The impact of embedment of the side arms of 52 mg levonorgestrel-intrauterine device on bleeding and pain: A prospective cohort study.

PURPOSE: The purpose of this study was to analyse the impact of embedment of side arms of the levonorgestrel 52 mg intrauterine device (LNG-IUD) in the myometrium (assessed by three-dimensional transvaginal ultrasound (3D-TVUS)) on uterine bleeding and pain. MATERIALS AND METHODS: We performed a prospective cohort study in a large Dutch teaching hospital between February 2015 and December 2016. Participants over 18 years of age who selected a LNG-IUD for contraception or because of heavy menstrual bleeding were eligible for inclusion. Six weeks after insertion, a 3D-TVUS was performed to diagnose embedment of the side arms. At that moment participants filled in questionnaires about their bleeding pattern and pelvic pain. Menstruation patterns 'no bleeding', 'regular menstruation', 'sometimes a day of spotting (maximum once a week)' were classified as favourable bleeding pattern. Menstruation patterns 'heavy menstrual bleeding', 'several days a week bleeding days', 'several days a week spotting days', 'continuously spotting', and 'completely irregular cycle' were classified as unfavourable bleeding pattern. Univariate and multivariate logistic regression analysis was used to calculate odds ratios (OR) and 95 %-confidence intervals (CI). The multivariate analysis included endometrial thickness, reason for insertion and parity. The analysis of pelvic pain additionally included previous insertion. RESULTS: A total of 220 participants were evaluated for the study of whom 176 returned the questionnaires. Embedment of the side arms was observed in 43 of the 176 responding participants (24.4 %). Favourable bleeding pattern was reported by 25/43 (58.1 %) participants with embedment and 53/133 (39.8 %) participants without embedment (ORadj 1.8, 95 % CI 0.9-3.9). Pelvic pain was reported by 4/43 (9.3 %) participants with embedment and 24/133 (18.1 %) participants without embedment (ORadj 0.3; CI 0.1-1.2). CONCLUSIONS: The present study suggests that embedment of the side arms of the LNG-IUD in the myometrium assessed by 3D-TVUS is not associated with a unfavourable bleeding pattern nor pelvic pain six weeks after insertion. From this point of view, we do not recommend to perform standard 3D-TVUS for the purpose of excluding or demonstrating embedment.

The effect of surgery or medication on pain and quality of life in women with endometrioma. A systematic review and meta-analysis.

For patients with endometrioma it is unclear what treatment: surgery and/or medication, is more effective in reducing pain and improving quality of life (QoL). This systematic review and meta- analysis aimed to provide an overview of the existing evidence on the effects of surgery and/or medication (i.e. analgesics and/or hormonal medication) on pain and QoL. A search through CENTRAL, MEDLINE and Embase was conducted. The study population had to be women treated for endometrioma. Retrospective or prospective studies reporting about QoL and/or the following types of pain were reviewed: dysmenorrhea, dyspareunia, chronic pelvic pain, and pain that was not well defined in the included article (referred to as pain). We performed a meta-analysis on mean visual analogue scale (VAS) scores and proportions of patients experiencing different types of pain over time. QoL was described narratively. Out of 11.515 articles, 76 studies including 7148 patients were included for the systematic review. The meta-analysis consisted of 52 studies including 4556 patients. No studies compared medication with surgery. And there were no studies on analgesics. Meta-analysis showed that surgery and/or medication often reduced VAS scores and proportions of all types of pain over time. Surgery and medication combined seems more effective in reducing VAS scores of pain compared to surgery alone, but not to medication alone (estimated mean difference = 0.17, p < 0.0001 and -0.98, p = 0.0339). QoL improved after medication (follow up ≤ 12 months) and QoL was unchanged or worsened after surgery and medication combined (follow up ≤ 24 months). However, these were results from a total of 5 studies. Both surgery and medication reduce endometriosis-related pain in patients with endometrioma. However, there is lack of uniform, good quality data comparing surgery with medication to draw firm conclusions. For better-informed treatment decisions, further studies including a standardized core-outcome set at fixed follow-up times, are necessary.

Current uptake and barriers to wider use of the International Ovarian Tumor Analysis (IOTA) models in Dutch gynaecological practice.

OBJECTIVE: Correct referral of women with an ovarian tumor to an oncology department remains challenging. The International Ovarian Tumor Analysis (IOTA) consortium has developed models with higher diagnostic accuracy than the alternative Risk of Malignancy Index (RMI). This study explores the uptake of the IOTA models in Dutch hospitals and factors that impede or promote implementation. Optimal implementation is crucial to improve pre-operative classification of ovarian tumors, which may lead to better patient referral to the appropriate level of care. STUDY DESIGN: In February 2021, an electronic questionnaire consisting of 37 questions was sent to all 72 hospitals in the Netherlands. One pre-selected gynaecologist per hospital was asked to respond on behalf of the department. RESULTS: The study had a response rate of 93% (67/72 hospitals). All respondents (100%) were familiar with the IOTA models with 94% using them in practice. The logistic regression 2 (LR2)-model, Simple ultrasound-based rules (SR) and Assessment of Different NEoplasias in the adneXa (ADNEX) model were used in respectively 40%, 67% and 73% of these hospitals. Respondents rated the models overall with an 8.2 (SD 1.8), 8.3 (SD 1.6) and 8.9 (SD 1.3) respectively for LR2, SR and ADNEX on a scale from 1 to 10. Moreover, 89% indicated to have confidence in the results of the IOTA models. The most important factors to improve further implementation are more training (43%), research on sensitivity, specificity and cost-effectiveness in the Dutch health care system (27%), easier usability (24%) and more consultation time (19%). CONCLUSION: The IOTA ultrasound models are adopted in the majority of Dutch hospitals with the ADNEX model being used the most. While Dutch gynecologists have a strong familiarity and confidence in the models, the uptake varies in reality. Areas that warrant improvement in the Dutch context are more uniformity, education and more research. These findings can be helpful for other countries considering adopting the IOTA models.

Prophylactic and therapeutic strategies for intraoperative bleeding in women with von Willebrand disease and heavy menstrual bleeding: A systematic review.

BACKGROUND: Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined. AIM AND METHODS: To evaluate (pre)operative management in relation to (post)operative bleeding after endometrial ablation (EA) and hysterectomy in VWD women with HMB by performing a database search between 1994 and 2023. RESULTS: Eleven cohort studies and 1 case-report were included, of overall 'low' quality, describing 691 operative procedures. Prophylaxis (Desmopressin, clotting factor concentrates or tranexamic acid) to prevent bleeding was described in 100% (30/30) of EA procedures and in 4% (24/661) of hysterectomies. Bleeding complications despite prophylaxis were described in 13% (3/24) of hysterectomies vs 0% (0/30) in EA. CONCLUSION: VWD women often seem to experience bleeding complications during hysterectomy and all women with VWD received preprocedural hemostatic agents during EA, indicating potential under- and overdosing of current prophylactic strategies. Prospective studies are needed to determine the optimal (pre)operative strategy for gynecological surgical procedures in women with VWD.

The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Endometrial polypectomy using tissue removal device or electrosurgical snare: a randomised controlled trial.

Background: Hysteroscopic transcervical resection of endometrial polyps is a widely used method and is increasingly performed in office or outpatient care. To ensure patient comfort is key, smaller instruments are preferred while also achieving a complete resection of the pathology. Objectives: To evaluate the effectiveness of the electrosurgical polyp snare (DPS) in comparison with a tissue removal device (TRD). Materials and Methods: This was a randomised controlled non-inferiority trial which included 66 women with symptomatic endometrial polyps who had been referred to the gynaecological outpatient clinic at the Máxima Medical Centre, Veldhoven, the Netherlands. The patients were randomly allocated by using sealed envelopes to treatment with either the DPS (Duckbill®, Cook) or the TRD (Truclear™, Medtronic). Clinicians and patients were not blinded to the treatment performed. An independent observer blindly assessed the results. Main outcome measures: The primary outcome was the complete removal of the endometrial polyp. Secondary outcomes were woman acceptability and pain during the procedure, operating time, peri-operative and immediate postoperative complications. Results: 57% of the polyps in the DPS group and 95% in the TRD group were completely removed (risk difference -0.39; 95% CI: -0.60 to -0.15). Average operating time was longer with DPS compared to the TRD (11.7 min. vs. 6.8 min., p = 0.018). The number of insertions of the hysteroscope was higher with the DPS compared to the TRD (3.9 vs. 1.7, p <0.001). One serious adverse event, a uterine perforation, occurred in the DPS group. Conclusion: The TRD was superior to the DPS in completeness of polyp removal. What is new?: TRD has a higher rate of complete polyp resection, overall safety and higher patient satisfaction, this instrument should be considered as the preferred option in outpatient and office gynaecology.

The cost-effectiveness of transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility.

STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group €4991 versus €5262 in the HSG group, mean cost difference = -€271 (95% CI -€273 to -€269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -€271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary. STUDY FUNDING/COMPETING INTEREST(S): The authors received no external financial support for the research. B.W.J.M. is supported by an NHMRC Investigator Grant (GNT1176437). B.W.J.M. reports consultancy for ObsEva, Merck KGaA, Guerbet. B.W.J.M. reports receiving travel support from Merck KGaA. C.T.P. reports consultancy for Guerbet, outside of this manuscript. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NTR3462.

Tubal flushing with oil-based contrast during transvaginal hydro laparoscopy, a case report.

Background: Oil-based contrast has been shown to have a fertility-enhancing effect during hysterosalpingography (HSG) but is not yet used during transvaginal hydro laparoscopy (THL). Objective: To asses if additional tubal flushing with oil-based contrast during THL is feasible. Materials and Methods: Case report with video assessment. A healthy 29-year-old woman with primary unexplained subfertility, underwent a THL under local anaesthesia. First, chromopertubation was performed by methylene blue. Afterwards, tubal flushing with 3mL oil-based contrast (Lipiodol® UltraFluid, Guerbet) was performed. Main Outcome Measures: In this case report we evaluated the feasibility of additional tubal flushing with oil- based contrast during THL, in terms of; the visibility of the oil-based contrast at the tubal fimbriae, the pain and acceptability scores. Results: Both fallopian tubes were patent to methylene-blue as well as to oil-based contrast. Interestingly, the oil-based contrast came out of the fallopian tube in the form of free droplets with strong internal bonding. Furthermore, some residue of the droplets was visible on the surface of the peritoneal wall in the form of oily micro-droplets. Conclusions: We present the first sub-fertile woman, in which additional tubal flushing with oil-based contrast during THL was performed. It is likely, that the residue of oily micro-droplets is also present inside the fallopian tube, where it may enhance the cilia movement by introducing lubrication. These lubricating characteristics of the oil-based contrast may be important for its fertility-enhancing effect. More research is necessary to confirm this hypothesis and the feasibility of tubal flushing with oil-based contrast during THL in more women.

Fertility-related quality of life in subfertile women undergoing tubal testing with transvaginal hydrolaparoscopy or hysterosalpingography.

OBJECTIVE: Both subfertility and its management can have significant impact on quality of life (QoL). Tubal patency testing as part of the fertility work-up, is considered to cause more physical complaints and stress than other tests. Pain scores for HSG are higher than for THL, but acceptability of the procedures was found to be comparable. Fertility-related QoL has not yet been studied in women undergoing tubal patency testing. STUDY DESIGN: We performed a standardized questionnaire study alongside a previously reported randomized controlled trial comparing THL and HSG in subfertile women, in which 24-month live birth rates occurred in 58.5% versus 55.4%, respectively. We randomly assigned 300 subfertile women to THL or HSG between May 2013 and October 2016. Women were eligible if they were undergoing a fertility work-up with an indication for evaluation of tubal patency. Fertility-related QoL was measured six weeks after the procedure with the validated FertiQoL questionnaire. The scores for the Core scale and subscales between THL and HSG were compared using Mann-Whitney-U test and multiple linear regression analysis. RESULTS: The questionnaire was completed by 84 women in the THL group (56%) and 96 women in the HSG group (64%). Core scores were 74.6 ± 12.8 for THL and 73.4 ± 12.4 for HSG (p = 0.39). Scores for the Emotional domain were 64.5 ± 19.0 for THL versus 66.0 ± 16.3 (p = 0.67) for HSG. Scores for the 'Mind-body' domain for THL were 76.9 ± 15.6 versus 74.1 ± 18.0 for HSG (p = 0.42), while scores for the Relational domain were 79.2 ± 12.9 for THL and 76.9 ± 15.6 for HSG (p = 0.21). Scores for the Social domain for THL were 77.9 ± 15.1 versus 76.7 ± 14.1, (p = 0.42). The multiple linear regression analysis showed only a statistical significant positive effect of older age on the score for the Emotional domain (p = 0.015). CONCLUSION: In a preselected group of women with low risk for tubal pathology we did not find differences in fertility-related QoL between tubal patency testing with THL versus HSG.

Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study).

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast. METHODS: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years. DISCUSSION: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ).

Patient-specific affect-abdominal pain interactions in endometriosis: an experience sampling method (ESM) study.

OBJECTIVES: Cross-sectional studies show that endometriosis-related pain is associated with affect. Measuring these symptoms in real-time in a longitudinal perspective yields the ability to analyze the temporal relationship between variables. The aim was to evaluate the association between affect and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, randomly repeated assessment. METHODS: Thirty-four endometriosis patients and 31 healthy subjects completed up to 10 real-time self-assessments concerning abdominal pain and affective symptoms during seven consecutive days. RESULTS: Endometriosis patients experienced more abdominal pain and negative affective symptoms, and scored lower on positive affect compared to healthy controls. A significant association was found between abdominal pain and both positive and negative affect in endometriosis patients. For healthy controls, less strong or non-significant associations were found. When looking at abdominal pain as a predictor for affect and vice versa, we found that only in endometriosis patients, pain was subsequently accompanied by negative affect, and positive affect may alleviate pain in these patients. CONCLUSIONS: This study confirms a concurrent and temporal relationship between affect and abdominal pain in endometriosis patients and supports the use of real-time symptom assessment to interpret potential influencers of abdominal complaints in patients with endometriosis.

Short-term recovery after NovaSure® endometrial ablation: a prospective cohort study.

Background: Endometrial ablation is a frequently performed treatment for heavy menstrual bleeding, but detailed information about recovery to help inform patients is lacking. Objective: To gain more insight into the short-term recovery after NovaSure® endometrial ablation, with the goal of improving preprocedural counselling. Materials and Methods: A total of 61 women who underwent endometrial ablation between March 2019 and November 2021 in a teaching hospital in the Netherlands were included in this prospective cohort study. Main outcome measures: Short-term recovery was investigated through questionnaires in the first week after the procedure. The primary outcome was the Recovery Index (RI-10). Secondary outcomes included health-related quality of life (EQ-5D-5L), pain intensity, use of analgesics, nausea, vaginal discharge, capability of performing activities (domestic chores, sports, work), self-rated health (EQ-VAS) and the feeling of full recovery. Results: A total of 33 women underwent the procedure under local anaesthesia and 28 women under procedural sedation. The RI-10 increased in the first week; median scores on day one, two and seven were 34 (IQR 28.5-41.5), 38.5 (IQR 31-47), and 42 (IQR 37.5-48), respectively. The median time for full recovery was five days. However, 23% of all women were not fully recovered within seven days. Women needed a median time of two days for returning to their work and 5.5 days for sporting activities. There were no differences in recovery between both anaesthesia techniques. Conclusions: Women undergoing endometrial ablation can be informed that most will fully recover within the first week of the procedure and that there is no difference in expected recovery time according to whether the procedure is undertaken with local anaesthesia or conscious sedation. What is New?: The short-term recovery after endometrial ablation has been mapped in this trial. This information can be used in counselling women with heavy menstrual bleeding.

The levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the costs and non-inferiority of a strategy starting with the levonorgestrel intrauterine system (LNG-IUS) compared with endometrial ablation (EA) in the treatment of heavy menstrual bleeding (HMB). DESIGN: Cost-effectiveness analysis from a societal perspective alongside a multicentre randomised non-inferiority trial. SETTING: General practices and gynaecology departments in the Netherlands. POPULATION: In all, 270 women with HMB, aged ≥34 years old, without intracavitary pathology or wish for a future child. METHODS: Randomisation to a strategy starting with the LNG-IUS (n = 132) or EA (n = 138). The incremental cost-effectiveness ratio was estimated. MAIN OUTCOME MEASURES: Direct medical costs and (in)direct non-medical costs were calculated. The primary outcome was menstrual blood loss after 24 months, measured with the mean Pictorial Blood Assessment Chart (PBAC)-score (non-inferiority margin 25 points). A secondary outcome was successful blood loss reduction (PBAC-score ≤75 points). RESULTS: Total costs per patient were €2,285 in the LNG-IUS strategy and €3,465 in the EA strategy (difference: €1,180). At 24 months, mean PBAC-scores were 64.8 in the LNG-IUS group (n = 115) and 14.2 in the EA group (n = 132); difference 50.5 points (95% CI 4.3-96.7). In the LNG-IUS group, 87% of women had a PBAC-score ≤75 points versus 94% in the EA group (relative risk [RR] 0.93, 95% CI 0.85-1.01). The ICER was €23 (95% CI €5-111) per PBAC-point. CONCLUSIONS: A strategy starting with the LNG-IUS was cheaper than starting with EA, but non-inferiority could not be demonstrated. The LNG-IUS is reversible and less invasive and can be a cost-effective treatment option, depending on the success rate women are willing to accept. TWEETABLE ABSTRACT: Treatment of heavy menstrual bleeding starting with LNG-IUS is cheaper but slightly less effective than endometrial ablation.

How to increase awareness of additional vaccinations; the case of maternal pertussis vaccination.

BACKGROUND: Effective and safe vaccines are available outside national immunization programs (NIP). Increased awareness and vaccine uptake can improve public health. Before the inclusion of maternal pertussis vaccination (MPV) in the Dutch NIP in December 2019, extra communication efforts were undertaken. Here we examine the success of these efforts, investigating women's awareness of and their decision-making process regarding MPV. METHODS: Between December 2018 and January 2019, one year before the introduction of MPV in the NIP, and about three years after MPV was recommended by the Dutch Health Council, pregnant and non-pregnant women (i.e. child younger than two years) were invited to fill out an online questionnaire. Participant's decision-making processes regarding MPV were assessed with an adapted Precaution Adoption Process Model (PAPM), including stages of awareness, engagement, information-seeking, and vaccination behaviour. Furthermore, factors related to the decision-making process were examined. RESULTS: In total, 942 women were included, of whom 62% were non-pregnant. Most of the pregnant and nonpregnant women were aware of MPV during pregnancy (respectively 69 and 56%). Most aware women had heard about MPV through their midwife and the Public Health Institute (PHI) website. Women unaware of MPV reported a need for information, preferably from their midwives. Most aware women felt MPV was important to them (88%) and were classified as "engaged". Of the eligible and "engaged" pregnant women, 58% were vaccinated, versus 38% of "engaged" non-pregnant women. CONCLUSIONS: As the most preferred and trusted source of information, midwives are essential to increasing awareness of MPV. The PHI website is considered to be a reliable information source and is often consulted. To increase awareness, appropriate healthcare workers should be encouraged to actively inform target groups about available, additional vaccinations.

Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial.

STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus? SUMMARY ANSWER: Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus. WHAT IS KNOWN ALREADY: A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant. STUDY DESIGN, SIZE, DURATION: We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%). LIMITATIONS, REASONS FOR CAUTION: Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance. WIDER IMPLICATIONS OF THE FINDINGS: The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery. STUDY FUNDING/COMPETING INTEREST(S): There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: Dutch trial registry: NTR 1676. TRIAL REGISTRATION DATE: 18 February 2009. DATE OF FIRST PATIENT'S ENROLMENT: 20 October 2010.

Prospective study for establishing minimal clinically important differences in patients with surgery for lower extremity metastases.

BACKGROUND: The clinical relevance of patient-reported outcomes score changes is often unclear. Especially in patients undergoing surgery due to lower extremity metastases - where surgery is performed in the palliative setting and the goal is to optimize functional mobility, relieve pain and improve overall quality of life. This study assessed the minimal clinically important difference (MCID) of Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference, Cancer-specific Physical Function, and Global (Physical and Mental Health) in patients treated surgically for impending or completed pathologic fractures. METHODS: Patients undergoing surgery for osseous metastasis of the lower extremity because of an impending or completed pathologic fracture were consecutively enrolled in this tertiary center study. Patients completed the three PROMIS questionnaires preoperatively (n = 56) and at postoperative follow-up (n = 33) assessment one to three months later. Of the 23 patients that did not complete the postoperative survey, 5 patients died within 1-3 months and 18 patients were alive at 3-months but did not respond or show up at their postoperative consult. Thirty-one patients (94%) of the 33 included patients reported at least minimal improvement and two patients (6.1%) no change 1-3 months after the surgery based on an anchor-based approach. RESULTS: The PROMIS MCIDs (95% confidence interval) for Pain Interference was 7.5 (3.4-12), Physical Function 4.1 (0.6-7.6), Global Physical Health 4.2 (2.0-6.6), and Global Mental Health 0.8 (-4.5-2.9). CONCLUSION: This prospective study successfully defined a MCID for PROMIS Pain Interference of 7.5 (3.4-12), PROMIS Physical Function of 4.1 (0.6-7.6), and Global Physical Health of 4.2 (2.0-6.6) in patients with (impending) pathological fractures due to osseous metastases in the lower extremity; no MCID could be established for PROMIS Global Mental Health. Defining a narrower MCID value for each subpopulation requires a large, prospective, multicenter study. Nevertheless, the provided MCID values allow guidance to clinicians to evaluate the impact of surgical treatment on a patient's QoL. LEVEL OF EVIDENCE: Level II Diagnostic study.

Effect of single- versus double-layer uterine closure during caesarean section on postmenstrual spotting (2Close): multicentre, double-blind, randomised controlled superiority trial.

OBJECTIVE: To evaluate whether double-layer uterine closure after a first caesarean section (CS) is superior compared with single-layer uterine closure in terms of postmenstrual spotting and niche development in the uterine caesarean scar. DESIGN: Multicentre, double-blind, randomised controlled superiority trial. SETTING: Thirty-two hospitals in the Netherlands. POPULATION: A total of 2292 women aged ≥18 years undergoing a first CS were randomly assigned to each procedure (1:1): 1144 women were assigned to single-layer uterine closure and 1148 women were assigned to double-layer uterine closure. METHODS: Single-layer unlocked closure and double-layer unlocked closure, with the second layer imbricating the first. MAIN OUTCOME MEASURES: Number of days with postmenstrual spotting during one menstrual cycle 9 months after CS. SECONDARY OUTCOMES: perioperative and menstrual characteristics; transvaginal ultrasound measurements. RESULTS: A total of 774 (67.7%) women from the single-layer group and 770 (67.1%) women from the double-layer group were evaluable for the primary outcome, as a result of drop-out and amenorrhoea. The mean number of postmenstrual spotting days was 1.33 (bootstrapped 95% CI 1.12-1.54) after single-layer closure and 1.26 (bootstrapped 95% CI 1.07-1.45) after double-layer closure (adjusted mean difference -0.07, 95% CI -0.37 to 0.22, P = 0.810). The operative time was 3.9 minutes longer (95% CI 3.0-4.9 minutes, P < 0.001) and niche prevalence was 4.7% higher (95% CI 0.7-8.7%, P = 0.022) after double-layer closure. CONCLUSIONS: The superiority of double-layer closure compared with single-layer closure in terms of postmenstrual spotting after a first CS was not shown. Long-term obstetric follow-up of our trial is needed to assess whether uterine caesarean closure guidelines should be adapted. TWEETABLE ABSTRACT: Double-layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single-layer closure performs slightly better on other outcomes.

SOMA-trial: surgery or medication for women with an endometrioma? Study protocol for a randomised controlled trial and cohort study.

STUDY QUESTIONS: The objective of this study is to evaluate the effectiveness and cost-effectiveness of surgical treatment of women suffering from pain due to an ovarian endometrioma when compared to treatment with medication (analgesia and/or hormones). The primary outcome is defined as successful pain reduction (-30% reduction of pain) measured by the numeric rating scale (NRS) after 6 months. Secondary outcomes include successful pain reduction after 12 and 18 months, quality of life, affective symptoms, cost-effectiveness, recurrence rate, need of adjuvant medication after surgery, ovarian reserve, adjuvant surgery and budget impact. WHAT IS KNOWN ALREADY: Evidence suggests that both medication and surgical treatment of an ovarian endometrioma are effective in reducing pain and improving quality of life. However, there are no randomised studies that compare surgery to treatment with medication. STUDY DESIGN SIZE DURATION: This study will be performed in a research network of university and teaching hospitals in the Netherlands. A multicentre randomised controlled trial and parallel prospective cohort study in patients with an ovarian endometrioma, with the exclusion of patients with deep endometriosis, will be conducted. After obtaining informed consent, eligible patients will be randomly allocated to either treatment arm (medication or surgery) by using web-based block randomisation stratified per centre. A successful pain reduction is set at a 30% decrease on the NRS at 6 months after randomisation. Based on a power of 80% and an alpha of 5% and using a continuity correction, a sample size of 69 patients in each treatment arm is needed. Accounting for a drop-out rate of 25% (i.e. loss to follow up), we need to include 92 patients in each treatment arm, i.e. 184 in total. Simultaneously, a cohort study will be performed for eligible patients who are not willing to be randomised because of a distinct preference for one of the two treatment arms. We intend to include 100 women in each treatment arm to enable standardization by inverse probability weighting, which means 200 patients in total. The expected inclusion period is 24 months with a follow-up of 18 months. PARTICIPANTS/MATERIALS SETTING METHODS: Premenopausal women (age ≥ 18 years) with pain (dysmenorrhoea, pelvic pain or dyspareunia) and an ovarian endometrioma (cyst diameter ≥ 3 cm) who visit the outpatient clinic will make up the study population. Patients with signs of deep endometriosis will be excluded. The primary outcome is successful pain reduction, which is defined as a 30% decrease of pain on the NRS at 6 months after randomisation. Secondary outcomes include successful pain reduction after 12 and 18 months, quality of life and affective symptoms, cost-effectiveness (from a healthcare and societal perspective), number of participants needing additional surgery, need of adjuvant medication after surgery, ovarian reserve and recurrence rate of endometriomas. Measurements will be performed at baseline, 6 weeks and 6, 12 and 18 months after randomisation. STUDY FUNDING/COMPETING INTERESTS: This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-85200-98-91041. The Department of Reproductive Medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck KGaA and Ferring not related to the submitted work. B.W.J. Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for ObsEva, Merck KGaA and Guerbet. V. Mijatovic reports grants from Guerbet, grants from Merck and grants from Ferring outside the submitted work. All authors declare that they have no competing interests concerning this publication. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7447, http://www.trialregister.nl). TRIAL REGISTRATION DATE: 2 January 2019. DATE OF FIRST PATIENT'S ENROLMENT: First inclusion in randomised controlled trial October 4, 2019. First inclusion in cohort May 22, 2019.