Uterine contractile activity in healthy women throughout the menstrual cycle measured using a novel quantitative two-dimensional transvaginal ultrasound speckle tracking method.

RESEARCH QUESTION: To explore normal uterine contractile function across the menstrual cycle using a novel quantitative ultrasound method. DESIGN: This multicentre prospective observational study took place in three European centres from 2014 to 2022. Uterine contraction frequency (contractions/minute), amplitude, direction (cervix-to-fundus, C2F; fundus-to-cervix; F2C), velocity and coordination were investigated. Features were extracted from transvaginal ultrasound recordings (TVUS) using speckle tracking. Premenopausal women ≥18 years of age, with normal, natural menstrual cycles were included. A normal cycle was defined as: regular (duration 28 ± 2 days), no dysmenorrhoea, no menometrorrhagia. Four-minute TVUS were performed during the menstrual phase, mid-follicular, late follicular phase, early luteal phase and/or late luteal phase. Of the 96 recordings available from 64 women, 70 were suitable for inclusion in the analysis. RESULTS: Contraction frequency (for the posterior wall) and velocity (for the anterior uterine wall in the F2C direction) were highest in the late follicular phase and lowest in the menstrual and late luteal phases (1.61 versus 1.31 and 1.35 contractions/min, P < 0.001 and 0.81 versus 0.67 and 0.62 mm/s, P < 0.001, respectively). No significant difference was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was least coordinated in the mid-follicular phase (P = 0.002). CONCLUSIONS: This is the first study to objectively measure uterine contraction features in healthy women during the natural menstrual cycle on TVUS. Likewise, it introduces contraction coordination as a specific feature of uterine peristalsis. Differences in uterine contractility across the menstrual cycle are confirmed, with highest activity seen in the late follicular phase, and lowest in the late luteal phase.

The ADENO study: ADenomyosis and its Effect on Neonatal and Obstetric outcomes: a retrospective population-based study.

BACKGROUND: Adenomyosis is a benign gynecologic condition arising from the uterine junctional zone. Recent studies suggest a relationship between adenomyosis and adverse obstetrical outcomes, but evidence remains conflicting. There is no large-scale study investigating obstetrical outcomes in women with adenomyosis using the gold standard of histopathologic diagnosis. OBJECTIVE: This study aimed to investigate the prevalence of adverse obstetrical and neonatal outcomes in women with histopathologic adenomyosis and that of the general (Dutch) population. STUDY DESIGN: This retrospective population-based study used 2 Dutch national databases (Perined, the perinatal registry, and the nationwide pathology databank [Pathologisch Anatomisch Landelijk Geautomiseerd Archief], from 1995 to 2018) to compare obstetrical outcomes in women before histopathologic adenomyosis diagnosis to the general Dutch population without registered histopathologic adenomyosis. The adjusted odds ratios (95% confidence interval) were calculated for adverse obstetrical outcomes. The outcomes were adjusted for maternal age, parity, ethnicity, year of registered birth, induction of labor, hypertensive disorders in previous pregnancies, multiple gestation, and low socioeconomic status. RESULTS: The pregnancy outcomes of 7925 women with histopathologic adenomyosis were compared with that of 4,615,803 women without registered adenomyosis. When adjusted for confounders, women with adenomyosis had adjusted odds ratios of 1.37 (95% confidence interval, 1.25-1.50) for hypertensive disorders, 1.37 (95% confidence interval, 1.25-1.51) for preeclampsia, 1.15 (95% confidence interval, 1.07-1.25) for small-for-gestational-age infants, 1.54 (95% confidence interval, 1.41-1.68) for emergency cesarean delivery, 1.24 (95% confidence interval, 1.12-1.37) for failure to progress, 1.29 (95% confidence interval, 1.10-1.48) for placental retention, and 1.23 (95% confidence interval, 1.10-1.38) for postpartum hemorrhage. No increased risk of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, placental abruption, or operative vaginal delivery or need for oxytocin stimulation was found. CONCLUSION: Women with a histopathologic diagnosis of adenomyosis showed an increased prevalence of hypertensive disorders of pregnancy and small-for-gestational-age infants, failure to progress in labor, and placental retention compared with the general population in previous pregnancies. This suggests that uterine (contractile) function in labor and during pregnancy is impaired in women with adenomyosis.

Reproductive and Obstetric Outcomes After Hysteroscopic Removal of Retained Products of Conception.

STUDY OBJECTIVE: To evaluate the reproductive outcomes in women treated for retained products of conception (RPOC) by hysteroscopy (morcellation vs loop resection). DESIGN: Cohort study. SETTING: A teaching and university hospital. PATIENTS: Patients included in a previous randomized controlled trial on hysteroscopic removal of RPOC comparing morcellation (n = 46) with loop resection (n = 40). INTERVENTIONS: Hysteroscopic morcellation versus loop resection. MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were live birth and pregnancy complications (including abnormal placentation [placenta accreta/increta/percreta], placenta previa, vasa previa, retained placenta after delivery or incomplete expulsion with the need for manual removal or curettage, and RPOC), uterine rupture, and other complications (blood loss, preterm labor, preterm premature rupture of membranes, hypertensive disorders of pregnancy, and intrauterine growth restriction). The live birth rate was 88.9% in the morcellation group and 68.2% in the loop resection group (p = .09). Uterine rupture occurred in 1 patient in the morcellation group (4.2%) (p = 1.00). Placental complications were found in 20.8% and 22.2% of the hysteroscopic morcellation and loop resection groups, respectively (p = .33), and other pregnancy complications were seen in 33.3% and 16.6% of the 2 groups (p = .33). The secondary outcome was time to pregnancy. The median time to pregnancy was 14 weeks (interquartile range [IQR], 5-33 weeks) in the morcellation group and 15 weeks (IQR, 6-37 weeks) in the loop resection group (p = .96). CONCLUSION: Hysteroscopic removal of RPOC seems to have no detrimental effect on reproductive outcome and no significant effect on pregnancy rate.

Quantitative ultrasound measurement of uterine contractility in adenomyotic vs. normal uteri: a multicenter prospective study.

OBJECTIVE: To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method. DESIGN: A multicenter prospective observational study took place in three European centers between 2014 and 2023. SETTING: One university teaching hospital, 1 teaching hospital and 1 specialised clinic. PATIENTS: A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included. INTERVENTION: Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm. MAIN OUTCOMES MEASURES: The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle. RESULTS: Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index. CONCLUSION: Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.

Operative hysteroscopy versus ultrasound-guided electric vacuum aspiration for removal of retained products of conception: A prospective cohort study.

Objectives: To compare intrauterine adhesion (IUA) formation after hysteroscopic removal (HR) of retained products of conception (RPOC) with IUA formation after ultrasound-guided electric vacuum aspiration (EVA) and externally validate the outcomes of an RCT. Study design: This prospective cohort study was conducted from April 2015 until June 2022 in 2 Dutch teaching hospitals and one Belgian university hospital. Women opting for EVA underwent the procedure as soon as possible. In the HR group, the therapeutic hysteroscopy was performed at least eight weeks after the end of pregnancy. Postoperatively, an office second-look hysteroscopy was offered to all patients. Women were included if they had been diagnosed with RPOC ranging from 1 to 4 cm on ultrasound and did not want to participate in the RCT. EVA was performed using a Karman cannula. Operative hysteroscopy consisted either of hysteroscopic morcellation with the TruClear™ System or the Intrauterine BIGATTI Shaver or cold loop resection with a bipolar resectoscope. Results: Of 178 included women, 124 were treated with HR and 28 with EVA. Outcomes of HR and EVA did not differ significantly in terms of complications (5.6 % vs 3.6 %; p = 1.00). Second-look hysteroscopy showed IUAs in 14 of 91 women (15.4 %) after HR and in 1 of 16 (6.3 %) after EVA (p = .461). Completeness of removal was significantly higher (90.1 %) after HR than after EVA (68.8 %) (p = .035). Additional operative hysteroscopy was required in 14.3 % of the HR group versus 37.5 % in the EVA group (p = .036). Conclusion: In our cohort study, no significant differences in IUAs or complications were found. RPOC removal with HR was more often complete than removal with EVA, and additional therapeutic hysteroscopy was less frequently required after HR. These findings need to be correlated with those of RCTs. Clinical trial registration: The study was registered in de Dutch Trial Register (NTR4923). Date of registration 23-11-2014. Date of first enrollment 01-01-2015. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923.

Hysteroscopic morcellation versus bipolar resection for removal of type 0 and 1 submucous myomas: A randomized trial.

OBJECTIVES: To compare hysteroscopic morcellation with bipolar resection for the removal of submucous type 0 and 1 myomas, in terms of procedure time (primary outcome), adverse events, tissue availability, short term effectiveness and postoperative adhesion formation (secondary outcomes). STUDY DESIGN: The study was performed from May 2011 to May 2018 in the Catharina hospital (Eindhoven, the Netherlands) and the Ghent University hospital (Ghent, Belgium). Women with type 0 and 1 submucous myomas up to 3 cm were randomized to hysteroscopic morcellation with the TruClearTM 8.0 Tissue Removal System or to bipolar resection with a rigid 8.5-mm resectoscope. Skewed time variables were log-transformed and analyzed with the Student t-test. Multiple linear regression analysis was performed to assess the effect of myoma diameter on operating time. RESULTS: Forty-five and 38 women were included in the hysteroscopic morcellation and resection group, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with resection (9.2 min [interquartile range 5.6-14.4] versus 13.4 min [interquartile range 8.6-17.5], P = .04). In the morcellation group, operating time, corrected for the myoma diameter, was reduced by 26 % (95 % CI 5-43%; P = .02). The median setup time was significantly longer in the morcellation group (5.2 min [interquartile range 4.2-6.9] versus 3.8 min [interquartile range 3.3-5.3], P = .006). The median total procedure time was not significantly different between the two techniques (14.4 min [interquartile range 11.4-19.2] versus 17.3 [interquartile range 12.7-23.8], P = .18). Two procedures of the morcellation group were converted to bipolar resection because of the myoma hardness. Complete resection was found in 89 % of the morcellation group and 95 % of the resection group. Adverse events occurred in 3 patients of the morcellation group, namely a fluid deficit > 2500 mL with the need of potassium suppletion, an asystolic vasovagal response after conversion to resection and postoperative fever requiring antibiotics. Tissue was available for pathology analysis in all cases. Routine second-look hysteroscopy performed in one center showed no intrauterine adhesions. CONCLUSION: Overall, there is no difference in total procedure time between hysteroscopic morcellation using the TruClearTM system compared to bipolar resection for the removal of smaller type 0 and 1 submucous myomas. Although hysteroscopic morcellation is faster, its setup time is longer. Calcified myomas can be challenging and fluid deficit remains a limiting factor.

Biphasic versus triphasic oral contraceptives for contraception.

Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We examined this potential disadvantage by conducting a systematic review comparing biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation because of side effects. We included randomized, controlled trials comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. Only two trials of limited quality met our inclusion criteria. Larranaga compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation because of medical problems was similar with all three pills. Percival-Smith compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review.

BACKGROUND: Side-effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. We compared biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control and discontinuation due to side-effects. Our a priori hypotheses were: (i) biphasic oral contraceptives are less effective in preventing pregnancy than monophasic oral contraceptives, and (ii) biphasic oral contraceptives cause more side-effects, give poorer cycle control and have lower continuation rates. METHODS: We searched computerized databases Medline, Embase, Popline and the Cochrane Controlled Trial Register. Additionally, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplementary information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding and study discontinuation due to intermenstrual bleeding. RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. This trial examined 533 user cycles of a biphasic pill (norethindrone 500 microg/ethinyl estradiol 35 microg for 10 days, followed by norethindrone 1000 microg/ethinyl estradiol 35 microg for 11 days) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 microg/ethinyl estradiol 30 microg daily). The study found no significant differences in intermenstrual bleeding, amenorrhoea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.