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  2. Recurrent pregnancy loss (RPL)  Recurrent pregnancy loss (RPL) is defined as two or more consecutive failed pregnancies documented by ultrasound or histopathology. 1Most studies report that RPL affects about 1–2% of women. About 50 percent of women with RPL have no clearly defined aetiology.2  According to ESHRE guidelines, age is a key factor, and RPL is more common in women above 40 years of age.3 The aetiology of recurrent pregnancy loss (RPL) is classified into:1  1. Genetic  2. Anatomic  3. Endocrine  4. Antiphospholipid antibody syndrome  5. Immunological  6. Environmental factors
  3. ULTRASOUND PARAMETERS TO DEFINE EARLY PREGNANCY FAILURE 1. Mean Gestation sac diameter (MGSD) of 20 mm & no yolk sac 2. MGSD of >25 mm & no embryo 3. Irregular gestational sac 4. Distended yolk sac > 7mm 5. Collapsed & echogenic yolk sac 6. Crown-rump length of 7 mm or more & no cardiac pulsations 7.Loss of a previously seen cardiac activity. Cardiac activity less than 85 beats per minute indicates poor prognosis 8. The MGSD-CRL ratio less than 5 mm are prone to first trimester miscarriage
  4. Figure 1: Transvaginal scan (TVS) image showing irregular gestation sac of 20mm& no yolk sac or embryo in a woman with eight weeks of amenorrhea.
  5. Figure 2: TVS image showing distended yolk sac of 5mm, embryo of 1.1mm CRL & no cardiac activity in a 39-year-old woman with 10 weeks amenorrhea
  6. Figure 3: 2D USG image showing echogenic yolk sac& embryo with no cardiac activity
  7. Figure 4: 2D USG image showing embryo of 13mm CRL correlating to 7 weeks 4 days with no cardiac activity in a 42-year-old with 11 week amenorrhea
  8. Figure 5: TVS showing sac volume smaller than the embryo at 8 weeks amenorrhea
  9. ANATOMIC/STRUCTURAL ANOMALIES  Anatomic/ Structural anomalies increase women’s risk and may account for 10–50% of RPL.1 These include:  1. Congenital Mullerian Duct Anomalies  2. Acquired abnormalities like fibroids, polyps and synechiae (Asherman syndrome)
  10. Müllerian Duct Anomalies (MDA)  Prevalence of MDA in RPL is about 7% to 28%.5  Accurate MDA recognition & their classification according to European Society of Human Reproduction and Embryology (ESHRE)6,  The American Society of Reproductive Medicine (ASRM)7 or Congenital Uterine Malformation by Experts (CUME)8 is essential for effective & efficient therapeutic planning to improve reproductive outcome.  Septate uterus is most commonly associated with first trimester spontaneous abortion.1  This may be from abnormal endometrium & septal vascularity.  Septum is the tissue resulting in an internal indentation at the fundal midline exceeding 50% of the uterine wall thickness.6
  11. Figure 6: 3D Coronal rendered images of uterus showing normal fundal contour but internal indentation dividing endometrial cavity into two. A.Partial septate: septum above the internal os B.Complete septate: Septum extends into cervix
  12. Bicorporeal/bicornuate uterus  Bicorporeal/bicornuate uterus has a higher prevalence of cervical incompetence.9  There is an abnormal external fundal contour; internal mid line indentation divides the cavity into two endometrial cavities and cervices. Figure 7: Coronal images of Bi-corporeal uterus (ESHRE classification) with abnormal external fundal contour &internal indentation. The American Society of Reproductive Medicine (ASRM) classifies these as A: Bicornuate & B: Uterine didelphys
  13. Hemi-uterus/ Unicornuate uterus  Hemi-uterus/ Unicornuate uterus has an abnormal configuration.  It is seen as a small, curved uterus which is located off-midline with a single endometrial cavity & cervix.7 Figure 8 : Coronal images of right & left hemi-uterus
  14. Figure 9: The International Federation of Gynecology and Obstetrics (FIGO) classification of Submucous uterine fibroids. A. Completely Intracavitary (Type 0) B. > 50% Intracavitary (Type 1) C. <50% Intracavitary (Type 2) D. Completely Intramural (type 4) Acquired anatomical factors: These include Uterine fibroids, endometrial polyps and uterine synechiae, which may be associated with RPL.1
  15.  Uterine fibroids are reported in 8.2% of women with RPL.10  Ultrasound evaluation of the uterine cavity and classifying the fibroids according to their growth into the endometrium (Fibroid mapping) are important in the diagnosis & management of RPL.11  Submucosal fibroids deform the endometrial cavity and may affect implantation & embryonic development.  Removal of submucosal fibroids reduces the chance of miscarriage.  Intra mural fibroids do not distort the uterine cavity & there is no evidence that myomectomy may reduce the chances of an abortion.10
  16. Endometrial polyps  Endometrial polyps are benign nodular protrusions of the endometrial surface. These have a higher prevalence in women with pregnancy loss.1 Figure 10: TVS & 3D rendered images of a homogenous echogenic polyp completely within the endometrial cavity & showing a vascular pedicle on color flow.
  17. Uterine synechiae  Uterine synechiae are seen as thin or thick strands of tissue crossing the endometrium.  These are better seen when there is fluid in the endometrial cavity.  Women with RPL are more likely to have uterine synechiae because of curettage; the prevalence ranges from 0.5 to 28%.12  Pathophysiology in RPL is due to an abnormal functional endometrium which may interfere with the invasion and normal development of the placenta.
  18. Fig 11 : Uterine Synechiae. A: TVS: thin endometrium &linear hypoechoic scar B. Thick bands distorting endometrium C. Mild adhesions D. Extensive Dense adhesions completely distorting the endometrial cavity. E. Synechiae seen better with fluid in the endometrial cavity
  19. Chronic endometritis  Chronic endometritis refers to inflammation or infection involving the endometrium. This has a prevalence of 12-13% in RPL.13 Figure 12: A: Thick, heterogeneous endometrium; increased vascularity on color flow B: Loss of normal myometrial endometrial interface C: Intra uterine air D: Intracavitary fluid E: Fluid in the pouch of Douglas
  20.  Cervical incompetence is painless cervical dilatation in the absence of uterine contractions due to a functional or structural defect resulting in a second-trimester miscarriage.  This may be due to embryological maldevelopment of the Müllerian ducts or acquired from cervical trauma.  TVS is modality of choice for assessment.1 Figure 13: Cervical incompetence A. Short cervical length < 25mm and widening of internal os B. Complete bulging giving an hour glassappearance. CERVICAL INCOMPETENCE
  21. CONCLUSION Ultrasonography has a significant role in detecting abnormal uterine morphology as a cause for RPL. 1st trimester U/S parameters are useful diagnostic tool to prognosis pregnancy outcome among patients with history of recurrent 1st trimester pregnancy loss. The introduction of pulsed Doppler ultrasonography has provided non-invasive means for the evaluation of uterine impedance, and gives physiologic data, rather than anatomic information alone. The use of transvaginal Doppler ultrasonography is proposed to detect impaired uterine perfusion as a screening test for women with RPL. Further studies will elucidate the mechanism of pregnancy loss associated with impaired uterine perfusion.
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  23. REFERENCES  1. Lopes, V. M. , Souza-Oliveira, M. C. , Goulart, A. E. C. , Pimentel, E. S. , Tierno, N. I. Z. , Ribeiro, T. Q. F. , Medina, C. T. , Castro, V. L. M. , Lima, L. G. N. , Souza, A. L. M. , Brasileiro, J. P. B. . Recurrent Pregnancy Loss: Investigations and Interventions. In: Sharma, N. , Chakrabarti, S. , Barak, Y. , Ellenbogen, A. , editors. Innovations In Assisted Reproduction Technology [Internet]. London: IntechOpen; 2019 [cited 2022 Sep 25]. Available from: https:// doi: 10.5772/ intechopen.89590  Pillarisetty LS, Mahdy H. Recurrent Pregnancy Loss. 2022 May 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 32119347.  3. The ESHRE Guideline Group on RPL, Ruth Bender Atik, Ole Bjarne Christiansen, Janine Elson, Astrid Marie Kolte, Sheena Lewis, Saskia Middeldorp, Willianne Nelen, Braulio Peramo, Siobhan Quenby, Nathalie Vermeulen, Mariëtte Goddijn, ESHRE guideline: recurrent pregnancy loss, Human Reproduction Open, Volume 2018, Issue 2, 2018, hoy004,  4. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 200: Early Pregnancy Loss. Obstet Gynecol. 2018 Nov;132(5):e197-e207. doi: 10.1097/ AOG.0000000000002899. PMID: 30157093.  5. Carbonnel M, Pirtea P, de Ziegler D, Ayoubi JM. Uterine factors in recurrent pregnancy losses. Fertil Steril. 2021 Mar;115(3):538-545. doi: 10.1016/j.fertnstert.2020.12.003. PMID: 33712099.
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