Fundal Myometrium Research Articles

Intramyometrial Pregnancy

Study Objective Hysteroscopic management of Extra cavitary ectopic pregnancy. Design Case presentation. Setting Operative Hysteroscopy using 1.8 mm 30degree telescope with operative sheath and hand instruments without electrocautery Patients or Participants single case study. Interventions Operative Hysteroscopy at low pressure of 8 mm Hg under trans abdominal ultrasound guidance. Measurements and Main Results A second para patient was referred to our tertiary center with failed attempt to perform dilatation and evacuation for a missed abortion. They did not find and product of conception in curettage specimen. At our center on 3d transvaginal ultrasound we diagnosed it to be an intra myometrial pregnancy. Under trans abdominal ultrasound guidance with full urinary bladder we decided to remove band of fibrotic adhesion near fundus with cold Scissors to release intra myometrial pregnancy in endometrial cavity. It was followed by suction with disposable cannula under trans abdominal ultrasound guidance for ensure complete evacuation. Integrity of fundal myometrium was checked at the end of the procedure. More than 1 cm myometrial thickness was present above ectopic gestation site. Conclusion Hysteroscopy under sonography guidance is safe management option for such complicated intramyometrial ectopic pregnancy. Hysteroscopic management of Extra cavitary ectopic pregnancy. Case presentation. Operative Hysteroscopy using 1.8 mm 30degree telescope with operative sheath and hand instruments without electrocautery single case study. Operative Hysteroscopy at low pressure of 8 mm Hg under trans abdominal ultrasound guidance. A second para patient was referred to our tertiary center with failed attempt to perform dilatation and evacuation for a missed abortion. They did not find and product of conception in curettage specimen. At our center on 3d transvaginal ultrasound we diagnosed it to be an intra myometrial pregnancy. Under trans abdominal ultrasound guidance with full urinary bladder we decided to remove band of fibrotic adhesion near fundus with cold Scissors to release intra myometrial pregnancy in endometrial cavity. It was followed by suction with disposable cannula under trans abdominal ultrasound guidance for ensure complete evacuation. Integrity of fundal myometrium was checked at the end of the procedure. More than 1 cm myometrial thickness was present above ectopic gestation site. Hysteroscopy under sonography guidance is safe management option for such complicated intramyometrial ectopic pregnancy.

Minimally invasive abdominal curettage for an intramural twin pregnancy: a new twist to the traditional D&C

Less than 1% of ectopic pregnancies are intramural and are located within the myometrium without connection to the fallopian tubes or endometrial cavity. Known risk factors include prior hysterotomy, uterine instrumentation, and myometrial pathology such as adenomyosis. The timely diagnosis and treatment of intramural pregnancies is important to reduce patient morbidity. This video demonstrates the laparoscopic removal of a twin intramural pregnancy in a 32-year-old primiparous patient with a history of myomectomy eight months prior to presentation. Two gestational sacs were visualized in the right fundal myometrium surrounded by only 4-6 millimeters of myometrial tissue. One sac was empty and the other with a live embryo measuring eight weeks gestation with fetal cardiac activity. After extensive counseling, the patient desired to proceed with surgical intervention. To safely excise the pregnancy without inadvertent injury to the fallopian tubes, a reverse U-shaped incision was made with electrosurgery. Dilute vasopressin was utilized to minimize blood loss and hydro-dissection was performed to assist with myometrial separation from the gestational sac. Finally, sharp curettage was performed laparoscopically to remove any remaining products of conception from the myometrium. This unique approach to curettage laparoscopically decreases the risk of endometrial disruption and perforation of a fresh hysterotomy repair, rather than if performed vaginally. We repaired the myometrial defect in multiple layers with barbed suture to avoid uterine wall weakness, which can be associated with spontaneous uterine rupture in future pregnancy. In conclusion, this video demonstrates a minimally invasive approach to the surgical treatment of an intramural pregnancy with laparoscopic resection and curettage.

Transcervical Radiofrequency Ablation for Symptomatic Adenomyosis: A Case Report

<h3>Study Objective</h3> To demonstrate the use of a transcervical radiofrequency ablation (RFA) device approved for symptomatic uterine fibroids as a possible treatment for adenomyosis. <h3>Design</h3> A case report. <h3>Setting</h3> Community hospital affiliate of a large university hospital. <h3>Patients or Participants</h3> 35-year-old gravida-2 para-0 female with uterine fibroids and infertility, presenting with heavy menstrual bleeding, dysmenorrhea, and recent 1^st trimester miscarriage. Pelvic MRI showed a 12 cm uterus with a 2 cm endometrial polyp, 4.5 cm pedunculated fundal fibroid, and diffusely thickened posterior and fundal myometrium consistent with adenomyosis. <h3>Interventions</h3> The patient desired uterine-sparing surgical management and underwent a laparoscopy, hysteroscopy and transcervical RFA. <h3>Measurements and Main Results</h3> Laparoscopically, extensive posterior adenomyosis, a 4.5 cm pedunculated fibroid, and sub-centimeter exophytic fibroid were noted. Endometriosis and small left ovarian fibromas were incidentally diagnosed. Hysteroscopically, there was a 2 cm endometrial lesion with an otherwise normal endometrial cavity. The patient underwent laparoscopic myomectomy of 2 fibroids (without myometrial incision), excision of left ovarian fibromas, and excision of endometriosis in 2 areas, as well as hysteroscopic resection of the endometrial lesion. Ultrasound-guided transcervical RFA then targeted the thickened posterior myometrium with ablation of two adenomyotic regions (measuring 3.4 × 2.6 cm and 3.8 × 2.6 cm). Outgassing was visualized on intrauterine ultrasound images in these regions similar to ablated uterine fibroids and suggestive of successful adenomyosis ablation. Concomitant laparoscopy confirmed no thermal spread beyond uterine serosa. The patient was discharged home the same day. Final pathology revealed fibroids, endometriosis, ovarian spindle cell tumor, and products of conception. On follow-up evaluation, she had no postoperative complaints and no pain medication requirements beyond the immediate postoperative period. Assessment of long-term symptomatic improvement and fertility outcomes are ongoing. <h3>Conclusion</h3> Transcervical radiofrequency ablation is a promising uterine-sparing treatment for patients with adenomyosis. Additional research is warranted to assess long-term symptom improvement and pregnancy outcomes.

Complete Longitudinal Vaginal Septum Resection and Hysteroscopic Metroplasty

<h3>Study Objective</h3> To provide a brief overview of the negative fertility and pregnancy implications of a uterine septum, as well as to demonstrate the surgical management of a complete uterine and vaginal septum. <h3>Design</h3> Surgical video. Women with septate uterus have an increased relative risk of first trimester spontaneous abortion, second trimester spontaneous abortion, pre-term delivery, fetal growth restriction, malpresentation at delivery, and placental abruption. <h3>Setting</h3> Academic tertiary care hospital. <h3>Patients or Participants</h3> 31-year-old nulligravida who presents for consultation for a septate uterus. Pelvic MRI showed a subtle concavity of the external fundal uterine contour, with a complete fibromuscular septum which extended through the cervix. <h3>Interventions</h3> A hysteroscopic metroplasty was planned. An exam under anesthesia showed a previously unidentified complete longitudinal vaginal septum, which extended and communicated with a complete cervical/uterine septum. Kelly clamps were used to demarcate the anterior and posterior attachments of the vaginal septum and a dilute solution of vasopressin along with bupivacaine/epinephrine was injected. The Bovie cautery was used to excise the intervening septum progressively up to the cervix. Diagnostic hysteroscopy showed normal hemi-cavities with fluffy endometrium. The 24.5 French bipolar resectoscope with a roller barrel was used to divide the cervical and uterine septum. Care was taken to stay midline, and once the tubal ostia could be easily seen bilaterally, a slight convexity to the fundus was maintained ensuring integrity of the fundal myometrium. An intrauterine balloon stent was left in place for one week. <h3>Measurements and Main Results</h3> Office hysteroscopy after natural menses showed a normal vagina, cervix, and endometrial cavity. <h3>Conclusion</h3> MRI is the imaging of choice for identifying Müllerian anomalies and for surgical planning; however, a vaginal septum could be missed, reaffirming the importance of a careful examination under anesthesia. Hysteroscopic metroplasty is a safe and relatively simple procedure in those experienced with operative hysteroscopy and results in an improvement in fertility and pregnancy outcomes.

JAZF1\u2013SUZ12 endometrial stromal sarcoma forming subserosal masses with extraordinary uptake of fluorodeoxyglucose on positron emission tomography: a case report

BackgroundLow-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboring JAZF1–SUZ12 rearrangement. Typical JAZF1–SUZ12 ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual.Case presentationA 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas < 1% positive cells in the intramural component (3). Reverse transcriptase-polymerase chain reaction showed the same-sized electrophoretic bands indicating JAZF1–SUZ12 gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery.ConclusionsPathologists and clinicians should not exclude the possibility of JAZF1–SUZ12 ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation of JAZF1–SUZ12 ESS with a complex growth pattern.

Three-dimensional reconstructed coronal plane in detection and differentiation of congenital uterine malformations

Background: Congenital uterine malformations develop during early embryogenesis, and their possible impact on female reproduction often represent a diagnostic and therapeutic challenge. In this study, the authors aimed to evaluate the possibility of detection and differentiation of Müllerian uterine anomalies on the basis of coronal plane obtained by three-dimensional transvaginal ultrasonography. Materials and Methods: The authors investigated 310 non-pregnant women who underwent three-dimensional ultrasound (3-D US) examination followed by the reconstructed three-dimensional images in the coronal plane. The patients were divided into two groups: infertile and unselected women. Results: Müllerian duct anomalies were diagnosed in 25 patients (8%). In the group of infertile patients the number of assessed anomalies was higher (16; 14.4%) as compared to the unselected patients (9; 4.6%). The prevalence of uterine anomalies was increased in the group of infertile patients. In the group of infertile patients, the length of uterine cavity was decreased compared to the unselected women (p = 0.0021). This difference was also visible in the case of nulliparous women from both groups (p = 0.0070). On the other hand, the thickness of fundal myometrium and the distance between the two internal tubal ostia did not vary among patients (p > 0.05). Conclusions: 3-D US represents a feasible and accurate technique for the detection and differentiation of congenital uterine malformations. Three-dimensional reconstructed coronal view could be used for the additional measurement of different uterine dimensions which were shown to differ between infertile patients and the control group, and according to the parity.

Uterine perforation and small bowel incarceration 11 months after dilatation and curettage: sonographic and surgical findings

In 2014, a 33-year-old primiparous woman was referred by her physician to the emergency department of the Catholic University of Rome for abnormal uterine findings at routine gynecological examination, performed 11 months after vaginal delivery. She was breastfeeding and her menstrual cycle had not yet recommenced. She had undergone dilatation and curettage (D & C) 4 weeks after delivery because of retained membrane. Gynecological examination revealed a tender uterus with a closed cervix and normal adnexa. Laboratory findings were not significant, with a normal white blood cell count and negative for β-human chorionic gonadotropin. On referral to our department, we performed a transvaginal ultrasound examination using a GE Voluson E8 (GE Medical Systems, Zipf, Austria) ultrasound system. A tubular structure, with distinct multilayered appearance of normal intestinal wall1, was seen penetrating into the uterine cavity through the anterior wall of the uterine body (Videoclip S1). The presence of typical normal echostructure of intestinal wall and peristaltic movement suggested perforation of the uterus with penetration of the bowel. Color Doppler ultrasound examination confirmed this hypothesis (Videoclip S2). A small amount of anechoic free fluid was seen in the cul-de-sac. Laparoscopy revealed about 10 cm of small intestine prolapsed through the uterine perforation, adherent to the myometrial wall. The uterine fundus had a hole of approximately 4 cm in size (Videoclip S3). The bowel had penetrated through this gap, occupying the entire endometrial cavity and reaching the upper part of the cervix. Adhesions between the bowel and the endometrial cavity and myometrium were removed and the uterine structure was reconstructed. A perforation of 1 cm was detected on the surface of the entrapped bowel that was resected laparoscopically. The patient was discharged after 5 days with no postsurgical complication. Delayed presentation of uterine perforation after D & C, as reported here, is rare2. Treatment usually consists of laparotomic surgery3; the laparoscopic approach described in this case is, we believe, one of few reported in the medical literature. A. De Cicco†, F. Mascilini‡, M. Ludovisi‡, F. De Cicco†, G. Scambia‡ and A. C. Testa*‡ †Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy; ‡Division of Gynecology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy *Correspondence. (e-mail: atesta@rm.unicatt.it) Videoclips S1 and S2 Grayscale (S1) and color Doppler (S2) ultrasound videoclips showing hyperechogenic tubular structure penetrating through anterior wall of uterine body. Videoclip S3 Intraoperative videoclip demonstrating defect in fundal myometrium of uterus, through which small bowel is incarcerated. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

HoxA13 Regulates Phenotype Regionalization of Human Pregnant Myometrium.

Bipedalism separates humans from most other animal species, but results in significant physiologic challenges, particularly with respect to the maintenance of pregnancy and induction of parturition. A contracted lower uterine segment (LUS) and a relaxed uterine fundal myometrium (FUN) during pregnancy are required to prevent pressure on the cervix from the fetal head due to gravity. With the onset of labor, this regionalization of myometrial function must be reversed, allowing descent of the fetus, dilation of the cervix, and expulsion of the fetus through the birth canal. However, the molecular mechanisms remain unclear. This study sought to identify phenotypic regionalization of LUS and FUN during pregnancy, RNA sequencing was performed to analyze the human myometrial transcriptome. Real-time PCR and immunoblotting were applied to validate sequencing results. Cell contraction/adhesion assays and gene microarrays were used to study the cellular functions of the identified genes. Homeobox A13 (HoxA13), prostacyclin synthase (PTGIS), and periostin (POSTN) genes are more highly expressed in LUS than FUN of nonlaboring, but not laboring, myometrial cells at term. HoxA13 up-regulates transcription of PTGIS and POSTN genes. Elevated HoxA13 expression enhances myometrial cell contractility and cell-cell adhesion. Gene microarray studies show that HoxA13-regulated genes are associated with immune response, gap junction/cell adhesion, and pregnancy. The LUS expresses higher levels of HoxA13, PTGIS, and POSTN, and is more contractile than the FUN at term prior to labor. This pregnancy-maintaining regionalization of myometrial function may be mediated by HoxA13.

Ultrasonographic Evaluation of Myometrial Thickness and Prediction of a Successful External Cephalic Version

To test the hypothesis that myometrial thickness predicts the success of external cephalic version. Abdominal ultrasonographic scans were performed in 114 consecutive pregnant women with breech singletons before an external cephalic version maneuver. Myometrial thickness was measured by a standardized protocol at three sites: the lower segment, midanterior wall, and the fundal uterine wall. Independent variables analyzed in conjunction with myometrial thickness were: maternal age, parity, body mass index, abdominal wall thickness, estimated fetal weight, amniotic fluid index, placental thickness and location, fetal spine position, breech type, and delivery outcomes such as final mode of delivery and birth weight. Successful version was associated with a thicker ultrasonographic fundal myometrium (unsuccessful: 6.7 [5.5-8.4] compared with successful: 7.4 [6.6-9.7] mm, P=.037). Multivariate regression analysis showed that increased fundal myometrial thickness, high amniotic fluid index, and nonfrank breech presentation were the strongest independent predictors of external cephalic version success (P<.001). A fundal myometrial thickness greater than 6.75 mm and an amniotic fluid index greater than 12 cm were each associated with successful external cephalic versions (fundal myometrial thickness: odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2, P=.029; amniotic fluid index: OR 2.8, 95% CI 1.3-6.0, P=.008). Combining the two variables resulted in an absolute risk reduction for a failed version of 27.6% (95% CI 7.1-48.1) and a number needed to treat of four (95% CI 2.1-14.2). Fundal myometrial thickness and amniotic fluid index contribute to success of external cephalic version and their evaluation can be easily incorporated in algorithms before the procedure. III.

Total Laparoscopic Conservative Surgery for an Intramural Ectopic Pregnancy

A 38-year-old woman, gravida 3, para 1 with a history of a left salpingectomy for an ectopic pregnancy was admitted for treatment of a presumed ectopic pregnancy. Transvaginal sonography revealed an ill-defined gestational sac and fetal heart beat within the fundal myometrium adjacent to the left cornua. Laparoscopy was performed for a suspected left cornual pregnancy or intramural pregnancy. A cystic mass 3 cm in diameter was visible within the fundal myometrium. Total laparoscopic removal of the gestational sac was performed, and the uterus was preserved. Pathologic evaluation of the excised mass demonstrated chorionic villi involving the myometrium. In the literature, only one other case describing the laparoscopic removal of an intramural pregnancy has been reported. However, in the prior report, the patient still required hysterectomy after conservative surgery. Therefore, this is the first report of the successful treatment of an intramural pregnancy exclusively with laparoscopy.

Laparoscopic resection of cystic adenomyosis in a teenager with arcurate uterus

Whereas diffuse adenomyosis is a common finding in parous women, cystic adenomyosis causing severe dysmenorrhoea is very rarely reported and possibly under-diagnosed, particularly in adolescents. We report a case of juvenile cystic adenomyosis in a 19-year-old nulliparous patient presenting with secondary dysmenorrhoea and non-cyclical pain. A 20-mm adenomyotic cyst in the fundal myometrium was successfully excised laparoscopically by modified myomectomy. It is mandatory to take persistent primary and early secondary dysmenorrhoea seriously, especially after poor response to medical treatment and to have a low threshold for further investigations, because a diagnosis of cystic adenomyosis requires targeted therapeutic intervention.

The endometrial–myometrial junction: a fresh look at a busy crossing

The endometrial–myometrial junction: a fresh look at a busy crossing

Migration of an Intrauterine Contraceptive Device during the Course of Pregnancy: A Case Report

Uterine perforation by a contraceptive intrauterine device (IUD) is a relatively rare event. These events may result secondary to mechanical force applied during placement (primary perforation) or migration by uterine contractions or surgical manipulation after placement (secondary perforation). A 33-year-old woman with an IUD placed 9 years before admission visited the emergency department with an early pregnancy and a 3-day history of vaginal bleeding. Vaginal examination revealed IUD strings visible at the cervical os, and transvaginal ultrasound confirmed the presence of an IUD in the lower uterine segment and upper cervix. The IUD migrated spontaneously to the fundal myometrium at 15 weeks’ gestation. Premature rupture of membranes ensued at 20 weeks’ gestation, and, at delivery, the IUD could not be retrieved. Subsequent computed tomography confirmed that the IUD was incompletely embedded in the fundal myometrium and partially extending into the peritoneal cavity. At laparoscopic sterilization 6 weeks later, the IUD had perforated the small bowel, and the device was removed with concomitant bowel repair. This case documents spontaneous migration of a copper IUD from the lower uterine segment through the fundus during early pregnancy and supports removal of asymptomatic ectopic IUDs whenever possible.

Ultrasonographic evaluation of myometrial thickness in twin pregnancies

The objective of the study was to evaluate longitudinally the in vivo changes in myometrial thickness (MT) during gestation in patients carrying twin gestations in relation to pregnancy outcome. Serial abdominal ultrasounds were performed prospectively in 92 patients carrying twin gestations through each trimester. Ninety-seven patients pregnant with singletons served as controls. For twins, the primary endpoint was spontaneous delivery at less than 35 weeks' gestational age (GA). The myometrium was defined sonographically as the echohomogeneous layer between the serosa and the decidua and was measured at the anterior, fundal, and lower uterine segment (LUS) walls. The estimated fetal weight, maximum vertical pocket of amniotic fluid, and placental thickness were also assessed ultrasonographically at the same time as the MT and served as estimates for the contribution of each to the uterine volume. In twins, cervical length measurements were performed transvaginally, as clinically indicated. Data analysis included 2-way analysis of variance and linear, nonlinear, and multivariate regression. A total of 41.3% of twin pregnancies (38 of 92) delivered preterm (< 35 weeks). There were no significant changes in measurements at the anterior and fundal site over time throughout pregnancy and no differences in these sites between twin and singleton gestations. Conversely, in both twins and singletons, there was a significant and gradual thinning of the LUS myometrium during gestation. In the absence of uterine contractions or symptoms of preterm labor, twins that delivered preterm had a significantly thinner LUS at an earlier gestation, compared with twins that delivered at term (P < .001), suggesting that LUS thinning occurred earlier in these cases. There was a significant correlation between cervical length and LUS thinning during gestation in twins that delivered 35 weeks GA or later (r = 0.352; P < .001) but not in those that delivered preterm (< 35 weeks GA; r = 0.125; P = .326). Twin pregnancy is characterized by a significant, selective, and gradual thinning of the LUS during gestation, which does not occur in the anterior and fundal myometrium. Thinning of the LUS occurs earlier in twin pregnancies destined to deliver preterm. These observations suggest that similar to the cervix, the LUS changes dynamically during twin pregnancy and that this too may be assessed through ultrasound imaging.

Expression of Transient Receptor Channel Proteins in Human Fundal Myometrium in Pregnancy

Cation channels comprised of transient receptor potential (TrpC) proteins may play a role in signal-regulated calcium entry and calcium homeostasis in myometrium. The objective of this study was to determine the relative abundance of specific TrpC mRNAs expressed in human myometrium and determine if TrpC mRNA and protein concentrations differ in fundal myometrium before and after the onset of labor. A quantitative real-time polymerase chain reaction (Q-RT-PCR) procedure was developed for determining the concentration of TrpC mRNA expression in immortalized and primary human myometrial cells and myometrial fundus tissues from patients before and after the onset of labor. The corresponding TrpC proteins were detected by Western blot analysis and immunohistochemistry. hTrpC1, 3, 4, 5, 6, and 7 mRNAs were expressed in two lines of immortalized human myometrial cells and in primary human myocytes. In all of these cells, hTrpC1 and hTrpC4 mRNAs were the most abundant, followed by hTrpC6. A similar distribution was observed in fundal myometrium samples from patients before and after the onset of labor. hTrpC4 mRNA was significantly lower after the onset of labor; there were no significant changes in the concentrations of other TrpC mRNAs. Immunohistochemistry identified hTrpC1, 3, 4, and 6 proteins in myometrial smooth muscle cells. Western blot analysis of myometrial membranes demonstrated no statistically significant changes in hTrpC1, 3, 4, and 6 proteins between samples collected before and after the onset of labor. We have demonstrated that hTrpC1 and hTrpC4 are the most abundant TrpC mRNAs in human myometrium, with TrpC6 being the next most abundant. There was no increase in TrpC mRNA or protein in fundal myometrium with the onset of labor. Nonetheless, these isoforms may play significant roles in signal regulated calcium entry in human myometrium.

Up-Regulation of the Progesterone Receptor (PR)-C Isoform in Laboring Myometrium by Activation of Nuclear Factor-κB May Contribute to the Onset of Labor through Inhibition of PR Function

Progesterone acting via the progesterone receptor (PR) plays a critical role in maintaining uterine quiescence during pregnancy. In the present study, we tested the hypothesis that the transactivating capability of the PR is down-regulated in the myometrium at term by a change in uterine PR isoform ratio resulting from local activation of the nuclear factor (NF)-kappaB pathway. Overexpression of the truncated PR-C isoform in human myometrial cells inhibited PR-B transactivation. Expression of PR isoforms, PR-A, PR-B, and PR-C, was characterized by immunoblotting and quantitative PCR (Q-PCR) in fundal and lower uterine segment myometrium from pregnant women in labor and not in labor and in the pregnant mouse uterus during late gestation. We observed a marked increase in levels of PR-C and transcriptionally active PR-B specifically in fundal myometrium of women in labor. In pregnant mouse uterus, levels of PR-B and PR-C also increased between 15 days post coitum and term, whereas expression of PR-A was dramatically up-regulated at 19 days post coitum. In studies of uterine tissues of mice injected intraamniotically with surfactant protein A and of human myometrial and T47D breast cancer cells in culture, up-regulation of PR isoform expression was observed in response to activation of the NF-kappaB pathway. Chromatin immunoprecipitation analysis revealed IL-1beta induced binding of NF-kappaB to the PR promoter. Collectively, these findings suggest that up-regulation of inhibitory PR isoform expression by NF-kappaB activation in both laboring human fundus and pregnant mouse uterus near term may inhibit PR transactivation and thereby lead to a loss of uterine quiescence and the onset of labor.

Frameless versus classical intrauterine device for contraception

The frameless intrauterine device (IUD) dispenses with the frame in the classical IUD and holds the device in the uterus by anchoring one end of a nylon thread in the fundal myometrium, to which copper sleeves are attached. This review examines the hypothesis that the frameless IUD Gynefix reduces risk of expulsion and pregnancy, and the problems of bleeding and pain necessitating early removal. We searched the Cochrane Controlled Trial Register (Cochrane Library Issue 2, 2004), MEDLINE, and Popline from 1980 to March 2004, and reference list of articles. We selected for the review randomised trials that compared the frameless device to a classical framed device for contraception. Both authors extracted data independently. We contacted study author for additional data. We calculated rate ratios and rate differences for cumulative rates for each outcome at yearly intervals. We used the inverse variance-based method to combine trials, and tested the results for heterogeneity. Four trials were included in the review involving 5,939 women randomised to either a frameless device or TCu380, with data up to eight years for the largest, and with a total experience of 23,180 years. Apart from one small trial, nulliparous women were excluded from the trials. The two earlier trials used a prototype introducer and there was a higher expulsion rate at one year (relative risk 2.48, 95% confidence intervals 1.89 to 3.26). However, between two and six years in the large WHO trial the risk of pregnancy was lower with the frameless device (relative risk 0.53, 95% confidence intervals 0.32 to 0.91). In a recent trial using GyneFix with a new introducer early expulsions and pregnancies were not statistically different from the control device. Removals rates for excessive bleeding and/or pain were no different between the devices (relative risks 0.92, 95% confidence intervals 0.74 to 1.14, at one year and 1.13, 0.93 to 1.37, at six years). There was a tendency towards fewer removals for pain in early years but no difference at six years (relative risk 1.13, 95% confidence intervals 0.93 to 1.37). There is insufficient data to show that problems of early expulsions have been overcome with the modified introducer used in GyneFix. Apart from that, the frameless device performs similarly to TCu380, and appears to have a lower pregnancy rate in later years, although the absolute difference is small.

Human Myometrial Gene Expression Before and During Parturition1

Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding of the coordinated regulation of myometrial contractions during parturition. The objective of this study was to compare the gene expression profiles of human fundal myometrium from pregnant women before and after the onset of labor using a functional genomics approach, and to further characterize the spatial and temporal expression patterns of three genes believed to be important in parturition. Fundal myometrial mRNA was isolated from five women in labor and five women not in labor, and analyzed using human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain reaction using myometrial RNA from pregnant women in labor or not in labor was used to examine mRNA levels for three of the genes; namely, prostaglandin-endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor (OXTR). The spatial expression pattern of these genes throughout the pregnant uterus before and after labor was also determined. Immunolocalization of cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and myometrium were analyzed by immunohistochemistry. Few genes were differentially expressed in fundal myometrial tissues at term with the onset of labor. However, there appears to be a subset of genes important in the parturition cascade. The cellular properties of S100A9, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor.

The reliability of the anchoring concept for suspension of bioactive substances in the human uterus evaluated by measuring the removal force: results after long-term use

Objective The objective of the present study is to report on the force needed to remove the implanted GyneFix® intrauterine contraceptive device (IUD) from the uterine cavity. This study is the first long-term study on the retrieval of the anchored IUD. Study design A two-center, noncomparative study to measure the force needed to remove the IUD in 251 women. A dynamometer (Pesola®, Switzerland) was used to measure the removal force in newtons. Results The results of this study show a mean removal force of 6.2 and 6.1 newtons, respectively (range, 0–10), in parous and nulligravid or nulliparous women (p = 0.62). There was no difference in removal force for those women with a duration of use either less than 60 months or longer than 60 months (median of 6 newtons in both groups; p = 0.22). Conclusions The force needed to remove the GyneFix IUD suggests that the implantation technology used in the insertion of the device is reliable, provided the anchoring knot is properly inserted in the fundal myometrium. The results of this study indicate that early expulsion of the device could be explained by failure to implant the knot adequately (no implantation or partial implantation), which requires a degree of skill. The present study does not provide an explanation for the occurrence of late expulsion, although some speculations can be made.

Myometrial thickness during human labor and immediately post partum

Objective: Morphologic studies suggest dramatic, asymmetric uterine growth during pregnancy that is caused by muscle cell hypertrophy. This growth is most marked at the fundus. Our objective was to evaluate sonographically the in vivo changes in myometrial thickness during active labor, second-stage labor, and after delivery. Study design: Abdominal ultrasound scans were performed on 52 term pregnant women to investigate the dynamic changes in myometrial thickness during the active and second stages of labor and immediately after delivery. Twenty-six women (mean ± SEM gestational age, 39.09 ± 0.3 weeks) were in active labor (cervical dilatation >4 cm with regular uterine contractions). An additional 26 nonlaboring women (gestational age, 39.8 ± 0.2 weeks) provided control measurements. The myometrium was defined sonographically as the echo homogeneous layer between the serosa and the decidua. Myometrial thickness was measured at the low segment and mid anterior, fundal, and posterior uterine walls by the same observer. Myometrial thickness was also measured during uterine contractions and after artificial rupture of the amniotic membranes. All laboring women had uncomplicated labor patterns when studied and were delivered spontaneously. Results: The myometrium was significantly thinner during active labor compared with nonlabor at each site studied: midanterior (mean [±SEM] myometrial thickness, 5.8 ± 0.27 vs 8.83 ± 0.51 mm; t test, P < .001), fundus (mean myometrial thickness, 6.78 ± 0.32 vs 8.49 ± 0.35 mm; P = .0015), and posterior (mean myometrial thickness, 6.22 ± 0.34 vs 8.12 ± 0.30 mm; P < .001). However, myometrial thickness did not differ among sites within the two groups. The thickness of the low segment was not affected by labor status (nonlabor, 4.68 ± 0.48 vs labor, 4.66 ± 0.37 mm; P = .97). Similarly, the myometrial thickness of the anterior uterine wall was unaffected by contractions (no contractions, 5.56 ± 0.2 vs contractions, 5.68 ± 0.22 mm; t test, P = .654). There was no change in myometrial thickness measured immediately before and after rupture of the amniotic membranes, despite a significant decrease of the amniotic fluid index. There was significant thickening of the anterior and fundal myometrium during the second stage of labor after the fetal head descended to +3 station by digital examination (anterior, 12.99 ± 0.60 vs 5.8 ± 0.27 mm; t test, P < .001; fundus, 10.61 ± 1.63 vs 6.78 ± 0.32 mm; t test, P = .04). Valsalva maneuver (pushing) during contractions did not affect myometrial thickness at the fundus (between contractions, 10.61 ± 1.63 vs pushing, 10.76 ± 1.95 mm; t test, P = .99). Immediately after delivery, the myometrial thickness at the placental insertion site was the thinnest. After completion of the third stage of labor, the uterine fundus remained significantly thinner than the anterior and posterior walls (fundus, 27.37 ± 3.5 mm vs anterior, 40.94 ± 3.5 vs posterior, 42.34 ± 2.44; one-way analysis of variance, P = .02). Conclusion: There is significant and widespread thinning of the myometrium during active labor. Descent of the fetal head during the second stage of labor is associated with a significant relative thickening of the anterior and fundal myometrium. After delivery, the relationship reverses. These findings suggest the directionality of the expulsive force vectors (fundal dominance) is not determined by asymmetric myometrial growth but, rather, may be a function of increased “myometrial mass” that results from increased surface area at the fundus. (Am J Obstet Gynecol 2003;188:553-9.)