gineco ro ultrasonography Müllerian Duct Anomalies: Clinical Issues and of 3D Ultrasound Diagnosis

Mihaela Grigore, MD, PhD1, Camelia Cojocaru, MD2, Alina Mareş, MD3, Anca Indrei, MD, PhD4 1. Department of and Gynecolgy, University of and Gr.T. Popa Iasi, Medis Medical Center; 2. Cuza Vodă Hospital Iași, Medis Medical Center Iasi; 3. Cuza Vodă Hospital Iași; 4. Deparment of Anatomy, University of Medicine and Pharmacy Gr.T. Popa Iaşi Correspondence: Mihaela Grigore e-mail: [email protected]

Abstract The incidence of uterine malformations is esti- two-dimensional pelvic sonogram is its inabil- mated to be between 3% and 4% in the general ity to reconstruct the uterine coronal axis. The population. Their impact is noted in infertility imaging of this axis has major significance in problems such as preterm labor, intrauterine diagnosing the uterine fundus malformation. growth restriction and pathological lie or pre- In recent years further advances in ultrasonog- sentation. Until recently, the use of invasive raphy have led to three-dimensional ultraso- tests, such as laparoscopy, hysteroscopy, or nography (3DUS). hysterosalpingography, was required for di- This review shows the advantages of the three- agnosing congenital uterine anomalies. Since dimensional ultrasound as a diagnostic tool. some of this malformation can be surgically The authors also present several examples of corrected, pre-surgical pelvic imaging has both uterine malformations from their own experi- a diagnostic and a therapeutic value. ence. One of the common imaging methods is the Keywords: uterine malformations, clinical is- pelvic sonogram. A major disadvantage of sues, 3D ultrasound

The incidence of uterine malforma- Embryology There are four other important facts tions is estimated to be between 3% The uterus develops from the two pa- to be kept in mind: and 4% in the general population. The ramesonephric ducts (Mullerian ducts). „ uterine malformations are often as- prevalence of the particular types of the The caudal two thirds of these ducts sociated with upper vaginal malfor- uterine malformations is difficult to give rise to the uterus and the upper mations because the 2/3 of the vagina assess due to the different populations third become the Fallopian tubes. The has the same embryologic origin as studied, to small sample sizes, to pros- development of the uterus is divided the uterus pective versus retrospective study into the three stages and failure or arrest „ uterine anomalies are often asso- designs, to different classification sys- of development during these stages ciated with urinary tract anomalies tems, and to the types of test used in explains the occurrence of uterine (kidneys, urethra) due to close em- diagnosing(1). malformations. bryological interactions;

100 Vol. 5, No. 2/may 2009 gineco ro

Table 1 The development of the uterus and uterine malformations Failure Stage Normal development Uterine malformations of normal development „ The appearance of Müllerian ducts and their caudal 6-9 weeks → Uterine aplasia midline fusion and connection with urogenital sinus „ The upward fusion of the caudal parts of the Müllerian Uterine duplications- uterus 10-13 weeks → ducts didelphys, bicornuate uterus

„ The resorption of the medial septum initially separating the caudal parts of the Müllerian ducts to form the uterine septation (septate 4-18 weeks → uterovaginal duct as the origin of both uterine cavity and uterus) superior 2/3 of the vagina

„ the independent ovarian and Mül- 5. Septate uterus - represent partial When the serosal indentation is more lerian ducts development explains or complete nonresorption of the utero- than 1 cm, this indicates a bicornuate the generally normal ovarian mor- vaginal septum; uterus(8). The configuration of the ex- phology and function in the cases 6. Arcuate uterus - result from near ternal uterine contour is essential for of uterovaginal developmental ano- complete resorption of the septum; the differentiation of a septate from a malies; 7. DES drug related uterus - com- bicornuate uterus, because different cli- „ uterine malformations are usually prises sequelae of in utero DES exposure. nical and therapeutic approaches are not associated with chromosomal As observed, this classification has sim- assigned to each anomaly(9). The sur- or sexual differentiation anomalies. plified the categorization of Müllerian gical treatment for a septate uterus is anomalies. However, some uterine ano- hysteroscopic resection of the septum. Classification malies may have characteristics of one Bicornuate uteri rarely necessitate The most basic classification of Mül- or more categories. Despite its flaws, the surgical intervention, although Stras- lerian duct defects consists of agenesis AFS classification provides a basis for sman metroplasty (wedge resection of and hypoplasia, defects of vertical fu- communication and comparison between the medial aspect of each uterine horn sion, and defects of lateral fusion. In investigators. and subsequent unification of the two 1979, Buttram and Gibbons proposed cavities) may be applied in patients a classification of Müllerian duct ano- Septate Uterus with recurrent second-trimester abor- malies that was based on the degree The septate uterus is the most com- tion and premature delivery(10). It is of failure of normal development, and mon Müllerian duct anomaly. Fifty- important to recognize that mild con- they separated these anomalies into five percent of uterine anomalies are cavity of the external uterine contour classes that demonstrate similar clinical septate(4,5). This anomaly results from should not be construed as a “partial” manifestations, treatment, and prognosis partial or complete failure of resorption bicornuate configuration, because these for fetal rescue(2). This classification of the uterovaginal septum after fusion patients may not be given the option of was modified in 1988 by the American of the paramesonephric ducts. Since the hysteroscopic metroplasty. Fertility Society (now the American paramesonephric ducts have previously In general, septate uteri have the Society of ), and fused, the serosa of the uterine fundus poorest reproductive outcomes of at the moment this represent the most is intact. The septum arises in the Müllerian anomalies(6). The poor repro- used one(3). The American Fertility midline fundus and can be complete ductive outcome can be explained by Society (AFS) classified Müllerian ano- or partial. A complete septum extends several mechanisms: malies according to the major uterine to the external cervical os(6). A partial „ endometrial mucosa covering the anatomic types: septum is variable in length and may septum does not respond appro- 1. Hypoplasia/agenesis - segmental be mild or extend to the endocervical priately to estrogen agenesis and variable degrees of utero- canal proximal to the external os. The „ abnormal distribution of vessels vaginal hypoplasia; external uterine contour may be convex, within the septum 2. Unicornuate uterus - partial or flat, or mildly concave(4,7). Although the „ irregular contractions of muscular complete unilateral; AFS classification do not specify the fibers in the septum(8,11,12,13). 3. Didelphys uterus - duplication minimal depth of fundic indentation Salim et al have reported that the of the uterus results from complete for differentiation of a septate from a more complete the septum, the higher nonfusion of the Müllerian ducts; bicornuate or a uterus didelphys the the pregnancy failure rate(12). It has 4. Bicornuate uterus - demonstrates general consensus is that a distance of not yet been determined why some incomplete fusion of the superior seg- less than 1 cm will differentiate between patients with a septate uterus carry ments of the uterovaginal canal; the septate uterus and bicorn uterus(4). a pregnancy to term and others have

Vol. 5, No. 2/may 2009 101 gineco ro ultrasonography

recurrent miscarriages(11). Because it is indentation and the distance between are two hemi-uteruses and two cer- not always associated with a poor obste- the lateral apices of the horns is calcu- vices. A longitudinal and transverse trical history, the incidental finding of a lated on the basis of HSG findings, an vaginal septum may also be present uterine septum is not an indication for adverse reproductive outcome is not with subsequent hematometrocolpos. hysteroscope incision(4,11). Hysteroscopic anticipated(4). However, a defining depth There is no communication between the incision of a septum (in order to restore of the indentation to differentiate an duplicated endometrial cavities. Non- normal uterine cavity) is indicated in arcuate configuration from a broad obstructive uterus didelphys is usually women with a longstanding history of septum has not been established. asymptomatic, while uterus didelphys unexplained infertility. When evaluating with unilateral vaginal obstruction may the uterus following hysteroscopic Bicornuate Uterus become symptomatic at menarche and metroplasty, no residual septum or evi- Ten percent of uterine anomalies manifest as dysmenorrhea. Due to the dence of a residual septum measuring up are bicornuate which results from retrograde menstrual flow in patients to 1 cm in length is considered indicative incomplete fusion of the uterine horns. with obstruction, endometriosis and of optimal resection(14). Reproductive A bicornuate uterus consists of two pelvic adhesions have an increased pre- outcome has been shown to improve symmetric cornua with communication valence(19). Spontaneous abortion rates after resection of the septum, with of the endometrial cavities most often are reported to range from 32% to 52%, reported decreases in the spontaneous at the level of the uterine isthmus.. premature birth rates range from 20% abortion rate from 88% to 5.9% after The intervening myometrium extends to 45% and fetal survival rates, from hysteroscopic metroplasty(4, 14,15,16). for a variable length from the fundus 41% to 64%(6). Strassman metroplasty, to the cervix. A complete bicornuate leaving the duplicated cervix intact in Arcuate Uterus uterus may have a single (bicornuate an attempt to prevent cervical incom- An arcuate uterus has a broad in- unicollis) or duplicated (bicornuate petence, is a consideration for selected dentation of the fundal endometrium. bicollis) cervix. The incidence of spon- patients with recurrent spontaneous The indentation of the endometrium taneous abortion is 28-35% and of the abortions and premature deliveries(10). As at the uterine fundus is a result of near premature delivery birth range from with the bicornuate uterus, however, the complete resorption of the uterovaginal 14% to 23%(6). Spontaneous abortion benefits of intervention remain unclear septum. It remains controversial as to rates and preterm delivery are reported because no controlled trials have been whether an arcuate uterus is a normal to be higher in women with a complete performed(6). variant or a true muellerian anomaly(5). bicornuate uterus than in those with a In the original Buttram and Gibbons partial bicornuate uterus(11). Unicorn Uterus classification, the arcuate uterus was It is important to differentiate between Approximately 20% of uterine ano- subclassified with the bicornuate uterus a partially septate and a partially malies are unicornous. A unicorn ute- because it “most closely resembles a bicornuate uterus. While hysteroscope rus occurs when one Müllerian duct ‘mild’ form of bicornuate uterus”(2). The resection is the treatment of choice for a develops normally and the other does AFS designated a separate class for this sub-septate uterus, it is contraindicated not - 1/3 are isolated, 1/3 have a non- anomaly, because the arcuate uterus for a bicornuate uterus(11). Surgical cavity rudimentary horn and 1/3 have a can be distinguished from a bicornuate intervention is usually not indicated, cavity rudimentary horn that may or may uterus on the basis of its complete and the length of subsequent gestations not communicate with the unicornous fundic unification. The depth of the often increases with increasing parity. cavity. indentation that would distinguish and Strassman metroplasty has been advo- The obstetrical impact is represented arcuate from a small partial septum cated in women with a history of by an increase incidence of spontaneous is not yet well defined(8). As result, it recurrent pregnancy loss and in whom abortion (41-66%), premature birth is not surprising that both poor and no other infertility issues have been (10-2-%), abnormal fetal lie, decrease good obstetric outcomes have been identified(10). However, the benefits of fetal survival rates (38% to 57%) and reported in patients with an arcuate metroplasty have never been formally intrauterine growth retardation(6,20). shaped uterus(17). Data regarding the studied in a prospective trial(6). Because The pathogenesis of pregnancy loss reproductive outcomes of patients with the bicornuate uterus has been reported and decreased fetal survival rate of the an arcuate uterus are extremely limited to have the highest associated prevalence unicorn uterus are incompletely under- and contradictory. Both poor and good (38%) of cervical incompetence among stood. It has been hypothesized that obstetric outcomes have been reported, Müllerian duct anomalies, prophylactic inadequate vascularization and com- although an arcuate configuration is placement of a cervical cerclage in promised uteroplacental blood flow generally thought to be compatible with selected patients has been reported to of the unicorn uterus result from the normal-term gestation, with a quoted increase fetal survival rates(18). decreased vascular contribution of the delivery rate of 85%(11). Hysteroscope uterine and utero-ovarian arteries from incision has been performed in patients Uterus Didelphys the abnormal side(20). with an arcuate shaped uterus and Uterine didelphys represents 5% Resection of a cavity rudimentary recurrent pregnancy loss(8). It has been of Müllerian anomalies. This uterine horn is recommended because of the proposed that when a ratio of less than anomaly is due to an almost complete substantial risk that a pregnancy in a 10% between the height of the fundic failure of Müllerian duct fusion - there non-communicating horn will rupture;

102 Vol. 5, No. 2/may 2009 gineco ro

even in a communicating horn a viable for categorizing uterine anomalies be- that these features offer the user the pregnancy is rarely achieved(8). Surgical cause of its very high accuracy (98%- following advantages in comparison to intervention in a rudimentary horn 100%). While ultrasound will remain the two-dimensional ultrasonography: without associated endometrium is primary modality utilized to evaluate „ accurate measurement of organ di- rarely indicated. Renal abnormalities Müllerian anomalies, MRI can offer mensions and volumes, are more commonly associated with additional diagnostic information in „ improved anatomic and blood flow unicorn uterus than with other Mül- patients with equivocal ultrasound information, lerian duct anomalies and have been findings. As a result, laparoscopy or open „ improved assessment of complex reported in 40% of these patients(21). is no longer required to make a anatomic anomalies, The anomaly is always ipsilateral to the definitive diagnosis of a uterine anomaly. „ better specificity in regard to the rudimentary horn. Renal agenesis is the However, access to this examination is confirmation of normality, most commonly reported abnormality, still limiting factor in many countries. „ standardization of the sonographic occurring in 67% of cases. Other renal Endovaginal ultrasound represents examination procedure, anomalies which could be present the main diagnostic method of ute- „ reduced scanning times with cost- are: ectopic kidney, horseshoe kidney, rine anomalies. The most precise in- effective use of equipment and cystic renal dysplasia, and duplicated vestigation of uterine morphology sonographer time, collecting systems. can be done during the second half of „ possibility of post processing the menstrual cycle or at the beginning volumes, DES-exposed Uterus of pregnancy (the thick and echoic „ telemedicine and tertiary consul- A T-shaped configuration of the endo- endometrium has a better contrast tation. metrial cavity is the most commonly with the adjacent myometrium). The Uniquely, three-dimensional sonogram associated abnormality, seen in 31% of evaluation of the uterine malformations allows demonstration of the coronal exposed women(22). Other uterine corpus should be accompanied by the renal plane perpendicular to the transducer anomalies include a small hypoplastic investigation in effort to find some face facilitating the identification of uterus, constriction bands, a widened associated anomalies. Although its cli- surface irregularities which can then be lower uterine segment, a narrowed nical importance is well defined, 2D accounted for during volume measure- fundic segment of the endometrial canal, ultrasound has several limitations. ment(24). With 3D ultrasound it is easy to irregular endometrial margins. Cervical For example unicorn uterus can be obtain the coronal view with the entire anomalies occur in 44% of cases and missed and discrete forms of septate endometrial canal, the relationship of include hypoplasia, anterior cervical and bicornuate uterus are not easy to the endometrium to myometrium and ridge, cervical collar, and pseudopolyps. distinguish among themselves. These the uterine serosa. It is best performed An abnormal cervical finding is as- inconveniences can be surpassed by 3D during the secretory phase of the men- sociated with abnormal uterine cor- ultrasound. Woelfer, et al, have shown strual cycle so the endometrial cavity pus changes in 86% of cases. Exposed that three-dimensional ultrasound is is easier to outline. The three planes women are reported to be predisposed accurate in depicting abnormal ute- (longitudinal, sagittal, coronal) can to cervical incompetence, secondary not rine shapes(23). The process of 3D scan- be correlated by placing the image only to structural changes but also to ning consists of four basic steps: data point or the intersection of the two histological changes such as abnormal acquisition, volume analysis and pro- perpendicular views at the region of smooth muscle–to-collagen ratio and cessing, image animation (cine loop), interest. By scrolling the upper line of decreased cervical elastin(22). archiving the volumes. Once the volume the field of view into the endometrial has been stored, a single point in space cavity, surface rendering of the serosa Imaging of uterine can be selected in the volume, and and endometrial cavity are visualized. malformations this point can be visualized in all three Three-dimensional US with surface- and perpendicular planes. The examiner can transparent-mode reconstructions of Hysterosalpingography (HSG) pro- navigate through the volume, keeping the uterus has reported advantages over vides a morphologic assessment of the track of a single point in space in all conventional two-dimensional scanning. endometrial and endocervical canals three planes. This is valuable not only In experienced hands, a sensitivity of and supplies important information for imaging the uterus and its adnexa, 93% and a specificity of 100% have been regarding tubal patency. The major but also for measuring distances and achieved(25). limitations of the procedure are the even volumes of organs. It is possible In order to accurately measure the inability to evaluate the external uterine to “rotate” the organ by spinning the endometrial extension of a septum, a contour adequately and exposure to image in any of the planes. Another true coronal plane through the fundus ionizing radiation in young women. advantage is navigation through a single and cervix must be obtained. If the Characterization of uterine anomalies plane while watching the corresponding plane is off center, an arcuate uterus can be difficult, however, and there can effect on the other two planes. This may not be detected, the measurement be considerable overlap in findings, gives us complete control of the volume of a septum will be inaccurate, and the notably with regard to differentiation of to view it or perform measurements in detection of the serosa indentation of a a septate from a bicornuate uterus. any display desired. Advocates of three- bicornate uterus may be missed. MRI has been the “gold standard” dimensional ultrasonography suggest In a septate uterus 3 D ultrasound is

Vol. 5, No. 2/may 2009 103 gineco ro ultrasonography

Figure 1. 3D ultrasound of septate uterus Figure 2. 3D ultrasound of a septate Figure 3. 3D ultrasound bicornuate uterus uterus and pregnancy

Figure 4. Bicornuate uterus-coronal plane Figure 5. Unicorn uterus-coronal plane Figure 6. 3D ultrasound of unicorn uterus

used to evaluate the size and extent of an angle of less than 75° between the In case of bicorn uterus on 3D ul- septa (Figure 1 - 3D ultrasound of septate uterine horns is suggestive of a septate trasound a large fundic cleft may be uterus). The sensitivity, specificity, po- uterus, and an angle of more than 105° is visualized (Figure 3 - 3D ultrasound sitive and negative predictive values more consistent with bicornuate uteri. bicornuate uterus). The depth of the of 3D ultrasound in the detection of a Unfortunately, the majority of angles of cleft is > 1.0 cm. The horns of the septate uterus is 98.4%, 100.0%, 100.0% divergence between the horns fall within endometrial cavity are usually widely and 96.0%, respectively(25). It is possible this range, and considerable overlap separated with an intercornual angle to confirm or exclude the diagnosis between the two anomalies is noted. The greater than 105°. Each horn has a of a associated septated cervix. On coronal 3 D plane permit a very precise fusiform appearance, with apices that coronal plane we can measure the measurement of this angle(10). US has taper and end in a single fallopian tube distance between the two internal been reported to allow differentiation (Figure 4 - Bicornuate uterus-coronal tubal ostia, the length of a septum, the of a septate from a bicornuate uterus if plane). As we have already stated the remaining cavity length, and the depth a true orthogonal view along the long differentiation from the septate uterus of an external fundic indentation(23,26). axis can be obtained. In this plane, a is sometimes very difficult. Quantification of these parameters line is drawn between the apices of the In case of a didelphic uterus on 3D provides a reproducible standard that endometrium at the level of the ostia. If ultrasound images, separate divergent can be used to compare studies from the fundic indentation of the external uterine horns are identified, with a large different institutions. It is useful for uterine contour is below the interostial fundic cleft. Endometrial cavities are differentiation of septate from bicor- line or less than 5 mm above the line, the uniformly separate, with no evidence of nuate uteri. Even so some difficulties uterus is considered to be bicornuate communication. Two separate cervices could appear in diagnosis of a septate or didelphic. The septate uterus is de- need to be documented. The distance uterus with an external indentation. In fined by a fundic indentation of more between the uterine horns frequently this case the differential diagnosis with than 5 mm above the interostial line(4). prevents their visualization on a single a bicornuate uterus could be difficult. Reconstruction of the coronal plane is 3D ultrasound image. The region of On the corornal plane obtained with also helpful in assessing gestational sac interest in the uterus must fit within the 3D it is easy to measure the length of location within a bicornuate or septate volume “box”. The horns of a didelphic indentation; if it is less than 1 cm than uterus thus not mistaking a sac within uterus are generally too far apart to be the diagnosis is bicornuate uterus and a horn as a cornual pregnancy (Figure 2 imaged with 3D ultrasound. if it is larger than 1 cm the diagnosis is - 3D ultrasound of a septate uterus and 3D is extremely useful in diagno- bicornuate uterus. Also it is stated that pregnancy). sing a unicorn uterus. The coronal

104 Vol. 5, No. 2/may 2009 gineco ro

plane shows a spindle-shape elon- Conclusion septum, for example, can be planned gated endometrial cavity and the Uterine anomalies represent an based on three-dimensional ultrasound characteristically asymmetric ellip- important issue due to their high pre- imaging without the need for MRI, soidal shape of the uterus (Figure 5 - valence in general population and which until now was the only modality Unicorn uterus-coronal plane). These their impact infertility. The advent of available to demonstrate uterine shape findings are very difficult to observe three-dimensional (3D) ultrasound is anomalies accurately. with 2D ultrasound and this explains one of the most important advances Cut-off values for distinguishing ar- why the unicorn uterus is often in gynecological ultrasound recently. cuate, bicornuate, and septate uteri misdiagnose if only 2D is performed. The ability to view the uterus and endo- on 3D coronal images have, to date, The identification of a uterine cavity metrium in virtually any plane, has been arbitrarily selected. By defining horn may be difficult to differentiate added greater diagnostic confidence 3D diagnostic criteria, inter and intra- from other types of duplicated uterus. to ultrasound imaging. While 2D trans- observer variability in detecting uterine Three-dimensional US may help fur- vaginal ultrasonography is an excellent malformations is quite good. The ac- ther characterize the anomaly (Figure screening examination for uterine cumulation of data on specifically de- 6 - 3D ultrasound of unicorn uterus). anomalies, it is not as effective as 3D fined uterine anomalies will provide The 3D coronal plane shows the T- ultrasound in distinguishing specific reliable incidence figures for uterine shape of the endometrial cavity and malformations. 3D ultrasound does not anomalies and outcome data that may other minor findings consistent with replace 2D ultrasound but, rather, com- result in anomaly-based management DES-expose. plements it. Uterine surgery to correct schemes. „

References 1. Acién P. Incidence of müllerian defects in fertile and infertile Hum Reprod 1996; 11:727-729tg. women. Hum Reprod 1997;12:1372-1376. 15. Valle RF. Hysteroscopic treatment of partial and complete 2. Buttram VC, Gibbons WE. Mullerian anomalies: a proposed uterine septum. Int J Fertil Menopausal Stud 1996; 41:310- classification (an analysis of 144 cases). Fertil Steril 1979; 32:40-46. 315. 3. American Fertility Society. The American Fertility Society 16. Niculescu M. Hodovanu L, Dinu V, Cristescu C. Improved classification of adnexal adhesions, distal tubal occlusion, fertility couple after the hysteroscopicmetroplasty, Gineco.ro, tubal occlusion secondary to tubal ligation, tubal pregnancies, 2008; 4(3):174-177. müllerian anomalies and intrauterine adhesions. Fertil Steril 17. Salim R, Jurkovic D. Assessing congenital uterine anomalies: 1988;49:944-55. 4. Homer HA, Li TC, Cooke ID. The septate uterus: a review of the role of three-dimensional ultrasonograhy. Best Prac Res management and reproductive outcome. Fertil Steril 2000; Clin Obstet Gynecol 2004;18:29-36. 73:1-14. 18. Golan A, Langer R, Wexler S, Seceg E, Niv D, Menachem PD. 5. Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pelli- Cervical cerclage: its role in the pregnant anomalous uterus. cer A. Reproductive impact of congenital mullerian anomalies. Int J Fertil 1990; 35:164-170. Hum Reprod 1997; 12:2277-2281. 6. Propst AM, Hill JA. Anatomic factors associated with recur- 19. Ugur M, Turan C, Mungan T, Kuscu E, Senoz S. Endometrio- rent pregnancy loss. Semin Reprod Med 2000; 18:341-350). sis in association with mullerian anomalies. Gynecol Obstet 7. Carrington BM, Hricak H, Nuruddin RN, Secaf E, Laros RK, Invest 1995; 40:261-264. Jr, Hill EC. mullerian duct anomalies: MR imaging evaluation. 20. Heinonen PK. Unicorn uterus and rudimentary horn. Fertil 1990; 176:715-720. Steril 1997; 68:224-230. 8. Troiano RN, McCarthy SM. Müllerian duct anomalies: imaging and clinical issues. Radiology 2004;233:19-34. 21. Fedele L, Bianchi S, Agnoli B, Tozzi L, Vignali M. Urinary 9. Fedele L, Dorta M, Brioschi D, Villa L, Arcaini L, Bianchi S. tract anomalies associated with unicornuate uterus. J Urol Re-examination of the anatomic indications for hysteroscopic 1996; 155:847-848. metroplasty. Eur J Obstet Gynecol Reprod Biol 1991; 39:127- 22. Goldberg JM, Falcone T. Effect of diethylstilbestrol on repro- 131). ductive function. Fertil Steril 1999; 72:1-7. 10. Strassmann EO. Fertility and unification of double uterus. Fertil Steril 1966; 17:165-176. 23. Woelfer B, Salim R, Banerjee S, Elson J, Regan L, Jurkovic 11. Kupesic S. Clinical implications of sonographic detection of D. Reproductive Outcomes in Women with Congenital Uter- uterine anomalies for reproductive outcome. Ultrasound Ob- ine Anomalies Detected by Three-dimensional Ultrasound stet Gynecol 2001;18:387-400. Screening. Obstet Gynecol 2001; 98:1099-1103. 12. Salim R, Regan L, Woelfer B, Backos M, Jurkovic D. A com- 24. Maymon, R; Herman, A; Ariely, S; Dreazen, E; Buckovsky, I; parative study of the morphology of congenital uterine anom- alies in women with and without a history of recurrent first Weinraub, Z. Three-dimensional vaginal sonography in obstet- trimester miscarriage. Hum Reprod 2003;18:162-166. rics and . Hum Reprod Update. 2000;6:475–84. 13. Sparac V, Kupesic S, Ilias M, Zodan T, Kurjak A. Histologic 25. Kupesic S, Kurjak A. Ultrasound and Doppler assessment of architecture and vascularization of hysteroscopically excised uterine anomalies. In: Kupesic S, de Ziegler D, eds. Ultrasound intrauterine septa. J Amer Assoc Gynecol Laparosc 2001;8:111- and infertility. Pearl River, NY: Parthenon, 2000; 147-153. 116. 14. Fedele L, Bianchi S, Marchini M, Mezzopane R, DiNola G, 26. Salim R, Jurkovic D. Assessment congenital uterine anoma- Tozzi L. Residual uterine septum of less than 1 cm after hys- lies: the role of three-dimensional ultrasonography.Best Prac teroscopic metroplasty does not impair reproductive outcome. Clin Obstet Gynecol 2004;18:29-36.

Vol. 5, No. 2/may 2009 105