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A mesothelial cyst of the round ligament presenting as an inguinal hernia after gonadotropin stimulation for in vitro fertilization
FERTILITY AND STERILITY威 VOL. 82, NO. 4, OCTOBER 2004 Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
A mesothelial cyst of the round ligament presenting as an inguinal hernia after gonadotropin stimulation for in vitro fertilization David A. Ryley, M.D.,a,b,c Donald W. Moorman, M.D.,a,c Jonathan L. Hecht, M.D.,a,c and Michael M. Alper, M.D.a,b,c Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and Boston IVF, Waltham, Massachusetts
Objective: To report the case of a round ligament cyst which, as the result of gonadotropin stimulation for IVF, simulated an incarcerated inguinal hernia. Design: Case report. Setting: A private infertility center and a university hospital. Patient(s): A 31-year-old woman who developed left lower quadrant pain after gonadotropin stimulation for IUI and a tender left inguinal mass after increasing ovarian stimulation for IVF/intracytoplasmic sperm injection. Intervention(s): Surgical excision of a mesothelial cyst of the left round ligament and exploration of the left inguinal canal. Main Outcome Measure(s): Successful surgical excision of left inguinal mass. Result(s): Resolution of symptoms. Conclusion(s): Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical repair. (Fertil Steril威 2004;82:944 – 6. ©2004 by American Society for Reproductive Medicine.) Key Words: Mesothelial cysts, round ligament, inguinal hernia, gonadotropin stimulation
Received November 19, 2003; revised and accepted March 1, 2004. Reprint requests: David A. Ryley, M.D., Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS322, Boston, Massachusetts 02215 (FAX: 617-975-5575; E-mail: dryley@bidmc. harvard.edu). a Beth Israel Deaconess Medical Center. b Boston IVF. c Harvard Medical School. 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 03.042
944
Mesothelial cysts of the round ligament are rare. They are often misdiagnosed as inguinal hernias, femoral hernias, or lipomas (1). To our knowledge, this is the first case report of a round ligament cyst that presented as an inguinal hernia after gonadotropin stimulation.
CASE REPORT A 31-year-old G0 and her husband presented with a 2-year history of primary infertility. Their evaluation revealed a day-3 FSH level of 6.34 mIU/mL and serum E2 of 24.6 pg/mL. Hysterosalpingography confirmed a normal uterine cavity and bilaterally patent fallopian tubes. Multiple semen analyses revealed mild oligospermia, consistent with a diagnosis of male factor infertility. The couple elected to pursue a treatment regimen consisting of con-
trolled ovarian hyperstimulation (COH) combined with IUI. Because of the oligospermia, they were counseled regarding IVF and intracytoplasmic sperm injection (ICSI), should the initial treatment plan fail. In her first cycle of COH/IUI, the patient was stimulated with 900 U (150 U daily on cycle days 2–7) of recombinant FSH (Gonal-F; Serono, Geneva, Switzerland) administered SC. She tolerated this regimen well, though it did not result in pregnancy. In her second cycle, the patient received 1500 U of recombinant FSH (225 U SC daily on cycle days 2–5, 150 U SC daily on days 6 –9). On cycle day 10, she received 10,000 U of hCG (Novarel; Ferring Pharmaceuticals, Tarrytown, NY) SC after ultrasonographic confirmation of three bilateral ovarian follicles measuring 16 –20 mm. Rou-
tine IUI was performed 36 hours after her hCG trigger, and no complications were noted. Six days after this insemination, the patient complained of increasing left lower quadrant tenderness with localized swelling. She denied gastrointestinal complaints, vaginal bleeding, or dysuria. Her examination was normal, and no intervention was required. The couple did not conceive, and her abdominal pain resolved soon thereafter.
FIGURE 1 (A) Gross inspection of the left inguinal mass revealed a 2.7 cm smooth walled cyst and attached pedicle. (B) The cyst wall is lined with a single layer of flattened epithelium consistent with a mesothelial origin. (C) A layer of smooth muscle supports the cyst wall. (D, E) Immunoperoxidase stains for estrogen and progesterone revealed nuclear reactivity in the smooth muscle layer.
A similar third cycle of COH/IUI was well tolerated, though it did not result in pregnancy. Controlled ovarian hyperstimulation was thus repeated in anticipation of IVF/ ICSI. Recombinant FSH (2025 U: 225 units SC daily for 9 days) resulted in the recruitment of 11 bilateral ovarian follicles measuring 13.0 –20.5 mm. A daily GnRH antagonist (.25 mg Cetrotide [Serono]) was given SC when a lead follicle measuring 14 mm had been identified. An uncomplicated follicular aspiration was performed with a transvaginal probe under general anesthesia. Six of the seven retrieved oocytes were successfully fertilized via ICSI, and three eight-cell embryos were transferred to the uterus without difficulty. Three days after her ET the patient presented to the emergency room with severe left lower quadrant pain. On examination she was noted to have a tense, tender, fluctuant, nonreducible left inguinal mass measuring 4 ⫻ 3 cm. Laboratory findings included a peripheral white blood cell count of 8800/L with a normal differential. Her urinalysis revealed no hematuria. Transabdominal ultrasonography demonstrated bilaterally enlarged ovaries containing multiple follicles. There was no evidence of ascites or hydronephrosis. The left inguinal region was notable for the presence of a 3.2 ⫻ 4.8 ⫻ 2.3-cm cystic mass containing a fluid–fluid level and no intrinsic color flow. The mass did not demonstrate peristalsis and was thought to be suspicious for herniated bowel. Parenteral narcotics were required for pain control, and the patient was taken to the operating room with a preoperative diagnosis of an incarcerated inguinal hernia. Intraoperatively, a 4 ⫻ 3-cm cystic mass arising from the left round ligament, prolapsing through the left external inguinal canal, was identified and excised. An associated hernia sac was opened, dissected away from the round ligament, and also excised. The procedure was well tolerated, and the patient had an uneventful postoperative recovery. The couple eventually conceived from a subsequent thaw ET. That pregnancy aborted early in the first trimester. Of note, the patient did not complain of any left lower quadrant pain in this unstimulated cycle. Gross inspection revealed the left inguinal mass to be a 2.7-cm smooth-walled cyst, with a wall thickness of 2 mm and an attached pedicle (Fig. 1A). On microscopic inspection, the cyst wall appeared to be lined with a single layer of flattened epithelium, consistent with a mesothelial origin (Fig. 1B), and was supported by a layer of smooth muscle FERTILITY & STERILITY威
Ryley. Round ligament cyst. Fertil Steril 2004.
(Fig. 1C). Immunoperoxidase stains for estrogen and progesterone revealed nuclear reactivity in the smooth muscle layer but not in the cyst lining (Fig. 1D and E).
DISCUSSION The round ligament of the uterus, a derivative of the gubernaculum, attaches to the paramesonephric duct near the uterotubal junction at 9 weeks of gestation (2). It 945
extends caudally through the inguinal canal to the labioscrotal swelling, forming a fibrous band by the end of the first trimester. Cysts of the mesothelial lining of the round ligament are believed to result from the inclusion of embryonic remnants during development of the supporting structures of the female genital tract (1). Because of its anatomic location, a round ligament cyst is often misdiagnosed as an indirect inguinal hernia, but it tends to be less symptomatic. Surgical intervention is recommended in the presence of symptoms and progressive increases in the size of the cyst. Small indirect inguinal hernias, as noted in the case presented, are found to be associated with round ligament cysts at the time of surgical intervention in 50% of cases. Recently, Hinckley et al. (3) reported the case of a percutaneous oocyte retrieval resulting from stimulation of an ectopically situated inguinal ovary. The ovary in that case, similar to the round ligament cyst described in this report, was discovered as the result of stimulation for IVF. Of interest, our patient had first developed symptoms, including complaints of localized abdominal swelling,
946
Ryley et al.
Round ligament cyst
during the second cycle of COH/IUI, as gonadotropins were increased. Immunoperoxidase staining of the smooth muscle cells of the round ligament confirmed the presence of estrogen and P (E/P) receptors. Although the epithelium of the cyst was negative for E/P activity, the response of the round ligament and uterine support structures to supraphysiologic serum E2 levels likely contributed to the perceived enlargement of the cyst within the inguinal canal. Direct gonadotropin stimulation might also have played a role in this process. Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical exploration and repair. References 1. Harper GB Jr, Awbrey BJ, Thomas CG Jr, Askin FB. Mesothelial cysts of the round ligament simulating inguinal hernia. Report of four cases and a review of the literature. Am J Surg 1986;151:515–7. 2. Larsen WJ. Human embryology. 2nd ed. New York: Churchill-Livingstone, 1997. 3. Hinckley MD, Milki AA. Percutaneous oocyte retrieval from and inguinal ovary. Fertil Seril 2003;80:445.
Vol. 82, No. 4, October 2004
A mesothelial cyst of the round ligament presenting as an inguinal hernia after gonadotropin stimulation for in vitro fertilization David A. Ryley, M.D.,a,b,c Donald W. Moorman, M.D.,a,c Jonathan L. Hecht, M.D.,a,c and Michael M. Alper, M.D.a,b,c Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and Boston IVF, Waltham, Massachusetts
Objective: To report the case of a round ligament cyst which, as the result of gonadotropin stimulation for IVF, simulated an incarcerated inguinal hernia. Design: Case report. Setting: A private infertility center and a university hospital. Patient(s): A 31-year-old woman who developed left lower quadrant pain after gonadotropin stimulation for IUI and a tender left inguinal mass after increasing ovarian stimulation for IVF/intracytoplasmic sperm injection. Intervention(s): Surgical excision of a mesothelial cyst of the left round ligament and exploration of the left inguinal canal. Main Outcome Measure(s): Successful surgical excision of left inguinal mass. Result(s): Resolution of symptoms. Conclusion(s): Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical repair. (Fertil Steril威 2004;82:944 – 6. ©2004 by American Society for Reproductive Medicine.) Key Words: Mesothelial cysts, round ligament, inguinal hernia, gonadotropin stimulation
Received November 19, 2003; revised and accepted March 1, 2004. Reprint requests: David A. Ryley, M.D., Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS322, Boston, Massachusetts 02215 (FAX: 617-975-5575; E-mail: dryley@bidmc. harvard.edu). a Beth Israel Deaconess Medical Center. b Boston IVF. c Harvard Medical School. 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 03.042
944
Mesothelial cysts of the round ligament are rare. They are often misdiagnosed as inguinal hernias, femoral hernias, or lipomas (1). To our knowledge, this is the first case report of a round ligament cyst that presented as an inguinal hernia after gonadotropin stimulation.
CASE REPORT A 31-year-old G0 and her husband presented with a 2-year history of primary infertility. Their evaluation revealed a day-3 FSH level of 6.34 mIU/mL and serum E2 of 24.6 pg/mL. Hysterosalpingography confirmed a normal uterine cavity and bilaterally patent fallopian tubes. Multiple semen analyses revealed mild oligospermia, consistent with a diagnosis of male factor infertility. The couple elected to pursue a treatment regimen consisting of con-
trolled ovarian hyperstimulation (COH) combined with IUI. Because of the oligospermia, they were counseled regarding IVF and intracytoplasmic sperm injection (ICSI), should the initial treatment plan fail. In her first cycle of COH/IUI, the patient was stimulated with 900 U (150 U daily on cycle days 2–7) of recombinant FSH (Gonal-F; Serono, Geneva, Switzerland) administered SC. She tolerated this regimen well, though it did not result in pregnancy. In her second cycle, the patient received 1500 U of recombinant FSH (225 U SC daily on cycle days 2–5, 150 U SC daily on days 6 –9). On cycle day 10, she received 10,000 U of hCG (Novarel; Ferring Pharmaceuticals, Tarrytown, NY) SC after ultrasonographic confirmation of three bilateral ovarian follicles measuring 16 –20 mm. Rou-
tine IUI was performed 36 hours after her hCG trigger, and no complications were noted. Six days after this insemination, the patient complained of increasing left lower quadrant tenderness with localized swelling. She denied gastrointestinal complaints, vaginal bleeding, or dysuria. Her examination was normal, and no intervention was required. The couple did not conceive, and her abdominal pain resolved soon thereafter.
FIGURE 1 (A) Gross inspection of the left inguinal mass revealed a 2.7 cm smooth walled cyst and attached pedicle. (B) The cyst wall is lined with a single layer of flattened epithelium consistent with a mesothelial origin. (C) A layer of smooth muscle supports the cyst wall. (D, E) Immunoperoxidase stains for estrogen and progesterone revealed nuclear reactivity in the smooth muscle layer.
A similar third cycle of COH/IUI was well tolerated, though it did not result in pregnancy. Controlled ovarian hyperstimulation was thus repeated in anticipation of IVF/ ICSI. Recombinant FSH (2025 U: 225 units SC daily for 9 days) resulted in the recruitment of 11 bilateral ovarian follicles measuring 13.0 –20.5 mm. A daily GnRH antagonist (.25 mg Cetrotide [Serono]) was given SC when a lead follicle measuring 14 mm had been identified. An uncomplicated follicular aspiration was performed with a transvaginal probe under general anesthesia. Six of the seven retrieved oocytes were successfully fertilized via ICSI, and three eight-cell embryos were transferred to the uterus without difficulty. Three days after her ET the patient presented to the emergency room with severe left lower quadrant pain. On examination she was noted to have a tense, tender, fluctuant, nonreducible left inguinal mass measuring 4 ⫻ 3 cm. Laboratory findings included a peripheral white blood cell count of 8800/L with a normal differential. Her urinalysis revealed no hematuria. Transabdominal ultrasonography demonstrated bilaterally enlarged ovaries containing multiple follicles. There was no evidence of ascites or hydronephrosis. The left inguinal region was notable for the presence of a 3.2 ⫻ 4.8 ⫻ 2.3-cm cystic mass containing a fluid–fluid level and no intrinsic color flow. The mass did not demonstrate peristalsis and was thought to be suspicious for herniated bowel. Parenteral narcotics were required for pain control, and the patient was taken to the operating room with a preoperative diagnosis of an incarcerated inguinal hernia. Intraoperatively, a 4 ⫻ 3-cm cystic mass arising from the left round ligament, prolapsing through the left external inguinal canal, was identified and excised. An associated hernia sac was opened, dissected away from the round ligament, and also excised. The procedure was well tolerated, and the patient had an uneventful postoperative recovery. The couple eventually conceived from a subsequent thaw ET. That pregnancy aborted early in the first trimester. Of note, the patient did not complain of any left lower quadrant pain in this unstimulated cycle. Gross inspection revealed the left inguinal mass to be a 2.7-cm smooth-walled cyst, with a wall thickness of 2 mm and an attached pedicle (Fig. 1A). On microscopic inspection, the cyst wall appeared to be lined with a single layer of flattened epithelium, consistent with a mesothelial origin (Fig. 1B), and was supported by a layer of smooth muscle FERTILITY & STERILITY威
Ryley. Round ligament cyst. Fertil Steril 2004.
(Fig. 1C). Immunoperoxidase stains for estrogen and progesterone revealed nuclear reactivity in the smooth muscle layer but not in the cyst lining (Fig. 1D and E).
DISCUSSION The round ligament of the uterus, a derivative of the gubernaculum, attaches to the paramesonephric duct near the uterotubal junction at 9 weeks of gestation (2). It 945
extends caudally through the inguinal canal to the labioscrotal swelling, forming a fibrous band by the end of the first trimester. Cysts of the mesothelial lining of the round ligament are believed to result from the inclusion of embryonic remnants during development of the supporting structures of the female genital tract (1). Because of its anatomic location, a round ligament cyst is often misdiagnosed as an indirect inguinal hernia, but it tends to be less symptomatic. Surgical intervention is recommended in the presence of symptoms and progressive increases in the size of the cyst. Small indirect inguinal hernias, as noted in the case presented, are found to be associated with round ligament cysts at the time of surgical intervention in 50% of cases. Recently, Hinckley et al. (3) reported the case of a percutaneous oocyte retrieval resulting from stimulation of an ectopically situated inguinal ovary. The ovary in that case, similar to the round ligament cyst described in this report, was discovered as the result of stimulation for IVF. Of interest, our patient had first developed symptoms, including complaints of localized abdominal swelling,
946
Ryley et al.
Round ligament cyst
during the second cycle of COH/IUI, as gonadotropins were increased. Immunoperoxidase staining of the smooth muscle cells of the round ligament confirmed the presence of estrogen and P (E/P) receptors. Although the epithelium of the cyst was negative for E/P activity, the response of the round ligament and uterine support structures to supraphysiologic serum E2 levels likely contributed to the perceived enlargement of the cyst within the inguinal canal. Direct gonadotropin stimulation might also have played a role in this process. Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical exploration and repair. References 1. Harper GB Jr, Awbrey BJ, Thomas CG Jr, Askin FB. Mesothelial cysts of the round ligament simulating inguinal hernia. Report of four cases and a review of the literature. Am J Surg 1986;151:515–7. 2. Larsen WJ. Human embryology. 2nd ed. New York: Churchill-Livingstone, 1997. 3. Hinckley MD, Milki AA. Percutaneous oocyte retrieval from and inguinal ovary. Fertil Seril 2003;80:445.
Vol. 82, No. 4, October 2004