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Ovarian vein syndrome: A review
International Journal of Surgery 7 (2009) 516–520
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.theijs.com
Review
Ovarian vein syndrome: A review Hina Y Bhutta a, *, Stewart R Walsh a, Tjun Y Tang a, Colin A Walsh b, James M Clarke a a b
Department of Surgery, Norfolk & Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY, UK Department of Obstetrics and Gynaecology, St George Hospital, Kogarah, New South Wales, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 June 2009 Received in revised form 23 September 2009 Accepted 25 September 2009 Available online 8 October 2009
The Ovarian Vein Syndrome was first reported in 1964, yet its existence as a true pathophysiological entity remains controversial. It may present as an acute or chronic disease, typically affecting young, multiparous women. This review discusses the literature to date on this poorly recognised cause of ureteric obstruction and pelvic pain, including developments in the diagnosis and management of this eminently treatable condition. Ó 2009 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Ovarian Vein Syndrome Chronic Pelvic Pain Congestion Ureteric Obstruction
1. Review criteria Using Embase and Medline, a literature search was undertaken. English and foreign language articles on the ovarian vein syndrome were appraised. Chronic pelvic pain, pelvic congestion syndrome and ureteric obstruction were key terms, which were also searched. In 1964, Clark published a series of 129 cases of right-sided ovarian vein syndrome in which he purported that an aberrant ovarian vein was the cause of an obstructive uropathy, occurring at the level of the pelvic brim.1 Since then, several others have published case reports of the ovarian vein syndrome (OVS),2–7 but the largest contemporary series includes only eight cases.7 That the syndrome truly exists as a distinct pathophysiological entity remains controversial. It is often encompassed within a larger collection of disorders, which share the unifying feature of chronic pelvic pain. 2. Pathophysiology OVS may present as an acute affliction during or soon after pregnancy, or as a chronic, recurring disease. Both acute and
* Corresponding author. Tel.: þ44 07773 420 717. E-mail address: [email protected] (H.Y. Bhutta).
chronic variants occur most commonly in multiparous women. Several pathophysiological mechanisms have been suggested. Clark postulated that an aberrant ovarian vein, which might arise from persistent embryological posterior subcardinal branches, exerts occlusive pressure on the ipsilateral ureter.1 By crossing the ureter at the level of the pelvic brim, where its position is relatively fixed, rather than at the usual more cephalad level of L3/L4, Clark felt the aberrant vessel is more likely to cause ureteric compression. He also described aberrant ovarian veins as being much larger than normal, more likely to branch into a number of distal tributaries, and more likely to drain into the right renal vein, all of which he felt could explain the phenomenon of right-sided OVS (Fig. 1). Dykhuizen described a sheath of connective tissue at the pelvic brim, which appeared to be a retroperitoneal continuation of the suspensory ovarian ligament, encasing both ovarian vessels and ureter. This, he surmised, contributed to ureteric fixity secondary to periureteral fibrosis.5 Radiographically he observed that, in suspected right-sided OVS, the ovarian vein fixed the right ureter as they crossed, whilst the right kidney moved with respiration. Others believe that the ureter becomes trapped within a fibrovascular mesh of tortuous dilated veins.3 Alternatively, pressure from the gravid uterus may cause ovarian vein dilatation and valvular incompetence. The dilated ovarian veins then compress the ureter against the external iliac artery or
1743-9191/$ – see front matter Ó 2009 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijsu.2009.09.008
H.Y. Bhutta et al. / International Journal of Surgery 7 (2009) 516–520
517
Fig. 1. Normal anatomy of ovarian arteries (1), veins (2) and ureters (3) demonstrated on left. Right-hand image demonstrates an aberrant, enlarged right ovarian vein (4), compressing the right ureter (5) between itself and the external iliac vessels (6).
psoas muscle. However, persistent, significantly elevated venous pressures are needed for the ovarian veins to feasibly occlude a thick-walled muscular ureter. Such pressures are not achieved, even during pregnancy.8 Dure-Smith argued that whilst the pressure of the gravid uterus itself may suffice to occlude the ureters, it seems unlikely that ovarian vein pressure could achieve this. Quoting studies demonstrating a 60-fold increase in blood flow through the ovarian veins during pregnancy, and a 3-fold increase in venous diameter, but a comparatively small rise in pressure in these capacitance vessels,9 he argued that ovarian veins could only reach pressures high enough to occlude the ureters during labour, or with transient activities such as the valsalva manoeuvre. He contested that post-partum, the ovarian veins collapse, so postpregnancy ureteric dilatation caused by the ovarian veins seems implausible. He also felt that the presence of a connective tissue sheath encasing vessels and ureter was dubious, and not described by anyone other than Dykhuizen, although subsequently, this observation has been corroborated.10 Canine experiments reproducing ovarian vein dilatation by ligating other main veins have failed to reproduce ureteric obstruction.11 In Dykhuizen’s series, extirpated ovarian veins demonstrated medial wall thickening, although others have found the vessels to be histologically normal.3 Hormonal changes associated with pregnancy may also explain OVS. Altered levels of circulating oestrogen and progesterone could affect the muscular ureteric wall, causing a decrease in tone that facilitates its compression.12,13 In Dykhuizen’s series, oral progestogen appeared to exacerbate symptoms, presumed to be due to increased ovarian vein blood flow.5 Oestrogen may account for the development of pelvic varicosities in the pelvic congestion syndrome, via nitric-oxide mediated vascular smooth muscle relaxation.14 Similarly, oestrogen/progesterone imbalances during pregnancy are a putative biological mechanism leading to ovarian vein dilatation and OVS. The hormonal hypothesis is strengthened by the trend for symptoms of OVS to be cyclical, and the
observation that it primarily affects pre and peri-menopausal women.1,6,7 However, that oophorectomy does not seem to be a successful treatment for OVS weakens the hormonal hypothesis.1 More rarely, an ovarian varicocele may develop as a result of back-pressure from the inferior vena cava or left renal vein. An example of this is the ‘nutcracker syndrome’, in which the left renal vein is compressed between the aorta and the superior mesenteric artery.15 Historically, the right ureter is involved in OVS more commonly than the left.1,4 This might be explained by its proximity to the iliac vessels, and the course of the right ovarian vein. The right ovarian vein usually forms a direct anastamosis with the inferior vena cava.8 Aberrant veins draining into the right renal vein might be responsible for the development of OVS.1,7 However, post-mortem examinations show that the left ovarian vein, which usually drains into the left renal vein, is twice as likely as the right to be valveless,16 and the left vein usually expands to a greater degree than the right both during and after pregnancy.17 These observations suggest that the left ovarian vein is more susceptible to becoming varicose. Incidental ovarian varices are present in 10–47% of females.18,19
3. Clinical features OVS is uncommon in nulliparous women.1,7 Symptoms are variable and non-specific, including abdominal pain, particularly in the iliac fossae, flanks and hypochondrium. The pain tends to be positional, and is worse lying down on the affected side. It is often cyclical, peaking shortly before menstruation.1,7 Urinary symptoms from ureteric obstruction include recurrent urinary tract infections, hydronephrosis, pyelonephritis, renal colic and frank haematuria. Whilst antibiotic therapy effectively treats infection, OVS pain is refractory, requiring more definitive treatment.5 Despite ureteric obstruction, there are few data regarding effects on renal
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function, unless there is a pre-existing anatomical renal tract abnormality.20,21 Given the non-specific features of OVS, the differential diagnosis is broad. Gynaecological conditions such as endometriosis, pelvic inflammatory disease and salpingitis must be considered. Ovarian vein thrombophlebitis, a condition which typically presents in the first few days post-partum with iliac fossa pain, fevers, and often a pelvic or abdominal mass should be excluded if such features are present. 3.1. Ovarian vein syndrome vs. pelvic congestion syndrome OVS should be distinguished from Pelvic Congestion Syndrome (PCS). Whilst sharing a similar pathology (dilated ovarian veins), affecting a similar demographic (women of child-bearing age), and responding to similar surgical treatment (venous embolization/ ligation), the clinical manifestation is different. OVS is attributed to dilated ovarian veins only, whilst PCS is thought to be a manifestation of dilatation of the entire anastomotic network of pelvic veins (ovarian, uterine, iliac), often with distal extension to involve lower limb veins22 . PCS is characterised by cyclical pelvic pain, often preceding the onset of menstruation. It typically, but not exclusively, begins during pregnancy in multiparous women, when the gravid uterus causes pressure on, with subsequent dilatation of, the ovarian veins.23 A dull ache and a sensation of perineal heaviness persist beyond pregnancy, and vascular congestion spreads distal to the ovarian veins giving rise to vulval and lower limb varicosities, with congestion of the pelvic organs. Pain is often postural, being worse on standing and eased on lying down, and patients complain of dyspareunia and post-coital pain.24 Urinary symptoms are infrequent, with urinary frequency and urgency being the most prevalent features. On clinical examination, there is commonly point tenderness over the region of the ovary and cervical excitation. By contrast, OVS is typified by a constellation of urinary symptoms. Extrinsic compression of the ureters such as tumour compression or retroperitoneal fibrosis, renal colic, and infections e.g. tuberculosis, are all possible differentials, as are general surgical emergencies such as appendicitis. Neurological and musculoskeletal disorders should also be considered. Consequently, many feel that OVS is ultimately a diagnosis of exclusion.20 4. Diagnostic testing First line investigations include both abdominal and transvaginal ultrasonography to assess the genitourinary tract, and principally to exclude mass lesions, which may be accountable for the presenting symptoms. An ovarian vein diameter 6 mm on ultrasound scan indicates an ovarian varicosity,25 while duplex scanning may demonstrate reversed or reduced flow. These findings form part of the imaging criteria for a diagnosis of PCS, but they may equally be applied to OVS. However, Park et al. found that the right ovarian vein was not identified with duplex scanning in 90% of subjects.26 Intravenous urography typically demonstrates a hydroureter, with a clearly demarcated transverse defect at the L3/4 level. The renal pelvis and calyces may be spared,4 and the middle third of the ureter may be laterally displaced, with medial displacement of a normal calibre pelvic ureter.5 Marked improvement in hydroureter may be seen on post-operative intravenous urogram, in keeping with a clinical improvement in many case reports.3,4,10 Secondary investigations include retrograde pyelography, which demonstrates a similar ureteric appearance as seen on intravenous urography, with an often normal pelvic ureteric segment, and delayed drainage.4 Percutaneous ovarian venography has
historically been regarded as the gold standard investigation in OVS, clearly identifying varicose veins and demonstrating retrograde blood flow.It is especially useful if considering ovarian vein embolization. Ovarian veins>10 mm in diameter are accepted as being varicose on venography.27 Ovarian varicosities may also be apparent on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). MRI is preferable as it avoids the large radiation dose associated with CT, which should be avoided where possible in young women. Additionally, contrast-enhanced MRI permits images to be obtained in arterial and venous phases, though this is being superseded by magnetic resonance venography,28 which may actually identify the cause of ovarian varicoceles. For PCS, an ovarian vein diameter 8 mm on CT or MRI is considered diagnostic.29 This criterion might equally be applied to identify ovarian varicosities in OVS. Up to 47% of women may have ovarian vein dilation observed incidentally on scans performed for other reasons.19 Use of MRI for OVS follow-up post-embolization with coils is limited by artefact. Laparoscopy may also have a diagnostic and therapeutic role, particularly in excluding other aetiologies, but is not typically a first line investigation. Pelvic pain is the commonest indication for diagnostic laparoscopy, but no diagnosis is made in the majority of cases.30 Studies to compare the sensitivity and specificities of these various investigations in either the ovarian vein syndrome, or the more well known pelvic congestion syndrome, have not been published. Whilst ultrasonography is clearly user-dependent, CT and MRI may both underestimate the presence of varicose veins as they collapse whilst the patient is supine during CT and MR imaging. 5. Treatment 5.1. Medical therapy Medical therapies with medroxyprogesterone acetate (MPA) as a method of causing venous contraction, and with goserelin acetate (gonadotrophin releasing hormone analogue), have been used in the treatment of chronic pelvic pain although long-term relief seems limited.31 In a randomised trial comparing MPA directly with goserelin acetate in the treatment of women with PCS, 12 months after the completion of treatment, goserelin acetate was found to be more effective than MPA, both subjectively, reducing pelvic symptoms and anxiety, and radiologically, reducing pelvic congestion on venography.32 Recently, the sub-dermal etonorgestrol implant (ImplanonÒ) has shown promise in treating PCS-related pelvic pain, with follow-up at 12 months showing significant reduction in pain scores and improved venographic appearances compared with no treatment.33 5.2. Radiological therapy Ovarian vein embolization has been used for many years as a treatment for OVS resistant to medical therapy. Coil embolization, first described in 1993,34 and now percutaneous chemical sclerotherapy with Gelfoam35 or sodium tetradecylsulphate35,36 can be offered on an out-patient basis as less invasive options than surgery. Short-term success from embolization therapy is estimated at 80–98%.37–39 Longer-term efficacy, as observed in PCS, also appears promising.40 Technical success rates from embolotherapy for the treatment of varices in PCS have been measured at 98–100%, and follow-up at 12 months has shown a mean reduction in pain scores of 65%.41 Side- effects of embolization include thrombophlebitis, recurrent disease, and embolic material occluding non-targeted veins.
H.Y. Bhutta et al. / International Journal of Surgery 7 (2009) 516–520
5.3. Surgical therapy The first case report of transperitoneal laparoscopic treatment for OVS was in 1996, by Elashry et al.42 Laparoscopy has subsequently been undertaken by many to achieve ovarian vein ligation,7,20,43–45 with promising short-term results, offering various degrees of resolution of symptoms and improvement in radiological appearances of the dilated ureteropelvicalyceal system. Prior to this, open ligation of the ovarian vein with ureterolysis was the preferred method of treatment.3,42,46 Clark reported good results with open surgery in his early series of 130 cases.1 Ligation of the ovarian veins is permitted by a vast collateral network formed with the uterine veins, and is not believed to affect future fertility or pregnancies.1,7 Laparoscopic treatment has progressed more recently to involve use of the retroperitoneoscopic approach10 and sophisticated robotic devices,47 and whilst it is preferable to operate post-partum, if symptoms are severe enough, laparoscopy can be undertaken during pregnancy. 6. Conclusion The debate around the ovarian vein syndrome continues since Dure-Smith questioned the plausibility of its pathophysiological development 30 years ago. However, it is deemed by many to be a very real and easily curable cause of chronic pelvic pain in young women, who might otherwise suffer considerable physical and psychological morbidity when no other explanation for their pain can be found. It should be considered as a last resort in all young female patients presenting with chronic pain. Author contributions HY Bhutta-Drafting and critical revision of review article, approval of submitted version SR Walsh- Critical revision of article, approval of submitted version TY Tang- Critical revision of article, approval of submitted version CA Walsh- Critical revision of article, approval of submitted version JM Clarke- Critical revision of article, approval of submitted version
Conflict of interest None Funding None Ethical approval None declared References 1. Clark J. The right ovarian vein syndrome. 2nd ed. Philadelphia: W.B. Saunders Company; 1964. 2. Marcondes Pereira R, Ferreira AA, Lane E. Diagnosis of the right ovarian vein syndrome. Am J Obstet Gynecol 1969 Mar 15;103(6):888–9. 3. Meiraz D, Savir A. Ovarian vein syndrome: a case report. J Urol 1981 May;125(5):737–8. 4. Shah MS, Tozzo PJ. Right ovarian vein syndrome. Urology 1974 Apr;3(4):488–90. 5. Dykhuizen RF, Roberts JA. The ovarian vein syndrome. Surg Gynecol Obstet 1970 Mar;130(3):443–52. 6. Maubon A, Ferru JM, Thiebaut C, Berger V, Hoche N, Rouanet JP. Left ovarian vein syndrome. J Radiol 1997 Mar;78(3):223–5. 7. Tourne G, Ducroux A, Bourbon M, Blinding H. The ovarian vein syndrome: eight cases and review of the literature. J Gynecol Obstet Biol Reprod (Paris) 2002 Sep;31(5):471–7.
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8. Dure-Smith P. Ovarian syndrome: is it a myth? Urology 1979 Apr;13(4):355–64. 9. Hodgkinson CP. Ovarian vein pressure studies. Am J Obstet Gynecol 1951 Feb;61(2):321–9. 10. Sato F, Nomura T, Shin T, Hirai K, Matsubara T, Hirata Y, et al. Retroperitoneoscopic treatment of ovarian vein syndrome. J Laparoendosc Adv Surg Tech A 2008 Oct;18(5):739–42. 11. Southwell TH, Bourne CW. Experimental ovarian vein dilation. J Urol 1971 Mar;105(3):346–50. 12. Marshall S, Lyon RP, Minkler D. Ureteral dilatation following use of oral contraceptives. JAMA 1966 Nov 14;198(7):782–3. 13. Kumar D. In vitro inhibitory effect of progesterone on extrauterine human smooth muscle. Am J Obstet Gynecol 1962;84:1300. 14. Foong LC, Gamble J, Sutherland IA, Beard RW. Altered peripheral vascular response of women with and without pelvic pain due to congestion. BJOG 2000 Feb;107(2):157–64. 15. Scultetus AH, Villavicencio JL, Gillespie DL. The nutcracker syndrome: its role in the pelvic venous disorders. J Vasc Surg 2001 Nov;34(5):812–9. 16. Ahlberg NE, Bartley O, Chidekel N. Circumference of the left gonadal vein. An anatomical and statistical study. Acta Radiol Diagn (Stockh) 1965 Nov;3(6):503–12. 17. Ahlberg NE, Bartley O, Chidekel N. Right and left gonadal veins. An anatomical and statistical study. Acta Radiol Diagn (Stockh) 1966 Nov;4(6):593–601. 18. Belenky A, Bartal G, Atar E, Cohen M, Bachar GN. Ovarian varices in healthy female kidney donors: incidence, morbidity, and clinical outcome. AJR Am J Roentgenol 2002 Sep;179(3):625–7. 19. Rozenblit AM, Ricci ZJ, Tuvia J, Amis Jr ES. Incompetent and dilated ovarian veins: a common CT finding in asymptomatic parous women. AJR Am J Roentgenol 2001 Jan;176(1):119–22. 20. Gettman MT, Lotan Y, Cadeddu J. Laparoscopic treatment of ovarian vein syndrome. JSLS 2003 Jul–Sep;7(3):257–60. 21. Gleason PE, Kelalis PP, Husmann DA, Kramer SA. Hydronephrosis in renal ectopia: incidence, etiology and significance. J Urol 1994 Jun;151(6):1660–1. 22. Liddle AD, Davies AH. Pelvic congestion syndrome: chronic pelvic pain caused by ovarian and internal iliac varices. Phlebology 2007;22(3):100–4. 23. Hobbs JT. The pelvic congestion syndrome. Br J Hosp Med 1990 Mar;43(3):200–6. 24. Beard RW, Reginald PW, Wadsworth J. Clinical features of women with chronic lower abdominal pain and pelvic congestion. Br J Obstet Gynaecol 1988 Feb;95(2):153–61. 25. Giacchetto C, Catizone F, Cotroneo GB, Cavallaro V, Cammisuli F, Minutolo V, et al. Radiologic anatomy of the genital venous system in female patients with varicocele. Surg Gynecol Obstet 1989 Nov;169(5):403–7. 26. Park SJ, Lim JW, Ko YT, Lee DH, Yoon Y, Oh JH, et al. Diagnosis of pelvic congestion syndrome using transabdominal and transvaginal sonography. AJR Am J Roentgenol 2004 Mar;182(3):683–8. 27. Kennedy A, Hemingway A. Radiology of ovarian varices. Br J Hosp Med 1990 Jul;44(1):38–43. 28. Ganeshan A, Upponi S, Hon LQ, Uthappa MC, Warakaulle DR, Uberoi R. Chronic pelvic pain due to pelvic congestion syndrome: the role of diagnostic and interventional radiology. Cardiovasc Intervent Radiol 2007 Nov– Dec;30(6):1105–11. 29. Coakley FV, Varghese SL, Hricak H. CT and MRI of pelvic varices in women. J Comput Assist Tomogr 1999 May–Jun;23(3):429–34. 30. Howard FM. The role of laparoscopy in chronic pelvic pain: promise and pitfalls. Obstet Gynecol Surv 1993 Jun;48(6):357–87. 31. Swanton A, Reginald P. Medical management of chronic pelvic pain: the evidence. Rev Gynaecol Pract 2004;4:65–70. 32. Soysal ME, Soysal S, Vicdan K, Ozer S. A randomized controlled trial of goserelin and medroxyprogesterone acetate in the treatment of pelvic congestion. Hum Reprod 2001 May;16(5):931–9. 33. Shokeir T, Amr M, Abdelshaheed M. The efficacy of implanon for the treatment of chronic pelvic pain associated with pelvic congestion: 1-year randomized controlled pilot study. Arch Gynecol Obstet; 2009 Feb 4. 34. Edwards RD, Robertson IR, MacLean AB, Hemingway AP. Case report: pelvic pain syndrome–successful treatment of a case by ovarian vein embolization. Clin Radiol 1993 Jun;47(6):429–31. 35. Venbrux AC, Lambert DL. Embolization of the ovarian veins as a treatment for patients with chronic pelvic pain caused by pelvic venous incompetence (pelvic congestion syndrome). Curr Opin Obstet Gynecol 1999 Aug;11(4):395–9. 36. Pieri S, Agresti P, Morucci M, de’ Medici L. Percutaneous treatment of pelvic congestion syndrome. Radiol Med 2003 Jan–Feb;105(1–2):76–82. 37. Maleux G, Stockx L, Wilms G, Marchal G. Ovarian vein embolization for the treatment of pelvic congestion syndrome: long-term technical and clinical results. J Vasc Interv Radiol 2000 Jul–Aug;11(7):859–64. 38. Capasso P, Simons C, Trotteur G, Dondelinger RF, Henroteaux D, Gaspard U. Treatment of symptomatic pelvic varices by ovarian vein embolization. Cardiovasc Intervent Radiol 1997 Mar–Apr;20(2):107–11. 39. Cordts PR, Eclavea A, Buckley PJ, DeMaioribus CA, Cockerill ML, Yeager TD. Pelvic congestion syndrome: early clinical results after transcatheter ovarian vein embolization. J Vasc Surg 1998 Nov;28(5):862–8. 40. Kim HS, Malhotra AD, Rowe PC, Lee JM, Venbrux AC. Embolotherapy for pelvic congestion syndrome: long-term results. J Vasc Interv Radiol 2006 Feb;17(2 Pt 1):289–97. 41. Venbrux AC, Chang AH, Kim HS, Montague BJ, Hebert JB, Arepally A, et al. Pelvic congestion syndrome (pelvic venous incompetence): impact of ovarian and internal iliac vein embolotherapy on menstrual cycle and chronic pelvic pain. J Vasc Interv Radiol 2002 Feb;13(2 Pt 1):171–8.
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42. Elashry OM, Nakada SY, Wolf Jr JS, Figenshau RS, McDougall EM, Clayman RV. Ureterolysis for extrinsic ureteral obstruction: a comparison of laparoscopic and open surgical techniques. J Urol 1996 Oct;156(4):1403–10. 43. Gargiulo T, Mais V, Brokaj L, Cossu E, Melis GB. Bilateral laparoscopic transperitoneal ligation of ovarian veins for treatment of pelvic congestion syndrome. J Am Assoc Gynecol Laparosc 2003 Nov;10(4):501–4. 44. Almeida A, Cavalcanti F, Barbosa S, Cohen R, Medeiros A. Laparoscopic approach in the ovarian vein syndrome. Int Braz J Urol 2003 Jan–Feb;29(1):45–7.
45. del Valle Gonzalez N, Estebanez Zarranz J, Escudero Caro T, Castroviejo Royo F, Mendo Gonza´lez M, Cepeda Delgado M, et al. Laparoscopic treatment of ovarian vein syndrome. Actas Urol Esp 2006 Jan;30(1):85–9. 46. Derrick Jr FC, Rosenblum R, Frensilli FJ. Right ovarian vein syndrome. Six-year critique. Urology 1973 May;1(5):383–5. 47. Badger WJ, De EJ, Kaufman Jr RP. Robotically assisted excision of ovarian vein for intermittent ureteral obstruction. JSLS 2008 Apr–Jun;12(2): 166–8.
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.theijs.com
Review
Ovarian vein syndrome: A review Hina Y Bhutta a, *, Stewart R Walsh a, Tjun Y Tang a, Colin A Walsh b, James M Clarke a a b
Department of Surgery, Norfolk & Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY, UK Department of Obstetrics and Gynaecology, St George Hospital, Kogarah, New South Wales, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 June 2009 Received in revised form 23 September 2009 Accepted 25 September 2009 Available online 8 October 2009
The Ovarian Vein Syndrome was first reported in 1964, yet its existence as a true pathophysiological entity remains controversial. It may present as an acute or chronic disease, typically affecting young, multiparous women. This review discusses the literature to date on this poorly recognised cause of ureteric obstruction and pelvic pain, including developments in the diagnosis and management of this eminently treatable condition. Ó 2009 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Ovarian Vein Syndrome Chronic Pelvic Pain Congestion Ureteric Obstruction
1. Review criteria Using Embase and Medline, a literature search was undertaken. English and foreign language articles on the ovarian vein syndrome were appraised. Chronic pelvic pain, pelvic congestion syndrome and ureteric obstruction were key terms, which were also searched. In 1964, Clark published a series of 129 cases of right-sided ovarian vein syndrome in which he purported that an aberrant ovarian vein was the cause of an obstructive uropathy, occurring at the level of the pelvic brim.1 Since then, several others have published case reports of the ovarian vein syndrome (OVS),2–7 but the largest contemporary series includes only eight cases.7 That the syndrome truly exists as a distinct pathophysiological entity remains controversial. It is often encompassed within a larger collection of disorders, which share the unifying feature of chronic pelvic pain. 2. Pathophysiology OVS may present as an acute affliction during or soon after pregnancy, or as a chronic, recurring disease. Both acute and
* Corresponding author. Tel.: þ44 07773 420 717. E-mail address: [email protected] (H.Y. Bhutta).
chronic variants occur most commonly in multiparous women. Several pathophysiological mechanisms have been suggested. Clark postulated that an aberrant ovarian vein, which might arise from persistent embryological posterior subcardinal branches, exerts occlusive pressure on the ipsilateral ureter.1 By crossing the ureter at the level of the pelvic brim, where its position is relatively fixed, rather than at the usual more cephalad level of L3/L4, Clark felt the aberrant vessel is more likely to cause ureteric compression. He also described aberrant ovarian veins as being much larger than normal, more likely to branch into a number of distal tributaries, and more likely to drain into the right renal vein, all of which he felt could explain the phenomenon of right-sided OVS (Fig. 1). Dykhuizen described a sheath of connective tissue at the pelvic brim, which appeared to be a retroperitoneal continuation of the suspensory ovarian ligament, encasing both ovarian vessels and ureter. This, he surmised, contributed to ureteric fixity secondary to periureteral fibrosis.5 Radiographically he observed that, in suspected right-sided OVS, the ovarian vein fixed the right ureter as they crossed, whilst the right kidney moved with respiration. Others believe that the ureter becomes trapped within a fibrovascular mesh of tortuous dilated veins.3 Alternatively, pressure from the gravid uterus may cause ovarian vein dilatation and valvular incompetence. The dilated ovarian veins then compress the ureter against the external iliac artery or
1743-9191/$ – see front matter Ó 2009 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijsu.2009.09.008
H.Y. Bhutta et al. / International Journal of Surgery 7 (2009) 516–520
517
Fig. 1. Normal anatomy of ovarian arteries (1), veins (2) and ureters (3) demonstrated on left. Right-hand image demonstrates an aberrant, enlarged right ovarian vein (4), compressing the right ureter (5) between itself and the external iliac vessels (6).
psoas muscle. However, persistent, significantly elevated venous pressures are needed for the ovarian veins to feasibly occlude a thick-walled muscular ureter. Such pressures are not achieved, even during pregnancy.8 Dure-Smith argued that whilst the pressure of the gravid uterus itself may suffice to occlude the ureters, it seems unlikely that ovarian vein pressure could achieve this. Quoting studies demonstrating a 60-fold increase in blood flow through the ovarian veins during pregnancy, and a 3-fold increase in venous diameter, but a comparatively small rise in pressure in these capacitance vessels,9 he argued that ovarian veins could only reach pressures high enough to occlude the ureters during labour, or with transient activities such as the valsalva manoeuvre. He contested that post-partum, the ovarian veins collapse, so postpregnancy ureteric dilatation caused by the ovarian veins seems implausible. He also felt that the presence of a connective tissue sheath encasing vessels and ureter was dubious, and not described by anyone other than Dykhuizen, although subsequently, this observation has been corroborated.10 Canine experiments reproducing ovarian vein dilatation by ligating other main veins have failed to reproduce ureteric obstruction.11 In Dykhuizen’s series, extirpated ovarian veins demonstrated medial wall thickening, although others have found the vessels to be histologically normal.3 Hormonal changes associated with pregnancy may also explain OVS. Altered levels of circulating oestrogen and progesterone could affect the muscular ureteric wall, causing a decrease in tone that facilitates its compression.12,13 In Dykhuizen’s series, oral progestogen appeared to exacerbate symptoms, presumed to be due to increased ovarian vein blood flow.5 Oestrogen may account for the development of pelvic varicosities in the pelvic congestion syndrome, via nitric-oxide mediated vascular smooth muscle relaxation.14 Similarly, oestrogen/progesterone imbalances during pregnancy are a putative biological mechanism leading to ovarian vein dilatation and OVS. The hormonal hypothesis is strengthened by the trend for symptoms of OVS to be cyclical, and the
observation that it primarily affects pre and peri-menopausal women.1,6,7 However, that oophorectomy does not seem to be a successful treatment for OVS weakens the hormonal hypothesis.1 More rarely, an ovarian varicocele may develop as a result of back-pressure from the inferior vena cava or left renal vein. An example of this is the ‘nutcracker syndrome’, in which the left renal vein is compressed between the aorta and the superior mesenteric artery.15 Historically, the right ureter is involved in OVS more commonly than the left.1,4 This might be explained by its proximity to the iliac vessels, and the course of the right ovarian vein. The right ovarian vein usually forms a direct anastamosis with the inferior vena cava.8 Aberrant veins draining into the right renal vein might be responsible for the development of OVS.1,7 However, post-mortem examinations show that the left ovarian vein, which usually drains into the left renal vein, is twice as likely as the right to be valveless,16 and the left vein usually expands to a greater degree than the right both during and after pregnancy.17 These observations suggest that the left ovarian vein is more susceptible to becoming varicose. Incidental ovarian varices are present in 10–47% of females.18,19
3. Clinical features OVS is uncommon in nulliparous women.1,7 Symptoms are variable and non-specific, including abdominal pain, particularly in the iliac fossae, flanks and hypochondrium. The pain tends to be positional, and is worse lying down on the affected side. It is often cyclical, peaking shortly before menstruation.1,7 Urinary symptoms from ureteric obstruction include recurrent urinary tract infections, hydronephrosis, pyelonephritis, renal colic and frank haematuria. Whilst antibiotic therapy effectively treats infection, OVS pain is refractory, requiring more definitive treatment.5 Despite ureteric obstruction, there are few data regarding effects on renal
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function, unless there is a pre-existing anatomical renal tract abnormality.20,21 Given the non-specific features of OVS, the differential diagnosis is broad. Gynaecological conditions such as endometriosis, pelvic inflammatory disease and salpingitis must be considered. Ovarian vein thrombophlebitis, a condition which typically presents in the first few days post-partum with iliac fossa pain, fevers, and often a pelvic or abdominal mass should be excluded if such features are present. 3.1. Ovarian vein syndrome vs. pelvic congestion syndrome OVS should be distinguished from Pelvic Congestion Syndrome (PCS). Whilst sharing a similar pathology (dilated ovarian veins), affecting a similar demographic (women of child-bearing age), and responding to similar surgical treatment (venous embolization/ ligation), the clinical manifestation is different. OVS is attributed to dilated ovarian veins only, whilst PCS is thought to be a manifestation of dilatation of the entire anastomotic network of pelvic veins (ovarian, uterine, iliac), often with distal extension to involve lower limb veins22 . PCS is characterised by cyclical pelvic pain, often preceding the onset of menstruation. It typically, but not exclusively, begins during pregnancy in multiparous women, when the gravid uterus causes pressure on, with subsequent dilatation of, the ovarian veins.23 A dull ache and a sensation of perineal heaviness persist beyond pregnancy, and vascular congestion spreads distal to the ovarian veins giving rise to vulval and lower limb varicosities, with congestion of the pelvic organs. Pain is often postural, being worse on standing and eased on lying down, and patients complain of dyspareunia and post-coital pain.24 Urinary symptoms are infrequent, with urinary frequency and urgency being the most prevalent features. On clinical examination, there is commonly point tenderness over the region of the ovary and cervical excitation. By contrast, OVS is typified by a constellation of urinary symptoms. Extrinsic compression of the ureters such as tumour compression or retroperitoneal fibrosis, renal colic, and infections e.g. tuberculosis, are all possible differentials, as are general surgical emergencies such as appendicitis. Neurological and musculoskeletal disorders should also be considered. Consequently, many feel that OVS is ultimately a diagnosis of exclusion.20 4. Diagnostic testing First line investigations include both abdominal and transvaginal ultrasonography to assess the genitourinary tract, and principally to exclude mass lesions, which may be accountable for the presenting symptoms. An ovarian vein diameter 6 mm on ultrasound scan indicates an ovarian varicosity,25 while duplex scanning may demonstrate reversed or reduced flow. These findings form part of the imaging criteria for a diagnosis of PCS, but they may equally be applied to OVS. However, Park et al. found that the right ovarian vein was not identified with duplex scanning in 90% of subjects.26 Intravenous urography typically demonstrates a hydroureter, with a clearly demarcated transverse defect at the L3/4 level. The renal pelvis and calyces may be spared,4 and the middle third of the ureter may be laterally displaced, with medial displacement of a normal calibre pelvic ureter.5 Marked improvement in hydroureter may be seen on post-operative intravenous urogram, in keeping with a clinical improvement in many case reports.3,4,10 Secondary investigations include retrograde pyelography, which demonstrates a similar ureteric appearance as seen on intravenous urography, with an often normal pelvic ureteric segment, and delayed drainage.4 Percutaneous ovarian venography has
historically been regarded as the gold standard investigation in OVS, clearly identifying varicose veins and demonstrating retrograde blood flow.It is especially useful if considering ovarian vein embolization. Ovarian veins>10 mm in diameter are accepted as being varicose on venography.27 Ovarian varicosities may also be apparent on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). MRI is preferable as it avoids the large radiation dose associated with CT, which should be avoided where possible in young women. Additionally, contrast-enhanced MRI permits images to be obtained in arterial and venous phases, though this is being superseded by magnetic resonance venography,28 which may actually identify the cause of ovarian varicoceles. For PCS, an ovarian vein diameter 8 mm on CT or MRI is considered diagnostic.29 This criterion might equally be applied to identify ovarian varicosities in OVS. Up to 47% of women may have ovarian vein dilation observed incidentally on scans performed for other reasons.19 Use of MRI for OVS follow-up post-embolization with coils is limited by artefact. Laparoscopy may also have a diagnostic and therapeutic role, particularly in excluding other aetiologies, but is not typically a first line investigation. Pelvic pain is the commonest indication for diagnostic laparoscopy, but no diagnosis is made in the majority of cases.30 Studies to compare the sensitivity and specificities of these various investigations in either the ovarian vein syndrome, or the more well known pelvic congestion syndrome, have not been published. Whilst ultrasonography is clearly user-dependent, CT and MRI may both underestimate the presence of varicose veins as they collapse whilst the patient is supine during CT and MR imaging. 5. Treatment 5.1. Medical therapy Medical therapies with medroxyprogesterone acetate (MPA) as a method of causing venous contraction, and with goserelin acetate (gonadotrophin releasing hormone analogue), have been used in the treatment of chronic pelvic pain although long-term relief seems limited.31 In a randomised trial comparing MPA directly with goserelin acetate in the treatment of women with PCS, 12 months after the completion of treatment, goserelin acetate was found to be more effective than MPA, both subjectively, reducing pelvic symptoms and anxiety, and radiologically, reducing pelvic congestion on venography.32 Recently, the sub-dermal etonorgestrol implant (ImplanonÒ) has shown promise in treating PCS-related pelvic pain, with follow-up at 12 months showing significant reduction in pain scores and improved venographic appearances compared with no treatment.33 5.2. Radiological therapy Ovarian vein embolization has been used for many years as a treatment for OVS resistant to medical therapy. Coil embolization, first described in 1993,34 and now percutaneous chemical sclerotherapy with Gelfoam35 or sodium tetradecylsulphate35,36 can be offered on an out-patient basis as less invasive options than surgery. Short-term success from embolization therapy is estimated at 80–98%.37–39 Longer-term efficacy, as observed in PCS, also appears promising.40 Technical success rates from embolotherapy for the treatment of varices in PCS have been measured at 98–100%, and follow-up at 12 months has shown a mean reduction in pain scores of 65%.41 Side- effects of embolization include thrombophlebitis, recurrent disease, and embolic material occluding non-targeted veins.
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5.3. Surgical therapy The first case report of transperitoneal laparoscopic treatment for OVS was in 1996, by Elashry et al.42 Laparoscopy has subsequently been undertaken by many to achieve ovarian vein ligation,7,20,43–45 with promising short-term results, offering various degrees of resolution of symptoms and improvement in radiological appearances of the dilated ureteropelvicalyceal system. Prior to this, open ligation of the ovarian vein with ureterolysis was the preferred method of treatment.3,42,46 Clark reported good results with open surgery in his early series of 130 cases.1 Ligation of the ovarian veins is permitted by a vast collateral network formed with the uterine veins, and is not believed to affect future fertility or pregnancies.1,7 Laparoscopic treatment has progressed more recently to involve use of the retroperitoneoscopic approach10 and sophisticated robotic devices,47 and whilst it is preferable to operate post-partum, if symptoms are severe enough, laparoscopy can be undertaken during pregnancy. 6. Conclusion The debate around the ovarian vein syndrome continues since Dure-Smith questioned the plausibility of its pathophysiological development 30 years ago. However, it is deemed by many to be a very real and easily curable cause of chronic pelvic pain in young women, who might otherwise suffer considerable physical and psychological morbidity when no other explanation for their pain can be found. It should be considered as a last resort in all young female patients presenting with chronic pain. Author contributions HY Bhutta-Drafting and critical revision of review article, approval of submitted version SR Walsh- Critical revision of article, approval of submitted version TY Tang- Critical revision of article, approval of submitted version CA Walsh- Critical revision of article, approval of submitted version JM Clarke- Critical revision of article, approval of submitted version
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