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• W2052820121 abstract "Magnetic resonance imaging was used to measure the endometrial T2 relaxation times of patients with infertility with fibroma. Although the location of fibromas did not influence the T2 relaxation times, we did observe a significant decrease in endometrial T2 relaxation times after myomectomy. Magnetic resonance imaging was used to measure the endometrial T2 relaxation times of patients with infertility with fibroma. Although the location of fibromas did not influence the T2 relaxation times, we did observe a significant decrease in endometrial T2 relaxation times after myomectomy. Although uterine fibroids, which occur in 20% to 50% of women, are the most common type of solid pelvic tumor (1Verkauf B.S. Myomectomy for fertility enhancement and preservation.Fertil Steril. 1992; 58: 1-15Abstract Full Text PDF PubMed Google Scholar), the relationship between fibroids and infertility is not well established (2Donnez J. Jadoul P. What are the implications of myomas on fertility? A need for a debate?.Hum Reprod. 2002; 17: 1424-1430Crossref PubMed Scopus (280) Google Scholar, 3Somigliana E. Vercellini P. Daguati R. Pasin R. De Giorgi O. Crosignani P.G. Fibroids and female reproduction: a critical analysis of the evidence.Hum Reprod Update. 2007; 13: 465-476Crossref PubMed Scopus (241) Google Scholar). It has been reported that myomectomy can increase the pregnancy rate for patients with infertility (4Bulletti C. De Ziegler D. Polli V. Flamigni C. The role of leiomyomas in infertility.J Am Assoc Gynecol Laparosc. 1999; 6: 441-445Abstract Full Text PDF PubMed Scopus (122) Google Scholar). However, the mechanisms by which this occurs are not well understood. Several theories have been proposed. First, it is possible that fibroids alter uterine cavity contour, resulting in mechanical pressure. Alternatively, the fibroids may induce abnormal uterine contractility (5Richards P.A. Richards P.D. Tiltman A.J. The ultrastructure of fibromyomatous myometrium and its relationship to infertility.Hum Reprod Update. 1998; 4: 520-525Crossref PubMed Scopus (58) Google Scholar, 6Yoshino O. Hayashi T. Osuga Y. Orisaka M. Asada H. Okuda S. et al.Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids.Hum Reprod. 2010; 25: 2475-2479Crossref PubMed Scopus (106) Google Scholar). Finally, local inflammation associated with the presence of fibroids may give rise to a hostile endometrial environment that impairs sperm transport and embryo implantation (5Richards P.A. Richards P.D. Tiltman A.J. The ultrastructure of fibromyomatous myometrium and its relationship to infertility.Hum Reprod Update. 1998; 4: 520-525Crossref PubMed Scopus (58) Google Scholar). It has been reported that excessive concentrations of inflammatory cytokines have deleterious effects on embryonic development and implantation (7Inoue T. Kanzaki H. Iwai M. Imai K. Narukawa S. Higuchi T. et al.Tumour necrosis factor alpha inhibits in-vitro decidualization of human endometrial stromal cells.Hum Reprod. 1994; 9: 2411-2417Crossref PubMed Scopus (58) Google Scholar, 8Kariya M. Kanzaki H. Takakura K. Imai K. Okamoto N. Emi N. et al.Interleukin-1 inhibits in vitro decidualization of human endometrial stromal cells.J Clin Endocrinol Metab. 1991; 73: 1170-1174Crossref Scopus (118) Google Scholar). Inagaki et al. (9Inagaki N. Ung L. Otani T. Wilkinson D. Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.Eur J Obstet Gynecol Reprod Biol. 2003; 111: 197-203Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar) demonstrated that uterine cavities containing fibroids exhibit a state of excess inflammation, with up-regulation of matrix metalloproteinases and inflammatory cytokines such as interleukin-1 and tumor necrosis factor α. Magnetic resonance imaging (MRI) is a high-resolution method of differentiating soft tissues. In MRI, the nuclei of atoms in samples first are aligned along a static magnetic field, then are excited to a higher-energy state by a radiofrequency signal, and then return to a lower-energy equilibrium state. T2 relaxation time is a parameter that describes the relaxation to the equilibrium state once the radiofrequency signal is turned off. As an assessment of inflammatory status, T2 relaxation time is a useful way to detect the inflammatory status of rheumatoid disease (10Kight A.C. Dardzinski B.J. Laor T. Graham T.B. Magnetic resonance imaging evaluation of the effects of juvenile rheumatoid arthritis on distal femoral weight-bearing cartilage.Arthritis Rheum. 2004; 50: 901-905Crossref Scopus (53) Google Scholar, 11Gasson J. Gandy S.J. Hutton C.W. Jacoby R.K. Summers I.R. Vennart W. Magnetic resonance imaging of rheumatoid arthritis in metacarpophalangeal joints.Skeletal Radiol. 2000; 29: 324-334Crossref Scopus (21) Google Scholar), dermatomyositis (12Maillard S.M. Jones R. Owens C. Pilkington C. Woo P. Wedderburn L.R. et al.Quantitative assessment of MRI T2 relaxation time of thigh muscles in juvenile dermatomyositis.Rheumatology (Oxford). 2004; 43: 603-608Crossref Scopus (174) Google Scholar), and Graves’ orbitopathy in Graves’ disease (13Utech C.I. Khatibnia U. Winter P.F. Wulle K.G. MR T2 relaxation time for the assessment of retrobulbar inflammation in Graves’ ophthalmopathy.Thyroid. 1995; 5: 185-193PubMed Google Scholar, 14Hosten N. Sander B. Cordes M. Schubert C.J. Schorner W. Felix R. Graves ophthalmopathy: MR imaging of the orbits.Radiology. 1989; 172: 759-762PubMed Google Scholar). In the present study, we investigated the endometrial T2 relaxation times of patients with infertility with fibroma. We compared T2 relaxation times before and after surgery to examine the effect of myomectomy on the endometrium of patients with uterine fibroids. A total of 35 patients with uterine fibroids who desire pregnancy were examined by MRI between September 2008 and October 2010 at Takinogawa Clinic. Inclusion criteria were as follows. First, patients had intramural- or submucosal-type fibroid. Second, in advance of MRI all patients underwent screening for ovulation and corpus luteum function. Patients had regular menstrual cycles of approximately 28 days. Basal levels of serum FSH, LH, and PRL on menstrual cycle day 3 through 5 were within normal range (criteria: FSH 3.5–12.5 mIU/mL, LH 2.4–12.6 mIU/mL, and PRL 4.9–29.3 ng/mL). Serum E2 and P concentration in midluteal phase were >100 pg/mL and 10 ng/mL, respectively. After the screening test, ovarian functional status was monitored by basal body temperature (BBT) chart. An analysis was performed of BBT graphs, in which a rise in temperature of at least 0.2°C above that of the preceding 6 days that was completed in <48 hours and sustained for at least 11 days would indicate the occurrence of ovulation (15Ayres-de-Campos D. Silva-Carvalho J.L. Oliveira C. Martins-da-Silva I. Silva-Carvalho J. Pereira-Leite L. Inter-observer agreement in analysis of basal body temperature graphs from infertile women.Hum Reprod. 1995; 10: 2010-2016Google Scholar). All patients included in this study showed unequivocal biphasic cycles in their BBT chart. We designated the first day showing elevated temperature of at least 0.2°C as luteal phase day 1. Third, MRI was performed during the time of implantation window (luteal phase day 5–day 9), judged retrospectively by BBT chart (judged by gynecologists O.Y. and H.T.). By routine MRI study, the information retrieved included the location, number, and size of fibroids. Magnetic resonance studies were performed with use of a 1.5-T magnet unit (MRI machine from Siemens Japan, Shinagawa, Japan). Subsequently, conventional axial and sagittal T2–weighted images (repetition time [TR]/echo time [TE] = 4560–4720/107–111 milliseconds) and axial T1–weighted images (TR/TE = 550/8.5 milliseconds) were obtained with use of fast spin-echo techniques. T2 relaxation times of endometrium were measured on the same slice (350-mm field of view, 132 × 192 matrix, 3-mm slice thickness, bandwidth 362 Hz) with use of a spin-echo sequence. Eight images were acquired at each of the following TEs: 1.7, 23.4, 35.1, 46.8, 58.5, 70.2, 81.9, 93.6, 105.3, 117, and 128 milliseconds. The TR was 3 seconds, giving a total of 509 seconds acquisition time. Ten out of 35 patients underwent myomectomy at Teikyo Mizonokuchi hospital. Among these 10 patients, 9 patients underwent laparoscopic-assisted myomectomy, and 1 patient underwent transcervical resection of fibroma. Four to 6 months after surgery, patients underwent a second MRI to evaluate T2 relaxation times during the implantation window. For statistical analysis, the Mann-Whitney U test was used for comparing between groups, and the paired t-test was used for comparing results before and after surgery. T2 relaxation times in uterine endometrium obtained from patients with infertility who had intramural-type (n = 24) and submucosal-type (n = 12) fibroids were compared. We examined data from the midluteal phase. As shown in Figure 1A, the median value and minimum to maximum data of the two groups were 213 milliseconds (99–368 milliseconds) and 187 milliseconds (111–455 milliseconds) in intramural fibroids and submucosal fibroids, respectively. There was no statistical difference between groups (P=.9). Because T2 relaxation times in the endometrium were comparable between intramural and submucosal fibroids (Fig. 1A), the data from both groups were combined in the subsequent study. After myomectomy, 10 patients underwent MRI at midluteal phase, and T2 relaxation times in the endometrium before and after surgery were compared. Of the 10 patients, 7 underwent surgery for intramural-type fibroids, and 3 underwent surgery for submucosal-type fibroids. As shown in Figure 1B, T2 relaxation times were decreased significantly after surgery (P=.03). In the present study, we investigated the endometrial T2 relaxation times of patients with infertility with fibroma. We found that the endometrial T2 relaxation times were comparable regardless of the location of fibromas. Moreover, endometrial T2 relaxation times obtained after myomectomy were shortened significantly compared with the results before surgery. Management of fibroids continues to present difficulties when used to treat infertility, because of a lack of understanding of the mechanisms by which fibroids impede pregnancy. Although myomectomy is recognized as a method to increase the rate of pregnancy (4Bulletti C. De Ziegler D. Polli V. Flamigni C. The role of leiomyomas in infertility.J Am Assoc Gynecol Laparosc. 1999; 6: 441-445Abstract Full Text PDF PubMed Scopus (122) Google Scholar), the precise mechanism of its contribution to fertility remains uncertain. It has been reported that the local inflammation associated with the presence of fibroids may result in a hostile endometrial environment that impairs fertility (7Inoue T. Kanzaki H. Iwai M. Imai K. Narukawa S. Higuchi T. et al.Tumour necrosis factor alpha inhibits in-vitro decidualization of human endometrial stromal cells.Hum Reprod. 1994; 9: 2411-2417Crossref PubMed Scopus (58) Google Scholar, 8Kariya M. Kanzaki H. Takakura K. Imai K. Okamoto N. Emi N. et al.Interleukin-1 inhibits in vitro decidualization of human endometrial stromal cells.J Clin Endocrinol Metab. 1991; 73: 1170-1174Crossref Scopus (118) Google Scholar, 9Inagaki N. Ung L. Otani T. Wilkinson D. Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.Eur J Obstet Gynecol Reprod Biol. 2003; 111: 197-203Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar). Inagaki et al. (9Inagaki N. Ung L. Otani T. Wilkinson D. Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.Eur J Obstet Gynecol Reprod Biol. 2003; 111: 197-203Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar) proved that the uterine cavities of patients with fibroids exhibited excessive inflammatory status. Accordingly, myomectomy might increase the fertility rate by decreasing the inflammatory status of the endometrium. In that study, 5 mL of saline solution was injected into the uterine cavity, and matrix metalloproteinase and cytokine levels of the fluid were measured to determine the inflammatory status directly (9Inagaki N. Ung L. Otani T. Wilkinson D. Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.Eur J Obstet Gynecol Reprod Biol. 2003; 111: 197-203Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar). However, the volume of the uterine cavity can be decreased after removal of fibroids, making it difficult to compare precisely the inflammatory status before and after surgery. Therefore, it is necessary to develop less-invasive techniques that can estimate the inflammatory status of the uterine cavity. In the present study, we focused on T2 relaxation times obtained by MRI. This technique has proved useful in detecting the inflammatory activity of rheumatoid disease (10Kight A.C. Dardzinski B.J. Laor T. Graham T.B. Magnetic resonance imaging evaluation of the effects of juvenile rheumatoid arthritis on distal femoral weight-bearing cartilage.Arthritis Rheum. 2004; 50: 901-905Crossref Scopus (53) Google Scholar, 11Gasson J. Gandy S.J. Hutton C.W. Jacoby R.K. Summers I.R. Vennart W. Magnetic resonance imaging of rheumatoid arthritis in metacarpophalangeal joints.Skeletal Radiol. 2000; 29: 324-334Crossref Scopus (21) Google Scholar), dermatomyositis (12Maillard S.M. Jones R. Owens C. Pilkington C. Woo P. Wedderburn L.R. et al.Quantitative assessment of MRI T2 relaxation time of thigh muscles in juvenile dermatomyositis.Rheumatology (Oxford). 2004; 43: 603-608Crossref Scopus (174) Google Scholar), and Graves’ orbitopathy in Graves’ disease (13Utech C.I. Khatibnia U. Winter P.F. Wulle K.G. MR T2 relaxation time for the assessment of retrobulbar inflammation in Graves’ ophthalmopathy.Thyroid. 1995; 5: 185-193PubMed Google Scholar). Here, we observed a significant decrease in T2 relaxation times in patients examined after myomectomy. This suggests that myomectomy may suppress inflammatory activity in the endometrium. T2 relaxation times in the human endometrium have been examined throughout the menstrual cycle. Varpula et al. (16Varpula M. Komu M. Irjala K. Relaxation time changes of the uterus during the menstrual cycle: correlation with hormonal status.Eur J Radiol. 1993; 16: 90-94Abstract Full Text PDF PubMed Scopus (10) Google Scholar) reported that a rapid increase in T2 relaxation times occurred during the proliferative phase, followed by little or no increase through the middle of the secretory phase. Hoad et al. (17Hoad C.L. Fulford J. Raine-Fenning N.J. Campbell B.K. Johnson I.R. Gowland P.A. In vivo perfusion, T1, and T2 measurements in the female pelvis during the normal menstrual cycle: a feasibility study.J Magn Reson Imaging. 2006; 24: 1350-1356Crossref PubMed Scopus (15) Google Scholar) also reported that, during the periovulatory phase, T2 relaxation times were longer than in the other phases. They also observed that the variation in uterine tissue relaxation times between subjects was greater than the intrasubject cycle variation. Because of the large “normal” range, it might be very difficult to compare subjects or determine pathologic changes in the tissues from just a single measurement. However, because individuals exhibited similar increases and decreases over the menstrual cycle, the changes in T2 relaxation times within the same subject can be evaluated (17Hoad C.L. Fulford J. Raine-Fenning N.J. Campbell B.K. Johnson I.R. Gowland P.A. In vivo perfusion, T1, and T2 measurements in the female pelvis during the normal menstrual cycle: a feasibility study.J Magn Reson Imaging. 2006; 24: 1350-1356Crossref PubMed Scopus (15) Google Scholar). Therefore, by comparing T2 relaxation times at the same menstrual phase obtained before and after myomectomy, the effect of surgery could be estimated. In our experiment, T2 relaxation times were measured during the “implantation window,” the luteal phase day 5 to 9. We observed that there is no significant difference in T2 relaxation times between patients with fibroma and healthy volunteers (data not shown). Thus, measurement of T2 relaxation times would not be an effective way to detect uterine abnormalities, but it can be used to assess the success of myomectomy and is valuable in increasing our understanding of the pathophysiology of uterine fibroids in infertility. Other than inflammation (12Maillard S.M. Jones R. Owens C. Pilkington C. Woo P. Wedderburn L.R. et al.Quantitative assessment of MRI T2 relaxation time of thigh muscles in juvenile dermatomyositis.Rheumatology (Oxford). 2004; 43: 603-608Crossref Scopus (174) Google Scholar, 14Hosten N. Sander B. Cordes M. Schubert C.J. Schorner W. Felix R. Graves ophthalmopathy: MR imaging of the orbits.Radiology. 1989; 172: 759-762PubMed Google Scholar), iron content (18Argyropoulou M.I. Metafratzi Z. Kiortsis D.N. Bitsis S. Tsatsoulis A. Efremidis S. T2 relaxation rate as an index of pituitary iron overload in patients with beta-thalassemia major.AJR Am J Roentgenol. 2000; 175: 1567-1569Crossref Scopus (48) Google Scholar) is also known to increase T2 relaxation times. Therefore, further study is needed to confirm that T2 changes after myomectomy actually represent the change of inflammatory status in endometrium. This work represents a first step toward better understanding the relationship between T2 relaxation times and uterine fibroids in patients with infertility. The authors thank Heather M. Martinez, Ph.D., for her helpful discussion and critical reading of the manuscript. They thank Yasufumi Shimizu, Ph.D., M.D., Kouji Motoyama, Ph.D., M.D., and Yasuhiro Kawamura, Ph.D., M.D. (Denentoshi Ladies’ Clinic); Kenichi Tatsumi, Ph.D., M.D. (Umegaoka Women’s Clinic); Susumu Tokuoka, Ph.D., M.D. (Tokuoka Women’s Clinic); Ryo Matsuoka, Ph.D., M.D. (Tokyo Hitachi Hospital); and Takayoshi Ogawa, Ogawa, Ph.D., M.D. (Ogawa Clinic) for their supporting this study. They also thank Mr. Ryuji Nojiri and Mr. Yoshitsugu Funatsu (Takinogawa Clinic) for their technical assistance." @default.
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• W2052820121 title "Myomectomy reduces endometrial T2 relaxation times" @default.
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