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Hum. Reprod. Advance Access published July 3, 2014
Human Reproduction, Vol.0, No.0 pp. 1 – 7, 2014 ORIGINAL ARTICLE Infertility Self-operated endovaginaltelemonitoring versus traditionalmonitoring of ovarian stimulation inassisted reproduction: a prospective RCT Jan Gerris1,*, Annick Delvigne2, Nathalie Dhont3,Frank Vandekerckhove1, Bo Madoc1, Magaly Buyle1, Julie Neyskens1,Ellen Deschepper4, Dirk De Bacquer4,5, Lore Pil6, Lieven Annemans6, Willem Verpoest7, and Petra De Sutter1 1Centre for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium 2Centre for Reproductive Medicine,Clinique St Vincent, Rue Lefebvre 207, 4000 Rocourt (Lie´ge), Belgium 3Centre for Reproductive Medicine, Ziekenhuis Oost-Limburg, SchiepseBos 6, 3600 Genk, Belgium 4Biostatistics Unit, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 5Department of Public Health, GhentUniversity, De Pintelaan 185, 9000 Ghent, Belgium 6Department of Health Economics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium 7Centre for Reproductive Medicine, Vrije Universiteit Brussel, Laarbeeklaan 1, 1090 Jette, Belgium *Correspondence address. Tel: +32-9-332-3758; E-mail: jan.gerris@uzgent.be Submitted on February 1, 2014; resubmitted on May 27, 2014; accepted on June 9, 2014 study question: Does self-operated endovaginal telemonitoring (SOET) of the ovarian stimulation phase in IVF/ICSI produce similarlaboratory, clinical, patient reported and health-economic results as traditional monitoring (non-SOET)? summary answer: SOET is not inferior to traditional monitoring (non-SOET).
what is known already: Monitoring the follicular phase is needed to adapt gonadotrophin dose, detect threatening hyperstimulationand plan HCG administration. Currently, patients pay visits to care providers, entailing transportation costs and productivity loss. It stressespatients, partners, care providers and the environment. Patients living at great distance from centres have more difficult access to treatment.
The logistics and stress during the follicular phase of assisted reproduction treatment (ART) is often an impediment for treatment.
study designs, size, duration: The study was a non-inferiority RCT between SOET and non-SOET performed between February2012 and October 2013. Sample size calculations of number of metaphase II (MII) oocytes (the primary outcome): 81 patients were needed ineach study arm for sufficient statistical power. Block randomization was used with allocation concealment through electronic files. The first sono-gram was requested after 5 days of stimulation, after that mostly every 2 days and with a daily sonograms at the end.
participants/materials, settings, methods: Inclusion criteria were age ,41 years, undergoing ICSI, no poor responseand having two ovaries. We used a small laptop with USB connected vaginal probe and developed a specific web site application. Sonographictraining was given to all women at the initiation of a treatment attempt at the centre. The website contained demonstration material consistingof still images and video sequences, as well as written instructions regarding the use of the instrument and probe handling. In total, 185 eligiblepatients were recruited in four centres: 123 were randomized; 121 completed SOET (n ¼ 59) or non-SOET (n ¼ 62), and 62/185 (33%) eligiblepatients declined participation for various reasons.
main results and the role of chance: Patient characteristics were comparable. The clinical results showed similar conceptionrates (P ¼ 0.47) and ongoing pregnancy rates (SOET: 15/59 ¼ 25%; non-SOET: 16/62 ¼ 26%) (P ¼ 1.00) were obtained. Similar numbers offollicles .15 mm diameter at oocyte retrieval (OR), ova at OR, MII oocytes, log2 MII oocytes, embryos available at transfer, top quality embryosand embryos frozen were obtained in the two groups, indicating non-inferiority of SOET monitoring. Regarding patient-reported outcomes, asignificantly higher contentedness of patient and partner (P , 0.01), a higher feeling of empowerment, discretion and more active partner par-ticipation (P , 0.001) as well as a trend towards less stress (P ¼ 0.06) were observed in the S versus the NS group. In the economic analysis, theuse of SOET led to reduced productivity loss, lower transportation costs, and lower sonogram and consultation costs (all P , 0.001 but higherpersonnel cost than NS).
& The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: journals.permissions@oup.com Gerris et al.
limitations, reasons for caution: The study was stopped (no further funding) before full sample size was reached. There werealso a few cases of unexpected poor response, leading to a wider SD than anticipated in the power calculation. However, although the study wasunderpowered for these reasons, non-inferiority of SOET versus non-SOET was demonstrated.
wider implications of the findings: Home monitoring using SOET may provide a patient-centred alternative to the standardmethods. ART sonograms can be made, and then sent to the care provider for analysis at any appropriate time and from anywhere if an internetconnection is available. This approach offers several advantages for patients as well as care providers, including similar results to the traditionalmethods with less logistical stress and potentially bringing care to patients in poor resource settings.
study funding/competing interest (s): Supported by an IOF (industrial research fund) of Ghent University (full protocolavailable at iBiTech) and as a demonstration project of Flanders Care (Flemish Government). There are no conflicts of interest to declare.
EC/2011/669 (Ghent University Hospital), B670201112232 (Belgian registration) and NCT01781143 (clinical trials number).
Key words: telemonitoring / IVF/ICSI / vaginal sonography / health-economy / patient empowerment and therefore allowed all participating centres to use their own clinical and During the ovarian stimulation phase of assisted reproduction treatment(ART), the patient needs to be monitored for two main reasons: to in- Design of the study crease or decrease the daily dose of gonadotrophins and to decide on A power calculation was performed prior to this RCT trial. Sample size cal- the timely injection of HCG,. In addition, ovarian hyperstimulation syn- culations were based on the primary laboratory efficacy variable and calcu- drome (OHSS) can be prevented. Monitoring is achieved using serial lated on the basis of historical data of numbers of metaphase-II oocytes at vaginal sonograms, and counting the number and measuring the size of oocyte retrieval (OR) for women ,41 years of age with at least four the follicles. The sonogram is performed by a gynaecologist, an IVF phys- oocytes at OR at our centre. Poor responders were excluded. Because ician, a nurse or midwife and often is a very strenuous aspect of ART.
the distribution of numbers of metaphase-II oocytes was skewed to the Patients need to come, often from far away, to the centre for a relatively right, the analysis was performed on the log2-transformed numbers of simple procedure. This entails an economic, logistic, emotional and metaphase-II oocytes. A sample size of 81 patients per group would allow potential environmental cost. For care providers sonograms represent for 80% power to demonstrate non-inferiority for the SOET group in a two-sample T-test on the log a very routine procedure, reducing their time for more complex tasks.
2-transformed value of the primary outcome vari- able. Non-inferiority is defined as the SOET treatment having a number of Monitoring of ovarian stimulation is also based on serial measure- metaphase-II oocytes at pick-up that is at least 80% of the number of ments of serum estradiol (E2), which is indeed essential in cases of metaphase-II oocytes at pick-up for standard monitoring (threshold limit OHSS but not for general use for the difference of 0.32 on the log2-scale). Sample size calculation was per- We have previously explored the possibility of monitoring patients at a formed under the further assumption that the true outcome of the SOET distance, by teaching them to make their own vaginal sonograms at home group is equal to the outcome of the standard nn-SOET stimulation.
). We have conducted aprospective RCT comparing self-operated endovaginal telemonitoring Patient recruitment, study counselling, (SOET) at home with traditional sonographic (non-SOET) follow-up.
ovarian stimulation, sonographic follow-up,embryo transfer Materials and Methods Eligible patients had to fulfil the following inclusion criteria: ,41 years of age,two ovaries, ICSI treatment. They needed a wireless internet connection at This study was approved by the Ethical Committee of the University Hospital home and basic computer skills. Exclusion criteria were documented causes Ghent (EC/2011/669) and supported by an industrial research fund from of severe distortion of the pelvic organs making sonography more difficult as Ghent University and a grant from the Flemish Government. Written well as poor responders (previously ,4 oocytes) and serum anti-Mullerian consent was obtained from all patients.
hormone value ,0.5 mIU/ml. Previous OHSS (at least 1 day of hospitaliza-tion in a previous ART attempt) and polycystic ovary syndrome (diagnosedusing the Rotterdam criteria) were considered risk factors but not formal exclusion criteria.
We hypothesized that self-monitoring (SOET) at home by the patient and Block randomization was conducted using electronic clinical research files, traditional monitoring by medical staff (non-SOET) could result in similar allotting each recruited patient at the time of enrolment to one of the groups.
laboratory and clinical outcomes, better patient-reported outcomes and a Eligible patients were given a first general explanation of the concept of more favourable health-economic result for the S group. The primary SOET as well as a letter of information explaining aims, methods and expec- outcome variable of the study, comparing the effect of ovarian stimulation, tations. Patients could be enrolled at the time of the initial sonogram. Those was the number of metaphase-II (MII) oocytes. Only ICSI attempts were who agreed to participate, were electronically randomized to either the therefore included, in which oocytes undergo denudation. Secondary SOET or the non-SOET arm of the study.
outcome variables were patient-reported outcomes and health-economic Enrolled patients were given a diary to fill in the data for calculating direct variables. We wanted to compare two different strategies of monitoring, and indirect costs. The CONSORT-diagram is shown in Figure ART patients provide useful vaginal sonograms from home Figure 1 CONSORT flow diagram for a prospective RCT of self-operated endovaginal telemonitoring (SOET) versus traditional monitoring of ovarianstimulation in assisted reproduction.
Typically, patients were prepared for ICSI using an oral contraceptive.
to make the best sweep using the screen of their laptop. After recording the After withdrawal, a GnRH agonist was started using a short protocol (e.g.
sweep, lasting between 60 and 90 s for each ovary, and 30 s for the uterus, Decapeptyl, 0.1 mg/day for 7 days); after 3 days of the agonist, gonadotroph- they could check the recorded images before sending them. If images were in stimulation was started, 150 IU being the usual starting dose. In case of pre- not considered appropriate, another recording could be made. Most patients vious OHSS, lower starting doses were used; in case of unexpected low learned quickly, finding their ovaries increasingly easily once they knew how response, a higher initial dose, with a maximum of 300 IU/day, was used.
to handle the probe within the vagina. With this pre-industrial hardware con- SOET patients were shown how the server based communication soft- figuration, each recording was carried out, files were compressed, uploaded ware, developed at the faculty of engineering of Ghent University, Belgium, and sent separately. This could take up to 1 h (depending on the band width) and the imaging software (NuWav, Laborie, Canada), worked. Patients but less than the time to travel to and from the centre, and was usually were shown how to make video images, an how to upload and send them performed during leisure time.
to the centre. They were given a laptop on which only the communication Patients entering the SOET arm were monitored using home-made software and the imaging software were installed, a vaginal sonography sonograms exclusively. They were not seen by a care provider between probe with USB connection, a mouse, a power connection, condoms and the day of the initial sonogram and the day of OR. If needed for clinical pur- gel. We used a 7.5 MHz endocavity probe for vaginal application (Laborie poses (e.g. threatening OHSS), serum E2 measurements could be performed Medical, Inc., Toronto, Canada). They were instructed to send a first video in a laboratory near to the patient's home. Criteria for threatening OHSS recording soon after withdrawal bleeding in order to establish functional were .15 follicles with a diameter of ≥15 mm or serum E2 values communication with the centre.
.3000 pg/ml. Patients entering the non-SOET arm were monitored as The video recordings were made by the patients by manually sweeping the usual: some in-house, even if they lived at a distance from the centre; probe. All measurements were performed by the care provider following up others by a ‘satellite' centre or physician.
the stimulation. Patients scanned first their right ovary, then the uterus, then Videos were downloaded and opened in the imaging software in order the left ovary. Before making actual recordings, the patient could explore how to perform 2D-measurements of the follicles. All measurements were Gerris et al.
performed by the principal investigators. Video images could be stopped, evaluate the non-inferiority hypothesis. Clinical outcome measures, like pro- played forward or backward using two callipers in order to measure each fol- portions of positive HCG results and ongoing pregnancies, and PRO compar- licle at its largest diameters. Using the report function of the website, the ing SOET and non-SOET are compared using Fisher's exact tests.
patient then obtained instruction concerning hormonal dose continuationor adjustment and planning of the subsequent sonogram. When follicleswere considered mature, an instruction for HCG administration was given and the patient returned the system at the time of puncture. Each participat-ing centre used its standard stimulation protocols and criteria for HCG ad- Patient characteristics ministration. At any time, direct communication by e-mail or telephone One hundred and eighty-five patients were recruited between February was possible in both directions, creating a direct line between the centre 2012 and October 2013, of whom 62 (34%) did not participate for a (midwives, doctor) and the patient.
variety of reasons listed in Table . Of 123 patients enrolled, 62 The midwives or nurse-practitioners taught the patients how to introduce and handle the probe, how to find the uterus and resting suppressed ovaries entered the non-SOET arm and 61 the SOET arm. Two patients, both with hardly visible follicles at the start of the cycle, which was not always pos- belonging to the SOET arm, dropped out: one because she learned sible. At the patient's side of the study website, still images of follicles in dif- she had no insurance coverage and one who stopped treatment for ferent stages of development and a video demonstration were available at all unknown reasons. Two patients attributed to the SOET arm switched times. The primary image quality criterion was to detect follicles that were to traditional monitoring because of technical fall-out of the probe. In identifiable and measurable in serial recordings. The patients took no respon- the ITT principle, they were analysed in the SOET arm. Table describes sibility whatsoever for measuring, interpreting or making decisions. The role the characteristics of 121 analysed patients (59 SOET, 62 non-SOET).
of the midwives was to assist when the system was explained to patients, to Both groups were comparable with respect to age of the patient, age communicate with the patient by mail or telephone if needed and to collect of the partner, BMI, smoking behaviour and duration of subfertility.
the diaries and fill out the patient reported outcomes (PRO) questionnairesduring the post-study visit.
All centres had to adhere to the Belgian legislation concerning the number Laboratory results of embryos to transfer aimed at minimizing the percentage of multiple Laboratory data are summarized in Table (primary variables) and pregnancies ; ; ; Table (secondary variables). The median of the number of M-II oocytes was eight in the SOET group versus seven in the non-SOETgroup (ITT analysis). After log2-transformation of the number of M-II Outcome variables oocytes, the mean is 3.01 (SD ¼ 1.06) for the SOET arm versus 2.78 For laboratory outcome we recorded the total number of oocytes at re- (SD ¼ 1.37) for the non-SOET arm (ITT analysis). The 95% CI for the trieval, the number of mature metaphase-II oocytes at retrieval, the percent- average difference in log2 n M-II oocytes non-SOET versus SOET is age of metaphase-II oocytes over the number of follicles punctured, the total 20.24 (20.68; 0.19) (P ¼ 0.27), indicating non-inferiority of SOET number of top quality embryos on Day 3 and Day 5 (; ) and the number of embryos transferred or cryo- A post hoc power analysis based on the most conservative PP analysis preserved (Day 5).
shows that group sample sizes of 57 women in the SOET arm and For clinical outcome we recorded the number of follicles ≥15 mm diam- 62 women in the non-SOET arm achieve 29% power to detect eter prior to puncture, the total number of positive HCGs, and the number ofongoing pregnancies (.12 weeks, at least one fetus with cardiac beats). Con-ceptions and ongoing pregnancies were counted cumulatively: each concep-tion resulting from a study cycle was counted. This allows us to include allconceptions both from fresh and from frozen/thawed embryo replace- Table I Reasons for not participating in the ments. The conception with the longest gestation was considered as the self-operated endovaginal telemonitoring (SOET) RCT one to include in the results.
in eligible patients.
Patient-reported outcome was assessed at the time of the SOET follow-up Input data for the health-economic analysis were collected through patient Uncertain they could produce good videos diaries. Costs related to these input data, calculated for the duration of the study, were obtained using published and unpublished sources.
Pregnant after FRET Practical reasons (timing) Primary non-inferiority efficacy analysis is based on the most conservative perprotocol (PP) analysis, which strictly includes patients that performed at least Interruption of treatment one sonogram as determined by the randomization. Protocol violators are excluded from this analysis. Non-inferiority is only concluded for the Spontaneous pregnancy primary end-point. Additional analyses based on the intention-to-treat Changed therapy to AID (ITT) and as-treated analysis also support the non-inferiority conclusion.
Intervening malignancy In order to demonstrate non-inferiority with respect to the primary outcome variable, we needed to show that the number of M-II oocytes at Did not accept ICSI OR was at least 80% of the number after standard monitoring.
FRET, frozen embryo transfer; AID, artificial insemination by donor sperm; OHSS, A two-sided 95% confidence interval (CI) for the difference in mean log2 n ovarian hyperstimulation syndrome.
metaphase II oocytes of NS versus SOET monitoring was calculated, to ART patients provide useful vaginal sonograms from home non-inferiority using a two-sided 95% CI for the difference in means, as- suming a common SD of 1.24, a true difference in means of 0 and a non- All patients finished their treatment attempt, except for two drop-outs.
inferiority limit of 0.32 on the log2-scale, comparing non-SOET versus Two patients from the S group had a technical fall-out of their probe SOET. Although underpowered, this study still shows non-inferiority and continued in the traditional monitoring, coming to the centre. In of SOET versus non-SOET monitoring of ovarian stimulation in ART.
two patients, imaging remained uncertain and they were asked to Results calculated for the PP analysis, excluding attempts with OR but come to the centre. One was a poor responder who had her daily without embryo transfer (either no eggs or no transferable embryos) dose increased and continued successfully with home follow-up. The (SOET: n ¼ 52; non-SOET: n ¼ 57), indicate non-inferiority for SOET other had follicles that were almost mature, and received HCG in this scenario as well (20.21 (20.57; 0.14)).
the day after the routine sonogram. This is the only patient where theSOET approach can be considered to have failed, because the patientdid not succeed in identifying the follicles. In all the other patients, no Table II Patient characteristics at the time of extra visits were needed between the initial sonogram and the OR.
Almost all patients experienced stress of uncertainty for some days, es-pecially when follicles were still small (,12 mm). Once the follicles Patient characteristics became clearly visible, patients succeeded in recording adequate video In the SOET group there were 58/61 OR procedures (one cancella- Age of the partner (years) tion) and 54/61 embryo transfers (four patients with either no or onlybad quality embryos). In the non-SOET group there were 59/62 retrie- vals and 57/62 transfers. All results are calculated per started attempt.
Smoking behaviour Smoker n (%) In the SOET arm, 26/59 (44%) attempts resulted in a positive HCG Subfertility (months) versus 32/62 (52%) in the non-SOET arm (P ¼ 0.47). The difference *Rank of attempt Median (Q1;Q3) in 95% CI in the proportion of conceptions between study arms was 20.08 [20.25; 0.10]. In the SOET group there were 15/59 ongoing AMH in serum (mg/ml) Mean (SD) pregnancies (25%) versus 16/62 (26%) in the non-SOET group AMH, anti-Mullerian hormone, Q1, quartile1.
(P ¼ 1.00). The difference with 95% CI in the proportion of ongoing All data are Mean (SD) unless stated otherwise.
pregnancies between study arms was 20.01 [20.16; 0.15]. Clinical *Rank of attempt refers to the rank of the stimulated ART cycle; an attempt may outcome measures are not statistically different between SOET and include one ‘fresh' and one or more cryo-transfers.
Table III Overview of laboratory results in patients after SOET/non-SOET for assisted reproduction treatment (ART):primary end variables, analysed without two protocol violators who were treated in the non-randomized arm (Per Protocol– analysis), analysed with these two in the as-treated arm (As-Treated – analysis) and analysed in the randomized arm(Intention To Treat – analysis).
Per Protocol analysis non-SOET (n 5 62) N metaphase II-ova (nMII) 9.0 (5.0;13.0) [0.0;24.0] 7.0 (4.3;13.0) [0.0;30.0] Median (Q1;Q3) [Min;Max] Log2 n metaphase II-ova Mean difference in log2 n metaphase II-ova (95% CI), comparing non-SOET versus SOET 20.25 (20.70;0.18) As-Treated analysis non-SOET (n ¼ 64) N metaphase II-ova (nMII) 9.0 (5.0;13.0) [0.0;24.0] 7.0 (4.8;13.0) [0.0;30.0] Median (Q1;Q3) [Min;Max] Log2 n metaphase II-ova Mean difference in log2 n metaphase II-ova (95% CI), comparing non-SOET versus SOET 20.27 (20.70;0.16) Intention To Treat analysis non-SOET (n ¼ 62) N metaphase II-ova (nMII) 8.0 (5.0;13.0) [0.0;24.0] 7.0 (4.3;13.0) [0.0;30.0] Median (Q1;Q3) [Min;Max] Log2 n metaphase II-ova Mean difference in log2 n metaphase II-ova (95% CI), comparing non-SOET versus SOET 20.08 (20.25;0.10) Mean difference in log2 n is indicated in bold.
Gerris et al.
Table IV Laboratory results in patients after SOET/non-SOET for ART: secondary end variables.
Secondary outcome variables Mann – Whitney U-test N follicles .15 mm at OR (NF) N oocytes at OR (NOR) 10.5 (6;15) [0;37] Proportion (nMII/NOR) 75 (68;88) [50;100] 81 (67;97) [14;100] N embryos available N top quality embryo's at transfer Median (Q1;Q3) [Min;Max] N embryos cryopreserved OR, oocyte retrieval; NF, number of follicles; NOR, number of oocytes retrieved.
All data are Median (Q1;Q3) [Min;Max].
We summarized the most important findings in Table Table V Average total cost per treatment attempt (E).
An average of 3.0 sonograms was performed in non-SOET cycles by care providers versus 5.4 sonograms in SOET cycles (P , 0.001). All patients used their car as means of transportation. In the non-SOET group, an average of 530 km (min: 26 km; max 5520 km) was covered Ultrasound – paid by insurance versus 146 km (min.: 0 km; max.: 900 km) in the SOET group Ultrasound – paid by patient (P , 0.001). With a cost of E0.3456E/km (average Transport – paid by patient transportation cost was calculated at E183 per non-SOET cycle (min Material – paid by insurance and/or E9, max E1908) versus E51 per SOET cycle.
Based on an average cost of E280 per day absence from work, the Productivity loss – paid by employer average cost related to productivity loss was E423 per non-SOETattempt (min Labour costs medical staff – paid by E0, max E2169) versus E96 per SOET attempt (min E0, max E837) (P , 0.001) More time was spent by care providers, on average, on SOET than on non-SOET attempts. However, midwives found their time was better Data were analysed using official cost data during the study period (February structured: they spent more time at the start of the stimulation but 2012 – October 2013).
Data are Cost (SD).
much less at each monitoring session.
When all costs were added the average total cost per SOET attempt is approximately half that of a non-SOET attempt: E455 (95% CI ¼E382–E529; min E199; max E1499) versus E894 (95% CI E729– E1058; min E121, max E4428). The largest difference between All patients were seen at a post-treatment consultation and asked to groups lies with the loss of productivity and the transportation costs, assess six outcome measures: satisfaction of the patient and of the favouring the home sonography.
partner, feeling of empowerment, active participation of the partner,stress and discretion. In five out of these six variables SOET scored better than non-SOET attempts (P-value ,0.001), while for stress theP-value was 0.06, indicating a trend. Almost all women indicated they The monitoring of ovarian stimulation for ART using home sonography experienced two types of stress. For stress that was related to organiza- performed by the patient and her partner, compares favourably with tional and logistic aspects of monitoring stimulation, they felt SOET the traditional follow-up method in which the patient has to present scored better. However, the application of a novel technique induced herself for each sonogram to a care provider. Patients and their partners stress, which disappeared as follicles became more clearly visible on were more satisfied; they felt empowered and experienced a higher the screen as days went by.
sense of discretion. Active participation of the partner was higher and,overall, the couple experienced less stress. Total costs were approxi-mately halved when using SOET, creating the possibility of a shift of the Health-economic analysis cost of transportation or productivity loss experienced by the employer A health-economic analysis was performed, with the aim to establish towards a reasonable service cost for the patient.
whether the cost for society and for the patient is different between Although the present study is a RCT and the results are statistically SOET and non-SOET. A total of 121 cycles were analysed (62 NS, 59 S).
valid, the trial was finally underpowered. Technological improvements The two drop-out cycles were excluded. Two other patients, who must still be made and tested with respect to both hard- and software.
started in the S arm but continued in the standard way, were analysed in External validation in luminary sites is important. Not all patients are the SOET group.
interested in using the system.
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Vandekerckhove F, Vansteelandt S, Gerris J, De Sutter P. Follicle measurements None declared.
using sonography-based automated volume count accurately predict theyield of mature oocytes in in vitro fertilization/intracytoplasmic sperm injection cycles. Gynecol Obstet Invest 2013;76:107–112.
Van den Abbeel E, Balaban B, Ziebe S, Lundin K, Cuesta M, Klein B, Helmgaard L, Ata B, Tulandi T. Ultrasound automated volume calculation in reproduction Arce JC. Association between blastocyst morphology and outcome of and in pregnancy. Fertil Steril 2011;95:2163 – 2170.
single-blastocyst transfer. Reprod Biomed Online 2013;27:353–361.
Ata B, Seyhan A, Reinblatt SL, Shalom-Paz E, Krishnamurthy S, Tan SL.
Van Royen E, Mangelschots K, De Neubourg D, Valkenburg M, Van de Comparison of automated and manual follicle monitoring in an Meerssche M, Ryckaert G, Eestermans W, Gerris J. Characterization of unrestricted population of 100 women undergoing controlled ovarian a top quality embryo, a step towards single embryo transfer. Hum stimulation for IVF. Hum Reprod 2011;26:127 – 133.
Reprod 1999;14:2345 – 2349.

Source: http://www.storkklinik.dk/fileadmin/user_upload/pdf/SOET_HR_2014.pdf

Script psychot ii

Prof. Dr. Wolfgang Hiller Stichworte aus den gezeigten Folien zur Vorlesung Klinische Psychologie II Thema: Schizophrenie-Spektrum und andere psychotische Störungen II Therapie der Schizophrenie Mehrere Ansatzpunkte entsprechend des Vulnerabilitäts-Stress-Modells Phasenspezifische Behandlung der Schizophrenie 1. Phase: Behandlung der akuten Symptomatik 2. Phase: Behandlung residualer Symptome und Vorbeugung von Rückfällen (Nachbehandlungsphase) evtl. weitere Phase: Behandlung chronischer Fälle

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"Little Women?": Karen JoyFowler's Adventure inAustenland Edward Neill has published widely in journals and periodicals, and is the author of four books: Trial by Ordeal?: Hardy and the Critics, The Politics of Jane Austen, The Secret Life of Thomas Hardy, and "The Waste Land" Revisited: Modernism, Intertextuality and the French Connection.