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Study Question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?Summary Answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution.What Is Known Already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth.Study Design, Size, Duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed.Participants/materials, Setting, Methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK).Main Results and the Role Of Chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth.Limitations, Reasons For Caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now.Wider Implications Of the Findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date.Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial.Trial Registration Number: Netherlands Trial Register (NL5193/NTR 5342). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Question: Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility?, Summary Answer: The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility., What Is Known Already: Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial., Study Design, Size, Duration: This is a nationwide multi-centre, unblinded, randomized controlled superiority trial (web-based randomization programme, 1:1 allocation ratio). This RCT intended to recruit 1164 couples within 3 years but was put on hold after having included 700 couples over 5 years (2016-2021). The web-based P&P programme contains psychosexual information and couple communication, mindfulness and sensate focus exercises aiming to help maintain or improve sexual health, mainly pleasure, and hence increase pregnancy rates. The P&P programme additionally offers information on the biology of conception and enables couples to interact online with peers and via email with coaches., Participants/materials, Setting, Methods: Heterosexual couples with unexplained infertility and a Hunault-prognosis of at least 30% chance of naturally conceiving a live-born child within 12 months were included, after their diagnostic work-up in 41 Dutch secondary and tertiary fertility centres. The primary outcome was an ongoing pregnancy, defined as a viable intrauterine pregnancy of at least 12 weeks duration confirmed by an ultrasound scan, conceived naturally within 6 months after randomization. Secondary outcomes were time to pregnancy, live birth, sexual health, and personal and relational well-being at baseline and after 3 and 6 months. The primary analyses were according to intention-to-treat principles. We calculated relative risks (RRs, pregnancy rates) and a risk difference (RD, pregnancy rates), Kaplan-Meier survival curves (live birth over time), and time, group, and interactive effects with mixed models analyses (sexual health and well-being)., Main Results and the Role of Chance: Totals of 352 (one withdrawal) and 348 (three withdrawals) couples were allocated to, respectively the P&P group and the expectant management group. Web-based tracking of the intervention group showed a high attrition rate (57% of couples) and limited engagement (i.e. median of 16 visits and 33 min total visitation time per couple). Intention-to-treat analyses showed that 19.4% (n = 68/351) of the P&P group and 22.6% (n = 78/345) of the expectant management group achieved a naturally conceived ongoing pregnancy (RR = 0.86; 95% CI = 0.64-1.15, RD = -3.24%; 95% CI -9.28 to 2.81). The time to pregnancy did not differ between the groups (Log rank = 0.23). Live birth occurred in 18.8% (n = 66/351) of the couples of the P&P group and 22.3% (n = 77/345) of the couples of the expectant management group (RR = 0.84; 95% CI = 0.63-1.1). Intercourse frequency decreased equally over time in both groups. Sexual pleasure, orgasm, and satisfaction of women of the P&P group improved while these outcomes remained stable in the expectant management group. Male orgasm, intercourse satisfaction, and overall satisfaction decreased over time with no differences between groups. The intervention did not affect personal and relational well-being. Non-compliance by prematurely starting medically assisted reproduction, and clinical loss to follow-up were, respectively, 15.1% and 1.4% for the complete study population. Per protocol analysis for the primary outcome did not indicate a difference between the groups. Comparing the most engaged users with the expectant management group added that coital frequency decreased less, and that male sexual desire improved in the intervention group., Limitations, Reasons for Caution: The intended sample size of 1164 was not reached because of a slow recruitment rate. The achieved sample size was, however, large enough to exclude an improvement of more than 8% of the P&P programme on our primary outcome., Wider Implications of the Findings: The P&P programme should not be offered to increase natural pregnancy rates but may be considered to improve sexual health. The attrition from and limited engagement with the P&P programme is in line with research on other eHealth programmes and underlines the importance of a user experience study., Study Funding/competing Interest(s): Funded by The Netherlands Organisation for Health Research and Development (ZonMw, reference: 843001605) and Flanders Research Foundation. C.B.L. is editor-in-chief of Human Reproduction. H.W.L. received royalties or licences from Prometheus Publishers Springer Media Thieme Verlag. J.B. received support from MercK for attending the ESHRE course 'The ESHRE guideline on ovarian stimulation, do we have agreement?' J.v.D. reports consulting fees and lecture payments from Ferring, not related to the presented work, and support for attending ESHRE from Goodlife and for attending NFI Riga from Merck. A.H. reports consulting fees by Ferring Pharmaceutical company, The Netherlands, paid to institution UMCG, not related to the presented work. H.V. reports consulting fees from Ferring Pharmaceutical company, The Netherlands, and he is a member of the ESHRE guideline development group unexplained infertility and Chair of the Dutch guideline on unexplained infertility (unpaid). M.G. declares unrestricted research and educational grants from Ferring not related to the presented work, paid to their institution VU Medical Centre. The other authors have no conflicts to declare., Trial Registration Number: NTR5709., Trial Registration Date: 4 February 2016., Date of First Patient’s Enrolment: 27 June 2016., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

In this educative article 10 medical questions related to the menopausal transition are answered. The questions are related to etiology, symptomatology, lab investigation, sexuality, need for contraception, hormonal and non-hormonal treatments and their risks and benefits. The purpose of this article is to assist the healthcare practitioner to understand the impact of the menopausal transition, to recognize the symptoms and to understand the risks and benefits of treatment. As women on average work and live longer, they are on average 30 percent of their lives postmenopausal. Attention should be paid to quality of life not only during menopausal transition, but also thereafter, with special awareness of the long term sequelae on women's health.

Study Question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?, Summary Answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution., What Is Known Already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth., Study Design, Size, Duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed., Participants/materials, Setting, Methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK)., Main Results and the Role of Chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth., Limitations, Reasons for Caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now., Wider Implications of the Findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date., Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial., Trial Registration Number: Netherlands Trial Register (NL5193/NTR 5342)., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

The revised Dutch College of General Practitioners' practice guideline on 'Vaginal bleeding' provides recommendations for abnormal bleeding in women in the reproduction phase of life and for post-menopausal bleeding. This guideline is closely attuned to the guideline on 'Heavy menstrual bleeding' of the Dutch Society of Obstetrics and Gynaecology. Transvaginal sonography is not reliable for excluding endometrial carcinoma in women with abnormal vaginal bleeding treated with tamoxifen. The choice of medical treatment is determined in consultation with the patient. The following factors are assessed: severity and bother, long-term need for contraception, preference for cycle control, desire to have a child, pain during menstruation, comorbidity and use of medication. Treatment options are nonhormonal (NSAIDs, or tranexamic acid) or hormonal (a levonorgestrel-releasing intrauterine system, or combined oral contraceptive). In women of reproductive age, referral is indicated if medical treatment is not effective. Other indications are intracavitary abnormalities diagnosed by transvaginal sonography, tamoxifen use, persistent contact bleeding, and suspicion of coagulation disorders. Indications for referral for post-menopausal bleeding include: sonographic endometrial thickness > 4 mm, abnormal cervical cytology, tamoxifen use, irregular bleeding during use of hormone therapy for vasomotor symptoms and persistent or recurrent bleeding, regardless of endometrial thickness.

A new multidisciplinary practice guideline on heavy menstrual bleeding (HMB) has recently been published. HMB may occur with or without structural abnormalities. The pictorial blood loss assessment chart (PBAC) is the best method for estimating the amount of blood loss and for distinguishing between heavy and normal blood loss. Haemoglobin levels should be determined at least once. Transvaginal ultrasound is the preferred imaging technique. Saline or gel infusion sonography should be used in cases where ultrasound results are suspect for intracavitary abnormalities. A hysteroscopy should only be performed if sonography results are inconclusive. The very first treatment of choice should be placement of a hormone-impregnated intrauterine system. For HMB without structural abnormalities, endometrial ablation is an alternative to hysterectomy, whereby second-generation ablation techniques are preferred to first-generation techniques. For HMB with uterine fibroids, uterine artery embolisation is a good alternative to hysterectomy. For HMB with submucosal fibroids, hysteroscopic resection of the fibroids is recommended.