Exploring the Impact of Endometrioma Aspiration and Dienogest Combination Therapy on Cyst Size, Inflammatory Cytokines in Follicular Fluid and Fertility Outcomes.

Endometriomas (chocolate cysts) are cystic lesions that can develop on ovaries, and are characterized by the presence of ectopic endometrial tissue or similar tissue. Such lesions can cause a decline in the number and quality of oocytes, and lead to implantation failure. In this study, we retrospectively assessed the efficacy of repeated endometrioma aspiration and dienogest combination therapy in patients suffering endometriosis-associated infertility with endometriomas. A comparison was made between a treated group that underwent combination therapy followed by controlled ovarian hyperstimulation (COH) (n = 30) and a control group that did not undergo treatment (n = 40), at the IVF Osaka Clinic from September 2019 to September 2021. There were no differences in patient background between the two groups. A reduction in endometrioma size continued for 12 months after treatment. The numbers of follicles that developed to 15 mm or greater in size following COH and mature oocytes were significantly lower in the treated group compared to those in the control group. The levels of inflammatory cytokines in the follicular fluid significantly decreased in the treated group (p < 0.05). In patients in the treated group who underwent a second ova retrieval, the results were compared between those in the first ova retrieval (immediately after the end of treatment) and those in the second ova retrieval (four months after the first retrieval). The numbers of follicles following COH, retrieved, mature and fertilized ova were significantly increased in the second ova retrieval.

Effectiveness of laparoscopic ultrasonography in laparoscopic myomectomy.

INTRODUCTION: Laparoscopic myomectomy (LM) has become increasingly common in recent years because it minimizes invasiveness. However, myoma can recur after myomectomy. Therefore, we began using laparoscopic ultrasonography, which involves inserting a probe into the peritoneal cavity via a trocar and placing it in direct contact with the uterus. During surgery, this enables the detection of myomas as a small as 1 mm in diameter, which are often undetectable on MRI. Here, we report the effectiveness of laparoscopic ultrasonography. METHODS: The subjects were 26 women who underwent LM at our institution from February 2015 to December 2016. Preoperative MRI was performed, and all myomas detected on MRI were removed during LM. Laparoscopic ultrasonography was then performed to assess for residual myomas, which were removed. RESULTS: In six patients (23%), residual myomas were identified on laparoscopic ultrasonography after the first enucleation of the myomas detected on preoperative MRI. All detected residual myomas, the largest of which was less than 10 mm in diameter, were removed. CONCLUSION: Small myomas undetectable on preoperative MRI were detected on laparoscopic ultrasonography and removed.

Association between preterm delivery and bacterial vaginosis with or without treatment.

The relationship between bacterial vaginosis (BV) and preterm delivery has become well known in recent years, although there are few studies on: (i) the differences in test results during the early gestational (EGP) and middle gestational (MGP) periods; (ii) the significance of the intermediate (I) group that does not develop overt BV; or (iii) the therapeutic effects of metronidazole. We performed a retrospective study to analyze the relationship between the vaginal bacterial status and the preterm delivery rate. Without treatment, the preterm delivery rate was higher in the BV subgroup than in the I and normal (N) subgroups (p = 0.021) in the EGP, whereas the rates in the BV and I subgroups were higher than in the N subgroup in the MGP (p = 0.0003). Although treatment of BV by metronidazole vaginal tablets significantly increased the N subgroup in the MGP (p = 0.020), there was no significant improvement in the preterm delivery rate. Decreasing the rate of preterm delivery requires development of treatment methods that will further increase the percentage of patients who test N during the MGP after BV during the EGP.

Recurrence of uterine myoma after myomectomy: Open myomectomy versus laparoscopic myomectomy.

AIM: Open myomectomy (OM) was previously frequently performed; however, laparoscopic myomectomy (LM) has recently become more common. Nevertheless, myoma can recur after both LM and OM. In this study, we report our retrospective investigation of myoma recurrence by comparing LM and OM. METHODS: A total of 474 patients underwent LM and 279 patients underwent OM. The patients were followed-up postoperatively from six months to eight years. Recurrence was confirmed when a myoma with a diameter of ≥ 1 cm was detected. Post-LM, post-OM and cumulative recurrence rates were investigated, and a Cox hazard test was performed. RESULTS: The cumulative recurrence rates between the two groups were 76.2% (LM) vs. 63.4% (OM) at eight years postoperatively. A log-rank test revealed a significant difference between the two groups. Cox hazard testing revealed that LM, a larger number of enucleated myoma masses and the absence of postoperative gestation significantly contributed to the postoperative recurrence rate. CONCLUSIONS: LM yielded a higher recurrence rate than OM, likely a result of manual myoma removal in OM, which is a more exhaustive extraction of smaller myoma masses than performed in LM. In other words, fewer residual myoma masses after OM contribute to a lower postoperative recurrence rate.

Reproductive Outcome of Infertile Patients with Fibroids Based on the Patient and Fibroid Characteristics; Optimal and Personalized Management.

AIMS: To analyze the detailed clinical course of infertile patients with uterine fibroids and to identify optimal and personalized treatment based on the patient or fibroid characteristics. METHODS: Retrospective analysis of a case series was performed on 176 infertile patients with fibroids. The patients were classified into different groups according to different treatments (conservative infertility treatment, myomectomy and non-myomectomy surgery). Patient or fibroid characteristics for different groups were analyzed for a possible correlation with the reproductive outcome. RESULTS: The cumulative pregnancy rates by conservative treatment plateaued in 1 year. Myomectomy improved the reproductive outcome in patients who did not conceive with conservative infertility treatments. The most important determinant of the reproductive outcome in patients by conservative treatment prior to surgery was a past patient history of pregnancy. The most important determinant of the reproductive outcome after myomectomy was patient age. CONCLUSION: Myomectomy should be considered when infertile patients with fibroids do not conceive within 1 year of conservative infertility treatments. The most important determinant of reproductive outcome after myomectomy is patient age. Therefore, for patients younger than 40, the treatment schedule should be carefully considered so that the patients can sufficiently benefit from myomectomy and assisted reproductive technology.

Nontuberculous Mycobacterial Infection in the Uterine Cervix Mimics Invasive Cervical Cancer in Immunocompetent Woman.

Nontuberculous mycobacterial (NTM) infection is increasing across the world. Although the most common clinical manifestation of NTM disease is lung disease, a rare form of disseminated NTM disease has also been documented. Disseminated NTM usually develops in severely immunocompromised individuals, especially those with advanced AIDS. This manifestation is rare in non-HIV-infected hosts and is associated with immunosuppressed conditions. However, recent reports have suggested that disseminated NTM disease in immunocompetent patients without HIV infection has been increasing. Dissemination may involve any organ system, but a case in the female genital tract has never been reported. We report a case in a 67-yr-old previously healthy woman who presented with a disseminated NTM infection in the uterine cervix. The primary presentation was general fatigue and body weight loss. The patient also presented with a mass formation that mimicked cervical cancer on magnetic resonance imaging. In addition to the cervical mass, the patient presented with a mass formation in the omentum; wall thickening of the vagina, bladder, and ureter; and retention of pleural/peritoneal fluid. Vaginal cytology was negative. A diagnosis was made only after detecting acid-fast bacilli in a biopsy specimen of cervical mass, which was conducted under suspicion of cervical malignancy. Then, Mycobacterium avium was confirmed in a polymerase chain reaction test of cervical tissue. After administration of antimycobacterial therapy, the mass and other findings on magnetic resonance imaging disappeared. Infection in multiple organs leads to the diagnosis of disseminated NTM. This case indicates that, for prompt and accurate diagnosis, efforts to detect specific lesions by an imaging study and to confirm diagnosis pathologically are equally important, especially when local cytology is not convincing. The clinical course of this case may serve as a useful reference in the diagnosis and treatment of NTM.

Long-term survival in metastatic malignant struma ovarii treated with oral chemotherapy: A case report.

Malignant struma ovarii is a rare type of ovarian tumor. Metastasis from malignant struma ovarii is rare and has only been documented in 5-6% of cases. The natural history and optimal treatment strategy for malignant struma ovarii remains controversial due to its rarity. The current report presents the case of a 45-year-old female who presented with a tumor of the rib bone. Following resection, the postoperative diagnosis was a metastasizing thyroid carcinoma. No abnormality was detected in the thyroid gland, however, computed tomography revealed a tumor in the left ovary. The patient underwent a left salpingo-oophorectomy and a wedge resection of the right ovary. The postoperative diagnosis was determined as a mature cystic teratoma with malignant struma ovarii (thyroid type, follicular carcinoma) of the left ovary and mature cystic teratoma of the right ovary. Four years subsequent to the initial diagnosis, multiple lung metastases were detected. The following chemotherapies were administered sequentially and intermittently: Tegafur-uracil, paclitaxel/carboplatin and oral etoposide. During this period, the metastatic lesions extended into the bone and progressed slowly. The patient continues to survive with the disease and 24 years have passed since the initial diagnosis, 20 years following the diagnosis of multiple lung metastates. The present report describes a rare case of malignant struma ovarii in which surgical resection and pathological examination of a metastatic rib tumor resulted in the identification of the primary ovarian lesion. The clinical behavior of malignant struma ovarii does not necessarily indicate a histological malignancy, therefore, prediction of future metastasis is difficult and the optimal treatment strategy for malignant struma ovarii is controversial. The present case indicates that the long-term use of oral anticancer agents may facilitate the maintenance of tumor dormancy.

Pregnancy following ovarian induction in a patient with premature ovarian failure and undetectable serum anti-Müllerian hormone.

We report the first case, to the best of our knowledge, of successful conception following ovarian induction in a patient with premature ovarian failure and undetectable serum anti-Müllerian hormone. A 34-year-old woman was referred because of ovarian amenorrhea. After endogenous gonadotrophins were normalized by hormone-replacement therapy and gonadotrophin-releasing hormone agonist, ovarian induction was performed using exogenous gonadotrophins. On ovarian induction day 8, one follicle had reached a mean diameter of 19.6 mm, the serum estradiol level had increased to 516 pg/mL, and human chorionic gonadotrophin (HCG) was injected. On HCG injection day 7, ultrasonography was unable to detect the follicle, and serum progesterone levels had increased to 6.1 ng/mL. One month after HCG injection, ultrasonography detected an intrauterine fetus with beating heart. Even with serum anti-Müllerian hormone levels below the threshold of detection, there is a chance for patients with premature ovarian failure.

The significance of laparoscopy in determining the optimal management plan for infertile patients with suspected tubal pathology revealed by hysterosalpingography.

The fallopian tube has numerous functions, including ovum pick-up, the place of fertilization of the ovum and cleavage of the embryo, and transfer of the embryo to the uterus. Tubal pathology impairs functions of the fallopian tube and reduces fertility. The degree of tubal pathology determines the possibility for fertility. The evaluation of the fallopian tube is necessary to determine the management plan of infertility. Hysterosalpingography (HSG) is often performed as a first line approach to assess tubal patency and the presence of adhesions; however, HSG has limitations in detecting tubal pathology. In the current study, we evaluated the significance of laparoscopy in determining the optimal management plan for infertile patients with suspected tubal pathology revealed by HSG. Between 1997 and 2009, 127 patients with suspected tubal pathology as demonstrated by HSG underwent laparoscopy at Kinki University Hospital, and a retrospective analysis was performed. Of 87 patients with unilateral tubal pathology revealed by HSG, 20 patients (23.0%) were given an indication for assisted reproductive technology (ART), based on the laparoscopic findings. Of 40 patients with bilateral tubal pathology revealed by HSG, 33 patients (82.5%) with bilateral tubal pathology detected by laparoscopy were given a high indication for ART. Laparoscopy enables exact evaluation of the fallopian tube and selection of the optimal management plan in infertile patients with suspected tubal pathology revealed by HSG. Therefore, laparoscopy should be performed in infertile patients with suspected tubal pathology revealed by HSG, as it is of diagnostic importance.

Benefit of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography findings.

Patients with unexplained infertility following standard infertility screening tests usually undergo timing therapy that coordinates the time of ovulation and coitus, controlled ovarian hyperstimulation, or intrauterine insemination. If the treatment is unsuccessful, diagnostic laparoscopy is performed. However, with recent improvements in the assisted reproductive technology (ART), there has been a growing tendency that bypasses diagnostic laparoscopy and proceeds directly to ART. Therefore, the value of diagnostic laparoscopy in current fertility practice is under debate. In the present study, we evaluated the usefulness of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography (HSG) findings. Between January 1997 and December 2006, 57 infertile patients with normal HSG findings underwent diagnostic laparoscopy at Kinki University Hospital. In 46 (80.7%) of these patients, diagnostic laparoscopy revealed pathologic abnormalities. Specifically, endometriosis and peritubal and/or perifimbrial adhesions were found in 36 (63.2%) and 5 (8.8%) of the patients, respectively. In 8 patients (14.0%), the management plan was switched to ART because of severe tubal diseases. Among the 57 patients, 29 pregnancies (50.9%) were achieved, including 6 ART-mediated pregnancies. We conclude that diagnostic laparoscopy is beneficial for patients with unexplained infertility and normal HSG findings. Indeed, by diagnostic laparoscopy, we are able to detect the cause(s) of infertility in the pelvic cavity and to design a suitable management plan, which could lead to postoperative pregnancy. Therefore, because of the potential diagnostic and therapeutic benefits, patients with unexplained infertility and normal HSG findings should undergo diagnostic laparoscopy prior to ART.

Feasibility study of docetaxel and nedaplatin for recurrent squamous cell carcinoma of the uterine cervix.

BACKGROUND: To determine a new taxane plus platinum treatment regimen for squamous cell carcinoma of the uterine cervix (CSCC), a phase I feasibility study of docetaxel (DTX) plus nedaplatin (CDGP) combination therapy was conducted. PATIENTS AND METHODS: Twenty consecutive patients were enrolled into the study. The starting dose of DTX/CDGP was 60 mg/m2 / 80 mg/m2, every 4 weeks for at least three courses and the dose was escalated to 70 mg/m2 / 100 mg/m2. DTX 60 mg/m2 / CDGP 100 mg/m2 was also evaluated as an extra dose level. RESULTS: Dose-limiting toxicity was granulocytopenia and the maximum tolerated dose was determined as 70 mg/m2 / 100 mg/m2. All 20 patients had measurable disease and a partial response was achieved in 8 (40.0%) patients. CONCLUSION: DTX/CDGP therapy appears to be a tolerable regimen for cervical squamous cell carcinoma, even in patients previously treated by cisplatin concurrent chemoradiotherapy. The recommended doses of DTX and CDGP were determined to be 60 mg/m2 and 100 mg/m2, respectively.

Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix.

BACKGROUND: Although the prognostic advantages of concurrent cisplatin (CDDP) chemoradiation therapy (CCRT), for uterine cervical cancer (UCC) has been demonstrated, the feasibility of concurrent CDDP administration has not yet been evaluated. We determined the optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC. METHODS: The study was conducted as a phase I, dose-escalation trial. Concurrent CDDP was started at the dose of 30 mg/m(2) for the weekly schedule and at 50 mg/m(2) for the monthly schedule, and the doses were steadily escalated to the maximum tolerated dose (MTD). RESULTS: A total of 45 patients with UCC (25 receiving primary CCRT and 20 receiving adjuvant CCRT) were entered in the study. In both the primary and adjuvant CCRT patients, the MTD was observed to be 40 mg/m(2) for the weekly schedule and 80 mg/m(2) for the monthly schedule. Dose-limiting toxicity was observed in 10 patients (granulocytopenia in 9 patients and diarrhea in 1 patient). Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of 22.4 +/- 13.2 months, and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 +/- 6.8 months. CONCLUSION: For Japanese patients with UCC receiving primary or adjuvant CCRT therapy, the recommended CDDP dose was determined to be 30 mg/m(2) for the weekly schedule and 75 mg/m(2) for the monthly schedule.

Inhibition of Oct4 expression in mouse preimplantation embryos using morpholino antisense oligonucleotides.

Morpholino oligonucleotides (MO) can induce gene silencing by binding to a target mRNA and inhibiting its translation, and this technique has been especially successful in studies of embryonic development in various vertebrates. But in mice MO-induced downregulation of target genes has not been widely reported. In this study, we examined whether MO delivery using ethoxylated polyethylenimine (EPEI) delivery reagent is useful for silencing gene expression in the mouse preimplantation embryo, by targeting endogenous gene Oct4. To optimize the conditions for MO delivery, we examined the MO concentration, the EPEI concentration, the treatment time, and the number of MO treatments. The MO treatment was performed at the 2-cell, the morula, the blastocyst, and the hatched blastocyst stage. We first determined the optimal conditions for MO delivery into the nucleus using fluorescein isothiocyanate (FITC)-labeled MO, and demonstrated that treatment with a combination of 20 microM MO and 0.56 microM EPEI for 3 hrs produced effective MO delivery. MO-induced downregulation of Oct4 was then examined. Two-step MO treatment at the 2-cell and blastocyst stages successfully suppressed Oct4 expression. This MO treatment resulted in marked reduction of Oct4 protein at the blastocyst stage. After cultivation of blastocysts for further 4 days, derivatives of embryos either differentiated to trophoblastic cells or showed developmental arrest at the blastocyst. This phenocopy is similar to Oct4-deficient embryos. Overall, our results indicate that MO delivery with EPEI is an effective tool for analyzing gene function in mouse preimplantation embryos.