Objective: To describe the gross and histological characters of MRKHS patients’ ovaries and assess their ovarian reserve directly for future pregnancy. Design: A prospective case-control study. Setting and population: A prospective case-control study involving 67 MRKH syndrome patients and 17 ovarian biopsies (with age-matched controls), from January 2017 to February 2020. Methods: We observed the gross appearance of 67 Chinese MRKHS patients during laparoscopically assisted neovagina creation surgery. Seventeen ovarian biopsies were obtained and compared with age-matched controls for the histological characters. Twelve biopsy specimens underwent a complete serial section and calculation of the primordial follicular density. Main Outcome Measures: Follicle density, morphology in ovarian cortex biopsies. Results: 5/67 MRKHS patients’ ovaries had abnormal gross appearance, including streak gonads and bilateral porcelain white ovaries. We observed corpus luteum or corpus albicans on 5/8 patients under 20 years old, but none of the controls. None of the biopsies from MRKHS type Ⅱ patients showed corpus luteum or corpus albicans. Two type Ⅰ patients presented with compromised ovarian reserve, and significant increase of atretic follicles and corpus albicans. A significant inverse correlation was observed between primordial follicular density and age in 12 patients aged 16 to 25 years old. Conclusion: The ovaries of MRKHS patients have higher rates of abnormalities regarding gross appearance and histological characters. Tweetable abstract: It is suggested that early preparation for fertility reserve and incorporated as a part of the treatment when reconstructing the neovagina in MRKH syndrome patients due to premature declination of the ovarian reserve.

Recommendations for müllerian anomalies classificationSi Su1,2, Lan Zhu1*1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing, China2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China*Corresponding Author: Lan Zhu, MD, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Obstetric and Gynecologic Diseases, No. 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, China ([email protected])The word count for the main text: 506.In 2021, a new müllerian Anomalies Classification was proposed by American Society for Reproductive Medicine (ASRM 2021), 1 which was based on the American Fertility Society (AFS) 1988 2 and combined the benefits of existing classifications. However, mullerian anomalies is a group of complex diseases with various manifestations. And no consensus has been reached about the classification and diagnosis in clinical practice. The purpose of this study is to test the clinical application value of this new classification through the analysis of the cases from Peking Union Medical College Hospital in the past 20 years, and put forward valuable recommendations.A retrospective study was conducted using clinical data of hospitalized patients from January 2003 to December 2022 from Peking Union Medical College Hospital. Inclusion criteria included patients with 46, XX karyotype, diagnosed of müllerian anomalies, and clearly identified alterations of the uterus, cervix, and vagina. Clinical data of patients were collected through the hospital information system, and classification was performed based on the ASRM 2021. SPSS 25.0 version was used for data analysis.2671 patients were included, with an average visiting age of 28.9±10.0 years. The most common is septate uterus with 1144 cases (42.8%), followed by MRKH syndrome (20.4%), Herlyn-Werner-Wunderlich syndrome (HWWS) (10.4%), unicornuate uterus (7.4%), cervical agenesis (6.5%), uterus didelphys (5.6%), bicornuate uterus (2.9%), longitudinal vaginal septum (without uterine malformation) (2.0%), transverse vaginal septum (1.2%), complex anomalies (0.5%) and other anomalies (0.3%) (Table 1). It should be emphasized that HWWS was taken as an independent classification for statistical analysis, with reference to the clinical definition (uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis).3,4 13 cases of complex anomalies were identified and 8 cases that could not be classified were classified as other anomalies (Supplement table 1).ASRM 2021 was proposed based on the AFS 1988, which is the most widely used classification in the past 30 years. We found ASRM 2021could distinguish most clinical patients well, but there are still some shortcomings. First, the classification of patients with uterine malformations and longitudinal/transverse/oblique vaginal septum is not clear. We recommend that patients with longitudinal vaginal septum and uterine anomalies should be classified into the uterine anomalies respectively, while others without uterine anomalies should be included in longitudinal vaginal septum. All transverse vaginal septum should be included in transverse vaginal septum, because the symptoms of transverse septum are prominent. A new type of HWWS should be added. Because the obstructive symptom is prominent. Second, we found several cases of complex anomalies. For these patients, multidisciplinary and individualized treatment should be carried out. The anomalies we found that are not currently classified include T-shaped uterus, congenital vaginal stenosis, and accessory and cavitated uterine masses (ACUM). With the deeper insight into this field, there may be a better way to classify them. The limitation of this study is that as a single-center retrospective study, there could be statistical biases.In conclusion, we put forward following suggestions for ASRM 2021 classification: 1) Minimize overlaps of classification and add a type of HWWS; 2) Update complex anomalies timely; 3) Add other anomalies classification.