The differences between adults and adolescents using a mobile health application for menstrual complaints: A usability and qualitative study.

BACKGROUND: A "Menstruatie Educatie Kalender" application (Menstruation Education Calendar, (MEK-APP)) was developed for adults to evaluate menstrual complaints. The future aim of this app is to use it as a self-diagnostic instrument for menstrual abnormalities for both adults and adolescents. Early identification of the potential of an application for future use by both user groups would increase implementation success and adoption of the application. OBJECTIVE: To compare differences in experienced usability by adults versus adolescents and to identify factors influencing future use for both age groups in one mHealth application (in this study the MEK-APP). METHODS: This study consisted of three phases: (1) usability testing of the MEK-APP for iOS and Android by think-aloud method, (2) two-month daily use and (3) in-depth individual interview. During the think-aloud sessions, twelve tasks were performed in the application while they were thinking aloud. Usability problems were rated for their severity with Nielsen' Severity Scale. Both the think-aloud sessions and in-depth interviews were verbatim transcribed and thematically analyzed to determine the factors influencing future use for both groups. In addition, the System Usability Scale (SUS) and Intrinsic Motivation Inventory (IMI) questionnaires were filled out during the interviews. RESULTS: Seven adults (>18 years) and seven adolescents (14-18 years) evaluated the MEK-APP. There were 14 usability issues and 16 bugs in both groups. There were no differences between adults and adolescents. In the thematic qualitative analysis, the following future use factors were identified: user-expectation, motivation, privacy, understandability, and user-experience. The user-expectation, motivation and privacy differed between both groups but did not influence usage. No differences were observed in SUS and IMI scores between both groups. CONCLUSIONS: There are five factors influencing the future use of a menstrual-related mHealth application for both adults and adolescents. It is possible to serve different age groups with a single application.

Instruments to Identify Menstrual Complaints and Their Impact on Adolescents: A Systematic Review.

STUDY OBJECTIVE: The aim of this review was to create an overview of available instruments used to evaluate the menstrual complaints of dysmenorrhea and heavy menstrual bleeding (HMB) in adolescents. METHODS: The search was conducted in PubMed, Web of Science, Embase, and PsycINFO on December 1, 2022. Studies published in English reporting on menstrual complaints among girls aged 10-19 were included. The quality and bias risk was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Of 8994 identified studies, 57 were included. In these studies, 19 instruments were described, of which 8 were validated in adolescents. One was difficult to use in daily practice, 1 had low sensitivity and specificity in the detection of HMB, 2 were validated by face validity, and 2 were not specifically developed to evaluate (the impact of) menstrual complaints. Therefore, only 2 were validated and feasible to measure adolescent menstrual complaints: the Period ImPact and Pain Assessment (PIPPA) and the Adolescent Menstrual Bleeding Questionnaire (aMBQ). Remarkably, the Pictorial Blood Loss Assessment Chart (PBAC) was the most frequently used instrument in adolescents. There was one modified version of the PBAC for adolescents, which had a lower cutoff value for HMB and low sensitivity and specificity. CONCLUSION: We found that the PIPPA and aMBQ are suitable for assessing menstrual complaints and their impact on daily activities and health-related quality of life in adolescents. The PBAC, which is used frequently in adults, needs to be further assessed specifically for adolescents. In particular, the clinical relevance of the PBAC cutoff value for HMB should be determined for this age group. Considering the different interpretations, experiences, and limited knowledge of menstrual complaints, instruments suitable for adults may not be suitable for adolescents.

Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

BACKGROUND: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. METHODS AND FINDINGS: This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. CONCLUSIONS: Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. TRIAL REGISTRATION: The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).

Single-layer vs double-layer uterine closure during cesarean delivery: 3-year follow-up of a randomized controlled trial (2Close study).

BACKGROUND: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. OBJECTIVE: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. STUDY DESIGN: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). RESULTS: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. CONCLUSION: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.

Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study).

INTRODUCTION: A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche. METHODS AND ANALYSIS: The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of >50% of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks' gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER DUTCH TRIAL REGISTER REF NO NL6350 : http://www.trialregister.nl.

Vaccination from the early second trimester onwards gives a robust SARS-CoV-2 antibody response throughout pregnancy and provides antibodies for the neonate.

OBJECTIVES: Preventive measures against COVID-19 are essential for pregnant women. Pregnant women are particularly vulnerable to emerging infectious pathogens due to alterations in their physiology. We aimed to determine the optimum timing of vaccination to protect pregnant women and their neonates from COVID-19. METHODS: A prospective observational longitudinal cohort study in pregnant women who received COVID-19 vaccination. We collected blood samples to evaluate levels of antispike, receptor binding domain and nucleocapsid antibodies against SARS-CoV-2 before vaccination and 15 days after the first and second vaccination. We determined the neutralizing antibodies from mother-infant dyads in maternal and umbilical cord blood at birth. If available, immunoglobulin A was measured in human milk. RESULTS: We included 178 pregnant women. Median antispike immunoglobulin G levels increased significantly from 1.8 to 5431 binding antibody units/ml and receptor binding domain from 6 to 4466 binding antibody units/ml. Virus neutralization showed similar results between different weeks of gestation at vaccination (P >0.3). CONCLUSION: We advise vaccination in the early second trimester of pregnancy for the optimum balance between the maternal antibody response and placental antibody transfer to the neonate.

Definition and Criteria for Diagnosing Cesarean Scar Disorder.

Importance: Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms. Objective: To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition. Design, Setting, and Participants: A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022. Main Outcomes and Measures: Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche. Results: In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis. Conclusions and Relevance: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.

Effectiveness, complications, and reproductive outcomes after cesarean scar pregnancy management: a retrospective cohort study.

BACKGROUND: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined. OBJECTIVE: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management. STUDY DESIGN: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth. RESULTS: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P=.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P=.01) after a curettage, and 6 months (interquartile range, 4-15; P=.03) after a laparoscopic niche resection. CONCLUSION: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies.

The link between intrauterine adhesions and impaired reproductive performance: a systematic review of the literature.

BACKGROUND: Intrauterine adhesions (IUAs) are one of the main reproductive system diseases in women worldwide. Fusion between the injured opposing walls leads to partial-to-complete obliteration of the cavity and/or cervical canal. The main clinical manifestations in case of IUAs are menstrual disturbances, cyclic pain and reproductive disorders. The reproductive outcomes of women with IUAs remain limited and inefficient compared to women without IUAs, even after adhesiolysis. An exact understanding of the underlying mechanisms and processes to explain the compromised reproductive performance and outcomes in case of IUAs are lacking. METHODS: A systematic literature review of MEDLINE-PubMed (1966 to January 2022) and EMBASE (1974 to January 2022) was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they reported underlying causes, related mechanisms and processes to explain the association between IUAs and impaired reproductive performance, pregnancy and obstetric complications. RESULTS: After an extensive review of the literature, 58 articles were identified reporting underlying mechanisms to explain the association between IUAs and impaired fertility. Intrauterine scarring influences the process of fertilization, reproductive performance and ultimately reproductive outcome. IUAs can disturb the cervico-utero-tubal sperm transport and result in an avascular and unresponsive endometrium with decreased receptivity and thickness. Abnormal decidualization and abnormal trophoblastic infiltration leads to placental attachment disorders. Moreover, the risk for premature delivery, intrauterine fetal growth restriction and fetal anomalies is increased in case of IUAs. CONCLUSION: The impact of IUAs on reproductive performance, even after adhesiolysis, is becoming more apparent. The postulated mechanisms to explain the association are related to sperm transport, embryo implantation and placentation. Prevention, by preserving the basal layer of the endometrium is essential. Effective and evidence-based strategies for the prevention of endometrial injury and formation of IUAs, are urgently needed.

Change of the residual myometrial thickness during pregnancy in women who underwent laparoscopic niche resection compared with controls without niche surgery: a prospective comparative cohort study.

BACKGROUND: Reduced residual myometrial thickness before and during pregnancy is associated with uterine rupture or dehiscence after vaginal birth after cesarean delivery. Laparoscopic niche resection performed in case of gynecologic symptoms has shown to increase residual myometrial thickness 6 months after surgery. OBJECTIVE: This study aimed to evaluate the change in residual myometrial thickness from baseline value before pregnancy to the third trimester of pregnancy in women with and without laparoscopic niche resection and evaluate niche presence, niche size during pregnancy vs before pregnancy, and obstetrical outcomes, including uterine rupture and dehiscence in both study groups. STUDY DESIGN: This was a prospective cohort study conducted in an academic medical center. Of note, 2 groups of pregnant women with a previously diagnosed niche were included: (1) women with a large symptomatic niche (residual myometrial thickness of <3 mm) followed by laparoscopic niche resection (LNR group) and (2) women with a niche without niche resection because of minimal symptoms or a residual myometrial thickness of ≥3 mm diagnosed before current pregnancy (expectant group). Participants underwent a transvaginal ultrasound at 12, 20, and 30 weeks of gestation. Changes in residual myometrial thickness and changes in niche measurements over time were analyzed with linear mixed models. RESULTS: A total of 100 women were included, 61 in the LNR group and 39 in the expectant group. The change in residual myometrial thickness from baseline value before niche resection to the third trimester of pregnancy was +2.0 mm in the LNR group vs -1.6 mm in the expectant group (P<.001). Residual myometrial thickness decreased from the first trimester of pregnancy onward in both groups. Although residual myometrial thickness was thinner at baseline in the LNR group, it was thicker in the LNR group than in the expectant group during all trimesters: 3.2 mm (P<.001) in the first trimester of pregnancy, 2.5 mm (P<.001) in the second trimester of pregnancy, and 1.8 mm (P=.001) in the third trimester of pregnancy. Uterine dehiscence was reported in 1 of 50 women (2%) in the LNR group and 7 of 36 women (19%) in the expectant group (P=.007) and was related to the depth of niche-to-residual myometrial thickness ratio before pregnancy (after niche resection) and residual myometrial thickness in the second trimester of pregnancy. No uterine rupture was reported. Most patients received a scheduled cesarean delivery in both groups. There was more blood loss during subsequent cesarean delivery in the LNR group than in the expectant group. CONCLUSION: Here, laparoscopic niche resection resulted in an increased residual myometrial thickness during a subsequent pregnancy. Moreover, a lower number of dehiscence was found in the LNR group than in the expectant group without niche surgery. Per-section blood loss was higher in the LNR group than in the expectant group. In general, laparoscopic niche resection is performed to improve gynecologic symptoms. Currently, there is no evidence to support a laparoscopic niche resection to improve obstetrical outcomes, but the trend toward more uterine dehiscence encourages further research.

Fear of childbirth in pregnancy was not increased during the COVID-19 pandemic in the Netherlands: a cross-sectional study.

INTRODUCTION: Fear of childbirth is a well-known problem during pregnancy and can have implications for childbirth, including prolonged labor, use of epidural analgesia, obstetric complications, presence of traumatic stress symptoms, or request for an elective cesarean section. The coronavirus disease 2019 (COVID-19) pandemic has affected mental health and therefore could have increased fear of childbirth during the pandemic. The aim of this study was to investigate fear of childbirth during the pandemic in the Netherlands compared with a reference group from before the pandemic. MATERIAL AND METHODS: We conducted a cross-sectional study to evaluate pregnant women during the first and second waves of COVID-19 compared with both each other and with pregnant women from before the pandemic. Participants were recruited through social media platforms, hospitals, and midwifery practices. Pregnant women aged ≥18 years who had mastered the Dutch language were eligible to participate. Fear of childbirth was measured with the Wijma Delivery Expectancy Questionnaire online using a cut-off score of ≥85 to indicate clinically relevant fear of childbirth. The primary outcome was the prevalence of fear of childbirth. We undertook additional analyses to specifically look at possible effect modification. RESULTS: In total, 1102 pregnant women completed the questionnaire during the first wave of the pandemic, 731 during the second wave, and 364 before the pandemic. Fear of childbirth was present in 10.6%, 11.4%, and 18.4%, respectively. We considered possible effect modification, which indicated that age and parity had a significant influence. In participants during the first wave of COVID-19, nulliparous women had significantly lower odds (odds ratio [OR] 0.50; 95% confidence interval [CI] 0.34-0.73; p < 0.01) of having a fear of childbirth than did the reference group. Both younger participants in the first wave (OR 0.59; 95% CI 0.37-0.93; p < 0.05) and older participants in the first wave (OR 0.44; 95% CI 0.28-0.71; p < 0.01) and the second wave (OR 0.36; 95% CI 0.21-0.62; p < 0.01) of COVID-19 had lower odds of fear of childbirth than the reference group. CONCLUSIONS: Pregnant women during the first and second waves of COVID-19 had lower fear of childbirth scores than pregnant women before the pandemic, indicating less fear of childbirth during the pandemic. This could be explained by an increased level of information, more time to consume information, and better work-life balance with more people working at home during the pandemic.

Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial.

STUDY QUESTION: Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs. SUMMARY ANSWER: Reproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs; fewer ongoing pregnancies and live births are achieved with a prolonged time to a live birth. WHAT IS KNOWN ALREADY: The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance. STUDY DESIGN, SIZE, DURATION: This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8-12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Additionally, the medical files of all participants were reviewed. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded. MAIN RESULTS AND THE ROLE OF CHANCE: In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value <0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups. LIMITATIONS, REASONS FOR CAUTION: In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol; the influence of IUAs on reproductive outcome may therefore be underestimated. Women undergoing a recurrent D&C for miscarriage were included, a specific group likely to generate clinically significant adhesions. The findings should therefore not be generalized to all women undergoing D&C for miscarriage. WIDER IMPLICATIONS OF THE FINDINGS: As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered. STUDY FUNDING/COMPETING INTEREST(S): The original PAPA study (NTR 3120) was an investigator initiated study that was funded by the Foundation for scientific investigation in Obstetrics and Gynaecology of the Saint Lucas Andreas Hospital (currently renamed OLVG Oost), SWOGA. The syringes containing ACP gel were received from Anika Therapeutics, the manufacturer of Hyalobarrier® Gel Endo. The current follow-up study was also an investigator-initiated study without funding. The funder and sponsor had no role in the design of this follow-up study, data collection, data analysis, data interpretation, trial design, patient recruitment, writing of the report or any aspect pertinent to the study. ABH, RAL, JAFH and JWRT have no conflict to declare. HAMB reports being a member of safety board research Womed. TRIAL REGISTRATION NUMBER: Netherlands Trial Register NTR 3120.

Pregnancy and neonatal outcomes 42 months after application of hyaluronic acid gel following dilation and curettage for miscarriage in women who have experienced at least one previous curettage: follow-up of a randomized controlled trial.

OBJECTIVE: To study whether intrauterine application of auto-crosslinked polymers of hyaluronic acid (ACP) gel after dilation and curettage (D&C) improves reproductive outcomes. DESIGN: Follow-up of a prospective randomized trial. SETTING: University and university-affiliated teaching hospitals. PATIENT(S): Women with a miscarriage at <14 weeks' gestation with at least one previous D&C were randomized to D&C plus ACP gel (intervention) or D&C alone (control). A hysteroscopy was performed after 8-12 weeks, and if intrauterine adhesion (IUAs) were encountered, adhesiolysis was executed. INTERVENTION(S): Participants received a questionnaire 30 months after treatment. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and outcome of subsequent pregnancies. RESULT(S): Ongoing pregnancies were recorded in 74.6% (50/67) of the intervention group versus 67.2% (43/64) of the control group, and in, respectively, 94.3% (50/53) versus 71.7% (43/60) in the women wishing to conceive. The median times to conception leading to a live birth were, respectively, 21.9 versus 36.1 months. Reduced menstrual blood loss was reported in 7.5% (5/67) versus 20.3% (13/64) and dysmenorrhea in 14.9% (10/67) versus 34.4% (22/64), respectively. CONCLUSION(S): Application of ACP gel following D&C performed after miscarriage seems to have a favorable effect on subsequent reproductive outcomes in women with at least one previous D&C. Given the fact that the study was not powered for reproductive outcomes, the data should be interpreted with caution. The effect may be underestimated due to routine removal of IUAs. DUTCH CLINICAL TRIAL REGISTRY NUMBER: NTR 3120.

Improved health-related quality of life in the first year after laparoscopic niche resection: a prospective cohort study.

OBJECTIVE: To evaluate changes in health-related quality of life (HRQOL) the first year after laparoscopic niche resection. STUDY DESIGN: Prospective cohort study in women with a large niche (residual myometrium thickness <3.0 mm) after caesarean section who underwent laparoscopic niche resection between May 2010 and January 2018. Women were included consecutively. 36-Item Short Form Survey (SF-36) was sent at baseline, three and twelve months postoperatively. All participants that filled out the questionnaire at baseline were included. Physical (PCS) and mental component summary scores (MCS) and scores for subdomains were calculated. Scores were analysed over time using Wilcoxon signed rank test. RESULTS: 146 participants responded to the SF-36 at baseline, of which 129 (88.4 %) responded at three or twelve months follow-up. After three months, median PCS and MCS improved, compared to baseline (p = 0.014 and p = 0.008, respectively). Subdomains physical functioning, bodily pain, general health, vitality, mental health and social functioning improved significantly. At twelve months follow-up, improvement in PCS and MCS did not reach statistical significance (p = 0.053 and p = 0.063, respectively). Subdomains bodily pain (77.6-89.8, p < 0.001), mental health (76-80, p = 0.004) and social functioning (75-87.5, p = 0.016) improved significantly. Women with symptom relief as main goal of the intervention showed larger improvement in PCS than women with distorted anatomy and to restore anatomy as main goal for the intervention (p = 0.001). CONCLUSION: Laparoscopic niche resection improves HRQOL in women with a large niche in physical and mental domains three and twelve months postoperatively.

Niche-related outcomes after caesarean section and quality of life: a focus group study and review of literature.

BACKGROUND: A niche in the uterus, present in 60% of women after caesarean section (CS), is associated with several gynaecological symptoms and possibly with subfertility. Studies that focus on quality of life (QoL) in relation to a niche are lacking. PURPOSE: To identify niche-related outcomes that influence QoL and to compare patient-reported outcomes with outcomes studied in the literature. METHODS: Two focus group discussions (FGDs, N = 8 and 5) were conducted in Amsterdam UMC-location VUmc. Participants were Dutch patients with a large niche, with (planned) surgical treatment for their symptoms. Niche-related symptoms and impact on functioning or participation were fixed topics. The transcripts of the FGDs were coded into outcomes, themes and domains of QoL according to the WHOQOL model. Additionally, participants created a top five important outcomes. Next, we performed a systematic review (SR) on niche-related outcomes and compared the FGDs with niche-related outcomes from the SR. RESULTS: In four domains (physical health, psychological domain, social relationships and environment), fifteen themes were reported in the FGDs. Abnormal uterine bleeding (AUB), subfertility, sexual activity, abdominal pain and self-esteem were themes prioritised by participants. In the literature, gynaecological symptoms and reproductive outcomes were predominantly studied. Sexuality and self-esteem were prioritised in the FGDs but hardly or never studied in the literature. CONCLUSION: We found a broad range of niche-related outcomes influencing QoL. Apart from symptoms evaluated in the literature such as AUB, abdominal pain and subfertility, clinicians and researchers should be more aware of sexual activity and self-esteem in this population.

Reproductive performance after the application of hyaluronic acid gel after dilation and curettage in women who have experienced at least one previous curettage: long-term results of a multicenter prospective randomized trial.

OBJECTIVE: To examine whether intrauterine application of auto-cross-linked hyaluronic acid (ACP) gel after dilation and curettage (D&C) improves reproductive performance. DESIGN: Multicenter prospective randomized trial. SETTING: One university and seven university-affiliated teaching hospitals. PATIENT(S): A total of 149 women who have experienced a miscarriage at <14 weeks of gestation, with at least one previous D&C for miscarriage or termination of pregnancy, were randomly assigned to either D&C plus ACP gel (intervention group) or D&C alone (control group). A hysteroscopy was performed 8-12 weeks after the procedure. Where intrauterine adhesions (IUAs) were found, adhesiolysis was executed. INTERVENTION(S): Participants received questionnaires 3, 6, and 12 months after the initial D&C procedure with questions regarding menstrual pattern, conception, and reproductive outcome. MAIN OUTCOME MEASURE(S): Reproductive outcomes during the 12 months after the D&C procedure. RESULT(S): Outcomes were available for 149 women: 77 in the intervention group and 72 in the control group. The conception rates were, respectively, 71% (46/64) and 59.7% (40/67). There was no significant difference in the miscarriage, ongoing pregnancy, and live birth rates. The median times to conception were 5.5 and 7.1 months, respectively. CONCLUSION(S): Reproductive performance was similar in both groups although there was a significant difference in the prevalence of IUAs. Given the favorable reproductive outcome in this underpowered study and the fact that adhesiolysis was executed, no solid conclusion can be drawn. Future studies are needed to evaluate the effect of ACP gel on fertility and reproductive outcomes. CLINICAL TRIAL REGISTRATION NUMBER: NTR 3120.