Role of Fat Transfer and Adipose-Derived Stem Cells in Rejuvenation & Treatment of Female Genital Area

Female Genital Aesthetic Surgery (Cosmetic Gynaecology)

The newly expanding branch of cosmetic and aesthetic surgery is the “Cosmetic Gynaecology” “Female Genital Aesthetic Surgery” which concern about the aesthetic and cosmetic side of the intimate part of female body, includes a number of surgical and non-surgical procedures designed to improve the appearance and functionality in some cases as, it is claimed that, occasionally, sexual function may be enhanced.

Most women who seeking to alter their intimate appearance that has been changed by pregnancies and labour, perimenopausal and menopausal changes, losing weight dramatically or due to pathological condition like infection or lichen planus, etc.

Role of Fat Transfer & Adipose-Derived Stem Cells ADSCs in Rejuvenation & Treatment of Female Genital Area

  1. Fat Transfer for Volume Restoration: restore the lost volume by aging or losing weight, in order to recover the youthful and vitalize appearance to these areas. Some young women with normal genitalia but, still ask for enlargement of labia majora size when its look and feel small in comparison to surrounding to give the area a better shape & appearance.
    • To the labia majora (outer lip) and called Augmentation Labiaplasty
    • fat injections to mons pubis to improve the shape changes by weight lost or aging

    2.Fat Transfer for Rejuvenation of vulvar skin and vaginal wall:  Rejuvenation by injection of stem cell from your own fatty tissue (ADSCs) to rejuvenate & treat menopausal symptoms or vulvar dystrophy of outer side of genital area to get rid from wrinkling and laxity of skin and in some case can do whitening the area if the pigmentation is secondary and not the area natural colour. The stem cells also can be used for vaginoplasty due to the changes in the area. to rejuvenate & treat menopausal symptoms or vulvar dystrophy and using the injected stem cells either as SVF (Stromal Vascular Fraction) or Cultured-ADSCs, PRP (Platelet Rich Plasma) or Nanograft may be used as a medium for SVF.

    3.Vaginal Recalibration by Lipograft Technique: this procedure consists in reducing the vaginal calibre by thickening the vaginal walls with adipose tissue transplant. It is indicated in those patients who feel concern by a sensation of a wide vagina. The causes are often post gravid in multiparous women and sometimes constitutional. Clinical and gynaecological examination many frequently normal. However, may reveal a prolapse which is contraindication for this intervention.

Labiaplasty of Labia Majora (Augmentation & Rejuvenation)

Labiaplasty of labia mojora is the plastic surgery on the outer or the larger lips of the vagina, can be done alone or in combination with vaginoplasty. Fat injections to the labia majora which is called (Augmentation Labiaplasty), to plump out these structures to make it bigger in cases where it is considered to be too small or to correct an asymmetry between them. Other cases are who lack the volume secondary to weight loss or aging to give it a more youthful appearance. However, it not always about the appearance and cosmetic concern. The candidate for labia augmentation and rejuvenatie:on ar

Normal Valvar Tissue: Normal gynaecological examination but, the patient has cosmetic concern:

  1. Normal size and good tone of tissue but, the women seeking labial enlargement as she has a concern about the size of her labia majora &/or shape.

As with many aspects of human anatomy, there are a wide variety of shapes, sizes and appearances of the female genitalia, all of which are within the limits of normal. Before undergoing any surgery, it is important to determine whether there is really a problem with the genitalia or whether another solution would be more rewarding.

  1. Normal size and good tone of tissue but, the women seeking labial symmetry, as she has a significant asymmetry in the size &/0r shape. Naturally there is asymmetry in size between the two labias as with breast in female and testes in male and other body parts but, when the asymmetry is significant and influences the woman self-esteem, in such cases labiaplasty which is a minor surgery can be helpful. The intervention either by doing augmentation labiaplasty for the smaller side (the most common approach) or reduce the larger one. Before any intervention, a proper clinical evaluation should be done to exclude a pathological lesion underlying the asymmetry like haemangioma, lump or cyst formation etc.
  2. Loss of volume and tissue tone, due to involutional changes in the area with aging (labia, mons pubis &/or vagina) or after significant fatty tissue loss from the whole body in short period. Now a day there are increasing in number of cases in need to rejuvenation of mons pubis and external female genital after bariatric surgeries.

Vulvar Dystrophy:  Physiological & Pathological

Vulvar Dystrophy is a condition which may occur in women both in physiological and in pathological conditions. Associated symptoms may include itching, burning, dyspareunia, vaginal dryness and bleeding.

Physiological Vulvar dystrophy (Postmenopausal Female Genital Atrophy)

Vaginal dystrophy commonly affects postmenopausal women, with prevalence ranging from 10% to 50% and it is estimated that up to 45% of all women are symptomatic. However, recognition of their etiology is poorly understood by women and their partners. The diagnosis of vaginal atrophy is typically based on history of certain symptoms and specific physical findings as vaginal tissue and urethral mucosa are altered as a result of the diminished amount of circulating estrogen. Recognized symptoms include;

Vaginal changes: vaginal dryness due to atrophy of the vaginal mucosa and decreased vaginal lubrication, burning, pruritus, abnormal vaginal discharge, and dyspareunia Vaginal inflammation develops due to estrogen-deficient atrophy of the soft tissues. The most common etiology of estrogen deficiency is the natural process of menopause.

External genitalia signs include; atrophy of the labia majora and minora, loss of subcutaneous fat, dry labia, vulvar dermatoses, vulvar lesions, and sparse pubic hair and these external signs also occur due to decreased estrogen level. All these annoying symptoms greatly affect woman’s sexuality and quality of life.

The aetiology of vulvovaginal atrophy among postmenopausal women is most commonly explained by the decrease in circulating estrogen associated with the menopausal transition, which has an adverse effect on skin collagen and elasticity. Even while taking systemic estrogen, 10% to 20% of women may still have residual symptoms.

Current Concept of Management of (Postmenopausal Female Genital Atrophy)

The primary goal of treating genitourinary syndrome of menopause is to relieve symptoms. For women with vulvovaginal symptoms unrelated to sexual activity, first-line therapies include long-acting vaginal moisturizers and a short course of low-dose vaginal estrogen and hormonal replacement therapies. The hormonal replacement therapy is widely available. The route of delivery can be systemic via the mouth, through the skin, via a nasal spray, and by injection. Local treatment includes vaginal ring, creams, tablets, and vaginal pessaries. Although estrogen-based treatments can be effective, according to the Women’s Health Initiative and other clinical trials, However, many patients are reluctant to be treated with such formulations due to health concerns.  Number of menopausal women have discontinued taking hormones, and have turned to herbs, phytoestrogens, and dietary supplements instead because they worry about their reactions to hormones.

Since many patients are reluctant to use estrogen-based treatments due to health concerns, physicians are eager to find acceptable alternatives.

In addition to diminished production of estrogen, vaginal changes are affected also by the aging process like elsewhere in the body. Due to loss of tone and volume of the

tissues by aging, decent and sagging of the skin may follow. These kinds of changes can cause an unattractive aged look of external genitalia. But there is no established treatment for contour correction of vagina.

Role of Stem Cells Therapy in the Management of
(Postmenopausal Female Genital Atrophy)

Lipofilling is an effective and minimally invasive modality to restore tissue volume in both aesthetic and reconstructive surgery. Autologous lipofilling has become a popular procedure for soft tissue rejuvenation and body contouring in aesthetic and reconstructive surgery. Autologous fat can be harvested by relatively simple procedure, and it is completely biocompatible and available in large quantities. But, the disadvantages of lipofilling are its unpredictability and variable reabsorption rate. In addition to the permanent volumetric effect of adipose tissue, certain dynamic phenomena of tissue regeneration occur at the recipient site after adipose tissue transfer. It has been noted by many researches the improvement of the quality of the overlying skin. Since vaginal changes occur following the aging process, we assumed that the regenerative features of lipograft and ADSCs might play a significant role. Recently, PRP has emerged as a new matrix that can enhance fat graft survival. We are using either PRP enriched lipofilling or ADSCs enriched lipofilling to improve the long-term outcome.

The addition of PRP to fat grafts improves graft survival in a simple and safe procedure and less cost. Stem cell enriched fat transfer will be costlier but, more efficient and longer outcome. Besides the volume correction, the patient experienced a substantial relief of symptoms.  

Lipofilling is now widely accepted in expectation of both for the filling and rejuvenating effect. While surgical manipulation and harvest of fatty tissue are generally simple procedures, the tissue itself is complex. Fatty tissue has been found to contain adipocytes and subpopulations of cells including adipose-derived stem cells (ADSCs), that have the potential to aid in tissue regeneration.

 

Pathological Vulvar dystrophy

  1. Lichen sclerosis (LS)

It is a chronic immune-mediated inflammatory skin disorder of poorly understood aetiology, which may be localized anywhere on the body but has a predilection for the anogenital area. The exact aetiology of lichen sclerosus is unknown and probably multifactorial. Although disease onset has been reported at all ages, it occurs most commonly in women in their fifth or sixth decade of life.

Lichen sclerosus is characterized by the presence of well-defined white papules and plaques. The skin affected by lichen sclerosus becomes atrophic or thickened. Genital lichen sclerosus causes both dryness and severe, persistent pruritus, and it often leads to functional impairment. Additionally, subcutaneous bleeding with ecchymosis or haematosis and fissures with superficial ulceration and erosion may occur. Late progressive symptoms include thinning of the mucosa, oedema and fibrosis of the dermis, shrinkage of the labia, and agglutination of the labia minora that can lead to stenosis of the introitus. Moreover, while the disorder is considered benign, some women with vulvar LS may later develop squamous cell carcinoma (SCC) of the vulva and some women have concomitant SCC when initially diagnosed with LS. Vulvar dystrophy may negatively affect the entire sexual response cycle, inducing significant changes in desire, arousal, orgasm, and satisfaction at menopause and beyond. Patients may be embarrassed by the disfiguring changes that may occur and avoid sexual intimacy. Furthermore, these patients may have increased risk to develop bacterial vaginosis due to vaginal pH changes and urinary tract infection or stress urinary incontinence. A vulvar biopsy is recommended when malignancy cannot be excluded or in those who have failed to respond to first-line treatment. But the diagnosis of lichen sclerosus is usually clinical.

2. Non-aging Oestrogen Deficiency:

Symptoms related to estrogen reduction may occur during other stages of women’s lives than menopausal period, in response to events associated with sustained decreases in estrogen such as lactation or also related to chemotherapy that induces premature ovarian failure in 14–100% of cases. These patients are at high risk of transient or permanent amenorrhea, and, for those women who continue to menstruate or who recover their cycles, there is an additional long-term risk of premature ovarian failure. In particular, breast cancer treatment increases the prevalence of vulvar dystrophy because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate this condition.

3. Iatrogenic cause of vulvar dystrophy:

It is related to allogeneic hematopoietic stem cell transplant. This procedure has found a place in the treatment of a variety of malignant and non-malignant diseases of the bone marrow and immune system. However, it may be complicated by chronic graft-versus-host disease (GVHD), due to activation of donor immunological cells against host tissues.

Current Concept of Management of (pathological Vulvar Dystrophy)

Vulvar dystrophy is negatively impacts women’s lives, but women lack knowledge of subject and are hesitant to consult about it. Main treatment for it is currently include drug therapies and lubricants but, in the majority of patients they have limited outcome. The goal of treatment is to reduce symptoms such as pruritus and dryness, improve the patient’s quality of life, and to detect any malignant transformation

Main treatments to solve urogenital and sexual dysfunction due to vulvovaginal tissue alteration currently include drug therapy and lubricants, the treatment of choice in adults and children and in both sexes is an ultrapotent topical steroid but, in the majority of patients these therapies do not imply a complete remission of symptoms.

Role of Stem Cells Therapy in the Management of (Pathological Vulvar Dystrophy Lichen Sclerosis)

In this case, lichen sclerosus was steroid-resistant so that the resolution could be achieved after transfer of autologous fat mixed ADSCs &/or with PRP. As mentioned earlier, ADSCs enriched lipograft has the regenerative properties and capabilities to produce anti-inflammatory and immunomodulatory effect. Besides the presence of ADSCs in the lipograft, PRP seemed to be an essential factor influencing the healing and regeneration process in this case. PRP has shown to enhance wound healing and has rejuvenation effects through the release of significant amounts of growth factors.

How does Stem Cell Therapy work for Vulvar Dystrophy?

Recent studies emphasized that adipose tissue is a rich source of adult stem cells, the which is called Adipose-Derived Stem Cells (ADSCs). They have tested in study published by Giuseppina el al. (2016), the hypothesis that ADSCs can enhance the trophism and tone of dystrophic tissue by applying it to dystrophic valvular tissue as the current treatments often do not imply a complete remission of symptoms. They have concluded that stem cell therapy using ADSCs injection represents a valid alternative therapy to treat vulvar dystrophies, with significant symptoms improvement compare to other modalities of treatment, since it can increase the vascularization due their angiogenic properties and proven eutrophic effect and ability to improve tone and trophism of the involuted and dystrophic tissue.

The process of Adipose-derived Stem Cells Therapy

Stem cell therapy is a term used to define the process of isolating adult stem cells from the host tissue, and then reintroducing them to the area of the body that needs healing or regeneration and in this case is the vulvar tissue and vagina.

The process gets started by locating the ideal place to harvest the adipose stem cells (stem cells that are stored in the fat deposits just below the skin). The extraction is only a limited amount of the fat that stores the stem cell reserves and needs only a local anaesthetic during the procedure.

Once this is harvested, the fat will transfer into sterile container or tube and either process it to prepare the Ready-to-use ADSCs Pellet (from the SVF) or send to specialized stem cells lab where expanded to get higher numbers stem cells (Cultured-ADSCs). The reinjection will be performed under local anaesthesia with sedation.  Recovery is short with extra-care about personal hygiene of the area.

Viginal Tightening & Rejuvenation (Vaginoplasty)

Vaginal laxity is a condition where the connective tissue that support the vagina have become loose, It is often experienced by women going through menopause or those who have recently been through childbirth  but, it can occur to young nulliparous women presenting with wide vagina without perineum lesions . Concerns about vaginal size are quite common because it can affect the sexual gratification, lesser sensitivity and urinary incontinence.

 Term “Vaginoplasty” used to use for procedure that aims to “tighten up” vaginal muscles to correct defects and deformities of vaginal canal, congenital deformities, acquired cause-physical trauma or cancer.

Today, vaginoplasty most commonly used for surgical and non-surgical approaches to manage the childbirth effect and postmenopausal changes. The aim today is not just to “tighten up” the vagina but to rejuvenate it again and revitalize the tissue that has become slack or loose from vaginal childbirth or natural oestrogen deficiency with aging. Post-menopausal vaginal changes include; dryness due to atrophy of the vaginal mucosa and decreased vaginal lubrication, burning, pruritus, abnormal vaginal discharge, and dyspareunia Vaginal inflammation develops due to estrogen-deficient atrophy of the soft tissues. For that, it is more important to address these symptoms too by natural way of treatment if possible and not just by having hormonal therapy & “tighten up” the vagina.

One of most advance technology today is by using your body fat tissue to get stem cell ADSCs and inject it back to the vagina with or without fat graft, this advance modality of treatment is showing a good promise in all clinical trials in treating the menopausal symptoms. Stem cell enriched lipofilling can also help in cases where clinically not a candidate for surgical tightening as no underlying muscular defect. They are more in need to recover the histological changes that happen to their vagina lining layer. This can help to treat all uncomfortable menopausal symptoms plus helping women who feel less wide vagina. Vagina can be recalibrating to smaller diameter but to limit by stem cell enriched lipofilling.

Combination of treatments can give a higher satisfactory outcome by adding laser therapy or Radiofrequency therapy for more vaginal tightening and help with mild stress incontinence symptoms.

It can also combine the surgical tightening of vaginal wall. It stars with tightening of posterior wall muscles followed by adding the fat graft to the side walls of the vagina. 

the complication are rare, corresponding to any other surgical procedure in this very area, and have not jeopardizes the final result. 

Vaginal Recalibration by Lipograft Technique: this procedure consists in reducing the vaginal calibre by thickening the vaginal walls with adipose tissue transplant. It is indicated in those patients who feel concern by a sensation of a wide vagina. The causes are often post gravid in multiparous women and sometimes constitutional. Clinical and gynaecological examination many frequently normal. However, may reveal a prolapse which is contraindication for this intervention. 

The Scientific Evidence Behind Using Stem Cells for Female Genital Rejuvenation

For symptomatic vulvar dystrophias:  Regardless of the aetiology of vulvar dystrophy, a remarkable pain and dryness reduction could be observed in all patients & for that all patients obtained an improvement of sexual function after ADSCs treatment has been documented

it has been documented symptomatic improvement within one month after the first ADSCs treatment, and dramatic pain reduction after one year. Sexual function improvement after second treatment. The clinical trials documented maintained improvement at 2 years follow-up. After treatment with ADSCs, a regression of the morphological alterations of epithelial cells and full attenuation of inflammatory signs in the connective tissue were observed. Biopsy specimens of patients affected with LS displayed after treatment with ADSCs, the dermis sclerosis was significantly reduced, capillaries that resulted were less dilated, and inflammatory infiltrate was dramatically reduced.

For Menopausal Dystrophy; A loss of vaginal rugae, vaginal pallor, and petechiae are evident in patients in menopause. Histological examination after ADSCs treatment for menopausal patients has been shown the improvement of the vaginal elastic network.

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This document is designed to supply useful information but is not to be regarded as advice specific to any particular case. It does not replace the need for a thorough consultation and all prospective patients should seek the advice of a qualified physician

Dr. Sahar Al Kazzaz

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