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

• 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.

• 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.`

• 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

• DSDs result when these processes expected during normal sexual development are arrested, disrupted, and/or occur inappropriately.

• 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

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.

• 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.

• 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

Androgen exposure aer 12 weeks Androgen exposure before 12 weeks presents primarily with clitoral à result in labioscrotal fusion and hypertrophy retenon of the urogenital sinus, which creates a single tract that the urethra and vagina empty into before reaching the perineum

• With labial fusion, the physician should palpate the groins and labial folds for evidence of gonads. • Gonads palpable in the inguinal canal, labioinguinal region, or labioscrotal folds are almost always testes, and this finding is typically seen in a male with ambiguous genitalia rather than a virilized female. • Conversely, an infant with ambiguous genitalia but without palpable testes in the scrotum is more likely to be a virilized female, most often the result of congenital adrenal hyperplasia. • A rectal examination may allow palpation of a cervix and uterus, thus helping with gender assignment.

• when necessary, perform imaging studies (ultrasound), karyotyping or chromosomal evaluations, serum electrolytes, and steroid hormone levels

• Until recently, gender was assigned primarily on the principle of “phallic adequacy,” with neonates with ambiguous phallus being assigned female gender.

• This principle is now inappropriate and full evaluation with chromosomal studies and appropriately timed corrective measures is now the desired approach.

Vagina Urethra

Urogenital Urogenital Urogenital sinus sinus sinus Figure 11.1 46,XX DSD induced by prenatal exposure to androgens. Exposure afer 12th fetal week leads only to clitoral hypertrophy (lef). Exposure at progressively earlier stages of diferentiation (from lef to right) leads to retention of the urogenital sinus and labioscrotal fusion. If exposure occurs sufciently early, the labia fuse to form a penile urethra. (From Grumbach MM, Hughes IA, Conte FA. Disorders of sex diferentiation. In Larsen RP, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:916.)

Te initial evaluation of ambiguous genitalia involves check- Box 11.1 Classification of 46,XX DSD ing a karyotype, performing a transabdominal pelvic ultrasound to assess pelvic anatomy, and obtaining blood for serum electro- I. Androgen-Induced lytes and steroid hormone levels. In a female neonate, an ultra- A. Fetal Source sound can easily identify a uterus because the estrogenized tissue 1. Congenital adrenal hyperplasia is easy to visualize. If further evaluation of neonatal pelvic anat- a. Virilism only, defective adrenal 21-hydroxylation (CYP21) b. Virilism with salt-losing syndrome, defective adrenal omy is necessary, cystoscopy and vaginoscopy can be performed 21-hydroxylation (CYP21) with a pediatric cystoscope to assess the pelvic structures, includ- c. Virilism with hypertension, defective adrenal ing the location of the urethra and vagina and the presence of a 11β-hydroxylation (CYP11B1) cervix. Possible causes of 46,XX DSD include congenital adrenal d. Virilism with adrenal insufciency, deficient 3β-HSD 2 hyperplasia, other genetic mutations that afect the steroid path- (HSD3B 2) way, maternal ingestion of androgens, or maternal production of 2. P450 aromatase (CYP19) deficiency excess androgens (Box 11.1) (Grumbach, 2003 ). 3. Glucocorticoid receptor gene mutation It is important to systematically evaluate the newborn’s geni- B. Maternal Source talia to make the appropriate gender assignment, when possible. 1. Iatrogenic In the past, gender was assigned primarily on the principle of a. Testosterone and related steroids “phallic adequacy,” with neonates with an ambiguous phallus b. Certain synthetic oral progestagens and rarely diethylstil- being assigned female gender. In contrast, the current approach bestrol is to initiate a thorough evaluation of the neonate and to defer 2. Virilizing ovarian or adrenal tumor gender assignment until the clinical picture is clear. For the eval- 3. Virilizing luteoma of pregnancy uation and management of an individual with DSD, most ter- 4. Congenital virilizing adrenal hyperplasia in mother* tiary centers utilize a multidisciplinary team including medical C. Undetermined Source genetics, pediatric urology, pediatric endocrinology, gynecology, 1. Virilizing luteoma of pregnancy and psychiatry (Allen, 2009). II. Non—Androgen-Induced Disturbances in Diferentiation of Urogenital Structures PERINEAL AND HYMENAL ANOMALIES From Grumbach MM, Hughes IA, Conte FA. Disorders of sex diferentiation. In: Larsen RP, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams Textbook of § Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Clitoral Anomalies Endocrinology. 10th ed. Philadelphia: Saunders; 2003. Congenital Abnormalities of the Female Reproductive Tract ; pp 205-218. In an adult female, the clitoris is generally 1 to 1.5 cm long * In pregnant patient whose disease is poorly controlled or who is noncompliant, and 0.5 cm wide in the nonerect state. Te glans is partially especially during the first trimester. covered by a hood of skin. Te urethra opens near the base of the clitoris. Abnormalities of the clitoris are unusual, although fndings occur in infants with congenital adrenal hyperplasia it may be enlarged because of androgen stimulation. In such and in those exposed in utero to exogenous or endogenous circumstances the shaft of the clitoris may be quite enlarged androgens (Fig. 11.3 ) (Black, 2003 ). Similar in appearance, and partial development of a penile urethra may have occurred males with partial androgen insensitivity syndrome have (Fig. 11.2) (Verkauf, 1970). Extreme cases of androgen stimu- underdeveloped male external genitalia and a small phallus lation are generally associated with fusion of the labia. Tese that appears as clitoral hypertrophy (Fig. 11.4) (Black, 2003 ).

Obstetrics & Gynecology Books Full 1. PERINEAL AND HYMENAL ANOMALIES 1. CLITORAL ANOMALIES

• Clitoral enlargement may be secondary to androgen stimulation • In such cases, the shaft of the clitoris may be enlarged and partial development of the penile urethra may have occurred • Extreme cases may involve fusion of the labia. • These findings are often found in babies with congenital adrenal hyperplasia or in fetuses exposed in utero to high levels of endogenous or exogenous androgen.

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. LABIAL FUSION

• Most commonly caused by Congenital Adrenal Hyperplasia (CAH) • The most common form of congenital adrenal hyperplasia is caused by an inborn error of metabolism involving deficiency of the enzyme 21- hydroxylase • transmitted as an autosomal recessive

gene coded on chromosome 6. Hutson J.M., Beasley S.W. (2013) Ambiguous Genitalia: Is It a Boy or a Girl?. In: The Surgical Examination of Children. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29814- 1_22; link.springer.com

Others: • 11-hydroxylase deficiency • 3b-hydroxysteroid dehydrogenase deficiency

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. • The majority of newborns (75%) who are homozygous for a CAH mutation are at risk for the development of a life-threatening neonatal adrenal crisis as a result of sodium loss because of lack of aldosterone production. • In individuals with a milder disease CONGENITAL presentation, delayed diagnosis may result in accelerated bone maturation due to high ADRENAL levels of androgens being aromatized to HYPERPLASIA estradiol and thus leading to premature (CAH) closure of the epiphyseal plates and short stature. • The development of premature secondary sexual characteristics in males and further virilization in females may also occur

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. • Treatment of congenital adrenal hyperplasia involves replacement of cortisol. • This suppresses ACTH output and therefore decreases the stimulation of the cortisol-producing pathways of the adrenal cortex and subsequently decreases androgen production. CONGENITAL • For women diagnosed with CAH who gets ADRENAL pregnant: daily administration of dexamethasone will suppress the fetal HYPERPLASIA adrenal glands until the fetal gender can be (CAH) verified with prenatal diagnosis. • Because of the profound gender identity issues related to ambiguous genitalia in females with CAH, ongoing psychological support and counseling are important.

Hymen Embryology: • The hymen represents the junction of the sinovaginal bulbs with the urogenital sinus and is composed of endoderm from the urogenital sinus epithelium.

• The hymen opens normally during embryonic life to establish a connection between the lumen of the vaginal canal and the vestibule. If this perforation does not take place, the hymen is imperforate.

• Diagnosed after puberty in the setting of primary amenorrhea (cryptomenorrhea) and hematocolpos (and/or hematometra), that can cause pelvic pain, urinary retention, and difficulty with bowel movements

• In some cases, due to retrograde flow of the blood, endometriotic implants may be noted on the pelvic cavity and masy possibly cause endometriotic cysts.

• The diagnosis determined by history and by the presence of a bulging membrane at the introitus. • Treatment: cruciate incision into the hymen extending to the 10 to 4o’clock positions, and 2 to 8 o’clock • Hemostasis is secured by fine suture, and evolution to normal usually occurs rapidly.

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. IMPERFORATE HYMEN

§ 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. 2. MULLERIAN ANOMALIES 2. MULLERIAN ANOMALIES

• otherwise known as congenital anomalies of the female reproductive tract, occur due to defects in development of the mullerian̈ ducts, which are the embryologic origin of the fallopian tubes, uterus, cervix, and a portion of the vagina.

• also known as Mullerian agenesis or Mullerian aplasia • associated with the Mayer– Rokitansky–Kuster–Hauser (MRKH) syndrome. • Congenital absence of the vagina and variable development of the uterus • differential diagnosis includes transverse vaginal septum, cervical agenesis, and androgen insensitivity syndrome.

• Up to 50% of women with Mullerian agenesis have concurrent urinary tract anomalies (eg renal agenesis, pelvic kidney, ureteral duplication etc). • Females with Mullerian agenesis present with normal pubertal development (46XX karyotype with normal ovaries), with primary amenorrhea • On PE, there is no vaginal opening or a short vaginal pouch, and there are no palpable midline structures on rectal exam

TREATMENT • Goal: the creation of a vagina when the patient wishes to become sexually active.

• Nonsurgical: • requires the use of progressive vaginal dilators à time consuming; requires the daily use of dilators for 15-20 minutes, for approx. 3-6 months à requires a well-motivated, mature patient • Dilator is pressed at the vaginal dimple to stretch the skin • Once a functional neovagina is created, maintenance dilatation must be done several times a week, unless the she is sexually active.

Surgical reconstruction:

Abbe-McIndoe: develop the potential space between the bladder and the rectum and replaced this space with a stent utilizing tissue, most commonly a split-thickness skin graft or synthetic materials • Must be done only when the patient will use the vagina frequently. • Early and regular postoperative coitus is important for long-term success à the timing of the operation to coincide with the opportunity for coitus is important.

TREATMENT • Intestinal vaginoplasty

TREATMENT

• Williams procedure: a neovagina is built by utilizing labial skin and results in a vaginal pouch whose axis is directly posterior.

TREATMENT

• Vecchietti procedure: laparoscopic procedure where sutures are placed in the peritoneal folds between the bladder and rudimentary uterus. • The sutures (two) are then fixed to a traction device on the anteriorabdominal wall and graduated traction applied for 6 to 8 days.

• Occurs due to partial canalization of the vaginal plate, leaving a band of thick tissue across the vagina • Commonly lies at the junction between the upper 1/3 and lower 2/3 of the vaagina

• Hematocolpos and hematometrium may occur in a fashion similar to that seen in the imperforate hymen, except that there is no bulging at the introitus • Primary amenorrhea with cyclic cramping. • Foul-smelling vaginal discharge (for cases of partial vaginal septum). • If an opening is noted, it may be expanded by manual dilation or simple incision, with suturing of the edges of the vagina on either side.

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. VAGINAL ADENOSIS

• In the female who was exposed to DES in utero, the junction between the Mullerian ducts and the sinovaginal bulb may not be sharply demonstrated. • If Mullerian elements invade the sinovaginal bulb, remnants may remain as areas of adenosis in the adult vagina. They are generally palpated submucosally, although they may be observable at the surface.

I Hypoplasia/agenesis II Unicornuate III Didelphys

• Categorized as lateral fusion defects

(a) Vaginal (b) Cervical (a) Communicating (b) Non-communicating (disordered duct IV Bicornuate fusion and septal resorption)

• Classification system (c) Fundal (d) Tubal (e) Combined (c) No cavity (d) No horn (a) Complete (b) Partial by the American V Septate VI Arcuate VII DES drug related Fertility Society

(a) Complete (b) Partial

circumstances (Bermejo, 2010; Benacerraf, 2015). Figure 11.15 may be due to a partial or microperforate vaginal obstruction Comprehensive Gynecology 7th edition, 2017 (Lobo RA,compares Gershenson MRI andDM, 3D Lentz US images GM, Valeaof someFA abnormalities editors); chapter using 11,or a longitudinal vaginal septum. A longitudinal vaginal sep- the American Fertility Society classifcation. Imaging with a tum, which is associated with septate, didelphys, and bicornu- Congenital Abnormalities of the Female Reproductivehysterosalpingogram, Tract ; pp 205 which-218. can show two uterine cavities ate uteri, may be a woman’s frst presentation with a uterine (Fig. 11.16), could be either a bicornuate uterus or a septate anomaly; associated symptoms include difculty with tampon uterus. Conventional two-dimensional (2D) US is not able to insertion, bleeding around one tampon (two are required), and make this distinction because it is not able to determine the dyspareunia. Hence, if a vaginal anomaly is identifed, then uter- external contour of the uterus, which is accomplished either ine imaging is warranted. by 3D US or MRI (Tro i a n o , 2 0 0 4 ). In obstetrics, congenital uterine anomalies are associated with a higher rate of poor obstetric outcomes: recurrent pregnancy loss Symptoms and Signs (RPL), frst- and second-trimester pregnancy loss, intrauterine It is important to recognize several gynecologic and obstetric growth restriction, preterm labor and delivery, placental abruption, signs and symptoms that may indicate a uterine anomaly and malpresentation, and intrauterine fetal demise. Among women to also remember that many females with congenital uterine with RPL, the incidence of uterine anomalies is highly variable and anomalies are asymptomatic. Uterine agenesis presents with ranges from 6% to 38%, but based on meta-analyses it is likely primary amenorrhea. Women with an obstructive anomaly closer to 12% to 16% and is as high as 25% in women with second- may report cyclic or noncyclic pelvic pain and dysmenorrhea, trimester pregnancy loss (Chan, 2011; Saravelos, 2008). In one study, and these symptoms can begin several months after menarche the odds ratio for preterm birth less than 34 weeks with a uterine or into adulthood. Obstructive uterine anomalies are associated anomaly was 7.4 (Hua 2011). However, many studies identify that with hematometra, retrograde menstruation, and endometriosis. in women with uterine anomalies, despite the high risk of miscar- Endometriosis is a common fnding in women with obstructive riage and midtrimester pregnancy loss, the chance of a live birth is and nonobstructive müllerian anomalies. Abnormal bleeding greater than 50% (Grimbizis, 2001). Uterine dysfunction is thought can also occur with uterine anomalies and has been associated to occur due to diminished cavity size, impaired ability to distend, with septate uteri. Furthermore, vaginal anomalies may occur abnormal myometrial and cervical function, inadequate vascularity, in conjunction with uterine anomalies, and abnormal bleeding or abnormal endometrial development. Due to higher rates of fetal

Obstetrics & Gynecology Books Full 214 Part III GENERAL GYNECOLOGY

ABNORMALITIES I Hypoplasia/agenesis II Unicornuate III Didelphys OF THE UTERUS

• Hypoplasia/agenesis (category I) and (a) Vaginal (b) Cervical (a) Communicating (b) Non-communicating IV Bicornuate unicornuate (category II) denote anomalies with developmental failure of one or both mullerian̈ ducts; • didelphys (category III) and bicornuate (category IV) describe (c) Fundal (d) Tubal (e) Combined (c) No cavity (d) No horn (a) Complete (b) Partial

anomalies involving a varying degree V Septate VI Arcuate VII DES drug related of failure of midline fusion; • septate (category V) and arcuate (category VI) identify anomalies with some degree of failure of resorption of the midline septum. (a) Complete (b) Partial

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 11, Congenital Abnormalities of the Female Reproductive Tract ; ppcircumstances 205-218. (Bermejo, 2010; Benacerraf, 2015). Figure 11.15 may be due to a partial or microperforate vaginal obstruction compares MRI and 3D US images of some abnormalities using or a longitudinal vaginal septum. A longitudinal vaginal sep- the American Fertility Society classifcation. Imaging with a tum, which is associated with septate, didelphys, and bicornu- hysterosalpingogram, which can show two uterine cavities ate uteri, may be a woman’s frst presentation with a uterine (Fig. 11.16), could be either a bicornuate uterus or a septate anomaly; associated symptoms include difculty with tampon uterus. Conventional two-dimensional (2D) US is not able to insertion, bleeding around one tampon (two are required), and make this distinction because it is not able to determine the dyspareunia. Hence, if a vaginal anomaly is identifed, then uter- external contour of the uterus, which is accomplished either ine imaging is warranted. by 3D US or MRI (Tro i a n o , 2 0 0 4 ). In obstetrics, congenital uterine anomalies are associated with a higher rate of poor obstetric outcomes: recurrent pregnancy loss Symptoms and Signs (RPL), frst- and second-trimester pregnancy loss, intrauterine It is important to recognize several gynecologic and obstetric growth restriction, preterm labor and delivery, placental abruption, signs and symptoms that may indicate a uterine anomaly and malpresentation, and intrauterine fetal demise. Among women to also remember that many females with congenital uterine with RPL, the incidence of uterine anomalies is highly variable and anomalies are asymptomatic. Uterine agenesis presents with ranges from 6% to 38%, but based on meta-analyses it is likely primary amenorrhea. Women with an obstructive anomaly closer to 12% to 16% and is as high as 25% in women with second- may report cyclic or noncyclic pelvic pain and dysmenorrhea, trimester pregnancy loss (Chan, 2011; Saravelos, 2008). In one study, and these symptoms can begin several months after menarche the odds ratio for preterm birth less than 34 weeks with a uterine or into adulthood. Obstructive uterine anomalies are associated anomaly was 7.4 (Hua 2011). However, many studies identify that with hematometra, retrograde menstruation, and endometriosis. in women with uterine anomalies, despite the high risk of miscar- Endometriosis is a common fnding in women with obstructive riage and midtrimester pregnancy loss, the chance of a live birth is and nonobstructive müllerian anomalies. Abnormal bleeding greater than 50% (Grimbizis, 2001). Uterine dysfunction is thought can also occur with uterine anomalies and has been associated to occur due to diminished cavity size, impaired ability to distend, with septate uteri. Furthermore, vaginal anomalies may occur abnormal myometrial and cervical function, inadequate vascularity, in conjunction with uterine anomalies, and abnormal bleeding or abnormal endometrial development. Due to higher rates of fetal

Obstetrics & Gynecology Books Full 214 Part III GENERAL GYNECOLOGY

ABNORMALITIES I Hypoplasia/agenesis II Unicornuate III Didelphys OF THE UTERUS

Imaging (a) Vaginal (b) Cervical (a) Communicating (b) Non-communicating IV Bicornuate • MRI is the gold standard for the diagnosis of these abnormalities. • However, three-dimensional (3D) ultrasound (US) is also useful (c) Fundal (d) Tubal (e) Combined (c) No cavity (d) No horn (a) Complete (b) Partial • Conventional (2D) US is not very useful because it is not able to V Septate VI Arcuate VII DES drug related determine the external contour of the uterus, which is accomplished either by 3D US or MRI

(a) Complete (b) Partial

Figure 11.13 American Fertility Society classiﬁcation. (From The American Fertility Society classiﬁ- cation of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, müllerian anomalies and intrauterine adhesions. Fertil Steril. 1988;49[6]:944-955.) 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. circumstances (Bermejo, 2010; Benacerraf, 2015). Figure 11.15 may be due to a partial or microperforate vaginal obstruction compares MRI and 3D US images of some abnormalities using or a longitudinal vaginal septum. A longitudinal vaginal sep- the American Fertility Society classifcation. Imaging with a tum, which is associated with septate, didelphys, and bicornu- hysterosalpingogram, which can show two uterine cavities ate uteri, may be a woman’s frst presentation with a uterine (Fig. 11.16), could be either a bicornuate uterus or a septate anomaly; associated symptoms include difculty with tampon uterus. Conventional two-dimensional (2D) US is not able to insertion, bleeding around one tampon (two are required), and make this distinction because it is not able to determine the dyspareunia. Hence, if a vaginal anomaly is identifed, then uter- external contour of the uterus, which is accomplished either ine imaging is warranted. by 3D US or MRI (Tro i a n o , 2 0 0 4 ). In obstetrics, congenital uterine anomalies are associated with a higher rate of poor obstetric outcomes: recurrent pregnancy loss Symptoms and Signs (RPL), frst- and second-trimester pregnancy loss, intrauterine It is important to recognize several gynecologic and obstetric growth restriction, preterm labor and delivery, placental abruption, signs and symptoms that may indicate a uterine anomaly and malpresentation, and intrauterine fetal demise. Among women to also remember that many females with congenital uterine with RPL, the incidence of uterine anomalies is highly variable and anomalies are asymptomatic. Uterine agenesis presents with ranges from 6% to 38%, but based on meta-analyses it is likely primary amenorrhea. Women with an obstructive anomaly closer to 12% to 16% and is as high as 25% in women with second- may report cyclic or noncyclic pelvic pain and dysmenorrhea, trimester pregnancy loss (Chan, 2011; Saravelos, 2008). In one study, and these symptoms can begin several months after menarche the odds ratio for preterm birth less than 34 weeks with a uterine or into adulthood. Obstructive uterine anomalies are associated anomaly was 7.4 (Hua 2011). However, many studies identify that with hematometra, retrograde menstruation, and endometriosis. in women with uterine anomalies, despite the high risk of miscar- Endometriosis is a common fnding in women with obstructive riage and midtrimester pregnancy loss, the chance of a live birth is and nonobstructive müllerian anomalies. Abnormal bleeding greater than 50% (Grimbizis, 2001). Uterine dysfunction is thought can also occur with uterine anomalies and has been associated to occur due to diminished cavity size, impaired ability to distend, with septate uteri. Furthermore, vaginal anomalies may occur abnormal myometrial and cervical function, inadequate vascularity, in conjunction with uterine anomalies, and abnormal bleeding or abnormal endometrial development. Due to higher rates of fetal

Obstetrics & Gynecology Books Full ABNORMALITIES OF THE UTERUS

Symptoms and Signs • Women with an obstructive anomaly may report cyclic or noncyclic pelvic pain and dysmenorrhea, and these symptoms can begin several months after menarche or into adulthood. • Obstructive uterine anomalies are associated with hematometra, retrograde menstruation, and endometriosis. • Endometriosis is a common finding in women with obstructive and nonobstructive mullerian̈ anomalies (retrograde menstruation). • A longitudinal vaginal septum, which is associated with septate, didelphys, and bicornuate uteri, may be a woman’s first presentation with a uterine anomaly; • associated symptoms include difficulty with tampon insertion, bleeding around one tampon (two are required), and dyspareunia.

Symptoms and Signs • In obstetrics, congenital uterine anomalies are associated with a higher rate of poor obstetric outcomes: recurrent pregnancy loss (RPL), first- and second-trimester pregnancy loss, intrauterine growth restriction, preterm labor and delivery, placental abruption, malpresentation, and intrauterine fetal demise. • Uterine dysfunction is thought to occur due to diminished cavity size, impaired ability to distend, abnormal myometrial and cervical function, inadequate vascularity, or abnormal endometrial development.

Management • Surgical intervention is indicated for women with obstructive anomalies with associated pelvic pain, endometriosis, and poor obstetric outcomes such as RPL, second-trimester loss, or preterm delivery. • The goals of surgery include restoration of pelvic anatomy, preservation of fertility, and treatment of pelvic pain and endometriosis. • Of the uterine anomalies, the septate uterus is amenable to surgical correction • In contrast, the unicornuate uterus is never considered operable, but excision of a functional rudimentary uterine horn and the attached fallopian tube is recommended to prevent a horn or tubal gestation and to treat hematometra and pelvic pain.

Management • a cervical cerclage can be done to improve pregnancy outcomes in women with uterine anomalies and a history of poor reproductive outcomes. • Hysteroscopic metroplasty to correct a partial or complete septate uterus can improve reproductive outcomes and is indicated in women with recurrent pregnancy loss or second- trimester pregnancy loss à the septum is visualized and incised with a cutting device and the cavity achieves a normal contour. • the hysteroscopic approach is preferred for surgical treatment of a uterine septum, and laparoscopy can be utilized to assess the fundal contour and guide the extent of septum resection but is not mandatory. • The surgical treatment of uterine septa in asymptomatic women is controversial, but some women elect to undergo surgery due to concerns regarding the obstetric risks associated with a uterine septum.

• abdominal metroplasty (Strassman technique) can be performed to unify a bicornuate or didelphys uterus, but it is only performed in certain patients with poor obstetric outcomes.

• Accessory ovary - excess ovarian tissue is noted near a normally placed ovary and connected to it. • Supernumerary ovary - a third ovary is separated from the normally situated ovaries.

• Such ovaries may be found in the omentum or retroperitoneally, • Patients with supernumerary ovary and accessory ovary had additional congenital defects, most frequently abnormalities of the genitourinary tract.

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. B. OVOTESTES

• Present in individuals with ovaries that have an SRY antigen present. The majority are true hermaphrodites (quite rare).

• When considerable amounts of testicular tissue are present within the organ, there is a tendency for descent toward the labial scrotal area. • Thus, palpation of the gonad in the inguinal canal or within the labial scrotal area is fairly common.

• Where testicular tissue is present, there is an increased risk for malignant degeneration, and these gonads should be removed after puberty.

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. SUMMARY