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.

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.

Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller’s cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report. (AU)

Mullerianosis of the urinary bladder: a case report.

Mullerianosis is a rare, complex, benign tumor most commonly found in the bladder and often mistaken for a neoplastic lesion.  Herein, we report a case of mullerianosis in a 65-year-old woman who presented with an incidental 2 cm bladder mass found on cross-sectional imaging.  A mixed cystic and solid tumor was identified on cystoscopy and a transurethral resection of the suspected tumor was performed with histopathology confirming a final diagnosis of mullerianosis.  While an unusual diagnosis, mullerianosis of the urinary bladder needs to be correctly identified to provide appropriate treatment and avoid misdiagnosis.

Anti-Müllerian hormone: A novel biomarker for detecting bovine freemartinism.

The anti-Müllerian hormone (AMH) indicates ovarian reserve in cattle, maintaining a consistent trajectory post-puberty. In heterosexual pregnancies, the development of the Müllerian duct in female foetuses is inhibited, resulting in an anticipated minimal or absent ovarian reserve capacity. This investigation aimed to compare AMH levels in healthy Holstein heifers that had reached puberty with those of freemartin animals of the same breed and age. The study incorporated Holstein heifers reaching puberty between 11 and 15 months of age in Group 1 (G1, n = 20) and freemartin animals in Group 2 (G2, n = 19, 16). AMH measurements (AMH-1/AMH-2) were recorded at 12-day intervals for the study participants. Notably, AMH levels in three freemartin animals could not be detected, prompting statistical analysis based on measurements from the remaining 16 freemartin animals in G2. A statistically significant correlation was observed between two separate measurements in G1 and G2 (p < .001). Furthermore, AMH-1 and AMH-2 levels were statistically higher in G1 than in G2 (p < .001). In G1, AMH-1 levels ranged from 227 to 677 pg/mL, with an average of 367.3 ± 25.5 pg/mL, and AMH-2 levels ranged from 234 to 645 pg/mL, with an average of 380.8 ± 24.4 pg/mL. Conversely, in G2, AMH-1 levels ranged from 10 to 72 pg/mL, with an average of 26.8 ± 4.44 pg/mL, and AMH-2 levels ranged from 12 to 68 pg/mL, with an average of 28.75 ± 4.18 pg/mL. The mean AMH levels in G1 were approximately 14 times higher than in G2 (p < .001). Consequently, ROC analysis utilizing AMH-1 and AMH-2 data established cut-off values of ≤72 and ≤ 68 pg/mL respectively for distinguishing freemartin animals. In conclusion, AMH could be used as a reliable biomarker for identifying Holstein freemartin animals.

Establishment of an organ culture system to maintain the structure of mouse Müllerian ducts during development.

We previously showed that the anti-Müllerian hormone (AMH), infiltrating from the testis to the mesonephros reaches the cranial and middle regions of the Müllerian duct (MD) and induces their regression using an organ culture in mice. However, it is difficult to maintain structural integrity, such as the length and diameter and normal direction of elongation of the caudal region of the MD, in conventional organ culture systems. Therefore, the pathway of AMH to the caudal MD region remains uncharted. In this study, we established an organ culture method that can maintain the morphology of the caudal region of the MD. The gonad-mesonephros complex, metanephros, and urinary bladder of mouse fetuses at 12.5 dpc attached to the body trunk were cultured on agarose gels for 72 hr. The cultured caudal region of the mesonephros was elongated along the body trunk, and the course of the mesonephros was maintained in many individuals. In males, mesenchymal cells aggregated around the MD after culture. Moreover, the male MD diameter was significantly smaller than the female. Based on these results, it was concluded that the development of the MD was maintained in the present organ culture system. Using this culture system, AMH infiltration to the caudal region of the MD can be examined without the influence of AMH in the blood. This culture system is useful for clarifying the regression mechanism of the caudal region of the MD.

Implication of androgen receptor gene dysfunction in human Müllerian duct anomalies.

BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders exhibiting as a variety of malformations of female reproductive tract. The identified etiology of MDAs is limited. The present study aimed to unravel the underlying genetic causes of MDAs. METHODS: Rare variants in androgen receptor (AR) were called from the cohort consists of patients with MDAs and underwent whole exome sequencing (WES) at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Sanger sequencing was used to confirm the causative genetic mutations. In silico analysis were used to classify the pathogenicity of each variant. Molecular modeling and simulations were conducted to investigate the conformational changes between the wild-type (WT) and mutant proteins. RESULTS: A total of 3 rare heterozygous variants in AR from the MDAs cohort in our institution were identified, with unknown effects. All variants were missense mutations, including c.173A > T, c.558C > A and c.1208C > T, and were absent or rare in East Asian populations in Genome Aggregation Database and the Exome Aggregation Consortium Database. According to the American College of Medical Genetics and Genomics guidelines, c.1208C > T variant was classified as likely pathogenic, while the other two were variants of uncertain significance. During molecular dynamics simulations, WT and mutant proteins all reached stable status according to root-mean-square variance. Values of radius of gyration showed that Q58L and S186R protein would be more compact than WT, while the structure of A403V became looser. Despite, in comparison with WT, the number of hydrogen bonds increased in Q58L, while decreased in the other two variants. Furthermore, the solvent-accessible surface area diminished in Q58L and A403V while enlarged in S186R proteins, when compared with WT. CONCLUSIONS: To our knowledge, this is the first report regarding the association of AR mutation and MDAs. The identification of these variants, predicted to damage the structure and function of AR protein, not only expanded the mutational spectrum of causative genes of MDAs, but provide novel molecular genetic reference for future studies.

Preventive Practices and Knowledge of Human Papillomavirus in Mayer-Rokitansky-Küster-Hauser Syndrome Individuals.

ABSTRACT: Mayer-Rokitansky-Küster-Hauser syndrome is a congenital disorder typified by an underdeveloped female reproductive tract. An exploratory online survey of adults with Mayer-Rokitansky-Küster-Hauser syndrome found that many did not recall receiving the human papillomavirus vaccine, and answers to knowledge questions suggested inadequate human papillomavirus counseling. However, recalled vaccine counseling was associated with improved uptake.

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.

Long-term Results of Sexual Function and Body Image After Vaginoplasty With Acellular Dermal Matrix in Women With Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To describe the long-term anatomic and sexual functional results of vaginoplasty with acellular dermal matrix (ADM) in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) and to evaluate the changes in body image pre- and postoperatively in these patients. DESIGN: A retrospective study from March 2015 to September 2021. SETTING: A tertiary teaching hospital. PATIENTS: Forty-two patients with MRKH syndrome who underwent vaginoplasty with ADM (the MRKH group) and 30 sexually active, nulliparous, aged-matched women (the control group). INTERVENTION: The relevant data were retrospectively collected via our electronic medical record system and were analyzed statistically. MEASUREMENTS AND MAIN RESULTS: Vaginal length was assessed using a 3-cm-diameter mold. The Chinese version of the Female Sexual Function Index questionnaire was used to evaluate sexual function. The Chinese version of the modified body image scale was applied to evaluate body image. The median follow-up time was 57 months (range, 13-91 months). Granulomatous polyps in the neovagina were the most common postoperative complication (7 of 42, 16.7%). Patients with MRKH syndrome can achieve long-term satisfactory outcomes both anatomically and functionally after vaginoplasty with ADM, comparable with those of healthy control women. The vaginal length in the MRKH group was comparable to that in the control group ( 8.04 ± 0.51 cm vs. 8.15 ± 0.46 cm, respectively). The FSFI scores were similar between the MRKH (26.54 ± 3.44) and control (26.80 ± 2.23) groups. The modified body image scale score was significantly decreased after vaginoplasty with ADM. CONCLUSION: Vaginoplasty with ADM is a minimally invasive and effective procedure for patients with MRKH syndrome.

Insights into enlarged prostatic utricles and Müllerian duct system remnants associated with posterior hypospadias.

INTRODUCTION: The prostatic utricle (PU) consists of the caudal remnant of the Müllerian duct and the urogenital sinus. The term "vagina masculina" is used if other Müllerian structures are associated with the PU. This work aims to investigate the incidence, management, and follow up of enlarged PUs and Müllerian remnants in males with posterior hypospadias. PATIENTS AND METHODS: This study presents a retrospective review of cases presented with posterior hypospadias over a 5-year period. Prior to hypospadias repair, retrograde urethrograms were used to investigate enlarged PU. Subsequently, they were classified according to the Ikoma score and further assessed by karyotyping and cystoscope. Surgical excision was indicated in cases with symptomatic utricles or vagina masculina. RESULTS: Thirty patients were included in the study in the period between 2015 and 2020 (Table). All cases were asymptomatic initially. Twelve patients were diagnosed with enlarged PU; three of them had vagina masculina. One case with perineal hypospadias had a separate perineal opening for PU. Following hypospadias repair, three of the eight cases treated conservatively turned symptomatic. DISCUSSION: The incidence of enlarged PU and Müllerian remnants varied among different studies. However, it increased as the severity of hypospadias increased. Preoperative urethrogram was helpful in the diagnosis and classification of PU, but it had its limitations. Cystoscope was more advantageous in diagnosing vagina masculina. Although most cases were asymptomatic, some turned symptomatic after hypospadias repair. Some cases with perineal hypospadias had PU with a separate perineal opening. CONCLUSION: The incidence of enlarged PUs or Müllerian remnants was 40%. Although cases were asymptomatic before hypospadias surgery, some cases turned into symptomatic after hypospadias repair. In some cases, the PU or Müllerian remnants had a separate perineal opening. They can be classified as a particular form of Ikoma grade III necessitating surgical intervention.

Successful Use of Acellular Small Intestinal Submucosa Graft in Vaginal Reconstruction.

PURPOSE: Various techniques for neovaginal construction have been employed in the pediatric and adult populations, including the use of intestinal segments, buccal mucosal grafts, and skin grafts. Small intestinal submucosa (SIS) extracellular matrix grafts have been described as a viable alternative, though prior experience is limited. Our purpose was to assess operative characteristics and patient outcomes with neovaginal construction using SIS grafts. METHODS: Thirteen patients underwent vaginoplasty with acellular porcine SIS grafts at our institution between 2018 and 2022. Operative and clinical data, postoperative mold management, vaginal dilating length, and complications were reviewed. RESULTS: Age at time of repair ranged from 13 to 30 years (median 19 years). Patient diagnosis included cloacal anomalies (n = 4), Mayer-Rokitansky-Küster-Hauser syndrome (n = 4), isolated vaginal atresia with or without a transverse vaginal septum (n = 4), and vaginal rhabdomyosarcoma requiring partial vaginectomy (n = 1). Following dissection of the neovaginal space, a silicon mold wrapped with SIS graft was placed with retention sutures and removed on postoperative day 7. Median (IQR) operative time was 171 (118-192) minutes, estimated blood loss was 10 (5-20) mL, and length of stay was 2 (1-3) days. The follow-up period ranged from 3 to 47 months (median 9 months). Two patients developed postoperative vaginal stenosis that resolved with dilation under anesthesia. Mean vaginal length on latest follow-up was 8.97 cm. All thirteen patients had successful engraftment and progressed to performing self-dilations or initiating intercourse to maintain patency. There were no cases of graft reaction or graft extrusion. CONCLUSIONS: We conclude that acellular small intestinal submucosa grafts are effective and safe alternatives for mold coverage in neovaginal construction. Our experience demonstrates minimal perioperative morbidity, early mold removal, and progression to successful dilation with maintenance of a functional vaginal length. Future study on sexual outcomes, patient satisfaction, and comparison against alternative techniques has been initiated. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective Study.

Alternative Biological Material for Tissue Engineering of the Vagina: Porcine-Derived Acellular Vaginal Matrix.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and α-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of ß-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the ß-catenin/c-Myc/cyclin D1 pathway. CONCLUSION: This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

SMAD2/3 signaling regulates initiation of mouse Wolffian ducts and proximal differentiation in Müllerian ducts.

Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.

Müllerian Anomalies: Presentation, Diagnosis, and Counseling.

Müllerian anomalies represent a complex collection of developmental defects occurring in up to 5% of the general population. They are increasingly more common in individuals with infertility (8.0%) and in those with a history of pregnancy loss (13.3%); they have the highest prevalence in individuals with a history of both (24.5%). A wide spectrum of anomalies can occur based on the stage at which müllerian development ceases in utero, ranging from mild (eg, a partial uterine septum) to severe, with complete absence of the cervix, uterus, and fallopian tubes (eg, müllerian agenesis). The components of the reproductive tract involved and, importantly, whether an obstruction of the tract is involved correlates with the timing of presentation, the constellation of associated symptoms, and the necessity for either medical or surgical management. Individuals, regardless of the severity of the defect, should be counseled on the gynecologic, reproductive, and obstetric risks associated with their specific müllerian anomaly to minimize adverse sequela and outcomes. We will review the clinical presentation, diagnostic evaluation, and clinical counseling of individuals with müllerian anomalies.

Issues of identity, perceptions and isolation: An interpretative phenomenological analysis of women's experience of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.

The objective of this study was to explore the personal experience of women with MRKH, a rare condition characterised by congenital abnormalities of the genital tract. There are very few qualitative studies into the lived experiences of women with MRKH. Interviews were conducted with 13 women with MRKH and analysed using interpretative phenomenological analysis. Four superordinate themes are discovered: maintaining a viable female identity; acceptance and coping; normality, secrecy and shame and the isolating impact of a lack of knowledge amongst the medical profession. This study also suggests that societal ideals of a 'normal woman' are influencing how MRKH impacts on the self-experienced psychological health. It is suggested that the psychological wellbeing of women with MRKH could be improved with continued multidisciplinary support beyond the initial diagnosis and alongside any vaginal correction.

A Case Report of Familial Mayer-Rokitansky-Küster-Hauser Syndrome as Part of the Phenotypic Spectrum of the 2q37 Deletion.

We performed a genetic investigation into the case of an inherited Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Our patients were an adolescent and her mother, both with MRKH syndrome. The delivery of a biological offspring was achieved via a gestational carrier. Karyotype and exome sequencing were used to complete a three-generation genetic analysis of the family. Both the mother and her daughter harbored a deletion of 4 Mb at the locus of 2q37, a syndrome rarely described in association with MRKH. No pathogenic single-nucleotide variant relevant to the phenotype was found. The deletion was not inherited from either parent of the mother. In addition, some physical findings suggesting 2q37 deletion syndrome were found in our patients. We conclude that when combined with the use of a gestational carrier or uterine transplantation, the identification of a genetic cause for MRKH may enable the application of preimplantation genetic testing on embryos, thus potentially averting the transmission of the genetic anomaly to subsequent generations.

Recurrent human 16p11.2 microdeletions in type I Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients in Chinese Han population.

BACKGROUNDS: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a severe congenital malformation of the female genital tract, is a highly heterogeneous disease which has no clear etiology. Previous studies have suggested that copy number variations (CNVs) and single-gene mutations might contribute to the development of MRKH syndrome. In particular, deletions in 16p11.2, which are suggested to be involved in several congenital diseases, have been reported in Chinese type II MRKH patients and European MRKH patients. However, few CNVs including 16p11.2 microdeletions were identified in Chinese type I MRKH cases although it accounted for the majority of MRKH patients in China. Thus, we conducted a retrospective study to identify whether CNVs at human chromosome 16p11.2 are risk factors of type I MRKH syndrome in the Chinese Han population. METHODS: We recruited 143 patients diagnosed with type I MRKH between 2012 and 2014. Five hundred unrelated Chinese without congenital malformation were enrolled in control group, consisting of 197 from the 1000 Genomes Project and 303 from Fudan University. Quantitative PCR, array comparative genomic hybridization, and sanger sequencing were conducted to screen and verify candidate variant. RESULTS: Our study identified recurrent 16p11.2 microdeletions of approximately 600 kb in two out of the 143 type I MRKH syndrome patients using high-density array-based comparative genomic hybridization (aCGH), while no 16p11.2 deletion was found in the control group. We did not find any mutations in TBX6 gene in our samples. CONCLUSIONS: The results of the study identify 16p11.2 deletion in Chinese MRKH I patients for the first time, as well as support the contention that 16p11.2 microdeletions are associated with MRKH syndrome in both types across populations. It is suggested that 16p11.2 microdeletions should be included in molecular diagnosis and genetic counseling of female reproductive tract disorders.