TABLE 1.

Study Characteristics, Patient Demographics, Intervention Types and Outcomes

Reference	Study type	Study population	Age (years)	Intervention	Follow‐up	Results	Complications
Casabona et al., 2010 32	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 15, female, histologically proven LS	Range 27–62	10–15 cc lipoaspirate Co‐intervention: 5 cc PRP pre‐treated with 0.5 cc of calcium chloride for platelet degranulation Intramucosal, subdermal and submucosal Patients with severe fibrosis underwent one or two extra procedures, after 3 months respectively	Questionnaires (non‐validated), photographic and physical evaluation up to 24 months postoperative. No specific index parameters were mentioned	After 15 days symptoms started to improve. Itching and burning disappeared within one month. Four months after surgery, all patients reported total disappearance of pain, regained sexual activity and normal appearance of anatomical features of the vulva. No statistical analysis	No adverse events were observed. All patients had moderate pain in the treated areas for 10 days after surgery
Boero et al., 2015 33	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 36, female, histologically proven LS	Range 25–80	8–15 cc lipoaspirate All perivulvar layers up to the fascia	Vulvoscopic examination and DLQI and FSFI questionnaires up to 24 months postoperative. Histological evaluation through punch biopsies preoperative and 8 months postoperative	94% showed improved vulvar trophism of the skin and mucosa. QoL was significantly improved for both DLQI (p < 0.0001) and FSFI (p < 0.0001). On a histological level, reduction of hyperkeratosis (67%), reduction of chronic inflammation (89%), reduction of fibrosis (67%), increased angiogenesis (44%) and reduction of dermal oedema (33%)	No adverse events were observed. 30% of patients had pain for 10 days after surgery
Tamburino et al., 2016 34	Case report	N = 1, female, histologically proven LS	48	40 cc lipoaspirate Co‐intervention: 20 cc Nanofat Subcutaneous, intradermal	Questionnaires (not validated) up to 8 months postoperative. No specific index parameters were mentioned	Decreased symptoms and anatomical features of LS with the greatest improvement in the first two months postoperative and maintained up till 8 months. No specifications were mentioned	Not described
Onesti et al., 2016 35	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 8, female, 1 with symptoms during menopause, 2 with vulvar scarring due to chronic GVHD and 5 affected by LS	Range 38–75	2 cc ASC‐HA solution Subcutaneous of labia minora	Histological, FSFI questionnaires and physical evaluation up to 24 months postoperative	All patients mentioned pain reduction and improved sexual function. Histological examination in LS patients showed significantly reduction of dermis sclerosis, less dilated capillaries and reduced inflammatory infiltrate. No statistical analysis	Not described
Kim et al., 2017 36	Case report	N = 1, female, affected by vaginal atrophy (no histologically proven LS)	67	36 cc lipoaspirate Co‐intervention: 4 cc PRP Subcutaneous	Physical evaluation up to 12 months postoperative. No specific index parameters were mentioned	Relieve of vaginal pruritis and irritation, restoration of labia majora contour. White patchy lesions improved	No adverse events were observed
Newman et al., 2018 37	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 111, female, histologically proven LS	Range 20–76	8–15 cc tSVF Co‐intervention: 2–3 cc PRP with Lidocaine with Epinephrine 1:100 000. Subcutaneous, intradermal	Questionnaires (not validated) up to 3 months postoperative. No specific index parameters were mentioned	All patients experienced improvement of symptoms, with a significant decrease per symptom of 38%–68% (p < 0.001)	No serious complications were described. Side effect, such as swelling, bruising, burning and discomfort were noted
Stark et al., 2020 38	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 10, females affected by vaginal atrophy, vulvovaginal dystrophy, and/or stress urinary incontinence	Range 30–60	8.5–32 cc (average of 24 cc) Nanofat Subcutaneous and subepithelial	Physical evaluation up to 12 months and questionnaires (not validated) up to 24 months. No specific index parameters were mentioned	All patients reported an improvement of symptoms after 6–16 months, differing from sexual activity, improved vaginal appearance and itching. No statistical analysis	No adverse events were observed
Almadori et al., 2020 39	Prospective, non‐controlled, non‐blinded, non‐randomized	N = 33, female, histologically proven LS	Range 38–63	10 cc lipoaspirate In labia majora, labia minora, clitoral area, posterior fourchette, perianal area	FSFI, FSDS, VASs, PASS‐20, HADS, RAS and WMQ‐R questionnaires up to a mean follow up of 12.9 months postoperative	Improvement of sexual function (p < 0.001), as well as the distress associated with sexuality (p < 0.0001), romantic relationship (p < 0.05), anxiety (p < 0.0001) and depression (p < 0.0001). Decrease of symptoms such as itching (p < 0.001), burning (p < 0.05), soreness (p < 0.001), pain (p < 0.0001)	Not described
Tedesco et al., 2020 40	Prospective, controlled, non‐blinded, non‐randomized	N = 40, female and male, histologically proven LS	Range 43–78	15 cc tSVF Co‐intervention for 20 patients: 4 cc PRP Two procedures per patient distanced over 4‐months. Intradermally	Physical examination during every visit and DLQI questionnaires up to 6 months follow up	Significant improvement of QoL was observed in both groups after one month. After 6 months the SVF‐group showed a significant improvement of QoL, the SVF‐PRP combination group little improvement compared to pre‐operative QoL	No severe or mild side effects were observed during and after the procedure

Abbreviations: (t)SVF, (tissue or mechanically isolated) stromal vascular fraction; ASCs, adipose‐derived stromal cells; DLQI, dermatology life quality index; FSDS, female sexual distress scale; FSFI, female sexual function index; GVHD, graft versus host disease; HA, hyaluronic acid; HADS, Hospital Anxiety and Depression Scale; LS, lichen sclerosus; PASS‐20, Pain Anxiety Symptom Scale Short Form 20; PRP, platelet rich plasma; QoL, quality of life; RASS, Richmond Agitation‐Sedation Scale; VASs, Visual Analogue Scale; WMQ‐R, Wound Management Questionnaire.