Mullerian Anomalies

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Today we are rejoined by Dr. Emily Seidler of the Division of Reproductive Endocrinology and Infertility at Beth Israel Deaconess and Boston IVF, as well as Margie Thorsen, a PGY-1 at Brown & Women and Infants, to talk through congenital uterine anomalies (CUAs), also known as Mullerian anomllies.

CUAs can cause pelvic pain, AUB/dysmenorrhea, recurrent pregnancy loss (RPL), and/or preterm deliver, or can be asymptomatic . They are often found during an evaluation for primary amenorrhea and infertility. On their own, CUAs are associated with skeletal and renal abnormalities (20-30% of women with CUAs have concomitant renal anomalies), and can also be associated with inguinal hernias. Due to these generally being asymptomatic, true prevalence is hard to estimate; but it’s estimated around 5-6% amongst all women. This increases to 8-10% in infertile women, 12-15% in women with history of SAB, and 20-25% in women with both infertility and prior history of SAB.

Frequency of types of CUAs in affected women, in decreasing order:

  • Septate (most common)

  • Bicornuate

  • Unicornuate

  • Didelphys

  • Agenesis 

“Arcuate” uteri, which refers to an up to 1cm “dip” i the fundal contour of the cavity, is considered a normal variant.

Embryology of Mullerian Structures

  • Wolffian ducts = mesonephric =  “male” (need Y chromosome🡪 SRY gene🡪 AMH).

  • Mullerian ducts = paramesonephric = “female” (default, no AMH means Wolfiann ducts regress).

    • Includes the UTERUS, TUBES, CERVIX & UPPER VAGINA

      • Ovaries are totally separate (urogenital ridge)

  • Mullerian ducts start to elongate caudally at ~6 wks GA.

    • By 12 wks GA, the caudal portion of Mullerian ducts fuse to form the early uterus and vagina.

      • Initially, Mullerian ducts are like 2 solid cylinders laying side by side. Later, each cylinder undergoes canalization, and then fuses (like putting your elbows together and then slowly bringing the arms together until your wrists join).

    • By 20 wks GA, septum absorption is complete.

      • Top part forms the fallopian tubes and fimbria

      • Bottom part becomes the uterus and upper vagina

The Mullerian Anomalies

  • Genetics are not well understood; mostly thought to be polygenic/multifactorial. For affected patients, karyotype is usually normal 46, XX.

  • 3 main types: agenesis/hypoplasia, lateral fusion defects, vertical fusion defects.

  • Agenesis or hypoplasia

    • Classic test question involves complete agenesis of uterus/cervix/upper vagina termed MRKH syndrome, presenting as primary amenorrhea with otherwise normal pubertal development.

      • On exam: overall look totally normal; pelvic exam = “blind pouch” + shortened vagina; normal breasts, normal pubic & axillary hair.

      • Exams may try to confuse this presentation with androgen insensitivity syndrome (AIS).

        • Key labs to differentiate: karyotype is 46,XX, total T is female range in MRKH, whereas 46, XY and elevated T in AIS.

      • Treatment: dilators to become sexually active; can have biologic children later in life with the use of a GC (ovaries/eggs are normal!)

  • Lateral fusion defects

    • i.e., your two arms don’t come together “elbows to hands” normally

    • Longitudinal vaginal/uterine septum, bicornuate, didelphys, etc.

      • Can have 2 cervices = “bicollis.”

      • If abnormal/absent uterine horn, that side’s tube will also be affected.

        • Same concept with renal abnormalities (abnormal uterine side = abnormal renal side).

      • Treatment depends on the anomaly, symptoms,  and patient’s goals.

        • Generally with infertility patients with a septum, will be resected,

        • If not associated with infertility and not surgically corrected, just helpful to know going into pregnancy (SABs, preterm labor/delivery, etc.).

  • Vertical fusion defects

    • Leads to a TRANSVERSE vaginal septum, partial vaginal agenesis, and/or cervical agenesis.

  • Miscellaneous uterine anomalies include those related to in-utero exposure to diethylstilbestrol (DES).

    • Moms were ironically given it to prevent pregnancy loss from 1950s-1971

    • Female babies born with classic uterine anomalies: T shaped uterine cavity, hypoplastic uterus, endometrial cavity adhesions.

Diagnostics for Suspected Anomalies

  • 2D ultrasound = initial imaging modality of choice, as it is widely available, noninvasive, relatively inexpensive, and can also look at renal system.

    • 3D sonohysterogram especially helpful if available.

  • MRI only necessary if ultrasound isn’t definitive; can be helpful for surgical planning.

  • HSG might make the initial diagnosis (infertility patient eval.) but this only evaluates the uterine CAVITY, not the fundus!

    • I.e., an HSG with 2 “bunny ears” could be a large uterine septum (normal fundus) or a bicornuate or didelphys (heart-shaped fundus).