Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome.

CONTEXT: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. OBJECTIVE: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. DESIGN AND SETTING: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. PARTICIPANTS AND INTERVENTIONS: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. RESULTS: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) µg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 µg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value. CONCLUSIONS: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice.

Cost-effectiveness of curettage vs. expectant management in women with an incomplete evacuation after misoprostol treatment for first-trimester miscarriage: a randomized controlled trial and cohort study.

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.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

STUDY QUESTION: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? SUMMARY ANSWER: Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. WHAT IS KNOWN ALREADY: Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. STUDY DESIGN SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. WIDER IMPLICATIONS OF THE FINDINGS: In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. TRIAL REGISTRATION DATE: 20 December 2010. DATE OF FIRST PATIENT'S ENROLMENT: 12 May 2011.

[Thrombosis in ovarian hyperstimulation syndrome]. / Trombose bij ovarieel hyperstimulatiesyndroom.

BACKGROUND: Ovarian hyperstimulation syndrome is a rare complication of IVF treatment. In severe ovarian hyperstimulation syndrome there is an increased risk of thrombo-embolic events. Venous thrombotic complications tend to occur several weeks after the resolution of ovarian hyperstimulation syndrome. Predominant sites of venous thrombosis in OHSS are the upper extremities. CASE DESCRIPTION: A 34-year old woman presented to the emergency department with complaints about a painful swelling in the neck and a bluish discoloration of the right arm. She had been admitted to the hospital six weeks before, because of shortness of breath from pleural effusion due to ovarian hyperstimulation syndrome. The diagnosis of jugular vein and subclavian vein thrombosis was made. She was treated with therapeutic doses of low-molecular-weight heparin. CONCLUSION: Venous thrombosis is a rare but serious complication of ovarian hyperstimulation syndrome. For patients who require admission because of severe ovarian hyperstimulation syndrome, thromboprophylaxis should be continued several weeks after discharge.

Dynamic magnetic resonance imaging before and 6 months after laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to correlate dynamic magnetic resonance imaging (MRI) with Pelvic Organ Prolapse Quantification (POP-Q) measurements and pelvic floor symptoms in order to determine the value of dynamic MRI for evaluating vaginal vault prolapse both before and 6 months after laparoscopic sacrocolpopexy. METHODS: This was a prospective, single-center cohort study in 43 patients who underwent a modified laparoscopic sacrocolpopexy/hysteropexy operation using bone-anchor fixation and synthetic mesh. The study included dynamic MRI, POP-Q staging, and validated questionnaires before and 6 months after laparoscopic sacrocolpopexy. To assess MRI data, the pubococcygeal reference line and specifically defined anatomical landmarks for the separate compartments were used. Differences between pre- and postoperative measurements were evaluated with the Wilcoxon signed-rank test, and correlations at the 0.05 level were considered to be significant (Pearson correlation, two tailed). RESULTS: At 6 months, a statistically significant improvement was seen in POP-Q staging for all compartments. Dynamic MRI measurements only revealed a significant improvement after surgery for the apical compartment. The correlation between (changes in) MRI measurements, POP-Q measurements, and validated questionnaires was poor. CONCLUSIONS: The value of dynamic MRI for evaluating and documenting changes in vaginal vault support and position after laparoscopic sacrocolpopexy is limited due to the poor correlation with both POP-Q staging and pelvic floor symptoms.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657.

Transmural migration of retained surgical sponges: a systematic review.

Retained surgical sponges have been reported to occur after a diversity of surgical procedures, but transmural migration is a very unusual sequela. This article reports a case in which a retained surgical sponge eroded from the intra-abdominal space into the intestinal lumen, migrated distally, and spontaneously passed with defecation 12 weeks after the cesarean section. We performed a systematic review of the literature in Pubmed and found 64 cases of transmural migration of retained surgical sponges. Sixty-four cases have been reported of transmural migration, mainly after intra-abdominal surgery. The most frequent site of impaction is the intestine (75%), but we also found 2 cases that describe migration into the stomach and 7 into the bladder. Five more cases have been published describing transdiaphragmic migration. Only 4 cases describe a sponge spontaneously expelled through the rectum, whereas more than 93% needed re-intervention. We strongly advise only the use sponges with radiopaque markers during surgery and additional methodical wound/body cavity examination.