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STUDY QUESTION Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between −0.7% and +9.9%. WHAT IS KNOWN ALREADY Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96–1.59]). These data are consistent with a true difference of between −0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71–2.07) and RR 0.73 (95% CI 0.38–1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between −1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports ‘other’ from Ferring BV, personal fees from Up to date Hyperthecosis, ‘other’ from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE 31 July 2015. DATE OF FIRST PATIENT’S ENROLMENT 26 January 2016.

Study question Does septum resection improve reproductive outcomes in women with a septate uterus? Summary answer In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management. What is known already The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2–2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies. Study design, size, duration We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK. Participants/materials, setting, methods We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders. Main results and the role of chance In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49–1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52–1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81–3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52–3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24–1.33)). Limitations, reasons for caution Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding. Wider implications of the findings Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. Study funding/competing interest(s) A travel for JFWR to Chicago was supported by the Jo Kolk Studyfund. Otherwise, no specific funding was received for this study. The Department of Obstetrics and Gynaecology, University Medical Centre, Groningen, received an unrestricted educational grant from Ferring Pharmaceutical Company unrelated to the present study. BWM reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck, personal fees from Guerbet, other payment from Guerbet and grants from Merck, outside the submitted work. The other authors declare no conficts of interest. Trial registration number N/A

INTRODUCTION: Curettage is more effective than expectant management in women with suspected incomplete evacuation after misoprostol treatment for first-trimester miscarriage. The cost-effectiveness of curettage vs. expectant management in this group is unknown.MATERIAL AND METHODS: From June 2012 until July 2014 we conducted a randomized controlled trial and parallel cohort study in the Netherlands, comparing curettage with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first-trimester miscarriage. Successful treatment was defined as a sonographic finding of an empty uterus 6 weeks after study entry, or an uneventful course. Cost-effectiveness and cost-utility analyses were performed. We included costs of healthcare utilization, informal care and lost productivity. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated using bootstrapping.RESULTS: We included 256 women from 27 hospitals; 95 curettage and 161 expectant management. Treatment was successful in 96% of the women treated with curettage vs. 83% of the women after expectant management (mean difference 13%, 95% confidence interval 5-20). Mean costs were significantly higher in the curettage group (mean difference €1157; 95% C confidence interval €955-1388). The incremental cost-effectiveness ratio for curettage vs. expectant management was €8586 per successfully treated woman. The cost-effectiveness acceptability curve showed that at a willingness-to-pay of €18 200/extra successfully treated women, the probability that curettage is cost-effective is 95%.CONCLUSIONS: Curettage is not cost-effective compared with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment. This indicates that curettage in this group should be restrained.

Objective: To assess the effectiveness of curettage versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Study design: We conducted a multicenter cohort study alongside a randomized clinical trial (RCT) between June 2012 until July 2014. 27 Dutch hospitals participated. Women with an incomplete evacuation after misoprostol treatment for first trimester miscarriage who declined to participate in the RCT, received treatment of their preference; curettage (n = 65) or expectant management (n = 132). A successful outcome was defined as an empty uterus on sonography at six weeks or uneventful clinical follow-up. We furthermore assessed complication rate and (re)intervention rateResults: Of the 197 women who declined to participate in the RCT, 65 preferred curettage and 132 expectant management. A successful outcome was observed in 62/65 women (95%) in the surgical group versus 112/132 women (85%) in the expectant group (RR 1.1, 95% CI 1.03-1.2), with complication rates of 6.2% versus 2.3%, respectively (RR 2.7, 95% CI 0.6-12).Conclusion: In women with an incomplete evacuation of the uterus after misoprostol treatment, expectant management is an effective and safe option. This finding could restrain the use of curettage in women that have used misoprostol in the treatment of first trimester miscarriage. (C) 2017 Elsevier B.V. All rights reserved.

Research question What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria? Design A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap resampling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed. Results The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468; 95% confidence interval [CI] €464–472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93–1.47), the ICER was €21,804 (95% CI €11,628–31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998–25,090) per additional live birth with gonadotrophins. Conclusions Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective.

Background Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. Methods Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. Discussion This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. Trial registration Dutch Trial Register (NTR5480). Registered 29 October 2015. Electronic supplementary material The online version of this article (10.1186/s12884-019-2221-y) contains supplementary material, which is available to authorized users.

Since the first successful live birth after in vitro fertilization (IVF) was reported in 1978, more than 5 million children have been born with the help of this and intracytoplasmic sperm injection (ICSI) procedures. However, only approximately 25% to 30% of cycles of IVF and ICSI lead to the birth of a child. The reasons for implantation failure are poorly understood. One major cause of implantation failure is abnormalities of the uterine cavity such as polyps, myoma, and adhesions. Hysteroscopy has been generally regarded as the standard procedure to detect these uterine abnormalities. It is thought to improve pregnancy rates in women scheduled for IVF by detection and surgical removal of uterine cavity abnormalities, dilatation of the cervical canal, or induction of inflammatory reactions in the endometriumby the procedure itself. Hysteroscopy is often performed routinely in infertile women scheduled for their first IVF cycle. However, there are no data from well-designed randomized controlled trials to support this practice. The inSIGHT trial is a pragmatic multicenter randomized clinical trial designed to determine whether routine hysteroscopy before the first IVF treatment cycle increases the live birth rate. The trial was conducted in 7 university hospitals and 15 large general hospitals in the Netherlands. Women eligible for the trial were infertile, scheduled to start their first IVF or ICSI treatment, had no previous hysteroscopy, and had a normal transvaginal ultrasound of the uterine cavity. Subjects were randomly assigned in a 1: 1 ratio to hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF followed by IVF (hysteroscopy group) or to immediate start of IVF treatment (immediate IVF group). Web-based randomization was done with a variable block size to allocate patients to groups and was stratified by center. The doctors, outcome assessors, and participants were not masked to the assigned group. The primary study outcome was an ongoing pregnancy (detection of a fetal heartbeat at > 12weeks of gestation) within 18 months of randomization and a live birth. Analysis was done according to intention to treat. Between May 25, 2011, and August 27, 2013, 750 women were randomized: 373 to the hysteroscopy group and 377 to the immediate IVF group. A live birth occurred during the trial period in 209 (57%) of 369 women in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group; the relative riskwas 1.06, with a 95% confidence interval of 0.93 to 1.20; P = 0.41. These findings demonstrate that hysteroscopy does not improve live birth rates in infertile women scheduled for their first IVF cycle, who have a normal transvaginal ultrasound of the uterine cavity. Therefore, routine hysteroscopy should not be performed in women with a normal transvaginal ultrasound.

The authors of the above article would like to apologise for an error in one of the authors' names. W. Kuchenbecker should be W.K.H. Kuchenbecker, as above. The electronic version of this article has been updated at https:// doi.org/10.1093/humrep/dez284. The print version is correct. The Authors would like to assure readers that this does not affect any other content of the article.

BACKGROUND: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility.METHOD: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months.DISCUSSION: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception TRIAL REGISTRATION: NTR6687 , registered August 31st, 2017.PROTOCOL VERSION: Version 2.6, November 14th, 2018.

Contains fulltext : 177721.pdf (Publisher’s version ) (Open Access) BACKGROUND: Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. METHOD: Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. DISCUSSION: Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. TRIAL REGISTRATION: NTR 5342 , registered July 31st, 2015. PROTOCOL VERSION: Version 4.10, January 4th, 2017.

Contains fulltext : 174671.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To study the effectiveness of four cycles of intrauterine insemination (IUI) with ovarian stimulation (OS) by follicle-stimulating hormone (FSH) or by clomiphene citrate (CC), and adherence to strict cancellation criteria. SETTING: Randomised controlled trial among 22 secondary and tertiary fertility clinics in the Netherlands. PARTICIPANTS: 732 women from couples diagnosed with unexplained or mild male subfertility and an unfavourable prognosis according to the model of Hunault of natural conception. INTERVENTIONS: Four cycles of IUI-OS within a time horizon of 6 months comparing FSH 75 IU with CC 100 mg. The primary outcome is ongoing pregnancy conceived within 6 months after randomisation, defined as a positive heartbeat at 12 weeks of gestation. Secondary outcomes are cancellation rates, number of cycles with a monofollicular or with multifollicular growth, number of follicles >14 mm at the time of ovulation triggering, time to ongoing pregnancy, clinical pregnancy, miscarriage, live birth and multiple pregnancy. We will also assess if biomarkers such as female age, body mass index, smoking status, antral follicle count and endometrial aspect and thickness can be used as treatment selection markers. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on Research involving Human Subjects (CCMO NL 43131-018-13). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NTR4057.

Item does not contain fulltext STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

This study assessed the efficacy of hysteroscopic polyp removal in the management of abnormal uterine bleeding (AUB) of premenopausal patients. The monthly menstrual blood loss, measured semi-objectively by the pictorial blood loss assessment chart (PBAC) and patients satisfaction were recorded prospectively preoperatively and postoperatively. Twenty-one patients were included. Median monthly PBAC-score before treatment was 288 (range 142-670) and 6 months after polyp removal 155 (range 39-560). It was concluded that hysteroscopic polyp removal in premenopausal women with AUB reduces the monthly blood loss significantly and has a high satisfaction rate on the short term.

BACKGROUND: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy.METHODS: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267.FINDINGS: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [INTERPRETATION: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy.FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Contains fulltext : 109856.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11-45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle. METHODS/DESIGN: Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study. DISCUSSION: The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment. TRIAL REGISTRATION: NCT01242852.

This study assessed the efficacy of hysteroscopic polyp removal in the management of abnormal uterine bleeding (AUB) of premenopausal patients. The monthly menstrual blood loss, measured semi-objectively by the pictorial blood loss assessment chart (PBAC) and patients satisfaction were recorded prospectively preoperatively and postoperatively. Twenty-one patients were included. Median monthly PBAC-score before treatment was 288 (range 142-670) and 6 months after polyp removal 155 (range 39-560). It was concluded that hysteroscopic polyp removal in premenopausal women with AUB reduces the monthly blood loss significantly and has a high satisfaction rate on the short term.

Background We have offered, for the first time in The Netherlands, carrier diagnostics for hemoglobinopathies (HbP) to early pregnant women. The aim of this study was to establish whether carrier analysis would be welcome by the public and feasible at the outpatient level. Method One hundred and thirty-nine randomly selected women were informed and offered basic carrier diagnostics at the first pregnancy control. Results Carrier diagnostics was accepted by 136 women (97.8%). The population consisted of 31% of recent immigrants and 69% of native Dutch. One carrier of HbS and one of β-thalassemia were found, both among the group of the recent immigrants. In both cases, partners were tested excluding a couple at risk. In addition, five carriers of α+-thalassemia were diagnosed at the molecular level, one of them in the native Dutch population. Basic carrier analysis was done both at the Hospital Laboratory and at the Reference Laboratory. No discrepancies were found. Conclusions This pilot study shows that (1) as predicted the prevalence of risk-related HbP and of α+-thalassemia is high in the immigrant population. (2) The compliance with carrier analysis in both native Dutch and immigrants is virtually total and (3) carrier diagnosis in early pregnancy and partner analysis in Hospital Laboratories is possible and is an effective tool for primary prevention of HbP in The Netherlands. Copyright © 2006 John Wiley & Sons, Ltd.

Objective To validate a simple, highly predictive test to discriminate between menorrhagia and normal menstrual blood loss. Methods The sanitary wear of 489 menstrual bleeding episodes was collected by 288 women for objective measurement of menstrual blood loss (alkaline hematin method); the women made a subjective assessment of the volume and, based on a pictorial chart, recorded the amount of and the degree to which their sanitary wear was soiled. Based on that degree, a score was calculated for each episode and a suitable cutoff point was chosen, above which the presence of menorrhagia was likely and below which it was unlikely. Results Using a score of 185 as the cutoff point, the predictive values of positive and negative tests were almost equally high, 85.9 and 84.8%, respectively. Whether or not the presence of clots was recorded, these values did not change. The predictive value of a woman's complaint of heavy bleeding for the presence of menorrhagia was 55.9% and that of anemia (hemoglobin less than 12.0 g/dL) was 74.4%. Conclusion We validated and refined a new, simple, visual assessment technique and demonstrated that it is superior to a woman's subjective assessment of menstrual blood loss and the occurrence of anemia for predicting menorrhagia, even if it is performed only once. We also demonstrated that the volume that clots contribute to menstruation is not as large as many clinicians believe. With this technique, the quality of therapy can be enhanced by making it more adequate and rational.