Successful pregnancy following extensive myomectomy for diffuse uterine leiomyomatosis

A 29-year-old nulligravid patient with DUL who had a desire for pregnancy was referred to our institution for further infertility treatment. Figure  1 summarizes the patient’s clinical course. At 27 years of age, she visited a prior institution with heavy menstrual bleeding and was diagnosed with multiple uterine fibroids (Fig.  2 A, B). Given the large number of fibroids, myomectomy was deemed difficult, and she attempted natural conception. However, she failed to conceive, and the fibroids increased in size and number. Magnetic resonance imaging (MRI) revealed numerous small fibroids replacing the myometrium, consistent with DUL (Fig.  2 C, D). Hysteroscopy revealed multiple submucosal fibroids protruding into the uterine cavity (Fig.  3 A). Because extensive myomectomy was considered highly invasive and technically challenging, ART was initially prioritized. Assessment of ovarian reserve via ultrasonography was limited because severe uterine enlargement and acoustic shadowing associated with DUL obscured visualization of the ovaries. At the first ovarian stimulation cycle, the antral follicle count was four (right ovary, three; left ovary, one) and serum follicle-stimulating hormone level was 3.06 mIU/ml. Semen analysis demonstrated normal sperm concentration (158 × 10⁶ /mL) and motility (65%), and no clinically significant male factor infertility was identified. No congenital uterine anomaly, thyroid dysfunction, diabetes mellitus, polycystic ovary syndrome, or vitamin D deficiency was detected. Between 29 and 31 years of age, the patient underwent three oocyte retrieval cycles and four single-blastocyst transfers. All transferred embryos were Day 5 expanded blastocysts of good morphological quality (Gardner grades 4AA, 4BA, 4BA, and 4BB), but implantation was not achieved in any cycle. Multiple submucosal fibroids may have caused significant distortion of the uterine cavity, contributing to implantation failure. Repeated implantation failure despite multiple embryo transfers and progression of DUL ultimately led to the decision to perform myomectomy. Fig. 1 Clinical timeline of the patient. A 29-year-old woman with diffuse uterine leiomyomatosis (DUL) underwent extensive myomectomy after repeated implantation failure. Following surgery, pregnancy was achieved through assisted reproductive technology. Serial ultrasonography and magnetic resonance imaging revealed progressive myometrial thinning during pregnancy. Elective cesarean delivery was performed at 36 weeks of gestation, resulting in the birth of a healthy infant. Postpartum imaging confirmed preservation of the uterine cavity and junctional zone Clinical timeline of the patient. A 29-year-old woman with diffuse uterine leiomyomatosis (DUL) underwent extensive myomectomy after repeated implantation failure. Following surgery, pregnancy was achieved through assisted reproductive technology. Serial ultrasonography and magnetic resonance imaging revealed progressive myometrial thinning during pregnancy. Elective cesarean delivery was performed at 36 weeks of gestation, resulting in the birth of a healthy infant. Postpartum imaging confirmed preservation of the uterine cavity and junctional zone Fig. 2 Serial T2-weighted MRI in a patient with DUL before extensive myomectomy. A , B MRI findings at the age 27 years, obtained when the patient presented with heavy menstrual bleeding before marriage. Multiple intramural fibroids are seen to obscure the junctional zone while preserving the serosal-side myometrium. A sagittal image, B axial image. C , D MRI findings at the age 29 years, obtained at referral to our department for fertility desire after marriage. The junctional zone is seen to be completely obliterated, and the uterine cavity is distorted by multiple submucosal fibroids. Multiple fibroids are also seen to be present in the serosal-side myometrium, leading to the diagnosis of DUL. C sagittal image, D axial image. E , F MRI findings at the age 32 years, obtained following the first myomectomy. Despite a slight reduction in the overall uterine volume, multiple fibroids persisted. E sagittal image, F axial image. MRI, magnetic resonance imaging; DUL, diffuse uterine leiomyomatosis Serial T2-weighted MRI in a patient with DUL before extensive myomectomy. A , B MRI findings at the age 27 years, obtained when the patient presented with heavy menstrual bleeding before marriage. Multiple intramural fibroids are seen to obscure the junctional zone while preserving the serosal-side myometrium. A sagittal image, B axial image. C , D MRI findings at the age 29 years, obtained at referral to our department for fertility desire after marriage. The junctional zone is seen to be completely obliterated, and the uterine cavity is distorted by multiple submucosal fibroids. Multiple fibroids are also seen to be present in the serosal-side myometrium, leading to the diagnosis of DUL. C sagittal image, D axial image. E , F MRI findings at the age 32 years, obtained following the first myomectomy. Despite a slight reduction in the overall uterine volume, multiple fibroids persisted. E sagittal image, F axial image. MRI, magnetic resonance imaging; DUL, diffuse uterine leiomyomatosis Fig. 3 Hysteroscopic findings before and after extensive myomectomy. A Initial visit to our department at the age of 29 years. Multiple FIGO type 1 and 2 submucosal fibroids are observed. B After the initial myomectomy at the age 32 years. Although the large submucosal fibroid was removed, multiple FIGO type 2 submucosal fibroids persisted. C Immediately after extensive myomectomy. The uterine cavity is seen to be filled with whitish fibrous tissue with insufficient endometrial regeneration. D Three months after extensive myomectomy. No submucosal fibroids protruding into the uterine cavity are observed, and the endometrium has regenerated. FIGO, International Federation of Obstetrics and Gynecology Hysteroscopic findings before and after extensive myomectomy. A Initial visit to our department at the age of 29 years. Multiple FIGO type 1 and 2 submucosal fibroids are observed. B After the initial myomectomy at the age 32 years. Although the large submucosal fibroid was removed, multiple FIGO type 2 submucosal fibroids persisted. C Immediately after extensive myomectomy. The uterine cavity is seen to be filled with whitish fibrous tissue with insufficient endometrial regeneration. D Three months after extensive myomectomy. No submucosal fibroids protruding into the uterine cavity are observed, and the endometrium has regenerated. FIGO, International Federation of Obstetrics and Gynecology The patient underwent an initial myomectomy at the age of 32, in which 25 fibroids were removed. At this time, serum anti-müllerian hormone level was 4.54 ng/ml. Following the initial myomectomy, three additional blastocyst transfer cycles were performed; however, implantation again failed to occur. Endometrial receptivity analysis had also been performed, and embryo transfer timing was adjusted accordingly; however, implantation was still not achieved. Thus, a total of seven blastocyst transfers before extensive myomectomy resulted in repeated implantation failure. Because the patient was relatively young during the treatment course, preimplantation genetic testing for aneuploidy was not performed. Moreover, new fibroids and remaining fibroids subsequently developed, resulting in the progression of DUL (Fig.  2 E, F, and Fig.  3 B). Therefore, we performed extensive myomectomy when she was aged 34 years, wherein 148 fibroids were removed (Fig.  4 a, b, c). The extensive myomectomy was performed using a fertility-preserving surgical technique introduced at our institution. After temporary cervical tourniquet placement using a Nelaton catheter and intramyometrial injection of diluted vasopressin (1:100 dilution), the uterus was opened through a longitudinal midline incision. Additional incisions parallel to the uterine cavity were then made on the exposed myometrial surface, allowing sequential enucleation of diffuse fibroid nodules while preserving the endometrial cavity. Numerous fibroids were removed by dividing larger nodules when necessary to facilitate enucleation. Following complete removal of visible nodules, the endometrial cavity was repaired using interrupted 2 − 0 absorbable sutures, and the myometrium was reconstructed in two layers using the same suture material, resulting in a three-layer uterine closure. No specific anti-adhesion procedure or postoperative hormonal treatment was performed. The operative time was 250 min, and intraoperative blood loss was 1,410 ml. Although 400 ml of autologous blood was reinfused intraoperatively, allogeneic transfusion was not required. Pathology confirmed leiomyomas without cytological or structural atypia. Hysteroscopy performed 3 months after myomectomy revealed no submucosal fibroids protruding into the uterine cavity but showed insufficient endometrial regeneration (Fig.  3 C). MRI demonstrated no clearly identifiable fibroid nodules (Fig.  4 D). Therefore, blastocyst transfer was deferred for 3 months to allow endometrial regeneration (Fig.  3 D). The first pregnancy was achieved after the first blastocyst transfer following extensive myomectomy; however, it resulted in miscarriage. The second pregnancy was achieved after the second blastocyst transfer following extensive myomectomy, corresponding to the ninth blastocyst transfer overall, at which time the patient was 35 years old. Fig. 4 Extensive myomectomy and postoperative MRI. A Longitudinal section of the uterus. Numerous small fibroids diffusely involve the myometrium. B Myometrium after myomectomy. Grossly, all fibroids were removed. The uterine cavity is visible at the center (arrow). C Enucleated fibroids. A total of 148 fibroids were removed, most measuring < 3 cm. D T2-weighted sagittal MRI image obtained 3 months after extensive myomectomy showing a slightly irregular uterine contour with no obvious residual fibroids. MRI, magnetic resonance imaging Extensive myomectomy and postoperative MRI. A Longitudinal section of the uterus. Numerous small fibroids diffusely involve the myometrium. B Myometrium after myomectomy. Grossly, all fibroids were removed. The uterine cavity is visible at the center (arrow). C Enucleated fibroids. A total of 148 fibroids were removed, most measuring < 3 cm. D T2-weighted sagittal MRI image obtained 3 months after extensive myomectomy showing a slightly irregular uterine contour with no obvious residual fibroids. MRI, magnetic resonance imaging Serial ultrasonography and MRI were performed to evaluate myometrial thinning, signs of uterine rupture, and PAS throughout pregnancy. Marked myometrial thinning was identified on ultrasonography at 10 weeks’ gestation, with a minimum thickness of 2.3 mm, and became evident on MRI at 17 weeks’ gestation (Fig.  5 A). Progressive thinning of the reconstructed myometrium was subsequently observed on serial MRI examinations, with the thinnest area measuring approximately 1 mm during pregnancy. Multiple placental lacunae were detected on ultrasonography at 19 weeks’ gestation, and MRI at 26 weeks demonstrated mild myometrial bulging, likely attributable to myometrial thinning (Fig.  5 B). Loss of the clear zone at the placental attachment site was observed on ultrasonography at 27 weeks’ gestation, and cervical shortening was noted at 28 weeks; the patient was subsequently managed with hospitalization. MRI at 30 weeks of gestation revealed a focal low-signal T2-dark sign, so-called T2-dark band, within the placenta, suggestive of PAS (Fig.  5 C). MRI at 34 weeks of gestation revealed placental tissue extending toward an area of severe myometrial thinning (Fig.  5 D). Fetal growth remained appropriate for gestational age throughout pregnancy and was even larger than expected for gestational age; therefore, we performed an elective cesarean section at 36 weeks of gestation after preoperatively storing autologous blood. Fig. 5 Serial MRI findings during pregnancy. A T2-weighted coronal image at 17 weeks of gestation showing thinning of the myometrium (minimum thickness 2.3 mm, arrow). B T2-weighted coronal image at 26 weeks of gestation showing focal bulging of the thinned myometrium (arrowhead). C A T2-weighted sagittal image obtained at 30 weeks of gestation showing a focal area of low signal intensity in the myometrium, the so-called T2-dark sign (arrow). D T2-weighted sagittal image obtained at 34 weeks of gestation showing uterine bulging and disruption of the myometrial–placental interface, suggestive of suspected placenta accreta spectrum (arrowheads). The thinnest area of the reconstructed myometrium measured approximately 1 mm. MRI, magnetic resonance imaging Serial MRI findings during pregnancy. A T2-weighted coronal image at 17 weeks of gestation showing thinning of the myometrium (minimum thickness 2.3 mm, arrow). B T2-weighted coronal image at 26 weeks of gestation showing focal bulging of the thinned myometrium (arrowhead). C A T2-weighted sagittal image obtained at 30 weeks of gestation showing a focal area of low signal intensity in the myometrium, the so-called T2-dark sign (arrow). D T2-weighted sagittal image obtained at 34 weeks of gestation showing uterine bulging and disruption of the myometrial–placental interface, suggestive of suspected placenta accreta spectrum (arrowheads). The thinnest area of the reconstructed myometrium measured approximately 1 mm. MRI, magnetic resonance imaging The patient delivered a healthy male infant weighing 3,261 g. Because prenatal imaging findings raised concern for PAS, intraoperative ultrasonography was performed to identify a placental-free area before uterine incision. A modified J-shaped incision in the lower uterine segment was made to avoid placental transection. No obvious serosal invasion or bladder involvement was observed intraoperatively. Following fetal delivery, the placental tissue attached to the uterine fundal side did not separate spontaneously. Therefore, partial manual placental removal was required, but it was partially retained. Persistent bleeding occurred in the myometrium after placental delivery and uterine hemostasis was achieved by suturing the uterine incision and using intrauterine balloon tamponade. The total blood loss, including amniotic fluid, was 2,068 ml. Although 1,200 mL of autologous blood was reinfused intraoperatively, allogeneic transfusion was not required. The patient’s puerperal course was unremarkable. Menstruation resumed 4 months after cesarean section, and the retained placental tissue became indistinct. The patient remains under follow-up 2 years after delivery. At 1 year postoperatively, MRI showed only a few small intramyometrial fibroids, with no evidence of recurrent DUL (Fig.  6 A–C). Hysteroscopy demonstrated a smooth uterine cavity (Fig.  6 D). She continues to desire a second pregnancy. Fig. 6 MRI and hysteroscopic findings at 1 year after cesarean section. A , B , C Sagittal T2-weighted MRI image showing a preserved junctional zone, with only a small FIGO type 4 fibroid in the posterior myometrium and no evidence of fibroid recurrence. (D) Hysteroscopy image demonstrates a smooth uterine cavity with adequate endometrial regeneration and no evidence of retained placental tissue. MRI, magnetic resonance imaging; FIGO, International Federation of Obstetrics and Gynecology MRI and hysteroscopic findings at 1 year after cesarean section. A , B , C Sagittal T2-weighted MRI image showing a preserved junctional zone, with only a small FIGO type 4 fibroid in the posterior myometrium and no evidence of fibroid recurrence. (D) Hysteroscopy image demonstrates a smooth uterine cavity with adequate endometrial regeneration and no evidence of retained placental tissue. MRI, magnetic resonance imaging; FIGO, International Federation of Obstetrics and Gynecology Patients with DUL may experience refractory infertility despite undergoing ART because distortion of the uterine cavity can impair implantation. Various fertility-preserving treatment options have been reported, including hysteroscopic surgery, medical therapy, high-intensity focused ultrasound, and extensive myomectomy; however, each approach has inherent advantages and limitations [ 6 ]. Hysteroscopic surgery is effective for submucosal lesions but cannot adequately treat diffuse intramural disease, whereas conservative treatments do not directly remove fibroids and may be associated with recurrence after treatment cessation. Extensive myomectomy allows comprehensive removal of fibroids and restoration of the uterine cavity, which may improve reproductive outcomes in selected patients. However, the procedure is technically demanding and carries substantial risks, including massive hemorrhage, difficulty in uterine reconstruction, and potential weakening of uterine integrity, which may increase the risks of uterine rupture and PAS in subsequent pregnancies [ 5 ]. Therefore, no standardized fertility-preserving treatment strategy has been established for DUL, and individualized management is required. Recently, a large-scale observational study suggested that DUL is classified into three subtypes based on the location of fibroid development: total replacement, myometrial replacement, and submucosal-fibroid–dominant types [ 7 ]. Treatment strategies for women who desire pregnancy may vary according to these subtypes. Hysteroscopic surgery for submucosal fibroids may improve the distortion of the uterine cavity; therefore, it may be associated with improved reproductive outcomes in patients with the submucosal myoma–dominant type [ 4 ]. Hysteroscopic surgery for International Federation of Obstetrics and Gynecology type 1–3 submucosal fibroids in patients with DUL improved heavy menstrual bleeding and led to live births following spontaneous conception [ 8 ]. Furthermore, pregnancies following conservative management with GnRH agonists or high-intensity focused ultrasound have been reported in patients with DUL [ 9 , 10 ]. According to our recently proposed classification system, the present case was classified as the total replacement type, in which diffuse leiomyomatous nodules replace nearly the entire myometrium [ 7 ]. Because severe intramural fibroids and marked distortion of the uterine cavity were present, hysteroscopic treatment alone was unlikely to restore fertility. Therefore, extensive myomectomy was ultimately selected after repeated implantation failure and progression of disease despite prior treatment. Although repeated implantation failure is multifactorial, several findings suggested that uterine factors related to DUL played a major role in this patient. Multiple high-quality blastocysts failed to implant despite the absence of significant male factor infertility or other identifiable infertility factors. Furthermore, implantation occurred in two consecutive embryo transfers after extensive myomectomy, supporting the hypothesis that restoration of the uterine cavity and reduction of diffuse leiomyomatous involvement improved endometrial receptivity. Only a limited number of live births following extensive myomectomy for DUL have been reported (Table 1 ) [ 3 , 6 , 11 , 12 ]. The present case involved one of the largest numbers of removed fibroids (148 nodules) and is unique in providing serial MRI assessment throughout pregnancy together with long-term postoperative follow-up. Despite marked myometrial thinning and imaging findings suggestive of PAS during pregnancy, delivery was successfully achieved at 36 weeks of gestation without uterine rupture or hysterectomy. We previously reported a successful pregnancy after extensive myomectomy using a longitudinal uterine incision technique, demonstrating the feasibility of fertility preservation in selected patients [ 3 ]. The surgical technique used in this case was derived from our institution’s experience with fertility-preserving surgery for diffuse adenomyosis and subsequently adapted for DUL [ 5 ]. The procedure combines a longitudinal uterine incision with additional cavity-parallel incisions, enabling extensive enucleation of diffuse nodules while preserving the endometrial cavity and facilitating uterine reconstruction. More recent reviews have summarized the available literature, highlighting the limited number of reported live births after extensive surgery for DUL [ 6 ]. However, detailed information regarding pregnancy surveillance, serial imaging findings, and long-term postoperative outcomes remains scarce. Table 1 Comparison of published live-birth cases following extensive myomectomy for diffuse uterine leiomyomatosis Author Age (years) No. of fibroids removed Blood loss at extensive myomectomy (mL) Conception Delivery PAS Uterine rupture Other complications Otsubo et al. [ 3 ] 33 100 900 Spontaneous CS, 35 weeks No No Preterm labor Yamamoto et al. [ 6 ] 32 79 2270 ART CS, 34 weeks followed by hysterectomy Suspected No None reported Suminaga et al. [ 11 ] 37 49 Not described IUI CS, 32 weeks Suspected No Placenta previa, genital bleeding, ileus Kitaya et al. [ 12 ] 29 ≥ 80 3300 ART CS, 34 weeks No No None reported Present case 35 148 1410 ART CS, 36 weeks Suspected No None PAS Placenta accreta spectrum, ART Assisted reproductive technologies, CS Cesarean section, IUI Intrauterine insemination Comparison of published live-birth cases following extensive myomectomy for diffuse uterine leiomyomatosis PAS Placenta accreta spectrum, ART Assisted reproductive technologies, CS Cesarean section, IUI Intrauterine insemination The present case contributes several important observations to the existing literature. First, successful live birth was achieved despite repeated implantation failure before extensive myomectomy. Second, serial ultrasonography and MRI were performed throughout pregnancy, allowing detailed assessment of progressive myometrial thinning and imaging findings suggestive of PAS. Third, long-term follow-up demonstrated preservation of the uterine cavity and no clinically significant recurrence of DUL. These findings provide clinically relevant information regarding reproductive management and obstetric surveillance after extensive myomectomy for DUL. Pregnancies after extensive myomectomy may carry increased risks of uterine rupture and PAS compared with conventional myomectomy [ 13 ]. Therefore, careful surveillance throughout pregnancy is essential. In the present case, ultrasonography was performed every 2 weeks during outpatient follow-up and weekly after hospitalization, whereas MRI was performed every 4 weeks after admission. Serial imaging was used to assess myometrial integrity, placental morphology, cervical length, and fetal growth. Particular attention was paid to progressive myometrial thinning, uterine bulging, placental lacunae, loss of the retroplacental clear zone, disruption of the myometrial–placental interface, and possible extrauterine placental extension. The reconstructed myometrium was already markedly thinned at 10 weeks of gestation, with a minimum thickness of 2.3 mm, and subsequent MRI demonstrated further thinning to approximately 1 mm. Although no validated threshold for predicting uterine rupture after extensive myomectomy for DUL has been established, serial imaging provided important information for risk assessment and delivery planning. MRI may be particularly useful in patients with extensive uterine reconstruction because evaluation of the reconstructed myometrium can be challenging using ultrasonography alone. Progressive bulging of a markedly thinned uterine wall, worsening placental abnormalities, and clinical symptoms such as abdominal pain or uterine contractions should prompt consideration of hospitalization and early delivery. The diagnosis of PAS requires integration of prenatal imaging findings, intraoperative findings, and, when available, histopathological confirmation [ 14 , 15 ]. In the present case, serial ultrasonography and MRI revealed placental lacunae, loss of the retroplacental clear zone, marked myometrial thinning, uterine bulging, and disruption of the myometrial–placental interface, raising concern for PAS [ 16 , 17 ]. These findings prompted careful preparation for cesarean delivery, including autologous blood storage and intraoperative ultrasonographic localization of a placental-free uterine incision site. A modified J-shaped incision in the lower uterine segment was made to avoid placental transection. Although abnormal placental adherence and substantial hemorrhage from the implantation site were encountered during delivery, hysterectomy was not required, histopathological confirmation was unavailable, and no obvious serosal or bladder invasion was identified intraoperatively. Therefore, this case should be regarded as suspected PAS rather than pathologically confirmed PAS. Nevertheless, the clinical course highlights the importance of meticulous prenatal surveillance and multidisciplinary perinatal planning in patients who conceive after extensive myomectomy for DUL. Although universally accepted diagnostic criteria for DUL have not been established, the diagnosis is generally based on characteristic imaging, surgical, and pathological findings. In the present case, MRI revealed diffuse replacement of the myometrium by innumerable small fibroids, hysteroscopy revealed extensive distortion of the uterine cavity, and surgical pathology confirmed multiple benign fibroid nodules. We also acknowledge that hereditary leiomyomatosis and renal cell cancer syndrome should be considered in patients with DUL; however, genetic testing was not performed in this patient [ 18 , 19 ]. In conclusion, extensive myomectomy may represent a feasible fertility-preserving option in carefully selected DUL patients with severe cavity distortion and repeated implantation failure, although successful pregnancy cannot be guaranteed and careful reproductive and obstetric management remains essential. This case highlights the importance of comprehensive preoperative assessment using MRI and hysteroscopy when selecting fertility-preserving treatment strategies for patients with DUL. Repeated hysteroscopic evaluation is also useful for confirming restoration of the uterine cavity following extensive myomectomy. Restoration of the uterine cavity, rather than simple reduction of uterine volume, may be particularly important for successful implantation in patients with DUL. The patient continues to desire future pregnancy and remains under follow-up 2 years after delivery. Although no clinically significant recurrence has been observed to date, the long-term risk of recurrence after extensive myomectomy for DUL remains uncertain. Future pregnancies should be managed as high-risk pregnancies, with careful surveillance of uterine integrity, placental implantation, and fetal growth, and elective cesarean delivery would likely be recommended.

Diffuse uterine leiomyomatosis (DUL) is a rare condition characterized by numerous leiomyomas (fibroids) distributed throughout the myometrium [ 1 ]. Patients with DUL frequently present with heavy menstrual bleeding and may experience severe anemia, impairing their quality of life [ 2 ]. DUL may cause recurrent implantation failure through the distortion of the uterine cavity and fail to conceive despite undergoing assisted reproductive technologies (ART). Myomectomy is a viable option for infertile patients with DUL, with successful live births documented via open and hysteroscopic myomectomies [ 3 , 4 ]. However, inadequate myomectomy fails to improve reproductive outcomes and results in early recurrence of fibroids. Extensive myomectomy for DUL involves exhaustive fibroid removal and longitudinal uterine bisection, increasing the risks of massive hemorrhage and reconstruction difficulties [ 5 ]. Subsequent pregnancies face higher rates of uterine rupture, placenta accreta spectrum (PAS), and atony-related postpartum hemorrhage [ 6 ]. Herein, we present the case of a patient with DUL who had a history of recurrent implantation failure during ART, in whom a live birth was achieved by a planned cesarean delivery after extensive myomectomy. Imaging findings during pregnancy suggested myometrial thinning, uterine bulging, and PAS.