This blog post is the summary of Scientific Impact Paper #62 “Reproductive Implications and Management of Congenital Uterine Anomalies” published in November 2019.
This paper provides important information regarding this topic. I found this SIP quite extensive and had to really dig in to make this summary. I have tried my best to extract main points but it is suggested to read through the original document to make sure nothing is missed.
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SIP # 62 Reproductive Implications and Management of Congenital Uterine Anomalies (CUA)
Background
- CUA → embryological maldevelopment of Müllerian ducts
- Most CUAs → asymptomatic & normal reproductive outcomes
- 3D USG → non-invasive, reproducible & provides visible evidence of internal/external contours of uterus
- Recent Meta-analysis
- Overall prevalence CUA → 5.5% in unselected women
- 8% in Infertile
- 13.3% in women with h/o Miscarriage
- 24.5% in women with h/o Miscarriage plus Infertility
- Presentation of anomalies is variable (from asymptomatic to very complex)
- Four main reason of being difficult counselling about CUAs
- Several classifications in literature
- Several different diagnostic modalities still being used
- Each CUA’s Reproductive Impact is different
- No single RCT for surgical management of CUAs
The aim of this Scientific Impact Paper is to address these four issues and make recommendations.
Classification
- Most classifications → based on extent of failure of Müllerian duct development
- Fault at ANY of 3 phases of Müllerian duct development → results in CUA
- Organogenesis → Defect leads to agenesis or hypoplasia (absent and unicornuate uterus)
- Fusion of both Müllerian ducts → formation of uterus & upper vagina occurs
- Horizontal fusion or unification→ bicornuate uterus or uterine didelphys
- Vertical fusion→ imperforate hymen or transvaginal septum
- Failure of resorption or canalization → complete/partial/ accurate uterus
- American Society of Reproductive Medicine (ASRM) classification most commonly used over past 3 decades
- There are new classifications as originals ones did not provide clear diagnostic criteria. They include:
- Vagina Cervix Uterus Adenexal-associated Malformation (VCUAM) classification
- Recent classifications developed jointly by ESHRE & ESGE in 2013
- ESHRE/ESGE classification includes description for ALL female genital tract malformations (not solely uterine)
- U0-U6 C0-C4 V0-V4
- Also provides pictorial guide e.g.
- Septate Uterus → internal indentation at fundal midline >50% of uterine wall thickness
- Bicorporeal Uterus → external indentation at fundal midline >50% of uterine thickness
Main classes of uterine anomalies based on recent ESHRE/ESGE
- U0 → normal uterus
- U1 → dysmorphic uterus (infantile & T-shaped mainly)
- U2 → septate uterus (cavity partitioned by fibromuscular septum but with normal external contour/shape
- U3 → bicorporeal uterus (partial & complete— bicornuate uterus and uterus didelphys based on AFS)- uterus is present as 2 separate horns, double uterus with or without 2 separate cervices and rarely double vagina. Each uterine horn linked to one fallopian tube & ovary
- U4 (hemi-uterus/ unicornuate) — only 1 horn present & linked to 1 Fallopian tube & ovary. Other horn is absent or rudimentary
- U5 → aplastic/ absent uterus
- U6 → still unclassified
- Arcuate uterus → not included in classification as it is the mildest form & is not clinically relevant
Criteria to diagnose septate and bicornuate uterus according to 2016 ARSM publication
- Normal/Arcuate—depth of interstitial line to apex: <1 cm Angle of indentation >90
- Septate— depth of interstitial line to apex: >1.5cm Angle of indentation <90
- Bicornuate — external fundal indentation >1cm
- There is a grey zone between normal/arcuate and septate for diagnosis
- Classifications are criticized for
- ESHRE/ESGE → overestimating prevalence of septate
- ASRM → underestimating prevalence of septate
- Higher proportion of septate uteri diagnosed using ESHRE/ESGE vs ASRM → RR 13.9
- ESHRE/ESGE criteria → an attempt to define CUA objectively based on 3D USG measurements. It should be used with caution until further refinements
Diagnosis
- To make a diagnosis and classify CUA → it is crucial to have accurate evaluation of internal and external contours of uterus
- 3D TVS and MRI can accurately classify CUAs
Conventional 2D TVS
- Minimally invasive and less expensive
- Scanning in 2nd half of menstrual cycle → more accurate visualization of endometrium & appropriate for evaluation of CUA
- 2 endometrial cavities visualized → indicative of CUA
2 endometrial cavities on 2D TVS → indicative of uterus didelphys BUT 3D TVS can confirm the diagnosis (in addition to clinical presence of 2 cervices or 2 vaginas)
3D TVS
- Provides coronal plane of uterus
- Helps to see both external / internal contours → easy to classify bicornuate, septate or partial septate uteri correctly
- Unicornuate (hemi-uterus)
- Normal long axis of uterus seen on one side of pelvis alongside absent or rudimentary uterine shadow on the other side
- Banana-shaped uterine cavity + single interstitial portion of fallopian tube in coronal plane seen on 3D USG
- Can also use saline infusion sonography to diagnose rudimentary horns
- Gold standard for assessment of CUAs is “3D-TVS”
MRI of pelvis
- Sensitive / specific for diagnosing CUAs
- Helpful in
- delineating endometrium & detecting uterine horns
- defining aberrant gonadal location or renal anatomy
- Less invasive than combined laparoscopy & hysteroscopy
- MRI → not routinely recommended in all with suspected CUAs
- It is useful for those with
- unconfirmed diagnosis on 3D USG
- suspected anomalies and for those
- who decline/ distressed by internal examination
- Congenital Renal Anomalies
- CUAs → may be associated with congenital renal anomalies
- Most common → unilateral renal agenesis
- All women with diagnosed CUA → recommended to have urinary tract USG, MRI or IVU depending on clinical picture
Reproductive Implications
Different presentations of CUAs
- Mostly diagnosed incidentally during investigations for subfertility, recurrent miscarriage or menstrual disorders
- Pelvic pain secondary to hematometra, hematocolpos or endometriosis → CUAs with obstruction (unicornuate uterus with rudimentary horn, uterine didelphys with obstructed hemivagina or vaginal/cervical agenesis or anomalies)
- Primary amenorrhea → MRKH or segmental hypoplasia
- Dysparunea or menstrual abnormalities → longitudinal vaginal septa
CUAs implicated as potential causes of
- Infertility
- Recurrent miscarriage
- Preterm Delivery
- Fetal Malpresentation
- Fetal Growth Restriction
- Increased rates of Pre-eclampsia & Stillbirth
Systemic review indicated
Canalizations defect (septate/partial septate uteri)
- Poorest reproductive outcomes
- ↓ conception rate OR 0.86
- ↑ risk of 1st trimester miscarriage OR 2.89
- Fetal Malpresentation at delivery OR 6.24
- Women with septate uterus have → poorer outcomes throughout pregnancies as compared to partial septate uterus
- Definitive etiology → uncertain
Unification defects(bicornuate /unicornuate)
- Do not reduce fertility but have ↑ risks of adverse outcomes during pregnancy
- Risks depend on the type of unification defect
- ↑ risk of 1st trimester miscarriage
- Bicornuate → OR 3.4 Unicornuate → OR 2.15
- Preterm Birth
- Bicornuate → OR 2.55 Unicornuate → OR 3.47
- Fetal Malpresentation
- Bicornuate → OR 5.38 Unicornuate → OR 2.74
- Uterus didelphys
- ↑ risk of preterm labour → OR 3.58 Fetal Malpresentation → OR 3.7
Dysmorphic uterus
- Uterine cavity is of abnormal morphology (T-shaped or tubal shaped — infantile uterus)
- Rare malformation
- Linked to DES in uteri exposure
- Poor reproductive outcomes
- Recent studies revealed that even though DES use in pregnancy prohibited 40 yrs ago, this malformation still exists in women with no h/o DES exposure
- 3D pelvis USG has helped to identify
- T-shaped uteri may also be associated with → marginal intrauterine adhesions (IUAs) and TB infection
Increased risk of spontaneous preterm birth
- Canalizations defects → RR 2.14
- Unification defects → 2.97
- Prospective study of women with CUAs evaluated transvaginal cervical length scanning performed between 14 and 23 weeks
- 16% had short cervical length of <2.5cm
- Overall incidence of spontaneous preterm birth 11%
- Chance is higher in women with short cervix RR 13.5
- Lack of robust data so not possible to draw conclusions
Management Options
Aims of CUA management are to
- Treat anatomical distortions associated with obstructive anomalies to relieve symptoms such as pain
- Improve QoL
- Avoid long-term health & reproductive adverse consequences
- For non-obstructive anomalies
- To improve reproductive outcomes in infertile or with recurrent miscarriages
- Ultimate goal → increase live births at term with associated reduction in long term neonatal morbidity and mortality
- Obstructive CUAs
- Functioning rudimentary uterine horns → need surgical removal
Non-obstructive CUAs (Bicornuate and didelphic uteri (unification or fusion defects)
- Only surgical treatment available for women with unification defects → abdominal metroplasy
- Not generally considered in the absence of significant adverse reproductive history because of higher risks of associated complications
Septate uterus (resorption or canalization defects)
Hysteroscopic Metroplasty or Hysteroscopic Transcervical division of Uterine Septum
- Current treatment of choice for septate uterus
- Good practice to measure septal length preoperatively using 3D USG or MRI to ensure surgical safety & efficacy
- Preoperative endometrial suppression not used routinely, but may improve visualization and operative precision
- Insufficient evidence to use GnRH agonists, danazol or any other medicine to thin the endometrium
- Procedure performed preferably in early follicular phase of menstrual cycle
- Length of septum may vary
- Residual septum of 0.5 - 1.0 cm may not adversely influence outcome
- Verification of resection completion can be done by moving hysteroscope from side to side and visualizing both ostia on a panoramic view from level of internal os or using graduated intrauterine palpator to objectively check the respected septum portion
- Risk of IUAs after the procedure
- Intrauterine auto-cross linked hyaluronic acid gel can reduce risk of IUAs after septum division (some evidence)
- Re-evaluation by second-look hysteroscopy at 1-3 months postoperatively can be offered
- Studies showed that uterine cavity is healed 2 months after septal division
- No evidence for specific length of time before conception
No published RCT for effectiveness & complications of hysteroscopic metroplasty
Observational studies showed
- Significant improvement in pregnancy outcomes in women with no h/o surgery
- Reduction in miscarriage rates
- Increased live birth rates
2014 meta-analysis
- Decreased probability of spontaneous miscarriages in woman treated with hysteroscopic resection of septum
- No difference in conception rates and preterm delivery rates
NICE Guidance states
- women with recurrent miscarriage should be offered hysteroscopic metroplasty of a uterine septum as long as appropriate clinical governance arrangements are put in place
- MDT including specialists in Reproductive medicine, uterine imaging and hysteroscopic surgery should undertake patient selection & treatment
Opinion
- No uniformly accepted and perfect classification of CUAs available currently
- 3D pelvic USG is recommended to diagnose and classify CUAs for those with suspected screening tests or women with recurrent miscarriages
- MRI or combined laparoscopy/hysteroscopy to be reserved for diagnosing complex CUAs
- Most women with CUA → normal reproductive outcome
- Important to advice women with CUA about certain ↑ risks
- Even though high quality evidence on efficacy and safety of surgical treatment not available still hysteroscopic septal division reduces miscarriage rates leading to improved live birth rates
- Abdominal/laparoscopic metroplasy for fusion defects NOT advisable
- Clinician should consider imaging renal tract of women with CUAs
- All women with CUAs and those with treated with hysteroscopic resection of uterine septum should be followed up by 12 weeks using an appropriate preterm birth care pathway
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