239; 46) Only in two studies 100% used dilators when Failure to dilate: Advised in (41; 319; 202; dilation could be overcome in dilation in (41; 81; 199; 44; 318; 23), 50–100% of patients post-operative reported (110; not sexually active, but unsatisfactory 206), but 25% did not management patients who dilated (183; 53; 119; 39; 335; 332; 49; dilated for 2–12 months or dilation: Anatomical 256), in which those who had poor (anatomical and dilate properly 125; 33; 104), but 333;238;231;170; 148; were currently still dilating success : 96–100% effect on compliance had strictures functional) results in most Anatomical success: 58% occasional problems with 84;207): Anatomical success: 87% Sexual activity: 33– anatomical and (277; 229) (300; 173; 7; 108; 46; Sexual activity: 73% disgust to dilator (183) and Anatomical success: 97% Sexual activity: 92% 67% (239; 46) to 100% functional outcome 140), except (283). Functional success: 92% vaginal bleeding were Sexual activity: 70% Functional success: 82% Functional success: is NR in (256). In Most evident in young reported (166) Functional success: 93% 95–100% (110) vaginal length patients (98) and due to Anatomical success: 97% No recommended dilation: increased from 7 to psychological reasons Sexual activity: 82% (127; 305; 302;249; 69;260; 9 cm in those who (140) Functional success: 95% 159; 263; 274; 245; 132): dilated, with none 40% reported it was daily Anatomical success: 91% of the women being nuisance (179) Sexual activity: 73% sexually active Post-operative dilation Functional success:90% Vaginal narrowing (min 6 months): good only in studies in results (291; 151; 179; 38) which patients did Long-term use: not seem to dilate permanence of (225; 101; 308; satisfactory results in 254) .90% of cases (275; 282; 174) Contracture yrs after operation if no dilator was used in non-sexually active women (38) Previous failed Surgery: 0.4% (312, 175) Surgery (peritoneal or Surgery: 2.8% (315; 289; 129; Dilation: 5% (164) Surgery: 2% (101; Surgery: 3% (10; 229; Surgery: 3.4% (35; 216; Surgery: 7.7% (11; 319; vaginal Anatomical success: 100% McIndoe): 10.5% (207; 46; 36; 70; 8) Anatomical success: 110) 163; 335) 97; 98; 60; 327; 38; 206; 111) reconstruction Sexual activity:83–100% 119; 200; 109; 249; 53; 69; 14; Anatomical success: 95% 100% Anatomical Anatomical success: 100% 11;179) Anatomical success: 85% Functional success: 100% 260; 148; 92; 333; 335; 49; 332; Sexual activity: 89% Sexual activity: 100% success: 95% Sexual activity: 56% Anatomical success: 76% Sexual activity: 80% 238;305; 188; 245) Functional success: 92% Functional success: Sexual activity:NR Functional success: 93% Sexual activity: 86% Functional success: 71% Anatomical success: 92% 86% Functional success: Functional success: 88% Sexual activity: 75% NR Follow-up: 6.5 + 8.5 Functional success: 90% years Dilation: 0.1% (172) Dilation: 1.5% (8) Dilation: 16% (10; Dilation: 4.6% (179; 300; Dilation:8% (202) Callens The woman had neither Anatomical success: NR 229;335) 287; 268; 38) Anatomical success: 78% sexual intercourse nor Sexual activity: 0% Anatomical success: 100% Anatomical success: 92% Sexual activity: 72% regular use of vaginal Functional success: 0% Sexual activity: 49% Sexual activity: 96% Functional success: 100% tal. et dilators as advised Functional success: 93% Functional success: 78% Follow-up: 12.6 + 9 years Review of surgery and dilation for vaginal hypoplasia 787

(Tiefer, 1995). When referring to satisfactory coital function, functional success for vaginal dilation techniques is at least 74%. This is significantly lower when compared with vaginoplasty studies, reporting success rates

1 year of 90–96%. When functional success is defined as ‘satisfaction with sex’, ,

1 year (286; including non-genital sex, differences disappear (93 versus 96%). Overall, ≥ 1.0 years (2 in both vaginoplasty and vaginal dilation studies, the terms ‘active sex life’ +

1.2 months–37 years) Follow-up versus 41; 111): Anatomical success: 83 versus 95% Sexual activity: 91 versus 81% Functional success: 92 versus 88% or ‘satisfied’ were often not operationally defined, so it is left unclearas to what was precisely meant by these terms (Bean et al., 2009). In early reports, as well as reports from developing non-Western countries,

1 year it was not uncommon to let functional success depend on the ability

, of the woman to provide pleasure to the partner. This suggests that out- 1 year ≥ 3.4 years (1 comes in the form of ‘satisfaction’ should not be taken at face value but, + rather, interpreted critically in the light of historical and cultural contexts. (102; 173; 11; 140) versus Anatomical success: 83 versus 86% Sexual activity: 89 versus 90% Functional success: 75 versus 88% month–50 years) Follow-up 4.0 Recently, available standardized questionnaires on sexual function, such as the Female Sexual Function Index (FSFI; Rosen et al., 2000) can reliably assess female sexual wellbeing and can provide an alternative 1 year way to compare the functional outcomes of different vaginal reconstruc- , 1 year tion options. Table VII provides an overview of the studies with FSFI ≥ 3.7 years (1

+ results. 2.3 month–11 years) Follow-up versus (85;335; 114; 171) Anatomical success: 97 versus 76% Sexual activity: 73 versus 93% Functional success: 94 versus 84% Mean total FSFI scores (range 0–36) indicate, in general, weaker func-

gh the majority had MRKH. tional scores (mean + SD), after both vaginal dilation (25.2 + 3.7) and 1 +

, vaginoplasty (27.9 3.0), compared with the standardization popula- tion (30.2 + 6.1). Lower scores are evident in four of the six subscales: 1.6 years

+ arousal, lubrication, orgasm and pain during intercourse (P , 0.01), with 1 year: (2 weeks–7.8 years) Follow-up year (256; 254; 130; 22) versus ≥ Anatomical success: 97 versus 93% Sexual activity: 55 versus 88% Functional success: 94 versus 93% 1.6 no differences for desire or satisfaction with sex life and/or relationship. As sexual distress is not assessed in most studies—a criterion essential to diagnose a according to the Diagnostic and Statistical 1 year

, Manual of Mental Disorders-Text Revision (DSM-IV-TR), the prevalence of sexual dysfunctions remains unclear. No differences are found

1 year (2–25 between different vaginoplasty methods, but the samples are small. Of NR (6weeks–25 years) Follow-up (6 weeks–1 year) (239; 108), versus ≥ years) (63; 164): Anatomical success: 100 versus 98% Sexual activity: 33– 55 versus 100 Functional success:96 versus 90% interest, women who were medically treated (surgery or vaginal dilation)

1 did not have better indicators of sexual wellness or sexual function than ≥ those who were untreated, suggesting an important role of other factors than treatment affecting sexual wellbeing in these women. Studies inves-

1 year (75; tigating other quality-of-life parameters suggested that psychological , variables, such as depression symptoms (Poland and Evans, 1985; Ismail- 4.5 years (1 month– Pratt et al., 2007; Djordjevic et al., 2011), doubts about female identity +

3.6 18 years) Follow-up 289; 200; 137) versus year: Anatomical success: 100 versus 89% Sexual activity: 81 versus 93% Functional success: 96 versus 90% (Freundt et al., 1993; Vates et al., 1999; Communal et al., 2003) and body image problems (Smith, 1983), are still prevalent after treatment 1 ster Hauser syndrome; (C)AIS, (Complete) Androgen Insensitivity Syndrome; GD, Gonadal Dysgenesis; CAH, Congenital Adrenal Hyperplasia. and that neither surgical or non-surgical options, even if satisfactory, ¨ ≥ solve all problems (Carrard et al., 2012). It is interesting in this respect that women who had undergone treatment still perceive their vagina 1 year (132;

, as abnormal (Minto et al., 2003). The repercussions of a negative

2.5 years (1 month– genital image on sexual satisfaction have been shown in the general popu-

+ lation (Berman et al., 2003). Stable relationships and a good communica- year: Anatomical success: 100 versus 89% Sexual activity: 48 versus 67% Functional success: 92 versus 87% 36; 14; 307) versus 4.3 24 years) Follow-up tion between partners were further suggested to be crucial contributors to overall sexual satisfaction, independent of neovaginal length or treat- ment (Lappo¨hn, 1995; Liu et al., 2009; Kimberley et al., 2011). As such,

1 year the importance of vaginal depth for satisfactory outcomes and the , general relationship between anatomical and functional success 1.5 years (6 remains difficult to determine (Klingele et al., 2003; Borruto et al., + 1 year: 1.9 months–13 years) Follow-up (166; 175; 33) versus ≥ Anatomical success: 100 versus 98% Sexual activity: 87 versus 95% Functional success: 100% (but with vaginal dryness) versus 89% 2007; Ismail-Pratt et al., 2007; Kapczuk and Friebe, 2012). With regard to the FSFI evidence, sexual problems were not more common in studies in which a mean vaginal length of ,6.6 cm was reported.

: See Supplementary data, Tables SI–SIII for numbered references. However, it is unclear from these studies if individual women with a Not further specified. Abbreviations: MRKH, Mayer–Rokitansky–Ku Excluding some studies with mixed treatment regimens because the specific diagnosis was not known according to the specific treatment regimen, althou Mean follow- up (years) a b Note smaller vaginal length were sexually active and had lower functional out- comes. Methodological problems have been noted with the FSFI when 788 Callens et al.

Table IV Other influencing factors on anatomical and functional success rates in vaginal surgery studies.

Hymen Psychological counselling Timing of treatment Diagnosis ...... No studies specifically In ≥50% of studies: psychological interventions Prepuberty versus puberty in same study (all 46,XX MRKH versus reporting the relevance of recommended, but no suggestions as to what type or bowel vaginoplasty): 46,XY CAIS in outcomes when to deliver Anatomical success: both 100% (149), NR in Vaginal length before Presence hymen in (44; Psychological counselling (support group or (260; 240) surgery: 1.4 + 1.1 versus 164; 172; 64; 34; 104;311; individual counselling) (239;183;166; 112; 287; 327; Complications: more common in puberty 3.3 + 2.6 cm (P ¼ 0.03) 312): highly variable results: 328; 179; 249; 159; 168; 143; 54; 228) versus no group (240; 260;149) Vaginal length after surgery: Anatomical success: psychological counselling: Functional success: unknown versus 0% 9.0 + 1.9 versus 81–100% Anatomical success: both 91% (260)2100%(240), NR in (149) 8.3 + 2.9 cm Functional success: Functional success: 89 versus 82% 13–18 years versus .19 years (7) (McIndoe Anatomical success: 92 55–100% procedure) versus 95% Anatomical success: 66.7 versus 86.5% Sexual activity: 81 versus Complications (graft infections): 53 versus 73% 15% Functional success:90 Functional success: 60 (33 for 13–15 years, versus 85% 85% for 16–18 years) versus 71% Older patients (.30 years): more disappointing, possibly because of an alteration of tissue elasticity (34) (Vecchietti procedure)

See Supplementary data, Tables SI–SIII for numbered references. women report not to be sexually active in the last 4 weeks preceding past decades in surgical techniques and improved knowledge of the the survey (Meyer-Bahlburg and Dolezal, 2007). In addition, standard anatomy and innervation of the female genitalia, there is, at present, instruments, such as the FSFI, might not be well-tailored to assess the no evidence that newer techniques improve long-term outcomes. specific situation of women with vaginal hypoplasia, suggesting that an In addition, anatomical (based on vaginal length) and functional improved research methodology is needed to fully assess the impact of success (based on coital activity) were not significantly lower in studies the involved conditions and its management on sexual experiences and in which previous surgery or dilation had failed, although there was a wellbeing. trend towards more complications in these studies. It could also be that patients in whom previous treatment had failed were those with more complex inherent anatomical features to begin with. As such, it Quest for the optimal vaginoplasty technique remains unclear if previous attempts at vaginal reconstruction jeopardize Based on the currently available evidence, it remains difficult to deter- surgical success. mine the superiority of one vaginoplasty technique over the other. Moreover, there is a lack of a standardized approach in reporting the This is due to problems including differences in technical terms used to results ofpost-operative dilation management. Inthose studiesthat men- describe surgical techniques and their modifications over the years tioned a proper post-operative dilation regimen, anatomical success making grouping of methods challenging, the heterogeneous group of rates were in general higher, and contractures and strictures (between patients, and the unavoidable reporting bias of surgeons towards the 5 and 7%) could be overcome, even in bowel vaginoplasty where post- techniques they are mostly experienced in. Another problem relates surgical dilation is generally said not to be necessary. Therefore, mainten- to the lack of concordance in recording the long-term outcomes and ance dilation seems to have an additive value, either with regular dilation complications of the different approaches. A follow-up of ,1 year or coital activity. Nuancing the need for maintenance dilation, however, seemed to be associated with less sexual activity and functional success rates are, in general, also high in studies without post-operative success, but the effect on anatomical success is unclear. It is possible dilation. thatthe severityof dyspareunia oradequatelubrication areinversely pro- Finally, from the available evidence, it remains unclear if age at surgery portional to the time since operation, resulting from the progressive is relatedto the outcomes or if there exits an optimal timewindowfor the epithelization of the neovagina, a process that is almost complete after most favourable anatomical outcomes. The majority of women felt, 1 year. By further considering surgical complications as independent however, that the appropriate time to undergo surgery was in adoles- primary outcomes, it is perhaps possible to further elucidate which com- cence (Parsons et al., 2002), seeming to underline that interventions plications, mainly intraoperative(bowel and urinary tract injury,bleeding) can only be undertaken when the patient is emotionally mature and or post-operative complications (e.g. infection, haematoma, necrosis, ready to engage in sexual activity (Capraro and Gallego, 1976; Alessan- need for second surgery), are important for the technique’s safety and drescu et al., 1996; Schatz et al., 2005; Brucker et al., 2008; Fotopoulou others for functional success (e.g. vaginal dryness, vaginal discharge, et al., 2010) or marriage in some cultures (Thompson et al., 1957; Sarwar granulation tissue; McQuillan and Grover, 2014). The major complica- et al., 2010). It has also been suggested that a vagina is not necessary for a tion rates (i.e. death and venous thrombo-embolic events) have anec- young girl prior to sexual intercourse (Creighton, 2004) and that early dotally decreased since laparotomy has been phased out or reserved psychological problems related to regular post-operative dilation can for only very difficult procedures. Despite significant advances over the be minimized by delaying surgery (Filipas et al., 2000). Review of surgery and dilation for vaginal hypoplasia 789

Table V Summary of vaginal dilation studies.

N patients 908 Sexual activity 86% Note: The mean average between completion of treatment and the start of sexual activity was 7.5 months + 3.5 months (range 1–60 months), with the majority within 1 year Diagnosis 93% MRKH Functional 96% 7% CAIS or disorders of androgen or success synthesis Anatomical success 78% Definition of Successful sexual function or satisfaction with sex life not further Note: No difference between MRKH functional specified: 96% (91; 204; 221; 59) and CAIS success Comfortable coital and orgasmic function: 74% (range 0–100%) MRKH:78% (313; 116; 46; 160; 287; 268; 30; 325; 185; 266; 265; 161; 164; 122; CAIS:77.5% 13) with worst results (,50%) in (13; 122; 268) Based on standardized questionnaires (FSFI): sexual dysfunction in 100%(42) to no differences compared with controls in 25% (49;233) Definition of anatomical .6 cm: 78% (116; 313; 102; 160;202; Failed dilation 11% (311; 268; 202; 266; 164; 215) success 59; 266; 5; 13; 42; 91) Reasons: .7 cm: 69% (161; 122; 215) Motivational problems (160; 268; 185; 202; 161; 122) .8 cm: 33% (185; 164; 329) Poor compliance (30; 122; 91; 116) Max 25% contracture of the vaginal Discomfort, pain (because of lichen sclerosis), vaginal prolapse or space: 43% (268) prior attempt at hymenectomy with secondary scar formation (311; Not further specified: .90% (46; 311; 268; 265; 122) 233; 265) Anatomical reasons: Absence of an appreciable dimple to begin with (46; 265) or sturdy perineum (185; 164) and multiple congenital abnormalities (91) Practical reasons such as lack of privacy (161; 122) or travel distance to the clinic (13) Psychosocial reasons such as no or an unstable relationship at the time of treatment (185; 266; 161), cultural or religious beliefs (91; 264),youngage (268),learning difficulties (91),interpersonal conflict related to the treatment (91) and significant mental health problems (91; 266) Not successful despite compliance with treatment recommendations (215; 161). Cause unclear (Note: Majority had MRKH, and thus likely a shorter vaginal start length) Proprotion of patients 2% (122; 215; 325; 311) with complications and Urinary complaints: 1% main complications Pain and bleeding: 0.5% and Vaginal prolapse: 0.3% Note: No differences in frequency or type of complications between CAIS and MRKH Mean follow-up (years) 4.2 + 3.4 years (0.3 months–27 years) Follow-up ,1 year (59,161) versus ≥1 year: Anatomical success: 88 versus 85 % Sexual activity: 91 versus 81% Functional success: 91 versus 85%

FSFI, female sexual function index. See Supplementary data, Tables SI–SIII for numbered references.

In sum, the quest for the optimal surgical method continues, as no complication rate, suggesting it to be an appropriate surgical technique technique is completely without failure risk, and some have (still) high either as first-line treatment or after failed vaginal dilation. complication rates. In general, however, traction vaginoplasty seems to have the highest anatomical (≥6 cm, 99%) and functional success rates (satisfactory coitus, 96%), followed by peritoneal vaginoplasty (92% ana- Effectiveness of vaginal dilation as first-line tomical success and 93% functional success), whereas both split- technique: a time-honoured practice? thickness and full-thickness skin graft procedures and intestinal proce- Combining data from published non-surgical series allows some import- dures have the lowest outcomes (83–95% anatomical success and ant insights into relevant factors that may impact on daily clinical vaginal 90–93% functional success). Traction vaginoplasty also has the lowest dilation practices and on decision-making in individual cases. 790

Table VI Influencing factors on anatomical and functional success rates in vaginal dilation studies.

Total duration of dilation treatment Frequency of dilation Age at start treatment Vaginal length at start treatment Hymen ...... 7.6 (+4.8 months; range 2 days–60 Frequency of dilation periods, not the total Positive association with Positive association between start vaginal length Absence (30): months) amount of minutes dilating per day (e.g. one anatomical success (R ¼ 0.6, and end vaginal length (R ¼ 0.69, P , 0.05) Anatomical success: NR No association with anatomical success time for 30 min versus three times for 10 min) P , 0.05) Start vaginal length not significantly correlated with Sexual activity: NR (R ¼ 20.2, P . 0.05) positively associated with anatomical success ,18 years (268; 266; 164; anatomical success (R ¼ 0.61, P . 0.05) Functional success: 92% Dilation ≤6 m (233; 221; 161; 163; 13; (R ¼ 0.514, P , 0.05) 329; 122; 205) versus ≥18 Larger vaginal start length associated with shorter Hymen, hymenal remnants or 215) versus .6 m (268; 202; 265; 5; 122) Dilation 2–4x/day (116; 160; 268; 30; 325; years (116; 313; 30; 202; 59; 5; duration of dilator therapy (R ¼ 20.9, P , 0.05). pseudo-hymen in (116; 311; 313; Anatomical success: 73 versus 63% 59; 266; 265; 5; 232; 221; 164; 122; 13; 91) 233; 221; 161; 13; 91; 215): Note: unclear how previous attempts at sexual 265;164) versus studies in which Sexual activity: 86 versus 73% versus 1x/d (203; 213; 327; 161; 185; 313): Anatomical success: 47 versus intercourse might have influenced the start vaginal parameter was unknown: Functional success: 70 versus 57% Anatomical success: 76 versus 49% (P ¼ 0.06) 78% (P , 0.05) length, as this information was not reported in Anatomical success: 68 versus Note: dilator treatment was stopped after Sexual activity:80 versus 91% Sexual activity: 77 versus 88% most studies 71% maximum 6 months of compliance, Functional success:78 versus 84% Functional success:78 versus Sexual activity: 89 versus 71% irrespective of results, or because no Totalduration oftreatment; 7.6 + 5.4months 76% Functional success: 92 versus 67% furtherelongation of the vaginal length was versus 5.1 + 0.1 months observed in (215; 202; 164) Psychological counselling Diagnosis Maintenance dilation In 63% of studies 46,XX MRKH versus 46,XY No studies compared women who did and did not maintain dilation when not being Definition: CAIS sexually active regarding functional or anatomical outcomes Emotional support from sensitive physician, not necessarily psychiatric care: (46) Start vaginal length: 3.1 + 0.5 Only in two studies (116; 161) women without coitus were still dilating at the time of Meeting with succesfully treated former patient: (160; 325) versus 4.5 + 2.1 cm follow-up: vaginal length: 6.5–8.5 cm Patient and family counselling: (268) End vaginal length: 6.8 + 1.8 Note: unclear whether women who used dilators had smaller vaginal lengths versus Input from nurse specialist and/or psychologist: (325; 5; 233; 221; 161; 122; 42; 91; 215) versus 8.2 + 0.8 cm those who were sexually active Psychodramatic therapy: (59) Anatomical success: 70 versus Possibly, sexual activity further lengthens the vagina (194), and a combination of dilators Support group meetings: (266) 79% and intercourse improves both anatomical and functional success rates (266; 185; 13) Not further specified: (313; 265; 329; 13) Sexual activity: 76 versus 42% Maintenance dilation recommended: 2–3 times/week when no regular coitus (313; Psychological counselling versus no psychological counselling: Functional success: 73 versus 202; 268; 59; 265; 161; 122; 204) Minimal amount of months dilating : 3.8 + 3.2 months versus 1.4 + 0.4 months, P , 0.05 44% Motive: to avoid shrinkage of vagina Anatomical success : 74 versus 63% P . 0.05 No further dilation recommended (325; 91) Functional success : 70 versus 77% P . 0.05 Motive: when embarking in a relationship after a substantial absence of dilators or Successful completion of treatment not dependent on psychological counselling (13) and intercourse, women very quickly regain their original length, eventually after dilating for a not different between inpatients or outpatients (13) short time (91) The quality-of-life was high in groups who attended counselling and thosewho did not (177); Anatomical success: NR however, mental health was poor compared with physical health (194) and scores for sexual Functional success: only assessed in small subgroup of women, reported in (233), with depression, sexual anxiety and fear of sexual relations remained high compared with groups sexual problems (difficulties with maintaining lubrication, pain during intercourse) of non-affected women (194)

See Supplementary data, Tables SI–SII for numbered references. NR, not reported. Callens tal. et eiwo ugr n iainfrvgnlhypoplasia vaginal for dilation and surgery of Review

Table VII FSFI values after alternative vaginoplasty techniques, vaginal dilation and no treatment in women with vaginal hypoplasia.

Ref. (270) (42) (194) (42) (194) (227) (167) (314) (44) (49) (84) (53) (85) (114) N 131 9 10 15 7 20 18 7 11 35 45 8 7 5 Diagnosis Control 46,XY DSD MRKH MRKH & MRKH MRKH MRKH MRKH MRKH MRKH MRKH MRKH MRKH MRKH 46,XY DSD Study Control No treatment No treatment Bowel (n ¼ 2), Vecchietti Bowel Wharton Wharton Bowel Bowel Bowel Bowel Oxidized Amnion Skin grafts (n ¼ 4), (n ¼ 12), cellulose (n ¼ 11), McIndoe Davydov Vecchietti (n ¼ 1), bowel (n ¼ 8) (n ¼ 2) (n ¼ 1) and skin flap (n ¼ 1) Desire 4.1 (1.1) 3.8 (0.6) 4.9 (1.0) 3.9 (1.2) 3.9 (1.3) 4.6 (0.8) 3.6 (1.2–6) 4.3 (1.3) 4.2 (0.2) 4.4 (0.9) NR 5.0 (0.5) NR 4.9 (1.2) Arousal 5.0 (1.0) 4.8 (1.2) 5.2 (1.0 4.3 (1.3) 4.8 (1.0) 4.3 (1.7) 4.5 (2.4–6) 5.4 (0.5) 4.2 (0.1) 4.7 (0.7) NR 4.9 (0.3) NR 5.0 (0.8) Lubrication 5.5 (0.9) 4.8 (0.9) 4.9 (1.3) 3.5 (1.8) 5.3 (0.7) 4.3 (1.8) 5.7(1.2–6) 5.1 (1.5) 4.2 (0.1) 5.2 (0.9) NR 5.0 (0.9) NR 4.0 (0.7) Orgasm 5.0 (1.2) 4.9 (1.0) 5.1 (1.1) 4.0 (1.3) 5.0 (0.8) 3.8 (1.9) 4.2 (1.2–6) 4.9 (1.0) 4.1 (0.3) 4.4 (1.1) NR 4.7 (0.9) NR 5.5 (1.0) Satisfication 5.1 (1.2) 4.9 (1.0) 5.6 (0.4 4.5 (1.2) 5.5 (0.8) 4.7 (1.7) 5.6 (2.4–6) 5.1 (1.5) 4.4 (0.3) 5.4 (0.6) NR 5.6 (0.3) NR 5.3 (1.4) Pain 5.5 (1.0) 5.0 (0.7) NR 4.1 (2.2) NR 3.6 (2.1) 4.8 (0–6) 5.1 (1.1) 4.2 (0.3) 3.9 (1.2) NR 4.8 (1.0) NR 5.3 (1.8) Total FSFI 30.2 (6.1) 27.6 (4.8) NR 23.9 (5.7) NR 25.3 (8.0) 28.2 (10.8–36) 29.9 (4.3) 24.8 (1.2) 28.0 (3.1) 28.9 (11.5 –35.7) 30.0 (3.0) 32.5 (1.1) 30.0 (6.9) % Sexual dsitress NR 55,6 NR 57,1 NR NR NR NR NR 85 NR NR NR NR % FSD NR 50 NR 62,5 NR NR 80 NR NR 30 14,8 12,5 NR NR Vaginal length (cm) 9.6 (1.5) 8.9 (2.6) 4.8 (2.6) 9.1 (2.7) 7.4 (2.6) NR 6.3 (4.5–12) 8.3 (7– 12.6 (0.4) NR 13 NR 9.6 (2.1) 9.8 (1.7) 10)

Ref. (44) (23) (8) (202) (129) (23) (66) (104) (42) (194) (49) (233) (227) N 21 40 6 31 25 40 23 27 8 20 5 56 20 Diagnosis MRKH MRKH MRKH and MRKH MRKH MRKH MRKH MRKH 46,XY MRKH MRKH MRKH MRKH CAIS DSD Study Davydov Davydov Davydov Davydov Davydov Vecchietti Vecchietti Vecchietti Dilation Dilation Dilation Dilation Dilation Desire 4.3 (0.1) 4.3 (0.7) 3.9 (1.2) 3.8 (0.9) 4.4 (0.9) 4.2 (0.9) 4.5 (0.7) 4.4 (0.8) 2.8 (0.8) 3.5 (1.2 4.7 (1.3) 3.7 (1.0) 4.5 (1.0) Arousal 4.2 (0.1) 4.7 (0.8) 4.0 (1.1) 4.2 (0.8) 4.4 (1.1) 4.6 (1) 5.9 (0.8) 4.8 (0.8) 4.3 (1.1) 3.6 (1.7 5.1 (1.0) 4.0 (1.4) 4.4 (1.6) Lubrication 4.0 (0.2) 5.1 (0.6) 4.4 (1.0) 5.1 (0.6) 4.5 (1.4) 4.5 (1.0) 4.3 (0.8) 5.0 (0.8) 4.8 (1.3) 4.2 (1.7 5.1 (1.1) 4.2 (1.4) 4.2 (2.0) Orgasm 4.0 (0.3) 5.0 (0.6) 3.3 (1.6) 3.8 (1.2) 4.1 (1.3) 4.4 (0.9) 4.6 (0.9) 4.6 (1.0) 4.3 (1.6) 3.32 (2.0) 4.8 (0.9) 3.9 (1.5) 4.0 (1.8) Satisfication 4.5 (0.2) 4.8 (1.5) 4.0 (1.8) 4.5 (1.1) 4.6 (1.1) 5.2 (1.2) 5.2 (0.6) 5.4 (0.6) 4.4 (1.0) 4.0 (2.0) 5.4 (1.2) 4.3 (1.2) 4.7 (1.6) Pain 4.4 (0.3) 4.7 (1.0) 1.9 (1.9) 4.7 (1.2) 4.4 (1.4) 5.2 (1.0) 4.7 (0.7) 5.0 (0.9) 2.4 (2.5) NR 5.2 (1.1) 3.6 (1.7) 3.4 (1.9) Total FSFI 25.3 (0.5) 31.8 (0.8) 21.4 (5.3) 26.1 (4.8) 26.5 (5.6) 30.2 (1.0) 30.1 (3.8) 29.0 (3.2) 21.6 (2.5) NR 30.3(6.2) 23.7 (4.3) 23.3 (7.5) % Sexual distress NR NR NR NR NR NR NR NR 43 NR 60 NR NR % FSD NR NR 75 71 72 NR NR 55 100 NR 25 NR NR Vaginal length (cm) 11.9 (1.2) 8.5 (1.6) NR 6.3 (1.3) 7.2 (1.5) 7.5 (1.1) 8.8 (1.1) 6 7.3 (1.3) 5.1 (2.6) NR NR NR

Data presented as mean (SD). DSD, disorders of sex development; FSFI (range 0–36, domain scores 0–6: higher FSFI values denote better sexual functioning), FSD, female sexual dysfunction; NR, not reported; Ref, reference. Note: See Supplementary data, Tables SI–SIII for numbered references. 791 792 Callens et al.

Anatomical success functional success are not entirely clear, it is possible that the emotionally Surprisingly, start vaginal length was not significantly associated with ana- charged nature of the dilation process may make it difficult for women to tomical success. This refutes the claims that success can only be achieved keep separating the long-term medical dilation treatment from ‘real in women with an existing vaginal dimple of 2–3 cm (Jasonni et al., 2007). sex’—with a possible disgust or withdrawal from sexual activities. Espe- For this reason, women with CAIS and androgen synthesis disorders, cially, younger women (,18 years) might be more vulnerable to such dif- who generally have a larger starting vaginal length, do not seem to ficulties, as motivational issues are already more prevalent in this age have an advantage over women with MRKH. Of note, women above group. This does, however, question the possible impact of the recom- 18 years of age at the start of treatment had significantly higher anatom- mended maintenance dilation on psychological grounds. Furthermore, ical success rates, which is probably related to motivational reasons.Dila- as in surgical series, the importance of assessing functional success in tion has to be actively managed by the patient and a sustained effort is the long-term is confirmed, as there seems to be a decrease with a required, while progress is slow (Liao et al., 2006). Therefore, we longer follow-up period. Although some researchers have suggested suggest dilator treatment only in women in whom motivation is high, that psychosexual functioning levels and coping abilities improve with for example when being in a current relationship or wanting to engage time (Hecker and McGuire, 1977; Wu et al., 2009), others—including in sexual activity, which has also been shown to be an important factor our research group—have indicated that women continued to feel far in post-operative dilation management. With regard to frequency and from normal in the areas of sexual potency and reproduction (i.e. per- duration of dilation treatment, it becomes clear that the best anatomical ceived loss of social role as potential mother, loss of sense of equality results were obtained when the frequency of dilation periods was high, with peers), contributing to high emotional distress, in different ways suggesting that regular stretching is more beneficent than the actual and at different times (Holt and Slade, 2003; Liao et al., 2011; Callens total time of stretching. Total duration of dilator treatment seems not et al., 2014). Continued long-term follow-up acknowledges the import- to be related to anatomical success. Although some studies (Wabrek ance of developmental–temporal factors to the distress. et al., 1971; Ingram, 1981), including our own research group (Callens Given the physical and psychological challenges then of this lifelong et al., 2014), suggested that the highest gain in vaginal depth was condition, it is unlikely that these women will achieve complete normal reached within 4–6 weeks, and that the gain thereafter is minimal, it is sexual function (Liao et al., 2011)—whatever enlargement technique is unclear from the available data if there exists an optimal window for used. Interestingly, however, women simultaneously reported relatively gaining length. Unfortunately, despite compliance, which can be high levels of sexual difficulties and sexual ‘satisfaction’. Problems related increased with psychological support (Alderson and Glanville, 2004; to the definition of ‘satisfaction’ with sex—for whom and with what (i.e. Edmonds et al., 2012), conservative therapy can fail (Liao et al., 2011; intercourse)—were already mentioned. In addition, women with MRKH Michala et al., 2012). No conclusions so far can be drawnon the presence or CAIS might have learnt to be ‘satisfied’ with barely satisfactory sexual or absence of the hymen relating to failure of treatment (Kimberley et al., experiences—that is, the women might have felt that sexual difficulties 2012), nor whether perineal skin is different from the vagina in its elastic were to be expected and thus that they should not be dissatisfied characteristics. However, failed dilation therapy does not preclude ana- (Minto et al., 2003). Although this raises concerns about the powerful in- tomical (nor functional) success if vaginoplasty afterwards is necessary. fluence of the current cultural context in which (sexual) difference is still Overall, complication rates were significantly lower within the vaginal taboo, it also questions how treatment success should be further dilation groups when compared with the different vaginoplasty techni- approached (Liao, 2003). Moreover, as it was shown in therapeutic ques, being its major advantage, but should be followed-up in the long- work that few women with vaginal hypoplasia allude to pleasure as a term as well. Displacement of the bladder neck might occur during reason for wishing to engage in sex but rather reasons related to vaginal lengthening, which may affect bladder function and cause ‘feeling’ and ‘acting’ normal through intercourse (Liao, 2007), assuming urinary symptoms (Michala et al., 2012). Also, the creation of a vagina intercourse will be a central therapeutic goal for these women is likely in this fashion does not preclude , and cases of vaginal to give misleading impressions of what constitutes a successful treatment intra-epithelial neoplasia and vaginal carcinoma have been described outcome (Roenand Pasterski,2013). A key messagehere isthat—where (Hopkins, 1987). To date 15 (case) reports of vaginal prolapse have earlier approaches may have considered ‘normative’ functions of the been reported (Williams, 1976; Vecchietti, 1979; Buss and Lee, 1989; genitalia and relative absence of patient complaints as indicators of Peters and Uhlir, 1990; Schaffer et al., 2002; Muir and Walters, 2004; Cal- good outcomes—future approaches need to reformulate outcome cagno et al., 2010; Christopoulos et al., 2011; Fedele et al., 2011; Burns evaluation and specifically raise a wider range of psychosexually oriented et al., 2012), which is still considerably less frequent than reported pro- questions (Liao, 2007; Roen and Pasterski, 2013). A simple questioning lapse after vaginoplasty (e.g. bowelvaginoplasty: 3%). Finally, although no on sexual ‘satisfaction’ is not a useful measure in these diagnostic groups. randomized control data exist regarding maintenance dilation, the avail- able evidence suggests that continued dilation is needed to maintain Pitfalls in treatment success patency in periods of coital inactivity. Psychological profile and the effect of counselling In general, an inaccurate evaluation of the emotional status before any Functional success treatment is suggested to lead to a poor result (Capraro and Gallego, From the available evidence, total duration of vaginal dilator treatment 1976; Strickland et al., 1993), as it was made clear that most women might have a detrimental effect on sexual activity levels and functional were struggling with body image (Smith, 1983; Carrard et al., 2012), or success rates, suggesting that dilation therapy should perhaps be felt anxious, socially unattractive, depressed or lacked self-control stopped after 6 months of compliance; moreover, because anatomical (Kaplan, 1968; Bryan et al., 1949; Langer et al., 1990; Coney, 1992). success seems thereafter not affected. While the reasons for decreased Psychological interventions, such as cognitive-behavioural group Review of surgery and dilation for vaginal hypoplasia 793 therapy, in these women have been shown to be effective in reducing lack of androgens affecting libido and orgasm (Wisniewski et al., 2000; anxiety and feelings of depression (Weijenborg and ter Kuile, 2000; Minto et al., 2003) and/or lack of androgen imprinting on the brain Heller-Boersma et al., 2009a,b). However, despite the expectancy (Kohler et al., 2012). Also, gonadectomy and the subsequent estrogen that the probability of further positive, functional or anatomical, out- substitution therapy is sometimes said to lead to insufficient vaginal lubri- comes are maximized with psychological counselling, this could not be cation (Michala et al., 2012). However, this information is not recorded in confirmed with the current data. The self-esteem, knowledge or inter- most studies and it is difficult to surmise how it might have impacted upon personal skills built up in therapy or by peer support did not seem to the results. be—both immediately and in the long-term—translated to satisfying sexual relationships (Liao et al., 2006; Heller-Boersmaet al., 2009b). Despite counselling, some women still felt depressed and extremely in- Theory informing practice secure relating to others (Kaplan, 1968; Hecker and McGuire, 1977), What emerges from this overview of selected publications is that evi- which is possibly also reflected in rather low sexual activity rates in any dence for both physical and psychosocial outcomes in women with treatment paradigm (85%). Findings from our group even showed an un- vaginal hypoplasia remains incomplete and uncertain. Some fundamental expected increase in emotional difficulties after a standardized dilation questions about whether, for instance, treatment harms genital sensitiv- programme with input from a clinical psychologist (Callens et al., 2014). ity or produces acceptable cosmetic results according to the affected The majority of participants refused psychological counselling after a women themselves are still disputed Bronselaer and Callens et al., few sessions because contact with psychologists was said to engender 2013. How these issues interplay in individual situations may perhaps powerful ambivalent emotions of abnormality as well as feelings of never be resolved definitively because the answer will always depend failure in not coping with the condition. Contact with peers was said to on too many variables: the woman’s individual anatomy and physiology, be motivating during treatment, but was further limited to discussion the clinician’s skills and judgment, the quality of post-operative care, the of subjects related to the shared condition (Alderson et al., 2004). psychosocial resources available and their perceived usefulness, relation- While the move to including psychological input in clinical teams special- ships within the family and the deeply subjective nature of satisfaction izing in DSD is significant, it is still open to negotiation how the psychol- with sexual sensation and function as wellas cosmetic outcomes (Tamar- ogist’s role in certain situations allows for a substantive and worthwhile Mattis et al., 2013). Women must have access to this balanced informa- contribution. It is of utmost importance to gain additional experience tion in order to fully weigh the potential risks and benefits of treatment. concerning the format of acceptable and efficient psychological care Furthermore, as the medical literature lacks high-quality comparative and how to integrate it in the regular medical follow-up (Liao, 2003). outcome studies, no evidence-based treatment guidelines can be pro- vided. Despite these limitations, however, with the obtained information Diagnosis effects concerning the results of current techniques, we are in a position to The presentreviewfurther underlinesthe importance of detailed report- advance thinking and practice in this field in various ways. ing on diagnosis, as there are differential outcomes for women with 46,XY and disorders of androgen action or synthesis (mainly CAIS), and 46,XX MRKH. Recommended treatment algorithm in Although no differences in anatomical outcomes were found, women women with vaginal hypoplasia with an 46,XY karyotype have a significantly larger start vaginal depth Figure 3 summarizes the treatment decision tree in women with vaginal compared with 46,XX women [e.g. (Ismail-Pratt et al., 2007)]. The ques- hypoplasia. Because of the physically low complication rate and an overall tion arises as to whether this is the reason why the majority of women success chance of 75%, vaginal dilation treatment (either with or without with CAIS do not opt for vaginal reconstruction interventions. The intercourse) as a first-line choice seems to be justified if women had no prevalence of vaginal hypoplasia within a CAIS population has not exten- prior treatment (i.e. reconstructive surgery). Dilator treatment has not sively been studied. Owing to the action of fetal testicular anti-Mu¨llerian only benefits (e.g. preservation of vaginal tissue), but also barriers, hormone on the developing Mu¨llerian ducts, it is hypothesized that CAIS which should not be minimized (Liao et al., 2006). Vaginal dilation is time- might be associated with 25–33% loss of vaginal length (Minto et al., consuming and some patients find it distressing. Overall, the laparoscopic 2003). In this study, however, despite a wide range, an average loss of Vecchietti procedure, becoming more and more available in specialized 66% was shown in women with CAIS who had no treatment or sexual centres, is considered an appropriate surgical option for the creation of a activity yet [3.8 + 2.2 versus 9.6 + 1.5 cm in non-affected women neovagina in patients who are poorly compliant and failed dilation (Lloyd et al., 2005)], contradicting previous studies (Wisniewski et al., therapy, or for those who do not want to start with vaginal dilation 2000; Minto et al., 2003; Purves et al., 2008; Wilson et al., 2011), and therapy. In addition, assisted uterovestibular anastomosis perhaps indicating that only those women with CAIS with the shortest through the Vecchietti technique is also possible in those women with start vaginal length and/or who have not been sexually active yet seek cervicovaginal agenesis and a functional uterus (Fedele et al., 2008a). It medical advice. After treatment, length of the neovagina is not necessar- is difficult to justify proceeding directly to some of the more complex ily proportional to satisfactory outcomes and this topic should deserve techniques, such as intestinal vaginoplasty, with its associated high mor- more detailed investigation. bidity and long-term side effects. These techniques can have a role in In contrast, functional success rates, with all reconstruction techni- complexpatients with previousextensiveabdominal surgery,particularly ques, were in general significantly lower in women with a 46,XY karyo- those cases with significant scarring from previous surgery. Choosing the type compared with women with 46,XX. A high rate of impairment of right operation in patients who require surgical reconstruction is integral desire and arousal and dyspareunia in women with CAIS has been to success.Moreover, it should be noted thatthe first attempt atany neo- shown before (Kohler et al., 2012), which could be due to the complete vaginal reconstruction has the best chance for success and every failed 794 Callens et al.

Figure 3 Decision tree for treatment options in vaginal hypoplasia. attempt leaves its traces and should be avoided. Therefore, it is crucial to Psychological difficulties mayact as a barrier to dilator treatment, or resolve whether the patient has the mental resources, including perhaps conversely, the dilator treatment may exacerbate pre-existing psy- certain personality traits, necessary to cope with the management of her chological symptoms (Edmonds et al., 2012) and must be delayed in condition in an effort to optimize therapeutic success (Coney, 1992). Re- the presenceof psychological disorders (e.g. depression) (Alderson gardless of the vaginal reconstruction technique used, patients should be and Glanville, 2004). The further timing of treatment should be managed in specialized centres by a multidisciplinary team, which can planned on an individual basis as there is considerable variation in provide adequate emotional and psychological support. Specialist psychosocial development and maturity. High motivation to start units should be able to offer all treatment options and also have a with sexual activity or a current relationship will benefit dilator duty to provide detailed long-term outcome data (Michalaet al., 2007; use. It is suggested not to start dilator treatment before the age Deanset al., 2010). of 16 years, due to motivational issues, which are more prone in adolescence (Alderson and Glanville, 2004). Also, younger New ideas from old concepts: vaginal dilation women may be less familiar with their genitalia or might have treatment in clinical practice anxious reactions toward the idea of inserting an instrument in the vulvar region (Alderson and Glanville, 2004), the more so A practical protocol, informed by the literature and our own experi- when dilators are perceived as highly sexualized objects (Cullen ence, for the management of women with vaginal hypoplasia is provided et al., 2012). For some women, negative genital perceptions may in Fig. 4. A further individual-based approach with skilful evaluation and also be exaggerated by an idealization of ‘normal’, and negative negotiation with the patient can help to prevent vaginal dilation treat- social comparisons may raise the anxiety further (Liao, 2006a, b). ment failure and limited compliance. Figure 5 illustrates how a vaginal Ideally, where appropriate, patients should be encouraged to dilation user model—based on a health belief model of behaviour access support from their personal contexts, as it enhances self- change (Bonner et al., 2012), and on therapeutic interventions within management in many chronic diseases (DiMatteo, 2004). a framework of cognitive-behavioural psychology and motivational However, because of the intimate nature of the syndromes, many interviewing (Miller and Rollnick, 1991; Liao et al., 2006; Ismail-Pratt women feel they cannot talk about it with family or friends and et al., 2007)—would incorporate the influencing factors identified in wish to hear about other patients’ experiences. Support groups this review. It provides useful pointers for understanding compliance dif- can provide a useful resource for sharing concerns or motivation ficulties with vaginal dilation and suggests that vaginal dilator use can be during treatment. Regular appointments with a clinical psychologist, increased by nurse specialist and/or physiotherapist can provide opportunities (i) Accounting for modifying factors before and during the course of for addressing other implications of the diagnosis, such as its treatment, such as diagnosis adjustment. Women may experience effect on fertility or body/genital image and for problem-solving a range of symptoms consistent with posttraumatic stress disorder. practical difficulties. Review of surgery and dilation for vaginal hypoplasia 795

Figure 4 Treatment protocol. Vaginal examination by a gynaecologist is followed by at least one therapy session by a clinical psychologist/sexologist to identify any contraindications to using dilators (e.g. depression) and maturity of the patient, optimizing the probability of a positive outcome of treatment. Potential benefits of dilation as perceived by the patient as well as potential obstacles associated with implementing the regime are elicited. The women are encouraged to solve problems around any identified difficulty. Once an initial trial of dilation treatment uptake is agreed upon, standardized spoken and written instructions on vaginal dilation are given and patients are shown by a specialized physiotherapist how to apply gentle pressure to the vaginal dimple using dilators for 20 min daily, 7 days a week. The dilators range upward gradually to the size of a man’s fully erect penis. The women are asked to self-monitor their practice and associated pain/discomfort ratings in a diary specially designed for this purpose, which includes extra information on pelvic floor muscle relaxation, genital anatomy, dilator use and pain relief. Moreover, they are given the opportunity to meet with patients who are currently dilating or (successfully) completed the programme, as was originally proposed by Ingram (1981). After 6 weeks, the initial trial is evaluated with the psych- ologistand physiotherapist to ensurethatthewomen arestill motivated tocontinue. If not, treatment is suspended and reasonsfor discontinuationexplored and discussed in multidisciplinary team meetings. If the patient decides to discontinue, the laparoscopic Vecchietti procedure is the method of choice for further neovaginal creation (Vecchietti, 1979). If dilator treatment is continued, patients attend for up to five follow-up visits at 6–8 weeks apart with the physiotherapist, and after 12 weeks with the gynaecologist to evaluate the anatomical results. Telephone and email contact is available if required. Emotional and psychological support from the team clinical psychologist is available as needed before, during or after treatment. Treatment is deemed completed when a patient is able to engage in pleasurable sex and/or coitus with no difficulty or if a vaginal dilator can be easily inserted to ≥7 cm. At completion of the treatment, women are encouraged to maintain dilation two times a week for 20 min when not sexually active.

(ii) Providing stronger cues to action, such as additional information (iii) Emphasizing the benefits (e.g. sexual function is possible by achiev- (e.g. websites, easy-to-follow instructions boosting patient’s ing greater vaginal length) and overcoming the barriers (e.g. having a confidence to correctly use the dilators), and easy dilator provision sense thatit is not right or natural to touch genitals or treatment trig- (e.g. through the hospital pharmacy). Also, regular vaginal examina- gers flashbacks to previous traumatic experiences such as unsuc- tions by clinicians and personal experience of anatomical and func- cessful attempts at intercourse) (Liao et al., 2006). The extent of tional success can act as confirmation of the efficacy of dilators. a positive attitude towards treatment (i.e. benefits outweighing However, as vaginal size in non-sexual situations can be a poor pre- the barriers) and the perceived efficacy (i.e. personal beliefs of dictor of pleasurable intercourse upon sexual arousal, clinicians how likely it is that dilation will work) will be central to a woman’s should reduce the level of preoccupation with vaginal size solely motivation to repeat the exercises regularly (Alderson and and also emphasize sexual enjoyment. Glanville, 2004). 796 Callens et al.

Figure 5 Determinants of vaginal dilator use.

(iv) Minimizing the perceived threat, such as pain during intercourse. the long-term, would provide a more precise indication of the effect of Anxiety can lead to a higher anticipation of pain, thereby exacerbat- any treatment. ing pain by intensifying muscular spasms. Relaxation training and Secondly, reports on the associated anomalies have not been the psychological pain management techniques in the treatment of dys- major focus of recent papers on vaginal agenesis. No firm conclusions pareunia associated with gynaecological conditions, such as vulvar can be drawn about certain anatomical prerequisites for treatment vestibulitis, might be useful (Bergeron et al., 2001). success (e.g. presence of hymen), and further comparative studies between 46,XXwomen and46,XY women with vaginalhypoplasia indif- ferent areas are highly valued. For instance, the relative contribution of Remaining questions and future hormonal factors in sexual dysfunction, in CAIS versus MRKH, has to be further elucidated. In addition, fertility considerations remain a chal- perspectives lenging aspect. To date, it is difficult to reach any conclusion about the The current review has highlighted the need for further investigations in a potential clinical pregnancy rate in women with MRKH, after ART and number of areas. First, a fuller awareness of a need to assess treatment gestational carriers, as national or international databases recording outcomes (i) at various developmental timepoints, (ii) both qualitatively this type of information are non-existent and numbers in the published and quantitatively and (iii) with an improved research methodology in- series are relatively small. Successful reports on uterine transplants cluding a wider range of psychosexual matters, such as the quality of in- open up the future possibility of this form of treatment, but also raise timate relationships, and partner-independent sexual activities. While it ethical issues. Given the considerable variability in Mu¨llerian structures is of relevance in these groups of women to defocus on penile–vaginal in patients with 46,XX MRKH, it is clear that all aspects of treatment intercourse and to discuss sexual intimacy in broader terms, the signifi- requireatailored approach. In parallel, in women with a 46,XYkaryotype cance of coital activity is, however, still culturally reinforced and will individualized gonadal management is necessary. therefore remain an important aspect of the clinical management and Thirdly, the possibility of coital dilation should be further taken into evaluation of women with vaginal agenesis for some time. Longitudinal consideration and explained to the patients as one of the available thera- studies, incorporating a head-to-head prospective evaluation of inter- peutic procedures. The impact of further sexual activity post-treatment ventions, should be undertaken. The majority of studies evaluated had on anatomical outcomes needs further investigation, as this could not be a retrospective design, and pretreatment measures were available for confirmed in all studies. comparison only in a handful of studies (El Saman et al., 2007, 2011; Fourthly, additional experience has to be gained on how psychological Ismail-Pratt et al., 2007; Walch et al., 2011; Cao et al., 2012; Michala input may impact on the processes of diagnosis and treatment. Psycho- et al., 2012). Comparing pre- and post-treatment results, specifically in therapy might provide an exploration of alternatives to penetrative Review of surgery and dilation for vaginal hypoplasia 797 intercourse. 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