Insertion of the Mirena Intrauterine System for Treatment of Adenomyosis-Associated Menorrhagia: A Novel Method

SummaryObjectiveInsertion of the levonorgestrel-releasing intrauterine system Mirena is difficult in women with adenomyosis, and the device is often subsequently expelled. We used a novel insertion technique (Yang's method) to overcome this problem.Materials and MethodsThis retrospective study enrolled 273 patients with adenomyosis who were receiving Mirena for treatment of menorrhagia and/or dysmenorrhea between 2001 and 2008. Clinical outcomes and expulsion rates were compared between patients treated using conventional insertion and those treated using Yang's insertion methods.ResultsExpulsion occurred in 25.3% of patients with the conventional method, compared with 10.2% of patients with Yang's method. Hemoglobin levels and dysmenorrhea improved greatly in both groups after Mirena insertion.ConclusionYang's insertion method for levonorgestrel-releasing intrauterine system is more reliable in some difficult cases, such as patients with severe adenomyosis. This method ensures correct positioning, thus reducing the risks of uterine perforation and/or expulsion

Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer

IntroductionThe failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.MethodsWe conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.ResultsSerum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 > 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.ConclusionWe found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation

Elevated E-2: Oocyte Ratio in Women Undergoing Ivf and Tubal Et - Correlation with a Decrease in the Implantation Rate

OBJECTIVE: To investigate the influence of various estradiol (E-2):oocyte ratios on reproductive outcome in women undergoing in vitro fertilization and tubal embryo transfer (IVF-TET).STUDY DESIGN: Two hundred seven women undergoing 251 IVF-TET cycles were recruited in this retrospective study. All the women received a flare-up gonadotropin releasing hormone agonist (GnRHa) protocol to achieve ovarian hyperstimulation. Oocyte retrieval was performed 34- 36 hours after human chorionic gonadotropin (hCG) injection , followed by TET two days later.RESULTS: An E-2:oocyte ratio greater than or equal to 350 pg/mL had a higher E-2 level ( 2,213 +/- 2,258 vs. 1,553 +/- 972 pg/mL, P < .05) and fertilization rate (77 +/- 23 vs. 64 +/- 23%, P < .001) but a lower oocyte number (4.8 +/- 4.7 vs. 7.6 +/- 4.8, P < .001 ) than in those with a ratio < 350 pg/mL, The pregnancy (17. 9% vs. 32.8% , P = .03) and implantation (5.3% vs. 12.9%, P = .008) rates were significantly decreased in cycles with an E-2:oocyte ratio greater than or equal to 350 pg/mL ns compared to those with a untie < 350 pg/mL. CONCLUSION: IVF- TET cycles with nn elevated E-2: oocyte ratio correlated with lower pregnancy and implantation rates. The poor reproductive outcome possibly was due to the relatively high E-2 concentration, which might have a detrimental effect on endometrial receptivity

Altered Apoptosis and Proliferation in Endometrial Stromal Cells of Women with Adenomyosis

The eutopic endometrium in a woman suffering from adenomyosis is known to be biologically different from that of healthy women. The aim of this study was to examine the apoptosis and proliferation of eutopic endometrium from women with adenomyosis. METHODS: We enrolled 23 women with adenomyosis (study group) and 21 without (control group). Eutopic endometrium was obtained and separated into single endometrial stromal cells (ESCs). ESCs were treated in vitro with hydrogen peroxide (H2O2) to examine their apoptosis using a fluorescence-activated cell sorter. Cells were also treated with estradiol (E-2), medroxyprogesterone acetate, interleukin (IL)-6, lipopolysaccharide and interferon-gamma( IFN-gamma) to test their proliferation using a non- radioactive cell proliferation assay. RESULTS: The percentage of annexin V (+)/7-amino-actinomycin D (+) ESCs was much lower in women with adenomyosis after 24 h culture with and without H2O2 treatment when compared with the control group. ESCs of adenomyosis proliferated more rapidly than those of the control group, whether they were cultured alone or were treated with E-2, MPA, IL-6 or IFN-gamma. The immunocytochemical Ki-67 labelling index was much more prominent in adenomyotic ESCs than that of the control group (7.7 % versus 1.1 %, P < 0.001). CONCLUSIONS: Altered apoptosis and proliferation of eutopic endometrium possibly elucidate some aspects of the pathophysiology of adenomyosis . A high Ki-67 labelling index in immunocytochemistry might be a potential indicator in predicting the occurrence of adenomyosis

Increased Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 Secretion but Unaffected Invasiveness of Endometrial Stromal Cells in Adenomyosis

Objective: To investigate cell invasiveness and the production of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase- 1 (TIMP-1) and TIMP-2 in endometrial stromal cells (ESCs) of adenomyosis. Design: Prospective study. Setting: Tertiary university hospital. Patient( s): Twenty-one women with adenomyosis (study group) and 25 women without adenomyosis (control group). Intervention(S): Endometrial stromal cells were purified from eutopic endometrium and were cultured in vitro. Main Outcome Measure(s): Matrigel invasion assay and measurement of MMP-2, MMP- 9, TIMP-1, and TIMP-2 concentrations. Result(s ): Endometrial stromal cell invasiveness of adenomyosis was not different from that of the control group (0.95 vs. 1, using the latter as the bench mark) in ESCs cultured alone. After the ESCs were cultured with IL-6, anti-IL-6, or GM6001 for 24 hours, the indices of cell invasion were not different between the two groups. MMP-2 (median 7.3 vs. 3.5 ng/mL) and TIMP-1 (median 12.1 vs. 3.9 ng/mL), but not MMP-9 and TIMP-2, secreted by ESCs in women with adenomyosis were much higher than those in women without adenomyosis. Conclusion(S): The formation of adenomyosis does not result from altered invasiveness of ESCs. The concomitant elevation of MMP-2 and TIMP-1 may partially justify why invasiveness was not increased, but other enzymes should also be considered

Decreased Suppression of Interleukin-6 after Treatment with Medroxyprogesterone Acetate and Danazol in Endometrial Stromal Cells of Women with Adenomyosis

Objective: To examine changes in local cytokine production in the eutopic endometrium of adenomyosis after treatment with medroxyprogesterone acetate (MPA) and danazol. Design: Prospective cohort study. Setting: Tertiary university hospital. Patient(s): Twenty-four women with adenomyosis ( study group) and 22 women without adenomyosis (control group ). Intervention(s): Eutopic endometrium was seperated into single endometrial stromal cells (ESCs), and was cultured in vitro alone, with MPA (10(-7) M), or with danazol (10(-7) M ) for 8 days. Main Outcome Measure(s): Messanger RNA expression of interleukin (IL)-6, IL-8. and tumor necrosis factor-alpha in ESCs, and their concentrations in the supernatants of ESCs. Result(s): A significant decrease of IL-6 concentration in the supernatant, measured by ELISA, was found with time of ESCs cultured with MPA and danazol in the control group, but not in adenomyosis . The IL-6 mRNA in ESCs determined by real-time quantitive polymerase chain, as well as its concentration in the supernatant, was much higher in adenomyosis than that in the control group after treatment with MPA and danazol for 8 days. Conclusion(s): Medroxyprogesterone acetate and danazol appeared to have a decreased effect on the suppression if IL-6 liberated by ESCs in adenomyosis. This aberrant secretion of IL-6 might play a role in the formation of ectopicendometrial implants in adenomyosis

Changes in Myometrial Thickness during Hysteroscopic Resection of Deeply Invasive Submucous Myomas

STUDY OBJECTIVE: To evaluate the efficacy of hysteroscopy in resecting submucous myomas with deep intramural invasion. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: Department of gynecology at a general hospital. PATIENTS: Sixteen women with a solitary submucous myoma, in which myometrial thickness between the outer edge of the myoma and inner edge of the serosa was between 5 and 10 mm. INTERVENTION: One- step hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS : Median myoma diameter and weight were 3.3 cm and 30 g, respectively. Myometrial thickness between the myoma and serosa increased gradually and significantly from 6.7 mm before, to 8.9 mm during, to 16.1 mm immediately after hysteroscopic myomectomy (p <0.001). The thickness of the opposite uterine wall increased from 10.1 mm before, to 11.4 mm during, to 18.8 mm after operation (p <0.001). CONCLUSION: One-step hysteroscopic myomectomy may be performed to remove deeply infiltrating submucous myomas when myometrial thickness at the implantation site is as thin as 5 mm

Association of Endometrial Blood Flow as Determined by a Modified Colour Doppler Technique with Subsequent Outcome of in-Vitro Fertilization

An endometrial thickness of 10 mm or more has been reported to be favorable for embryo implantation in in-vitro fertilization (IVF) programs . Nevertheless, many women, although having adequate endometrial thickness , have been unable to achieve satisfactory implantation. With the aid of power Doppler sonography, we attempt to test the association of intra- endometrial vascularity and reproductive outcome. In this study, we only enrolled women who had an endometrial thickness &sup3; 10 mm. This group was made up of 95 women undergoing IVF cycles, which resulted in 37 intrauterine pregnancies. Those who had apparent endometrial pathologies were excluded from the study. Among women with similar ages, body mass indices, peak estradiol levels, endometrial thickness, and after transferring a similar number of embryos, those women having cycles with an intra-endometrial power Doppler area (EPDA)< 5 mm2 achieved a significantly lower pregnancy rate (23.5% vs. 47.5%, p = 0.021) and implantation rate (8.1% vs. 20.2%, p = 0.003) than those with an EPDA &sup 3; 5 mm2. We conclude that, in addition to endometrial thickness, EPDA may serve as a valuable factor that was closely associated with endometrial receptivity. Women having adequate endometrial thickness but a small EPDA were correlated with an unfavorable reproductive outcome

Office Hysteroscopic Early Lysis of Intrauterine Adhesion after Transcervical Resection of Multiple Apposing Submucous Myomas

Objective: To analyze the prevalence of intrauterine adhesion (IUA) formation in women undergoing transcervical resection (TCR) for submucous myomas. Design: Retrospective cohort study. Setting: Tertiary university hospital. Patient (s): One hundred fifty-three women undergoing TCR for submucous myomas were retrospectively analyzed. Among them, 132 women had a solitary myoma (group 1), 5 had two submucous myomas not in apposition to each other and who received postoperative intrauterine device (IUD) placement ( group 2), 9 had two or more apposing submucous myomas and received IUD placement (group 3), and 7 had two or more apposing submucous myomas and who underwent subsequent office hysteroscopic early lysis of IUA (group 4). Intervention(s): Placement of an IUD for 1 month (groups 2 and 3) or office hysteroscopy for early lysis of IUA within 2 weeks after hysteroscopic myomectomy (group 4). Main Outcome Measure(s): Diagnostic office hysteroscopy was done 1-3 months after hysteroscopic myomectomy to evaluate whether there was permanent formation of IUA. Result(s): Two (1.5 %) of 132 women in group 1 had IUA. For women receiving IUD placement; none of the 5 women in group 2 and 7 (78%) of 9 women in group 3 had IUA. For women undergoing office hysteroscopic early lysis of adhesion bands ( group 4), none of 7 women had IUA. Conclusion(s): Intrauterine adhesion is a common complication after TCR for apposing submucous myomas, but not for a solitary myoma. Office hysteroscopy within 2 weeks after TCR is an easy and effective procedure in separating the newly formed IUA