Results

Study selection and Characteristics

The PRISMA flow diagram of the meta-analysis is shown in (Figure 1). A total of 3954 articles were identified. Of 47 included articles (overview in table i), 19 reported on operation times (Figure S1), 26 on vaginal length (Figure 2), 40 on surgical complications (Figure S2), 20 on complaints (Figure S3), 30 on satisfaction (Figure S4), 40 on sexual function (Figure S5) and 9 on QoL (table ii). A high intercontinental diversity of patient-population and techniques was observed (Figure S6a/S6b).

Risk of bias of included studies

Quality of nonrandomised studies was assessment by NOS and judgment of: study group selection; group comparability; and ascertainment of exposure or outcome of interest (Figure S8). Manuscripts were judged as 31 (66.0%) (B) high risk of bias, 15 (31.9%) (C) very high risk of bias and one (2.1%) (A) high quality, based on likelihood of bias and completeness of reporting (Figure S9). Bias was assessed with the NIH tool (Figure S10). Studies were judged as 1 (2.1%) (A) bad, 9 (19.1%) (B) poor, 19 (40.4%) (C) fair, 18 (38.3%) (D) good and 0 (E) excellent (Figure S11). In both assessments no weighting was used. MOOSE guidelines were followed.53

Synthesis of results

Surgical outcomes of 2927 MtF Gender Dysphoria-patients were reported in 32 articles (Figure S7a). The majority is treated by penoscrotal- or penile-inversion vaginoplasty, to allow reconstruction from local tissue as the inversed penile skin forms the neovaginal cavity and penile/scrotal skin the external genitalia with alternative neovaginal lining by an intestinal- graft-, Skin flap- or Combined interventions. Treatment of 853 MRKHS-patients was reported in 15 articles and predominantly (44,20%) involved Davydov surgery. Even though non-surgical MRKH-treatment options are associated with low satisfaction, vaginal prolapse, fatigue, long-term agony and mental as well as emotional stress,4,5 this is still favoured by many patients and physicians. The intestinal surgery proportion of MRKH-patients, differs significantly from GD-patients (p<0.00001) based on one-tailed Z-score Calculation (Figure S7a). The Skin flap vaginoplasty proportion of MRKH- and GD-patients, are not significantly different. Vecchietti-, Davydov- and Intestinal vaginoplasty can alternatively be performed laparoscopically to decrease complication rates,54 all other techniques are performed by open or vaginal approaches.
Highest publication quantity involved penoscrotal SRS, that was reported in 18 out of 32 GD-related articles, with continuous attention since 1995 (Figure S7b). Davydov was reported in the majority of MRKHS-surgeries, due to simplicity and good aesthetics.55 The oldest publication (1987) involved penile-inversion vaginoplasty and stayed unpublished next until 2009, when vaginoplasty publications and performed techniques grew rapidly. The oldest included MRKHS publication dates from 2008 and Wharton-Sheares-George (2019) is the latest surgical technique.
Surgical outcomes - complications
The average vaginoplasty duration is 198.0 min (152-244 min) (Figure S1). Combined vaginoplasty (312 min) is the longest procedure, where penile-inversion- (216 min) or penoscrotal (286 min) surgery is combined with a secondary approach. SRS duration increased with required tissue quantity for reconstruction and were slightly longer (216-378 min) than MRKH-procedures (26-300 min).
Pooled complications showed 5% hemorrhage and 1% gastrointestinal complications (peri-operative), and 1% prolapse, 3% tissue necrosis, 6% stenosis and 31% revisions (long-term post-operative) after complications or patient-reported aesthetic complaints (Figure S2).
Combined vaginoplasty reported most hemorrhagic complications (29%) (Figure S2a). Hemorrhage only resulted from SRS, was often non-severe and treated non-operatively by dressings, transfusion, cooling or adrenalin injection. Bleedings resulted from hematoma, necrosis, infection, dilation injury, granulation or fistula and delayed wound healing. Associated risk factors are clotting disorders and smoking, peri-operative estrogen continuation (depending on administration route and also decreases bleeding during sponge body dissection by erectile reflex elimination) and NSAIDs are sometimes avoided (Hontscharuk et al. 2021).
Gastrointestinal complications were predominantly reported after SRS, with 2% after penile-inversion- and penoscrotal surgery and 3% after intestinal vaginoplasty (Figure S2b) and were associated with dilation injury, infection and retraction, abscess, hematoma or (rare) neovaginal malignancy. Recto-neovaginal fistula presented after peri-operative rectal injury or vascular lesion by perineal dissection and may require temporary colostomy or graft interposition between rectum and vagina. Rectal injury may be avoided by meticulous dorsal preparation from perineal body to prostate along Denonvilliers fascia to the tips of seminal vesicals.
Intestinal vaginoplasty reported most prolapses (4%) (Figure S2c), after inadequate vaginal canal dissection or non-adherence of skin grafts, with BMI as only known predictor. Treatment entailed neovaginal flap repositioning/reinsertion (using fibrin glue) and revisions for mucosal prolapse, whereas sacropexy (graft fixation to the sacrospinous ligament) or penoscrotal apex fixation to Denonvillier’s fascia help avoid prolapse.
McIndoe surgery reported most tissue necrosis (17%) (Figure S2d), often at points of maximum tension (i.e., the vaginal introitus) due to vascular spasm, restricted blood flow or altered blood supply after transverse lesion of the spinal cord. Smoking, diabetes and cardiopulmonary conditions are predictors and may be reduced by patient-behaviour. Treatment involved local wound care and surgical debridement or reconstruction for major necrosis, but labia majora disunion or graft loss was sporadically observed.
Most reported complication is introital-, meatal- or vaginal stenosis14,58 and is mainly seen after penile-inversion vaginoplasty (19%) (Figure S2e), due to lack of compliance with dilation (or regular intercourse) to prevent contraction in the initial 3 post-operative months. Treatment entailed daily self-dilation, pelvic floor physiotherapy and occasional revisions after suture line rupture by forceful dilation. Meatal stenosis is treated by urethral dilation or meatotomy with optional resection of corpus spongiosum remains that obstruct urine flow by thickening during excitement. Predictor for meatal stenosis is early transurethral catheter removal, whereas prolonged catheterization increases risk of urinary tract infections. A pedicled flap from rectosigmoid colon or four sutures at the introital, mucosa-peritoneum interface during Davydov surgery help avoid stenosis.
Revisions were reported after penile-inversion- (37%), penoscrotal- (29%), intestinal- (42%) and combined (12%) SRS (Figure S2f), for introital/meatal stenosis, necrosis, prolapse, fistula, hematoma, infection/wound dehiscence, corpora tissue resection and mostly esthetical enhancement (of labia). High revision rates were associated with full health-insurance coverage and post-operative transparency of options and rarely led to patient regret or dissatisfaction with (aesthetic or functional) surgery outcome.
Wharton-Sheares-George interventions reported no complications.
Anatomy
The average neovagina length was 10.18 cm (9.05-11.31 cm) (Figure 2). Intestinal vaginoplasty reported the longest (13.08 cm) and Wharton-Sheares-George the shortest neovagina (7.60 cm). Only Intestinal- and Penoscrotal vaginoplasty resulted in ‘successful’ lengths of ≥11 cm. Complications were associated with length reduction and dilation prevents up to 4 cm depth loss in the first 10 post-operative days.
Complaints
Complaint-reports were rare and included 25% excessive secretion, 6% genital pain, 42% hair growth, 11% fecal- and 17% urinary issues (Figure S3). Surgeons consider self-lubrication an advantage of Intestinal vaginoplasty and 28% of the patients consider it a gradually decreasing, non-excessive or non-irritating problem. All McIndoe patients complained about excessive secretion with scant as major issue and only this group reported hair growth. Davydov patients reported 8% excessive secretion during the initial 3 months. Pain (clitoral or pain during sexual arousal or intercourse) was reported after Penile-inversion- (4%) and Penoscrotal (8%) interventions. Fecal issues involved bowel complaints after intestinal SRS (3%) and fecal urgency or incomplete bowel emptying after penoscrotal (17%) interventions. Urinary issues (urgency, stress incontinence or misdirection of the stream) were solely reported with SRS after penile-inversion- (21%), penoscrotal- (21%) and combined (1%) surgery. Small prostates, pelvic floor dysfunction (by perineal dissection) and urethral sphincter injury are known predictors for urinary incontinence and is often non-surgically resolved by medication or pelvic floor physiotherapy.

Satisfaction

Patient-reported outcomes (Figure S4) included 10% overall dissatisfaction, 1% regret, 95% aesthetics- and 93% anatomical satisfaction. Highest reports were seen for dissatisfaction after Intestinal vaginoplasty (23%), overall satisfaction after Combined interventions (98%) and anatomical satisfaction after McIndoe-, Peritoneal- and Vecchietti surgery (100%). Sporadic regret was reported after Penile-inversion- (4%) and Penoscrotal interventions (1%), and was associated with hair, clitoral pain and lower satisfaction. One patient regretted an unfulfilling new life and another (without mentioned cause) would undertake surgery again.

Sexual functionality

Pooled outcomes (Figure S5) showed 75% sexual activity, 13% dyspareunia, 87% sensation and 84% function satisfaction. Penoscrotal surgery (61%) reported lowest and Skin flap surgery (100%) the highest sexual activity. Dyspareunia was reported for all except Wharton-Sheares-George technique. McIndoe-surgery (69%) reported lowest and Intestinal vaginoplasty (98%) reported highest dyspareunia. Functionality was reported good/excellent for Combined-, Intestinal-, Penoscrotal- and Peritoneal surgery, acceptable for McIndoe- and poor for Penile-inversion surgery. Intercourse initiation variated with 6-8 months, if desired, or at 70% epithelialization.
Most MRKH-patients initiated intercourse 1-4.5 months after intestinal-surgery and after Skin flap-surgery with 110.3% improvement despite dyspareunia. All sexually active patients from a mixed cohort declared full functional- and aesthetic satisfaction. All MRKH-patients were highly to fully satisfied. After McIndoe- and intestinal-vaginoplasty there was respectively one complaint on excessive secretion and sexual arousal. Fertility was restored in 3 MRKH-cases. Wharton-Sheares-George surgery required molds for 6 months, with increased FSFI-scores from 6 to 12 post-operative months. Most peritoneal-vaginoplasty patients had full functional- and anatomical satisfaction within 12 months, except for one mild dyspareunia complaint (resolved by lubrication) and one case of sexual dysfunction due to vaginal stenosis. GD-patients were less sexually active, but FSFI-scores were similar for transwomen after intestinal- and penile-inversion vaginoplasty and for MRKHS-patients after sigmoid vaginoplasty. SRS-subjects mostly confirmed sexual responsiveness, although orgasmic capacity was post-surgically diminished in some to most patients. Penile-inversion-surgery reported ≥50% sexual dysfunction with good overall and aesthetic satisfaction, but low functionality satisfaction (caused by inadequate depth, lubrication issues, sexual discomfort and sporadic ejaculation, clitoral erection and pain during initial penetration or after sex). Most penoscrotal-patients had regular intercourse, adequate or satisfactory depth and achieved neoclitorus-stimulated orgasms. Excessive erectile tissue, recurrent bleeding after or suture line rupture during intercourse, pain, cosmetical dissatisfaction, orgasm difficulties, inadequate depth, stenosis or insensate clitoris (corresponding with penile-inversion-patients) caused sexual dysfunction. Some SRS-complaints about sexual function, are correlated to gender dysphoria and the old male body physique. Penoscrotal-surgery significantly increased femininity and sexual activity.

Quality of Life

Patient-reported QoL was studied in 9 articles (table ii), with one MRKHS-patient assessment mixed with intestinal-patients, showing 22.2% mild/moderate post-operative depression. Happiness after Intestinal-vaginoplasty was normal, with 100% slight-to-extreme satisfaction with life.59–61 QoL after Penile-inversion-vaginoplasty was normal62 and partnered patients scored higher on vitality, social functioning and mental health. Penoscrotal-surgery improved personality, lifestyle, self-esteem and overall QoL63,64 with low depression-scores and normative anxiety.64,65 It also increased body and femineity satisfaction.66–69Skin-flap GD-patients reported minimal depression, due to decreased sexual satisfaction.70 More in general, anatomical satisfaction and sensation increased, whereas genital pain correlated to decreased QoL-scores.