Results

Study selection and Characteristics

A total of 3954 articles (Figure 1) were identified and 51 included (Table i), of which 21 reported surgery duration (Figure S2), 29 vaginal depth (Figure 2), 44 surgical complications (Figure S3), 20 complaints (Figure S4), 33 satisfaction (Figure S5), 44 sexual function (Figure S6) and 9 QoL (Table ii). A high intercontinental diversity of patient-population and techniques was observed (Figure S7).

Risk of bias of included studies

A NOS quality assessment judged on: study group selection; group comparability; and ascertainment of exposure or outcome of interest (Figure S8). Articles rated as 34 (66.7%) high risk, 15 (29.4%) very high risk of bias and two (3.9%) high quality, based on bias likelihood and completeness of reporting (Figure S9). Bias according to the NIH tool (Figure S10) was rated as 1 (2.0%) bad, 9 (17.6%) poor, 21 (41.2%) fair and 20 (39.2%) good (Figure S11). MOOSE guidelines were followed.39

Synthesis of results

Gender Dysphoria

Vaginoplasty outcomes of 3,310 MtF GD-patients were reported in 35 articles (Figure S7C). The majority discussed Penoscrotal- or Penile-inversion-vaginoplasty for reconstruction with local tissue, where inversed penile skin forms the neovaginal cavity and penile/scrotal skin the external genitalia. Other neovaginal lining approaches are Intestinal-, Skin flap-, Combined- or Peritoneal-intervention. Penoscrotal Gender Assignment Surgery (GAS) was covered most often (19 articles), with continuous attention since 1995 (Figure S7D). GAS duration (Figure S2) increased with required tissue quantity for reconstruction (from Penile-inversion-, to Penoscrotal- and to Combined-intervention). GAS resulted in ‘successful’ lengths of ≥11 cm after Penoscrotal- and Intestinal-vaginoplasty and 11.57 cm (range 9.6-13.5 cm) total average length. Peritoneal-vaginoplasty for GAS is the most recent development.

Mayer-Rokitansky-Küster-Hauser

Despite similar prevalence, surgical vaginoplasty of only 906 MRKH-patients was reported in 15 articles. These predominantly (43.93%) involved Davydov-surgery, for simplicity and good aesthetics.40 The oldest MRKH-publication dates from 2008 and Wharton-Sheares-George (2019) is the most recent technique. Only Intestinal-vaginoplasty created ‘successful’ lengths and 9.45 cm (range 8.1-10.8 cm) total average length was shorter than GAS-results.

Comparison

The oldest publication (1987) involved Penile-inversion-vaginoplasty and remained unpublished next until 2009, when vaginoplasty techniques and publications grew rapidly. GAS was significantly longer (274.75 min, range 211-640 min) than MRKH-procedures (84.27 min, range 22-198 min), where not only a partial neovagina but also the labia (minora and majora) and clitoris are created. In both patient cohorts, Intestinal-vaginoplasty was most time consuming (Figure S2) and reported the longest neovaginas (Figure 2), because of abundantly available graft tissue. Intestinal-vaginoplasty is performed significantly less often on GD-patients (p<0.00001) based on one-tailed Z-score Calculation (Figure S7C). Vaginoplasty is performed open or vaginally, but Vecchietti-, Davydov- and Intestinal-vaginoplasty have laparoscopic alternatives to decrease complication rates.41Complications were associated with length reduction and dilation prevents up to 4 cm depth loss in the first 10 post-operative days.

Surgical complications

Data on complications were retrieved from patient files. Wharton-Sheares-George- and Skin Flap-interventions reported no complications.

Gender Dysphoria

Hemorrhage was only reported after GAS (Figure S3A/B), with peri-operative estrogen continuation as associated risk factor. Hemorrhage (Clavien-Dindo classification II) was often non-severe and treated non-operatively by dressings, transfusion, cooling or adrenalin injection. Causes included hematoma, necrosis, infection, dilation injury, granulation or fistula and delayed wound healing.
Tissue necrosis was reported after Penile-inversion- and Penoscrotal-GAS and decreased with graft quantity (Figure S3C). Treatment (of Clavien-Dindo classification I – IIIb) ranged from local wound care and surgical debridement to complete reconstruction for major necrosis, but labia majora disunion or graft loss was sporadically observed.
Vaginal prolapse was caused by inadequate vaginal canal dissection or non-adherence of skin grafts. This is prevented by sacropexy (fixation to sacrospinous ligament) or penoscrotal apex fixation to Denonvillier’s fascia. Treatment (Clavien-Dindo classification IIIa, b,) entailed neovaginal flap reinsertion (using fibrin glue) or revisions for mucosal prolapse (Figure S3E).
Stenosis 25,42 is the most common complication reported after GAS, caused by contraction in the initial 3 post-operative months by dilation incompliance and inversely proportional to graft quantity (Figure S3G). Treatment (Clavien-Dindo classification IIIa, b) of introital/vaginal stenosis consists of self-dilation, pelvic floor physiotherapy and occasional revisions. Meatal stenosis can result from corpus spongiosum remains that obstruct urine flow by thickening during excitement and is treated by urethral dilation or meatotomy (with corpus spongiosum resection).
Gastrointestinal complications were caused by peri-operative rectal injury or vascular lesion after perineal dissection or by post-operative dilation injury, infection and retraction, abscess, hematoma or (rare) neovaginal malignancy (Figure S3I). This is avoided by meticulous dorsal preparation from perineal body to prostate along Denon Villiers fascia to the tips of seminal vesicals. Treatment (Clavien-Dindo classification IIIb) required temporary colostomy or graft interposition between rectum and vagina.
Revisions (with Clavien-Dindo classification IIIb) were required for introital/meatal stenosis, necrosis, prolapse, fistula, hematoma, infection/wound dehiscence, corpora tissue resection and mostly esthetical enhancement (of labia). These GAS-reported revisions were inversely proportional to graft quantity (Figure S3K). High revision rates were explained by full health-insurance coverage and post-operative transparency of options and were associated with decreased patient regret and dissatisfaction with (aesthetic or functional) surgery outcome.

Mayer-Rokitansky-Küster-Hauser

Necrosis was reported often after McIndoe-surgery (Figure S3D) with sporadic graft loss and was associated with points of maximum tension (i.e., vaginal introitus) due to vascular spasm, restricted blood flow or altered blood supply after transverse lesion of the spinal cord.
Most prolapses were reported after Intestinal-vaginoplasty and were related to inadequate vaginal canal dissection or non-adherence of skin grafts (Figure S3F).
Stenosis after Peritoneal-vaginoplasty correlates to dilation incompliance and is avoided by a pedicled flap from rectosigmoid colon or four sutures at the introital, mucosa-peritoneum interface (Figure S3H).
Gastrointestinal complications were reported after Peritoneal-vaginoplasty (Figure S3J).

Complaints

Complaints were rarely reported. Only Bouman et al.17and Uncu et al.43 evaluated patient-reported outcomes by a short questionnaire and satisfaction scores, respectively. Excessive vaginal discharge (Clavien-Dindo classification I) was mostly reported during follow up or by secretion scent assessment by physicians (Figure S4A/B). Most studied grafts reported 0% vaginal hair14,43,44 and are praised for their non-hair bearing property like penile, scrotal and intestinal tissue. Complaint treatments were not discussed.

Gender Dysphoria

Excessive vaginal discharge was rarely reported, because mostly penile and/or penoscrotal skin is applied without inherent mucous producing tissue properties.
Vaginal hair growth was reported 5% by Gupta and Gupta45 after Combined-GAS and 26.3% by Gentile et al.46 through a patient satisfaction questionnaire.
Genital pain (Clavien-Dindo classification I) was reported after Penile-inversion- and Penoscrotal-GAS (Figure S4E), no treatment was mentioned. Buncamper et al.47 questioned patient satisfaction and Rossi Neto et al.48 studied clitoral and genital pain during follow up. Only Lawrence49 and Sigurjonsson et al.50 applied extensive self-made questionnaires to investigate satisfaction and pain, respectively.
Fecal issues (diarrhea, bowel complaints, incomplete emptying - Clavien-Dindo classification I) were assessed after Intestinal-GAS by Amsterdam Hyperactive Pelvic Floor Scale-Women (AHPFS-W)51 by Bouman et al.17 and after Penoscrotal-GAS by established questionnaires52–54 by Kuhn et al.55 and were left untreated (Figure S4F). These questionnaires also assessed urinary issues.
Urinary issues (urgency, stress incontinence, stream misdirection - Clavien-Dindo classification I-II) were reported during follow up after Penile-inversion-, Penoscrotal- and Combined-GAS (Figure S4E).25,48,56–60 Only Lawrence49and Kuhn et al.55 used self-made and established questionnaires.52–54 Urinary issues were caused by small prostates, perineal dissection and urethral sphincter injury and often non-surgically resolved by medication or pelvic floor physiotherapy.

Mayer-Rokitansky-Küster-Hauser

Excessive vaginal discharge was predominantly reported after MRKH-vaginoplasty with mucus producing applied grafts. All McIndoe-patients experienced vaginal discharge with scent and Intestinal-vaginoplasty reported more discharge complaints amongst MRKH-patients. Vaginal discharge was often gradually decreasing and mainly present in the initial 3-6 post-operative months. Physicians often consider self-lubrication an advantage of Intestinal-vaginoplasty, but not all patients agree on this.
Vaginal hair growth was reported 42% during follow up by Hayashida et al.61 after McIndoe-surgery.

Satisfaction

Body self-image was often assessed with the General Health Survey (SF-36)62,63 and Female Genital Self-Image Satisfaction (FGSIS) questionnaire.16,17,25,47,64Diverse evaluation tools assessed 2-point,14,43,65–673-point,68 5-point56,60 or 10-point satisfaction scales42,69 or surgeons’ view on aesthetics.70,71 Dissatisfaction was assessed with 2-point,58,65,72,73 3-point17,25,47or 5-point50,70,71 scales or by examiner’s rating of the vulva59 and the Short Questionnaire for Self-Evaluation of Vaginoplasty (SQSV) was applied most often.17,25

Gender Dysphoria

Aesthetic satisfaction (Figure S5A) was high after Penoscrotal-, Intestinal- and Combined-GAS. Penile-inversion-, Penoscrotal- and Intestinal-GAS reported dissatisfaction (Figure S5E) and highanatomical satisfaction (Figure S5C), based on patient-reported outcome as yes/no14,50,58,60,65,66,74 or ‘deep enough for vaginal intercourse with a man’.17,25,59Regret was solely investigated after GAS, absent in 2-point evaluations,65,66,69,74 sporadic and present after Penile-Inversion- and Penoscrotal-GAS (Figure S5G). Regret was associated with pain, vaginal hair and lower satisfaction and caused once by an unfulfilling new life. Another regretful patient (without mentioned cause) would undertake surgery again.

Mayer-Rokitansky-Küster-Hauser

Aesthetic satisfaction (Figure S5B) was high after Intestinal- and Peritoneal-vaginoplasty. Full anatomical satisfaction was achieved for all MRKH-procedures (Figure S5D), based on assessment of patient-satisfaction72,73,75 or anatomical standard.41,64,76 Intestinal-vaginoplasty reporteddissatisfaction (Figure S5F) and Peritoneal-Vaginoplasty reported full anatomical and overall satisfaction.

Sexual functionality

Intercourse initiation was at 6-8 months, at 70% epithelialization or when desired. Sexual activity varied gravely as 21-100% at 1-132 post-operative months during assessment (Figure S6A/B). The definitions of sexual activity in the included articles varied as regular activity,58,73,74,77any14,17,78–80,41,44,60,61,66,70,72,75 in the last month,47,62 vaginal intercourse43,45,81,82 with a man25or married with sexual activity.83
Sexual function was assessed most often with the Female Sexual Function Index (FSFI).16,17,76,78,80,81,84,25,47,62–64,70,72,73Dyspareunia was also reported by 5-point,604-point,59 3-point68 and 2-point17,25,70,72,73,76,79,83,43,44,48,55,58,61,64,66self-made questionnaires and present after all but the Wharton-Sheares-George-technique (Figure S6C/D).
Satisfaction with sexual function (overall, orgasmic function or vagina depth) amongst sexually active (or married76) patients was also reported by diverse 10-point,695-point,46,60 3-point,68,71,852-point14,41,87,43,55,61,65,66,75,79,86 and self-made questionnaires (Figures S6E/F). Sexual dysfunction associated with inadequate depth,45 lubrication issues, sexual discomfort, sporadic ejaculation and clitoral erection (after Penile-inversion-surgery)25 and excessive secretion, dyspareunia25,61,79 and vaginal stenosis.43

Gender Dysphoria

Dyspareunia was inversely proportional to graft quantity. Intestinal-GAS reported full functional satisfaction 16 and fullsensation 16,17 (Figure S6G). Despite high sexual responsiveness, orgasmic capacity was post-surgically diminished in some to most GAS-patients.

Mayer-Rokitansky-Küster-Hauser

Sexual activity was higher and initiated earlier after (Intestinal) MRKH-procedures than after (Intestinal-)GAS. With Wharton-Sheares-George-surgery, satisfaction increased over time from 6-12 post-operative months.78 Orgasmic and erotic sensation were seldom reported (Figure S6H).64,75,76 Fertility was restored in three patients.44

Quality of life

QoL was assessed in 9 articles (Table i) with Self-designed, Beck Depression Inventory (BDI),88 Short-Form-36 (SF-36),89 Fragen zur Lebenszufriedenheit (FLZ),90–92 Patient Health Questionnaire 4 (PHQ-4),93 Rosenberg Self-esteem Scale (RSES),94 Subjective Happiness Scale (SHS),95 Satisfaction With Life Scale (SWLS)96,97 and Cantril’s Ladder of Life Scale (CLL)98 questionnaires.

Gender Dysphoria

Intestinal-GAS reported 100% slight-to-extreme satisfaction with life, that ranged from struggling to thriving life.17Penile-inversion-vaginoplasty reported normalQoL 99 and partnered patients scored higher on vitality, social functioning and mental health.63 Skin flap-GAS reported minimal depression by decreased sexual satisfaction.62 Penoscrotal-vaginoplasty improved personality, lifestyle and self-esteem,71,100 body and femineity satisfaction100 and overall QoL49,69,77 with low post-operative depression71,100 and anxiety.100Anatomical satisfaction and sensation correlated to increased and genital pain to decreased QoL-scores.49 Despite mostly positive QoL-outcomes, one study reported low general life satisfaction and unaltered aesthetic satisfaction compared to pre-operative results.69

Mayer-Rokitansky-Küster-Hauser

One QoL -study reported on MRKH-patients and showed 22.2% mild/moderate depression.70