Anatomical and Functional Evaluation of Modified Abbe-McIndoe Vaginoplasty at a Tertiary Care Hospital.

BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome, the second important cause of primary amenorrhea, is characterized by complete mullerian agenesis in the presence of normal karyotype and normal functioning ovaries. Incidence is one in 4500 females. Treatment options include surgical and non-surgical methods. Surgical treatment by creating a neovagina between bladder and rectum is preferred as it gives immediate results. AIM: To evaluate the anatomical and functional outcomes of modified vaginoplasty procedures conducted in our institution. METHODS: An ambispective cohort study was conducted in the Department of Obstetrics and Gynaecology, at a tertiary care hospital and included 10 cases of MRKH syndrome, who underwent surgical treatment in our department. Postoperative outcome was noted. Sexual function was evaluated using the Female Sexual Function Index (FSFI) score. RESULTS: The mean duration of surgery was 40 minutes. The average blood loss during surgery in patients undergoing vaginoplasty was 60 ml. The mean length of the neovagina as measured 1 month after surgery was 7.9 cms. FSFI score was >30 in eight patients. Two patients were lost to follow-up. CONCLUSION: Modified McIndoe vaginoplasty is a simple, safe, and cost-effective procedure in the hands of experts. Only mature patients willing to follow the instructions and planning to get married soon should undergo this surgery.

A Minimally Invasive Approach for Laparoscopic-Perineal Sigmoid Colpoplasty: Case Report and Innovations.

BACKGROUND Laparoscopic-perineal neovagina construction by sigmoid colpoplasty is a popular therapeutic approach for patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. The conventional approach requires an auxiliary abdominal incision to exteriorize the descending colon to fix the anvil for end-to-end colorectal anastomosis. We modified the natural orifice specimen extraction surgery (NOSES) approach by exteriorizing the descending colon through the artificial neovaginal tunnel to replace the anvil extracorporeally, without requiring an auxiliary abdominal incision. It was a more minimally invasive technique. CASE REPORT We performed this modified laparoscopic-perineal sigmoid colpoplasty in a 26-year-old woman with MRKH syndrome. We cut off a segment of the sigmoid colon with a vascular pedicle to make a new vagina out of it, the same as in the traditional laparoscopic-perineal sigmoid colpoplasty. What is new about this technique is that it has no need for abdominal incision and is more minimally invasive. The operating time was 315 min. No postoperative complications occurred. The postoperative hospital stay was 4 days. The modified laparoscopic-perineal approach, free from an auxiliary abdominal incision, demonstrated advantages, including a shorter hospital stay, expedited recovery, and comparable anatomical outcomes, when compared with the traditional approach. This innovation improves the surgical experience for patients with MRKH syndrome, addressing the physical and psychological aspects of their condition. CONCLUSIONS This refined laparoscopic-perineal neovagina construction by sigmoid colpoplasty represents a feasible and minimally invasive technique. It is an attractive option for MRKH syndrome patients in need of vaginal reconstruction, offering a streamlined procedure with reduced postoperative recovery time and enhanced patient outcomes.

[Adolescent female reproductive system dysplasia: a clinical study of 356 cases].

Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Sexuality and quality of life of patients operated for Rokitansky syndrome Mayer Kuster Hauser.

INTRODUCTION: Rokitansky syndrome or Mayer Rokitansky Kuster Hauser (SRKMH) is a rare congenital malformation defined by uterovaginal aplasia. The aim of the treatment is to create a neovagina and restore sexual life. However, postoperative results in terms of sexual and overall quality of life of patients remain controversial. AIM: To evaluate the quality of life and sexuality of patients operated on for Rokitansky syndrome. METHODS: This was a retrospective and comparative study between two groups of patients. The first group consisted of patients who had undergone vaginoplasty as part of SRKMH. The second group was that of the controls. Control in terms of sexual function by the Ar FSFI (Arab FemaleSexualFunction Index) and quality of life by the SF36 (Short Forms Health Survey) were used in both groups. RESULTS: The average age of patients operated on for SRKMH was 22.53 years. Eighteen of these patients (60%) were sexually active at the time of the study. Patients operated on for SRKMH had a significantly lower Ar FSFI score compared to the control group. The two areas most affected were lubrication and pain. Likewise, patients who underwent vaginoplasty had a significantly lower SF 36 score compared to the control group. The psychological component was the most affected of the different components of quality of life. CONCLUSION: Sexual function and quality of life after vaginoplasty in the context of Rokitansky syndrome remains unsatisfactory despite the anatomical result.

Diagnosis and management of non-CAH 46,XX disorders/differences in sex development.

Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by exposure to exogenous androgens. The most common cause of 46,XX disorders/differences in sex development (DSD) is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, comprising >90% of 46,XX DSD cases. Deficiencies of 11ß-hydroxylase, 3ß-hydroxysteroid dehydrogenase, and P450-oxidoreductase (POR) are rare types of CAH, resulting in 46,XX DSD. In all CAH forms, patients have normal ovarian development. The molecular genetic causes of 46,XX DSD, besides CAH, are uncommon. These etiologies include primary glucocorticoid resistance (PGCR) and aromatase deficiency with normal ovarian development. Additionally, 46,XX gonads can differentiate into testes, causing 46,XX testicular (T) DSD or a coexistence of ovarian and testicular tissue, defined as 46,XX ovotesticular (OT)-DSD. PGCR is caused by inactivating variants in NR3C1, resulting in glucocorticoid insensitivity and the signs of mineralocorticoid and androgen excess. Pathogenic variants in the CYP19A1 gene lead to aromatase deficiency, causing androgen excess. Many genes are involved in the mechanisms of gonadal development, and genes associated with 46,XX T/OT-DSD include translocations of the SRY; copy number variants in NR2F2, NR0B1, SOX3, SOX9, SOX10, and FGF9, and sequence variants in NR5A1, NR2F2, RSPO1, SOX9, WNT2B, WNT4, and WT1. Progress in cytogenetic and molecular genetic techniques has significantly improved our understanding of the etiology of non-CAH 46,XX DSD. Nonetheless, uncertainties about gonadal function and gender outcomes may make the management of these conditions challenging. This review explores the intricate landscape of diagnosing and managing these conditions, shedding light on the unique aspects that distinguish them from other types of DSD.

Testicular differentiation in 46,XX DSD: an overview of genetic causes.

In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of SRY to the X chromosome or an autosome. In the absence of SRY, other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.

Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: advancements and implications.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by agenesis/aplasia of the uterus and upper part of the vagina in females with normal external genitalia and a normal female karyotype (46,XX). Patients typically present during adolescence with complaints of primary amenorrhea where the diagnosis is established with significant implications including absolute infertility. Most often cases appear isolated with no family history of MRKH syndrome or related anomalies. However, cumulative reports of familial recurrence suggest genetic factors to be involved. Early candidate gene studies had limited success in their search for genetic causes of MRKH syndrome. More recently, genomic investigations using chromosomal microarray and genome-wide sequencing have been successful in detecting promising genetic variants associated with MRKH syndrome, including 17q12 (LHX1, HNF1B) and 16p11.2 (TBX6) deletions and sequence variations in GREB1L and PAX8, pointing towards a heterogeneous etiology with various genes involved. With uterus transplantation as an emerging fertility treatment in MRKH syndrome and increasing evidence for genetic etiologies, the need for genetic counseling concerning the recurrence risk in offspring will likely increase. This review presents the advancements in MRKH syndrome genetics from early familial occurrences and candidate gene searches to current genomic studies. Moreover, the review provides suggestions for future genetic investigations and discusses potential implications for clinical practice.

Long-term outcomes in non-CAH 46,XX DSD.

Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.

Vaginoplasty with Amnion Graft: Management of Mayer-Rokitansky-Kuster-Hauser Syndrome.

Mayer-Rokitansky-Kuster-Hauser syndrome also known as mullerian agenesis is a rare congenital condition in which there is absence of uterus along with upper vagina. Patient usually presents with primary amenorrhea with or without cyclical lower abdominal pain but have normal secondary sexual characters. Modified McIndoe Vaginoplasty with amnion graft is the commonest surgery performed worldwide. A 23 year old girl with normal secondary sexual characters presented with primary amenorrhea with cyclical lower abdominal pain; on examination blind vagina was present. Vaginoplasty with amnion graft was done and vaginal mould was placed. Vaginal dilatation with Hegar's dilator was done weekly until 6 weeks. She is under regular follow-up at present and advised for regular manual dilation at home. McIndoe Vaginoplasty with amnion graft is a simple yet rewarding procedure especially in low resource countries like ours, with good success rate and with minimal postoperative complications. Keywords: Amnion graft; Mayer-Rokitansky-Kuster-Hauser Syndrome; Modified McIndoe Vaginoplasty; Primary amenorrhea; Secondary sexual characters.

Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.

The molecular basis of mullerian aplasia, also known as Mayer-Rokitansky-Kuster Hauser (MRKH) or congenital absence of the uterus and vagina, is largely unknown. We applied a multifaceted genetic approach to studying the pathogenesis of MRKH including exome sequencing of trios and duos, genome sequencing of families, qPCR, RT-PCR, and Sanger sequencing to detect intragenic deletions, insertions, splice variants, single nucleotide variants, and rearrangements in 132 persons with MRKH. We identified two heterozygous variants in ZNHIT3 localized to a commonly involved CNV region at chromosome 17q12 in two different families with MRKH. One is a frameshift, truncating variant that is predicted to interfere with steroid hormone binding of the LxxLL sequence of the C-terminal region. The second variant is a double missense/stopgain variant. Both variants impair protein expression in vitro. In addition, four more probands with MRKH harbored the stopgain variant without the nearby missense variant. In total, 6/132 (4.5%) of patients studied, including five with associated anomalies (type 2 MRKH), had ZNHIT3 variants that impair function in vitro. Our findings implicate ZNHIT3 as an important gene associated with MRKH within the 17q12 CNV region.

A rare variant of mullerian agenesis: a case report and review of the literature.

INTRODUCTION: Menstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here. CASE REPORT: We present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri-a horseshoe band cervix-were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation. CONCLUSION: Mullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.

Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17ß-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.

Unification and orificing of two functional noncommunicating uterine horns through the created neovagina using peritoneum.

OBJECTIVE: To demonstrate the surgical approach for Müllerian agenesis with bilateral uterine remnants containing functional endometrium. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Reproductive surgery unit of a tertiary university hospital. PATIENT: An 18-year-old adolescent was admitted to a tertiary university hospital with complaints of primary amenorrhea and cyclic pelvic pain. Physical examination and magnetic resonance imaging scans suggested a complex Müllerian abnormality. The patient had uterine remnants with bilateral functional endometrium and cervicovaginal agenesis. INTERVENTION: An operation was planned to reconstruct her anatomy by providing a neovagina and anastomosing the uterine remnants. Gonadotropin-releasing hormone analogs were prescribed to suppress her menstruation until the procedure. The operation was performed in the third month after the initial diagnosis. A laparoscopy was conducted, revealing approximately 5 × 6-cm bilateral uterine horns with healthy adnexa. As the first step, a neovagina was created using a modified peritoneal pull-down technique, a standard approach in our clinic. A vaginal incision was made, and a blind vaginal dissection was performed to reach the peritoneum vaginally. Subsequently, an acrylic vaginal mold was inserted. The vaginal orifice was laparoscopically incised using ultrasonic energy with guidance from the inserted vaginal acrylic mold. The orifice was gradually dilated with larger molds. The entire pelvic peritoneum was dissected circularly, and the distal part of the dissected peritoneum was pulled down using four 2.0 Vicryl sutures at 0°, 90°, 180°, and 270° from the opened vaginal orifice. The uterine cavities of both remnants were incised, and two separate Foley catheters were placed in both cavities. A mold with a hole was used to insert the catheters through the vagina. Both catheters were secured in the cavities with Prolene sutures pulled up from the anterior abdominal wall. The next step involved uterine anastomosis. The uterine remnants were unified through continuous suturing, resulting in the formation of a normally shaped uterus. In the final step, the created uterus and neovagina were anastomosed. The patient received instructions on how to perform mold exercises and follow-up care. MAIN OUTCOME MEASURE: Description of laparoscopic management of a rare Müllerian abnormality. RESULTS: The postoperative magnetic resonance imaging scan at 1 month revealed healed unified uterine cavities and vagina. The patient experienced spontaneous menstruation in the second month after surgery and now maintains regular menses with an approximately 9-10 cm functional vagina. Within 3 months after surgery, the visual analogue scale scores for chronic pelvic pain and dysmenorrhea decreased from 9 to 2-3. CONCLUSIONS: Müllerian abnormalities are exceptionally rare, and their spectrum is broad, making it challenging to identify an exact surgical method to restore functional anatomy. Therefore, a customized surgical approach should be designed for each patient on the basis of their unique condition.

Histological Features of Neovaginal Epithelium after Vaginoplasty in Mayer-Rokitansky-Küster-Hauser Syndrome.

OBJECTIVE: To analyze the features of the epithelia coating neovaginas after vaginoplasty in women affected by Mayer-Rokitansky-Küster-Hauser syndrome STUDY DESIGN: We conducted a retrospective analysis of prospectively collected data. Women affected by Rokitansky syndrome who underwent neovaginal biopsy after vaginoplasty (McIndoe surgery, intestinal vaginoplasty, Vecchietti surgery, and Davydov surgery) were included. Macroscopic mucosal features were assessed through clinical examination and the Schilling test. Each biopsy specimen was prepared for examination by light microscopy and in some cases by scanning electron microscopy (SEM). RESULTS: Thirty-six patients (4 McIndoe, 2 intestinal vaginoplasty, 14 Vecchietti, and 16 Davydov) were included. All biopsies were performed without complications. In McIndoe's neovaginas, the mucosal microscopic features were similar to normal skin, with large areas of preserved epithelium, heterogeneous presence of dermal papillae, and superficial keratinization. The characteristics of the intestinal neovagina's surface were similar to those of a sigmoid colon, with well-shaped glands, cylindrical cells, and a secreting mucosa. In Vecchietti neovaginas, the surface the epithelium was flat and multilayered, highly similar to that of a normal vagina, with the presence of glycogen and superficial desquamation. On medium SEM magnification evaluation, the epithelium presented flattened polygonal cells. Finally, in Davydov neovaginas, none of the specimens had persistent mesothelial elements. The squamous neo-epithelium had regular aspects of differentiation with the presence of glycogen. At greater SEM magnification, microridges were evident, with a regular distribution. CONCLUSION: Each different technique of vaginoplasty leads to unique histological and structural features of the neovagina's mucosa. Knowledge of these elements must be the basis for the choice of the most appropriate intervention.

Neovagina creation methods in Müllerian anomalies and risk of malignancy: insights from a systematic review.

PURPOSE: This systematic review aims to provide a data synthesis about the risk of neovaginal cancer in women with Müllerian anomalies and to investigate the association between the adopted reconstructive technique and the cancer histotype. METHODS: PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov and Web of Science databases were searched from inception to March 1st, 2023. Studies were included if: (1) only women affected by Müllerian malformations were included, (2) the congenital defect and the vaginoplasty technique were clearly reported, (3) the type of malignancy was specified. RESULTS: Literature search yielded 18 cases of squamous cell carcinoma and two cases of vaginal intraepithelial neoplasia 3 (VAIN 3). Of these, 3 had been operated on according to the Wharton technique, 8 according to the McIndoe technique, 3 with a split-skin graft vaginoplasty, 2 according to the Davydov technique, 2 with a simple cleavage technique, 1 according to the Vecchietti technique and 1 with a bladder flap vaginoplasty. A total of 17 cases of adenocarcinoma and 1 case of high-grade polypoid dysplasia were also described. Of these, 15 had undergone intestinal vaginoplasty, 1 had been operated on according to the McIndoe technique and 1 had undergone non-surgical vaginoplasty. Finally, 1 case of verrucous carcinoma in a woman who had undergone a split-skin graft vaginoplasty, was reported. CONCLUSION: Although rare, neovaginal carcinoma is a definite risk after vaginal reconstruction, regardless of the adopted technique. Gynaecologic visits including the speculum examination, the HPV DNA and/or the Pap smear tests should be scheduled on an annual basis.

Müllerian Agenesis in a patient with Rubinstein-Taybi Syndrome: A Case Series and Review of the Overlapping Developmental Biologic Pathways.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multi-system neurodevelopmental condition caused by deficiency of CREBBP (16p13.3) or EP300 (22q13.2). Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is defined as congenital agenesis of the uterus, cervix, and upper vagina without a definite genetic cause. INDEX CASE AND CASE SERIES: We present a 14-year-old female with RSTS type 1 (CREBBP, c.4395-2A>C) and MRKH, the first documented in the literature. Following presentation to Gynecology for anticipatory guidance regarding future menstrual suppression and follow-up of previously diagnosed labial adhesions, exam under anesthesia revealed a single urogenital opening with cystoscopy demonstrating a normal urethra and bladder. Laboratory evaluation was consistent with peripubertal female gonadotropins and estradiol, 46,XX karyotype, and normal microarray, and a pelvic MRI confirmed Müllerian agenesis. Given this case, we assessed our cohort of females with RSTS and found that 4 of 12 individuals also had Müllerian anomalies. CONCLUSION: Gynecologic evaluation should be a part of medical care for females with RSTS, particularly in individuals with delayed menarche or abnormal menstrual history, on the basis of the observed association between RSTS and Müllerian anomalies in this case series. Although several candidate genes and copy number variants are associated with MRKH, no candidate genes in close proximity to the 16p13.3 region have been identified to explain both RSTS and MRKH in the index patient. Due to the regulatory nature of CREBBP during embryonic development, we theorize that CREBBP may play a role in the migration of Müllerian structures during embryogenesis.

46,XX aromatase deficiency: A single-center experience with the varied spectrum and recurrent variants, and a systematic review of hormonal parameters.

BACKGROUND: Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters. METHODS: Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens. RESULTS: In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively. CONCLUSION: We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.

A life course perspective on Mayer-Rokitansky-Küster-Hauser syndrome: women's experiences and negotiations of living with an underdeveloped uterus and vagina.

PURPOSE: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by the absence or underdevelopment of the uterus and upper part of the vagina. It is usually diagnosed during adolescence, and the present study investigates how women experience and negotiate to live with MRKH syndrome long-term. METHODS: From January to March 2021, eighteen Danish women with MRKH syndrome participated in semi-structured interviews via video conference. The mean time since diagnosis was 11.5 years. A thematic analysis using the life course framework as a theoretical approach was applied. RESULTS: The analysis identified the diagnosis as a turning point, that dramatically altered the women's imagined futures. Not conforming to dominant social norms regarding sexuality and pregnancy meant that the women continuously managed and negotiated the meaning and impact of MRKH syndrome in relation to the five principles of the life course perspective: (1) Lifelong development, (2) Timing, (3) Human agency, (4) Linked lives, and (5) Historical time and place. CONCLUSION: Using the life course framework contributed to a holistic understanding of life with MRKH syndrome by showing how the meaning and consequences of the congenital condition changed over time and in adaptation to gendered and age-related social norms and expectations.IMPLICATIONS FOR REHABILITATIONThe perceived meaning and impact of living with Mayer-Rokitansky-Küster-Hauser syndrome change over time, and women's information and support needs thus change accordinglySensitive, clinical communication is essential when discussing treatment optionsOnline communities may provide support and reduce feelings of loneliness.