[Endometriosis, you won't see it until you think of it]. / Endometriose, je gaat het pas zien als je het doorhebt.

For many people, including health care providers, endometriosis is an unknown disease. It can present in many different ways, making it difficult to diagnose. As a result the diagnosis is often missed and the right treatment cannot be started. This delay can lead to a huge reduction in the quality of life. Based on three cases of endometriosis we show you when to think about this disease. In the cases we describe the most common symptoms of endometriosis are mentioned: pelvic pain, dysmenorrhea and, dyspareunia. It is important to ask a patient with pelvic pain or subfertility about these complaints. If endometriosis is suspected on the basis of these or other complaints, empirical hormonal treatment can be offered to patients who are not trying to conceive at that time.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. OBJECTIVE: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. STUDY DESIGN: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. RESULTS: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. CONCLUSION: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study.

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 rate RESULTS: 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.

Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As an alternative, endometrial ablation is also very effective, but this treatment has to be performed by a gynaecologist. Due to lack of direct comparison of LNG-IUS with endometrial ablation, there is no evidence based preferred advice for the use of one of these treatment possibilities. METHOD/DESIGN: A multicenter randomised controlled trial, organised in a network infrastructure in the Netherlands in which general practitioners and gynaecologists collaborate. DISCUSSON: This study, considering both effectiveness and cost effectiveness of LNG-IUS versus endometrial ablation may well improve care for women with heavy menstrual bleeding. TRIAL REGISTRATION: Dutch trial register, number NTR2984.

Surgical versus expectant management in women with an incomplete evacuation of the uterus after treatment with misoprostol for miscarriage: the MisoREST trial.

BACKGROUND: Medical treatment with misoprostol is a non-invasive and inexpensive treatment option in first trimester miscarriage. However, about 30% of women treated with misoprostol have incomplete evacuation of the uterus. Despite being relatively asymptomatic in most cases, this finding often leads to additional surgical treatment (curettage). A comparison of effectiveness and cost-effectiveness of surgical management versus expectant management is lacking in women with incomplete miscarriage after misoprostol. METHODS/DESIGN: The proposed study is a multicentre randomized controlled trial that assesses the costs and effects of curettage versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Eligible women will be randomized, after informed consent, within 24 hours after identification of incomplete evacuation of the uterus by ultrasound scanning. Women are randomly allocated to surgical or expectant management. Curettage is performed within three days after randomization.Primary outcome is the sonographic finding of an empty uterus (maximal diameter of any contents of the uterine cavity < 10 millimeters) six weeks after study entry. Secondary outcomes are patients' quality of life, surgical outcome parameters, the type and number of re-interventions during the first three months and pregnancy rates and outcome 12 months after study entry. DISCUSSION: This trial will provide evidence for the (cost) effectiveness of surgical versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. TRIAL REGISTRATION: Dutch Trial Register: NTR3110.

A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial.

BACKGROUND: Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs. METHODS: We did a randomised, non-inferiority effectiveness trial. 404 patients were randomly assigned to undergo either mild treatment (mild ovarian stimulation with gonadotropin-releasing hormone [GnRH] antagonist co-treatment combined with single embryo transfer) or a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos). Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after randomisation (with a non-inferiority threshold of -12.5%), total costs per couple up to 6 weeks after expected date of delivery, and overall discomfort for patients. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN35766970. FINDINGS: The proportions of cumulative pregnancies that resulted in term livebirth after 1 year were 43.4% with mild treatment and 44.7% with standard treatment (absolute number of patients=86 for both groups). The lower limit of the one-sided 95% CI was -9.8%. The proportion of couples with multiple pregnancy outcomes was 0.5% with mild IVF treatment versus 13.1% (p<0.0001) with standard treatment, and mean total costs were 8333 euros and 10745 euros, respectively (difference 2412 euros, 95% CI 703-4131). There were no significant differences between the groups in the anxiety, depression, physical discomfort, or sleep quality of the mother. INTERPRETATION: Over 1 year of treatment, cumulative rates of term livebirths and patients' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for standard stimulation with two embryos transferred. However, a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs.

A case study of the applicability of a prediction model for the selection of patients undergoing in vitro fertilization for single embryo transfer in another center.

OBJECTIVE: To evaluate the application in a different fertility clinic of a prediction model for selecting IVF patients for elective single embryo transfer. DESIGN: Retrospective analysis of a large database obtained from a tertiary infertility center. SETTING: University medical center. PATIENT(S): The model, derived at the "development center" was applied in 494 consecutive first IVF cycles carried out at the "application center." INTERVENTION(S): After adjustment of embryo scoring system to be compatible with that used by the prediction model, it was applied to the development center data. A score chart for predicting the probability of singleton or twin pregnancy was constructed. MAIN OUTCOME MEASURE(S): The area under the receiver operator curve (ROC) was determined to measure the ability of the model to discriminate between ongoing pregnancy and twin pregnancy. Calibration plots were made to assess agreement between predicted and observed pregnancy rates (PR). RESULTS: The areas under the ROC for predicting ongoing pregnancy and twin pregnancy were 0.63 and 0.66, respectively. Insertion of a correction factor equivalent to the difference in odds ratios for ongoing PR between the two centers was required to improve the calibration of the model. CONCLUSION(S): After adaptation, the model performed well in the application center.

FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF.

Two very common single nucleotide polymorphisms at positions 307 and 680 in exon 10 of the FSH receptor gene have been associated with ovarian response in IVF. This observational study evaluated the role of the FSH receptor genotype in the prediction of poor response and clinical pregnancy in IVF in comparison with other markers, such as age, basal FSH, anti-Müllerian hormone and antral follicle count. In addition, the in-vitro cAMP response towards recombinant FSH in cultured granulosa cells of patients with different FSH receptor genotypes was determined. A total of 105 IVF patients undergoing ovarian stimulation in a long suppression protocol were included in the study. The ovarian response was comparable between patients with different FSH receptor genotypes. Patients with polymorphism Ser/Ser had implantation and pregnancy rates that were three times higher compared with patients with polymorphism Asn/Asn. FSH receptor genotype was not associated with a poor response in IVF, but showed a positive association with pregnancy, independent of age. There was no difference in cAMP production in cultured granulosa cells of patients with different FSH receptor genotypes (n=62). It is concluded that FSH receptor genotype is associated with pregnancy in IVF, but not with ovarian response.

The antral follicle count is a better marker than basal follicle-stimulating hormone for the selection of older patients with acceptable pregnancy prospects after in vitro fertilization.

This observational study shows that the antral follicle count is a better predictor of ongoing pregnancy in IVF patients aged >38 years of age than is basal FSH. Patients aged <44 years with a normal antral follicle count still have acceptable pregnancy rates after IVF and therefore deserve treatment.

A poor response in the first in vitro fertilization cycle is not necessarily related to a poor prognosis in subsequent cycles.

OBJECTIVE: To calculate the cumulative ongoing pregnancy rate in patients with a poor response in their first IVF cycle. DESIGN: Retrospective cohort study. SETTING: In vitro fertilization unit of a university hospital. PATIENT(S): Two hundred twenty-five women who experienced a poor response in their first IVF or intracytoplasmic sperm injection cycle. These patients were divided into 64 expected (aged > or =41 years and/or elevated FSH level) and 161 unexpected poor responders (aged <41 years and FSH level not elevated). INTERVENTION(S): In vitro fertilization treatment with a long-suppression protocol with FSH-urofollitropin or recombinant FSH. MAIN OUTCOME MEASURE(S): Cumulative ongoing pregnancy rate. This rate was calculated in two ways to correct for dropouts: pessimistic (zero chance of pregnancy for the dropouts) and optimistic (the same chance for the dropouts as for patients who continued). RESULT(S): The cumulative ongoing pregnancy rate of women with an unexpected poor response in the first cycle was 37% (pessimistic) to 47% (optimistic) after three cycles. Women with an expected poor response had a cumulative ongoing pregnancy rate of 16% (pessimistic) to 19% (optimistic) after 3 cycles. Sixty-four percent of the unexpected poor responders and 31% of the expected poor responders had a normal response in the second cycle, most of them after receiving a higher dose of gonadotropins. CONCLUSION(S): Most patients with an unexpected poor response in the first cycle had a normal response in the second cycle, leading to an acceptable cumulative ongoing pregnancy rate after three cycles. Patients with an expected poor response in the first cycle should be advised to withdraw from treatment after the first cycle because of a poor prognosis.