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Congenital Abnormalities of the Female Reproductive Tract

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Congenital Abnormalities of the Female Reproductive Tract CONGENITAL ABNORMALITIES OF THE FEMALE REPRODUCTIVE TRACT Ina S. Irabon, MD, FPOGS, FPSRM, FPSGE Obstetrics and Gynecology Reproductive Endocrinology and Infertility Laparoscopy and Hysteroscopy TO DOWNLOAD LECTURE DECK: MAIN REFERENCES • Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. • Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com • OUTLINE • Review Mullerian embryogenesis • Musset’s 3 stage process • Examination of the newborn’s external genitalia • Ambiguous genitalia • Perineal and vaginal defects • Abnormalities of the cervix and uterus • Abnormalities of the ovary REVIEW REVIEW OF MULLERIAN EMBRYOGENESIS • Paramesonephric ducts = Mullerian ducts • Mesonephric ducts = Wolffian ducts REVIEW OF MULLERIAN EMBRYOGENESIS Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. Review of Mullerian embryogenesis Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. NORMAL SEX DEVELOPMENT • In XY individuals, the expression of the SRY (sex- determining region on the Y chromosome) gene activates pathways that cause the gonads to differentiate into a testis. • The Leydig cells of the testis produce testosterone, which is converted to dihydrotestosterone by the peripherally expressed enzyme 5-alpha-reductase type 2. • Dihydrotestosterone activates the androgen receptor, and this activation in turn causes virilization of the external genitalia Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com NORMAL SEXUAL DEVELOPMENT: XY • The genital tubercle grows to develop into the glans penis • The genital swellings fuse to develop into the scrotum • The genital plate fuses to form the shaft of the penis • Fusion of the genital plate also results in the migration of the urethral meatus to the tip of the glans penis Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com NORMAL SEXUAL DEVELOPMENT: XY • Local testosterone secretion causes ipsilateral development of the Wolffian ducts into the: • epididymis • vas deferens • seminal vesicle • ejaculatory duct Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com NORMAL SEXUAL DEVELOPMENT: XY • Leydig cell production of insulin- like 3 (INSL3) and testosterone cause the gonads to descend to the scrotum. • The Sertoli cells of the testis produce anti-Müllerian hormone (AMH, also known as Müllerian- inhibiting substance, MIS, and Müllerian regression factor), which leads to ipsilateral regression of the Müllerian ducts. Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com NORMAL SEXUAL DEVELOPMENT: XX In XX individuals, the active repression of testicular pathways allows the gonad to differentiate into an ovary. In the absence of activation of the androgen receptor •The genital tubercle develops into the clitoris with an open vestibular groove •The genital swellings do not fuse and develop into the labia majora •The genital folds do not fuse and develop into the labia minora •The urethra becomes divided from the vagina, leading to distinct orifices for the two structures Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com NORMAL SEXUAL DEVELOPMENT: XX • The absence of testosterone and dihydrotestosterone action results in regression of the Wolffian ducts • in the absence of INSL3 and testosterone, the gonads remain in the abdomen. • The absence of AMH/MIS leads to retention of the Müllerian ducts, which develop into the uterus, Fallopian tubes, and upper two-thirds of the vagina. Chan YM, Levitsky LL. Evaluation of the infant with atypical genitalia (disorder of sex development). www.uptodate.com MUSSET’S 3 STAGE PROCESS • The first stage is described as short, taking place at the beginning of the 10th week. • The medial aspects of the more caudal portions of the two ducts fuse, starting in the middle and proceeding simultaneously in both directions. • In this way a median septum is formed. Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. MUSSET’S 3 STAGE PROCESS • The second stage: 10th – 13th week • rapid cell proliferation and the filling in of the triangular space between the two uterine cornua. • a thick upper median septum is formed à wedge like and gives rise to the usual external contour of the fundus. • lower portion of the median septum is resorbed, unifying the cervical canal first and then the upper vagina.` Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. MUSSET’S 3 STAGE PROCESS • The third stage lasts from the 13th – 20th week. • the degeneration of the upper uterine septum occurs, starting at the isthmic region and proceeding cranially to the top of the fundus. • In this way a unified uterine cavity is formed Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. DISORDER OF SEXUAL DEVELOPMENT (DSD) • DSDs result when these processes expected during normal sexual development are arrested, disrupted, and/or occur inappropriately. Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. DISORDER OF SEXUAL DEVELOPMENT • The term hermaphrodite is no longer used and was derived from the child of the Greek gods Hermes and Aphrodite, Hermaphroditus, who was part female and part male. • A true hermaphrodite is now called ovotesticular DSD and has both ovarian (including follicular elements) and testicular tissue, either in the same or opposite gonads Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. DISORDER OF SEXUAL DEVELOPMENT Ovotestes are present in individuals with ovaries that have an SRY antigen present and testicular tissue present. The degree to which mullerian̈ and wolffian development occurs depends on the amounts of testicular tissue present in the ovotestes and the proximity to the developing duct system. When testicular tissues are present within the organ, there is a tendency for descent toward the labial/scrotal area; Ovulation and menstruation may occur if the mullerian̈ system is appropriately developed. Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. AMBIGUOUS GENITALIA EXAMINATION OF THE NEWBORN FOR AMBIGUOUS GENITALIA • A detailed assessment of the neonate’s genital anatomy is necessary upon delivery: • The clitoris should be noted for any enlargement • the opening of the urethra should be identified • labia should be gently separated to see if the introitus can be visualized • the hymen is perforate, revealing the entrance into the vagina. • Posteriorly the labia fuse in the midline at the posterior fourchette of the perineum. • Posterior to the perineal body the rectum can be visualized, and it should be tested to be sure that it is perforate (Meconium staining evidence for anal patency; If there is doubt, the rectum may be penetrated with a moistened cotton-tipped swab) • Palpation of the inguinal area and labia for any masses is also important. Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. EXAMINATION OF THE NEWBORN FOR AMBIGUOUS GENITALIA • The current terminology for individuals with abnormal external genitalia and associated issues is DISORDER OF SEXUAL DEVELOPMENT (DSD) • These disorders are related to in utero androgen exposure that can affect development of external genitalia. • Females (XX karyotype) with masculinized or virilized external genitalia are identified as 46,XX DSD • Males (XY karyotype) with undervirilized external genitalia are identified as 46,XY DSD Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. EXAMINATION OF THE NEWBORN FOR AMBIGUOUS GENITALIA Androgen exposure a4er 12 weeks Androgen exposure before 12 weeks presents primarily with clitoral à result in labioscrotal fusion and hypertrophy reten0on of the urogenital sinus, which creates a single tract that the urethra and vagina empty into before reaching the perineum Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. EXAMINATION OF THE NEWBORN FOR AMBIGUOUS GENITALIA
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