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197 results on '"Broekmans, F. J. M."'

2. Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study

Author

Stevens Brentjens, L B P M, primary, Obukhova, D, additional, Delvoux, B, additional, den Hartog, J E, additional, Bui, B N, additional, Mol, F, additional, de Bruin, J P, additional, Besselink, D, additional, Teklenburg, G, additional, Morgan, F, additional, Baker, M, additional, Broekmans, F J M, additional, van Golde, R J T, additional, Zamani Esteki, M, additional, and Romano, A, additional

Published
2023
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5. Prevention of multiple pregnancies in couples with unexplained or mild male subfertility : randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation

Author

Bensdorp, A J, Tjon-Kon-Fat, R I, Bossuyt, P M M, Koks, C A M, Oosterhuis, G J E, Hoek, A, Hompes, P G A, Broekmans, F J M, Verhoeve, H R, de Bruin, J P, van Golde, R, Repping, S, Cohlen, B J, Lambers, M D A, van Bommel, P F, Slappendel, E, Perquin, D, Smeenk, J M, Pelinck, M J, Gianotten, J, Hoozemans, D A, Maas, J W M, Eijkemans, M J C, van der Veen, F, Mol, B W J, and van Wely, M

Published
2015

7. Economic evaluation of endometrial scratching before the second IVF/ICSI treatment: a cost-effectiveness analysis of a randomized controlled trial (SCRaTCH trial)

Author

van Hoogenhuijze, N E, primary, van Eekelen, R, additional, Mol, F, additional, Schipper, I, additional, Groenewoud, E R, additional, Traas, M A F, additional, Janssen, C A H, additional, Teklenburg, G, additional, de Bruin, J P, additional, van Oppenraaij, R H F, additional, Maas, J W M, additional, Moll, E, additional, Fleischer, K, additional, van Hooff, M H A, additional, de Koning, C H, additional, Cantineau, A E P, additional, Lambalk, C B, additional, Verberg, M, additional, van Heusden, A M, additional, Manger, A P, additional, van Rumste, M M E, additional, van der Voet, L F, additional, Pieterse, Q D, additional, Visser, J, additional, Brinkhuis, E A, additional, den Hartog, J E, additional, Glas, M W, additional, Klijn, N F, additional, van der Zanden, M, additional, Bandell, M L, additional, Boxmeer, J C, additional, van Disseldorp, J, additional, Smeenk, J, additional, van Wely, M, additional, Eijkemans, M J C, additional, Torrance, H L, additional, and Broekmans, F J M, additional

Published
2021
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9. Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure: a cost-effectiveness analysis

Author

Bordewijk, E. M., Weiss, N. S., Nahuis, M. J., Bayram, N., van Hooff, M. H. A., Boks, D. E. S., Perquin, D. A. M., Janssen, C. A. H., van Golde, R. J. T., Lambalk, C. B., Goddijn, M., Hompes, P. G., van der Veen, F., Mol, B. W. J., van Wely, M., Smeenk, J. M. J., Hoek, A., Broekmans, F. J. M., Fleischer, K., de Bruin, J. P., Kaaijk, E. M., Laven, J. S. E., Hendriks, D. J., Gerards, M. H., Bourdrez, P., Gianotten, J., Koks, C., van Hooff, M., Kwee, J., Lambeek, A. F., van Unnik, A. F., Vrouenraets, F. P. J., Cohlen, B. J., van de Laar-van Asseldonk, T. A. M., Nap, A. W., van Rijn-van Weert, J. M., Vollebergh, J. H. A., Klijn, N. F., Rijnsaardt-Lukassen, H. G. M., Sluijmer, A. V., Gastroenterology & Hepatology, Obstetrics & Gynecology, Emergency Medicine, Erasmus School of Economics, Orthopedics and Sports Medicine, Neurology, Erasmus MC other, Obstetrics and gynaecology, APH - Health Behaviors & Chronic Diseases, Amsterdam Reproduction & Development (AR&D), VU University medical center, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Graduate School, APH - Methodology, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, Center for Reproductive Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
Male, Pregnancy Rate, Cost effectiveness, Cost-Benefit Analysis, medicine.medical_treatment, M-OVIN, law.invention, IUI, Indirect costs, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, FSH, Treatment Failure, 030212 general & internal medicine, Birth Rate, Insemination, Artificial, CLOMIFENE CITRATE, Netherlands, 030219 obstetrics & reproductive medicine, Obstetrics, Rehabilitation, CYCLES, Obstetrics and Gynecology, Health Care Costs, Cost-effectiveness analysis, POLYCYSTIC-OVARY-SYNDROME, Female, Live birth, Infertility, Female, Live Birth, Anovulation, Adult, medicine.medical_specialty, Clomiphene, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, clomiphene citrate, medicine, Humans, cost-effectiveness, gonadotrophins, business.industry, INFERTILE WOMEN, Fertility Agents, Female, medicine.disease, Pregnancy rate, OVULATION INDUCTION, Reproductive Medicine, polycystic ovary syndrome, SINGLETON, Ovulation induction, business, Gonadotropins
Abstract

STUDY QUESTION: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC?SUMMARY ANSWER: Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC.WHAT IS KNOWN ALREADY: In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown.STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization.PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap resampling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle.MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were (sic)4495 versus (sic)3006 (cost difference of (sic)1475 (95% CI: (sic)1457-(sic)1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24: 95% CI: 1.05-1.46). The ICER was (sic)15 258 (95% CI: (sic)8721 to (sic)63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were (sic)4497 versus (sic)3005 (cost difference of (sic)1510 (95% CI: (sic)1492-(sic)1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14: 95% CI: 0.97-1.35). The ICER was (sic)24 361 (95% CI: (sic)-11 290 to (sic)85 172) per additional live birth with IUI.LIMITATIONS, REASONS FOR CAUTION: We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC.WIDER IMPLICATIONS OF THE FINDINGS: Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines.STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by the Netherlands Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). The Eudract number for this trial is 2008-006171-73. The Sponsor's Protocol Code Number is P08-40. CBLA reports unrestricted grant support from Merck and Ferring. BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva and Guerbet.TRIAL REGISTRATION NUMBER: NTR1449.

Published
2019

11. The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis.

Author

Casarramona, G., Lalmahomed, T., Lemmen, C. H. C., Eijkemans, M. J. C., Broekmans, F. J. M., Cantineau, A. E. P., and Drechsel, K. C. E.

Subjects
INDUCED ovulation, LUTEAL phase, ARTIFICIAL insemination, PROGESTERONE, MULTIPLE pregnancy, FROZEN human embryos
Abstract

The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drugdosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice. [ABSTRACT FROM AUTHOR]

Published
2022
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12. Effect of parental and ART treatment characteristics on perinatal outcomes

Author

Pontesilli, M, primary, Hof, M H, additional, Ravelli, A C J, additional, van Altena, A J, additional, Soufan, A T, additional, Mol, B W, additional, Kostelijk, E H, additional, Slappendel, E, additional, Consten, D, additional, Cantineau, A E P, additional, van der Westerlaken, L A J, additional, van Inzen, W, additional, Dumoulin, J C M, additional, Ramos, L, additional, Baart, E B, additional, Broekmans, F J M, additional, Rijnders, P M, additional, Curfs, M H J M, additional, Mastenbroek, S, additional, Repping, S, additional, Roseboom, T J, additional, and Painter, R C, additional

Published
2021
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14. Reply: Endometrial scratching: the light at the end of the tunnel.

Author

Hoogenhuijze, N E van and Broekmans, F J M

Subjects
*EMBRYO implantation, *EMBRYO transfer, *REPRODUCTIVE technology
Abstract

This article is a response to a comment on a meta-analysis of endometrial scratching, a procedure that has been investigated for its effectiveness in improving pregnancy outcomes. The authors acknowledge that the research on endometrial scratching has produced varying results, and they believe that their meta-analysis provides the best available evidence at the moment. They discuss the challenges of analyzing the data and suggest that further research should focus on identifying women who may benefit from endometrial scratching and understanding its biological mechanism of action. Overall, they agree that the meta-analysis is currently the most reliable source of information on the topic, but more research is needed to fully understand its effects. [Extracted from the article]

Published
2024
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16. Corrigendum:The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: A prospective study (Human Reproduction (2018) 33 (2002-2009) DOI: 10.1093/humrep/dez065)

Author

Koedooder, R., Singer, M., Schoenmakers, S., Savelkoul, P. H. M., Morré, S. A., de Jonge, J. D., Poort, L., Cuypers, W. J. S. S., Beckers, N. G. M., Broekmans, F. J. M., Cohlen, B. J., den Hartog, J. E., Fleischer, K., Lambalk, C. B., Smeenk, J. M. J. S., Budding, A. E., and Laven, J. S. E.

Abstract

The authors of the above article would like to apologise for errors in Figure 3 of their article. An old version of the figure file image was uploaded by the authors, with sub-sections A, B, C and D rearranged. The correct version of Figure 3 is included overpage. The electronic version of this article has been updated at https://doi.org/10.1093/humrep/dez065. The authors would liketo assure readers that this does not affect any content of the article. (Figure Presented).

Published
2019

17. Endometrial scratching in women with one failed IVF/ICSI cycle—outcomes of a randomised controlled trial (SCRaTCH)

Author

van Hoogenhuijze, N E, primary, Mol, F, additional, Laven, J S E, additional, Groenewoud, E R, additional, Traas, M A F, additional, Janssen, C A H, additional, Teklenburg, G, additional, de Bruin, J P, additional, van Oppenraaij, R H F, additional, Maas, J W M, additional, Moll, E, additional, Fleischer, K, additional, van Hooff, M H A, additional, de Koning, C H, additional, Cantineau, A E P, additional, Lambalk, C B, additional, Verberg, M, additional, van Heusden, A M, additional, Manger, A P, additional, van Rumste, M M E, additional, van der Voet, L F, additional, Pieterse, Q D, additional, Visser, J, additional, Brinkhuis, E A, additional, den Hartog, J E, additional, Glas, M W, additional, Klijn, N F, additional, van der Meer, S, additional, Bandell, M L, additional, Boxmeer, J C, additional, van Disseldorp, J, additional, Smeenk, J, additional, van Wely, M, additional, Eijkemans, M J C, additional, Torrance, H L, additional, and Broekmans, F J M, additional

Published
2020
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24. Follicle stimulating hormone versus clomiphene citrate in intrauterine insemination for unexplained subfertility : a randomized controlled trial

Author

Danhof, N A, van Wely, M, Repping, S, Koks, C, Verhoeve, H R, de Bruin, J P, Verberg, M F G, van Hooff, M H A, Cohlen, B J, van Heteren, C F, Fleischer, K, Gianotten, J, van Disseldorp, J, Visser, J, Broekmans, F J M, Mol, B W J, van der Veen, F, Mochtar, M H, and SUPER study group

Subjects
IUI, cancellation criteria, clomiphene citrate, unexplained subfertility, ovarian stimulation
Abstract

STUDY QUESTION: Is FSH or clomiphene citrate (CC) the most effective stimulation regimen in terms of ongoing pregnancies in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria as a measure to reduce the number of multiple pregnancies? SUMMARY ANSWER: In IUI with adherence to strict cancellation criteria, ovarian stimulation with FSH is not superior to CC in terms of the cumulative ongoing pregnancy rate, and yields a similar, low multiple pregnancy rate. WHAT IS ALREADY KNOWN: FSH has been shown to result in higher pregnancy rates compared to CC, but at the cost of high multiple pregnancy rates. To reduce the risk of multiple pregnancy, new ovarian stimulation regimens have been suggested, these include strict cancellation criteria to limit the number of dominant follicles per cycle i.e. withholding insemination when more than three dominant follicles develop. With such a strategy, it is unclear whether the ovarian stimulation should be done with FSH or with CC. STUDY DESIGN, SIZE, DURATION: We performed an open-label multicenter randomized superiority controlled trial in the Netherlands (NTR 4057). PARTICIPANTS/MATERIALS, SETTING, METHODS: We randomized couples diagnosed with unexplained subfertility and scheduled for a maximum of four cycles of IUI with ovarian stimulation with 75 IU FSH or 100 mg CC. Cycles were cancelled when more then three dominant follicles developed. The primary outcome was cumulative ongoing pregnancy rate. Multiple pregnancy was a secondary outcome. We analysed the data on intention to treat basis. We calculated relative risks and absolute risk difference with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Between July 2013 and March 2016, we allocated 369 women to ovarian stimulation with FSH and 369 women to ovarian stimulation with CC. A total of 113 women (31%) had an ongoing pregnancy following ovarian stimulation with FSH and 97 women (26%) had an ongoing pregnancy following ovarian stimulation with CC (RR = 1.16, 95% CI: 0.93-1.47, ARD = 0.04, 95% CI: -0.02 to 0.11). Five women (1.4%) had a multiple pregnancy following ovarian stimulation with FSH and eight women (2.2%) had a multiple pregnancy following ovarian stimulation with CC (RR = 0.63, 95% CI: 0.21-1.89, ARD = -0.01, 95% CI: -0.03 to 0.01). LIMITATIONS, REASONS FOR CAUTION: We were not able to blind this study due to the nature of the interventions. We consider it unlikely that this has introduced performance bias, since pregnancy outcomes are objective outcome measures. WIDER IMPLICATIONS OF THE FINDINGS: We revealed that adherence to strict cancellation criteria is a successful solution to reduce the number of multiple pregnancies in IUI. To decide whether ovarian stimulation with FSH or with CC should be the regimen of choice, costs and patients' preferences should be taken into account. STUDY FUNDING/COMPETING INTEREST(S): This trial received funding from the Dutch Organization for Health Research and Development (ZonMw). Prof. Dr B.W.J. Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for Merck, ObsEva and Guerbet. The other authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: Nederlands Trial Register NTR4057. TRIAL REGISTRATION DATE: 1 July 2013. DATE OF FIRST PATIENT’S ENROLMENT: The first patient was randomized at 27 August 2013.

Published
2018

25. Corrigendum. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

Author

Koedooder, R, primary, Singer, M, additional, Schoenmakers, S, additional, Savelkoul, P H M, additional, Morré, S A, additional, de Jonge, J D, additional, Poort, L, additional, Cuypers, W J S S, additional, Beckers, N G M, additional, Broekmans, F J M, additional, Cohlen, B J, additional, den Hartog, J E, additional, Fleischer, K, additional, Lambalk, C B, additional, Smeenk, J M J S, additional, Budding, A E, additional, and Laven, J S E, additional

Published
2019
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26. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

Author

Koedooder, R, primary, Singer, M, additional, Schoenmakers, S, additional, Savelkoul, P H M, additional, Morré, S A, additional, de Jonge, J D, additional, Poort, L, additional, Cuypers, W J S S, additional, Beckers, N G M, additional, Broekmans, F J M, additional, Cohlen, B J, additional, den Hartog, J E, additional, Fleischer, K, additional, Lambalk, C B, additional, Smeenk, J M J S, additional, Budding, A E, additional, and Laven, J S E, additional

Published
2019
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28. Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial

Author

Bui, B. N., primary, Torrance, H. L., additional, Janssen, C., additional, Cohlen, B., additional, de Bruin, J. P., additional, den Hartog, J. E., additional, van der Linden, P. J. Q., additional, Deurloo, K. L., additional, Maas, J. W. M., additional, van Oppenraaij, R., additional, Cantineau, A., additional, Lambalk, C. B., additional, Visser, H., additional, Brinkhuis, E., additional, van Disseldorp, J., additional, Schoot, B. C., additional, Lardenoije, C., additional, van Wely, M., additional, Eijkemans, M. J. C., additional, and Broekmans, F. J. M., additional

Published
2018
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29. Birthweight and other perinatal outcomes of singletons conceived after assisted reproduction compared to natural conceived singletons in couples with unexplained subfertility: follow-up of two randomized clinical trials.

Author

Wessel, J A, Mol, F, Danhof, N A, Bensdorp, A J, Fat, R I Tjon-Kon, Broekmans, F J M, Hoek, A, Mol, B W J, Mochtar, M H, Wely, M van, Group, INeS and SUPER Study, Tjon-Kon Fat, R I, van Wely, M, and INeS and SUPER Study Group

Subjects
INFERTILITY treatment, RESEARCH, CLINICAL trials, BIRTH rate, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, INFERTILITY, COMPARATIVE studies, BIRTH weight, FERTILIZATION in vitro, INDUCED ovulation, LONGITUDINAL method
Abstract

Study Question: Does assisted reproduction, such as ovarian stimulation and/or laboratory procedures, have impact on perinatal outcomes of singleton live births compared to natural conception in couples with unexplained subfertility?Summary Answer: Compared to natural conception, singletons born after intrauterine insemination with ovarian stimulation (IUI-OS) had a lower birthweight, while singletons born after IVF had comparable birthweights, in couples with unexplained subfertility.What Is Known Already: Singletons conceived by assisted reproduction have different perinatal outcomes such as low birthweight and a higher risk of premature birth than naturally conceived singletons. This might be due to the assisted reproduction, such as laboratory procedures or the ovarian stimulation, or to an intrinsic factor in couples with subfertility.Study Design, Size, Duration: We performed a prospective cohort study using the follow-up data of two randomized clinical trials performed in couples with unexplained subfertility. We evaluated perinatal outcomes of 472 live birth singletons conceived after assisted reproduction or after natural conception within the time horizon of the studies.Participants/materials, Setting, Methods: To assess the possible impact of ovarian stimulation we compared the singletons conceived after IUI with FSH or clomiphene citrate (CC) and IVF in a modified natural cycle (IVF-MNC) or standard IVF with single embryo transfer (IVF-SET) to naturally conceived singletons in the same cohorts. To further look into the possible effect of the laboratory procedures, we put both IUI and IVF groups together into IUI-OS and IVF and compared both to singletons born after natural conception. We only included singletons conceived after fresh embryo transfers. The main outcome was birthweight presented as absolute weight in grams and gestational age- and gender-adjusted percentiles. We calculated differences in birthweight using regression analyses adjusted for maternal age, BMI, smoking, parity, duration of subfertility and child gender.Main Results and the Role Of Chance: In total, there were 472 live birth singletons. Of the 472 singleton pregnancies, 209 were conceived after IUI-OS (136 with FSH and 73 with CC as ovarian stimulation), 138 after IVF (50 after IVF-MNC and 88 after IVF-SET) and 125 were conceived naturally.Singletons conceived following IUI-FSH and IUI-CC both had lower birthweights compared to naturally conceived singletons (adjusted difference IUI-FSH -156.3 g, 95% CI -287.9 to -24.7; IUI-CC -160.3 g, 95% CI -316.7 to -3.8). When we compared IVF-MNC and IVF-SET to naturally conceived singletons, no significant difference was found (adjusted difference IVF-MNC 75.8 g, 95% CI -102.0 to 253.7; IVF-SET -10.6 g, 95% CI -159.2 to 138.1). The mean birthweight percentile was only significantly lower in the IUI-FSH group (-7.0 percentile, 95% CI -13.9 to -0.2). The IUI-CC and IVF-SET group had a lower mean percentile and the IVF-MNC group a higher mean percentile, but these groups were not significant different compared to the naturally conceived group (IUI-CC -5.1 percentile, 95% CI -13.3 to 3.0; IVF-MNC 4.4 percentile, 95% CI -4.9 to 13.6; IVF-SET -1.3 percentile, 95% CI -9.1 to 6.4).Looking at the laboratory process that took place, singletons conceived following IUI-OS had lower birthweights than naturally conceived singletons (adjusted difference -157.7 g, 95% CI -277.4 to -38.0). The IVF group had comparable birthweights with the naturally conceived group (adjusted difference 20.9 g, 95% CI -110.8 to 152.6). The mean birthweight percentile was significantly lower in the IUI-OS group compared to the natural group (-6.4 percentile, 95% CI -12.6 to -0.1). The IVF group was comparable (0.7 percentile, 95% CI -6.1 to 7.6).Limitations, Reasons For Caution: The results are limited by the number of cases. The data were collected prospectively alongside the randomized controlled trials, but analyzed as treated.Wider Implications Of the Findings: Our data suggest IUI in a stimulated cycle may have a negative impact on the birthweight of the child and possibly on pre-eclampsia. Further research should look into the effect of different methods of ovarian stimulation on placenta pathology and pre-eclampsia in couples with unexplained subfertility using naturally conceived singletons in the unexplained population as a reference.Study Funding/competing Interest(s): Both initial trials were supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (INeS 120620027, SUPER 80-83600-98-10192). The INeS study also had a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). B.W.J.M. is supported by an NHMRC investigator Grant (GNT1176437) and reports consultancy for ObsEva, Merck Merck KGaA, Guerbet and iGenomix, outside the submitted work. A.H. reports grants from Ferring Pharmaceutical company (the Netherlands), outside the submitted work. F.J.M.B. receives monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands), Ferring Pharmaceutics BV (the Netherlands) and Gedeon Richter (Belgium), he receives personal fees from educational activities for Ferring BV (the Netherlands) and for advisory and consultancy work for Roche and he receives research support grants from Merck Serono and Ferring Pharmaceutics BV, outside the submitted work. The remaining authors have nothing to disclose.Trial Registration Number: INeS study Trial NL915 (NTR939); SUPER Trial NL3895 (NTR4057). [ABSTRACT FROM AUTHOR]

Published
2021
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31. Association between vascular health and ovarian ageing in type 1 diabetes mellitus

Author

Yarde, F, Spiering, W, Franx, A, Visseren, F L J, Eijkemans, M J C, de Valk, H W, Broekmans, F J M, and OVADIA Study Group

Subjects
ovarian reserve, anti-Müllerian hormone, Reproductive Medicine, cardiovascular disease, vascular risk factors, Rehabilitation, Obstetrics and Gynaecology, Journal Article, type 1 diabetes mellitus
Abstract

STUDY QUESTION: Is vascular health associated with ovarian reserve status using type 1 diabetes mellitus (DM-1) as a model for vascular compromise? SUMMARY ANSWER: No conclusive evidence for an association between vascular health and ovarian ageing was found in women with DM-1. WHAT IS KNOWN ALREADY: The mechanism behind advanced ovarian ageing has not yet been elucidated. We hypothesize that vascular impairment precedes ovarian ageing. DM-1 is hallmarked by premature vascular complications that may consequently play a role in the rate of primordial follicle decline. STUDY DESIGN, SIZE, DURATION: A cross-sectional, patient-control study was performed in 150 premenopausal, regular cycling women with DM-1, as well as a reference population of 177 healthy, fertile women. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a single-study visit, an inventory of both ovarian reserve and vascular status was carried out in the DM-1 group. A transvaginal ultrasound to calculate the antral follicle count (AFC) and blood sampling for anti-Müllerian hormone (AMH), lipids, C-reactive protein and HbA1c measurements were performed. Furthermore, vascular screening including measurements of blood pressure, flow-mediated dilation, peripheral arterial tonometry, pulse wave velocity, pulse wave analysis and intima-media thickness was carried out. The relative decrease in serum AMH levels in women with DM-1 compared with healthy references was investigated. MAIN RESULTS AND THE ROLE OF CHANCE: Systolic blood pressure was negatively correlated with both serum AMH (P= 0.006) and AFC (P= 0.004) in the DM-1 group. A non-linear relationship between HDL-cholesterol and serum AMH was found (P= 0.0001). No associations were detected between other vascular risk factors or vascular function tests and serum AMH or AFC in women with DM-1. With regard to the comparison of AMH levels between women with and without DM-1, mean AMH levels were 2.5 ± 1.9 ng/ml and 3.0 ± 2.8 ng/ml, respectively. After adjustment for confounders the difference in AMH levels between both groups appeared non-significant (fold change: 0.92, 95% confidence interval: 0.68-1.23). LIMITATIONS, REASON FOR CAUTION: The use of different AMH assays and the cross-sectional design may limit the interpretation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The lack of evident association between vascular health and ovarian ageing may be the result of an insufficient vascular compromise in the relatively young, DM-1 group. STUDY FUNDING/COMPETING INTERESTS: No external funding was received for conducting or publishing this study. F.Y., W.S., A.F., F.L.J.V., M.J.C.E. and H.W.d.V. have nothing to disclose. F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors and Roche. TRIAL REGISTRATION NUMBER: Not applicable.

Published
2016

32. Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342)

Author

van Hoogenhuijze, N. E., primary, Torrance, H. L., additional, Mol, F., additional, Laven, J. S. E., additional, Scheenjes, E., additional, Traas, M. A. F., additional, Janssen, C., additional, Cohlen, B., additional, Teklenburg, G., additional, de Bruin, J. P., additional, van Oppenraaij, R., additional, Maas, J. W. M., additional, Moll, E., additional, Fleischer, K., additional, van Hooff, M. H., additional, de Koning, C., additional, Cantineau, A., additional, Lambalk, C. B., additional, Verberg, M., additional, Nijs, M., additional, Manger, A. P., additional, van Rumste, M., additional, van der Voet, L. F., additional, Preys-Bosman, A., additional, Visser, J., additional, Brinkhuis, E., additional, den Hartog, J. E., additional, Sluijmer, A., additional, Jansen, F. W., additional, Hermes, W., additional, Bandell, M. L., additional, Pelinck, M. J., additional, van Disseldorp, J., additional, van Wely, M., additional, Smeenk, J., additional, Pieterse, Q. D., additional, Boxmeer, J.C., additional, Groenewoud, E.R., additional, Eijkemans, M. J. C., additional, Kasius, J. C., additional, and Broekmans, F. J. M., additional

Published
2017
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36. Age at menopause in women with type 1 diabetes mellitus : the OVADIA study

Author

Yarde, F., van der Schouw, Y. T., de Valk, H. W., Franx, A., Eijkemans, M. J. C., Spierings, W., OVADIA Study Grp, and Broekmans, F. J. M.

Subjects
RISK, COMPLICATIONS, type 1 diabetes, REPRODUCTIVE LIFE, MORTALITY, Research Support, Non-U.S. Gov't, HEART-DISEASE, RETINOPATHY, natural menopause, POLYCYSTIC-OVARY-SYNDROME, vascular health, THERAPY, Multicenter Study, ovarian ageing, CARDIOVASCULAR-DISEASE, age at menopause, Journal Article, Controlled Clinical Trial
Abstract

STUDY QUESTION: Is type 1 diabetes a determinant of advanced ovarian ageing, resulting in an early age at natural menopause? SUMMARY ANSWER: No clear evidence was provided that type 1 diabetes is a determinant of accelerated ovarian ageing resulting in an early menopause. WHAT IS KNOWN ALREADY: The association between type 1 diabetes and early menopause has been examined previously with inconsistent results. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was performed in 140 post-menopausal women with, and 5426 postmenopausal women without, diabetes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both women with and without diabetes had experienced natural menopause. Study participants filled out a standardized questionnaire including report of their age at last menstrual period. Differences in menopausal age were analysed using linear regression analyses, with adjustment for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at natural menopause was 49.8 +/- 4.7 years in women with type 1 diabetes and 49.8 +/- 4.1 in women without diabetes. Linear regression analyses showed that type 1 diabetes was not associated with an earlier menopause compared with the reference group without diabetes, after adjustment for age, smoking history and parity (difference in age at menopause between women with type 1 diabetes and reference group 0.34 years, 95% confidence interval -0.34, 1.01). LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. We had no information regarding microvascular complications therefore a possible association between vascular health and menopausal age could not be investigated. WIDER IMPLICATIONS OF THE FINDINGS: It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes.

Published
2015

37. Endometrial scratching prior to IVF; does it help and for whom? A systematic review and meta-analysis.

Author

Hoogenhuijze, N E van, Kasius, J C, Broekmans, F J M, Bosteels, J, and Torrance, H L

Subjects
ENDOMETRIAL diseases, HUMAN in vitro fertilization, EMBRYO implantation
Abstract

STUDY QUESTION What is the effect of endometrial scratching in patients with or without prior failed ART cycles on live birth (LBR) and clinical pregnancy rates (CPR)? SUMMARY ANSWER It remains unclear if endometrial scratching improves the chance of pregnancy and, if so, for whom. WHAT IS KNOWN ALREADY Endometrial scratching is hypothesized to improve embryo implantation in ART. Multiple studies have been published, but it remains unclear if endometrial scratching actually improves pregnancy rates and, if so, for which patients. STUDY DESIGN, SIZE, DURATION For this review, a systematic search for published articles on endometrial scratching and ART was performed on 12 February 2018, in Pubmed, Embase and the Cochrane Library. PARTICIPANTS/MATERIALS, SETTING, METHODS Randomized controlled trials (RCTs) that evaluated endometrial scratching in the cycle prior to the stimulation cycle and reported CPR or LBR were included. RCTs investigating the effect of scratching during the stimulation cycle, or prior to cryo-thaw cycles were excluded. Studies were assessed using the Cochrane Risk of Bias tool. The effect of scratching was assessed for three different patient groups: patients with no prior IVF/ICSI treatment (Group 0), patients with one failed full IVF/ICSI cycle, including cryo-thaw cycles (Group 1) and patients with two or more failed full IVF/ICSI cycles (Group 2). A meta-analysis was performed when statistical heterogeneity was low; otherwise, a descriptive analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE Fourteen RCTs involving 2537 participants were included. Most RCTs contained a high or unclear risk of bias on one or more items. Substantial clinical and statistical heterogeneity was present; therefore meta-analysis for LBR and CPR could only be performed on Group 1. For this group, no differences between scratch and control were found for both LBR (risk ratio (RR) 1.01 [95%CI 0.68–1.51]) and CPR (RR 1.04 [95%CI 0.74–1.45]). For Groups 0 and 2, pooled analysis could not be performed, and for both groups the results of the individual RCTs were negative, neutral and positive. Miscarriage and multiple pregnancy rates were evaluated for the three groups (0, 1 and 2) together. Both outcomes were not significantly different between scratch and control (miscarriage rate RR 0.82 [95%CI 0.57–1.17] and multiple pregnancy rate RR 1.06 [95%CI 0.84–1.35]). Subgroup analysis, excluding trials with a risk of unintentional endometrial injury in the control group, was performed for Group 0 and 2 for LBR and CPR, and for the overall groups for miscarriage rate and multiple pregnancy rate. This reduced the heterogeneity and allowed for pooled analysis in these subgroups. Results of pooled analysis for the subgroups of Group 0 and 2 showed no significant difference for LBR, but CPR was significantly improved after endometrial scratching (Group 0 RR 1.28 [95%CI 1.02–1.62] and Group 2 RR 2.03 [95%CI 1.20–3.43]). Subgroup analysis of the overall groups showed no significant difference for miscarriage and multiple pregnancy rate. LIMITATIONS REASONS FOR CAUTION The main limitations were that many RCTs had a high or unclear risk of bias on one or several items, clinical heterogeneity was still present despite categorizing into three populations, and that not all RCTs could be included in the analyses because separate data for our three groups could not be provided. WIDER IMPLICATIONS OF THE FINDINGS It remains unclear if endometrial scratching improves the chance of pregnancy for women undergoing ART and, if so, for whom. This means endometrial scratching should not be offered in daily practice until results from large and well-designed RCTs and an individual patient data analysis become available. STUDY FUNDING/COMPETING INTERESTS No specific funding was sought for the study. The Department of Reproductive Medicine and Gynaecology funds of the University Medical Center of Utrecht were used to support the authors throughout the study period and preparation of the manuscript. None of the authors has a conflict of interest to declare. REGISTRATION NUMBER Not applicable. [ABSTRACT FROM AUTHOR]

Published
2019
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38. BRCA1/2 mutation carriers do not have earlier natural menopause compared to proven non-carriers: report from the Dutch hereditary breast and ovarian cancer study group (HEBON)

Author

van Tilborg, T. C., Broekmans, F. J. M., Schrijver, L. H., Mooij, T. M., Pijpe, A., Oosterwijk, J. C., Verhoef, S., Garcia, E. B. Gomez, van Zelst-Stams, W. A. G., Adank, M. A., van Asperen, C. J., van Doorn, H. C., van Os, T. A. M., Rookus, M. A., Ausems, M. G. E. M., Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Published
2014

39. The Significance of Fragile X Mental Retardation Gene 1 CGG Repeat Sizes in the Normal and Intermediate Range in Women With Primary Ovarian Insufficiency EDITORIAL COMMENT

Author

Voorhuis, M., Onland-Moret, N. C., Janse, F., van Amstel, H. K. Ploos, Goverde, A. J., Lambalk, C. B., Laven, J. S. E., van der Schouw, Y. T., Broekmans, F. J. M., Fauser, B. C. J. M., Obstetrics and gynaecology, ICaR - Ischemia and repair, RS: GROW - Developmental Biology, and RS: GROW - R4 - Reproductive and Perinatal Medicine

Abstract

Primary ovarian insufficiency (POI) refers to the cessation of menses before the age of 40 years and occurs in 1% to 2% of women. The specific cause of POI is unknown in the majority of cases. Known causes include gene mutations of fragile X mental retardation 1 (FMR1), a gene located on the X chromosome. This gene codes for a protein essential for normal cognitive development and female reproductive function. FMR1 contains a CCG trinucleotide segment in an untranslated region of its DNA that is repeated less than 45 times in normal individuals (normal range of repeats). Mutation of FMR1 results in abnormal expansion of an unstable CGG triplet, leading to impaired cognitive and reproductive function. Between 55 and 200 CCG repeats is called premutation; affected individuals with premutation are at risk for POI and further expansion of repeats in subsequent generations. People with 45 to 54 CCG repeats (intermediate range of repeats) are considered to be at borderline risk for POI and further expansion of repeats. This case-control study was designed to determine whether the risk of POI is associated with CGG repeat length of normal and intermediate range (up to 55 repeats) in a large cohort of Dutch women with idiopathic POI. The second aim of the study was to examine a possible association between the number of CGG repeats and age at first manifestation of POI as a measurement for the severity of POI. The study population was composed of 375 well-phenotyped Dutch women diagnosed with POI; control subjects were 3368 women with natural menopause at 40 years or older. The FMR1 CGG repeat number was determined by polymerase chain reaction amplification of DNA extracted from blood samples drawn from each patient. Fisher exact test was used to assess the prevalence of intermediate-size CGG repeats in POI cases and control subjects. Analysis of variance tested differences in mean CGG repeat lengths on alleles 1 and 2 between POI cases and control subjects. Allele 1 has the lowest triple repeat number, and allele 2 has the highest triple repeat number. There was no significant difference between POI cases and control subjects in the frequency of intermediate-size CGG repeats on allele 2 (POI 2.7 vs control subjects 3.8%; the odds ratio was 0.72, with a 95% confidence interval of 0.38-1.39; P = 0.38). Linear regression analysis showed no association between the number of CGG repeats and age at first POI manifestation ( = 20.019, P = 0.72). These data suggest that intermediate-size CGG repeats are not associated with risk of POI. Therefore, evaluation of normal and intermediate FMR1 repeat size appears to be of little or no value in the diagnostic workup of women affected by POI or in the prognostic assessment of women at risk of developing POI. Reasons for caution in interpreting these results are as follows: (1) FMR1 CGG repeat lengths in POI cases and control subjects were genotyped in 2 different laboratories; technical differences could have affected the results; (2) distributions of CGG repeats could vary among ethnic populations; (3) women with primary amenorrhea (n = 17) were included in the POI group. The last 2 possible limitations were unlikely because exclusion of data from nonwhite women or women with primary amenorrhea did not affect the results.

Published
2014

40. Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization: an external validation study.

Author

Leijdekkers, J A, Eijkemans, M J C, Tilborg, T C van, Oudshoorn, S C, McLernon, D J, Bhattacharya, S, Mol, B W J, Broekmans, F J M, Torrance, H L, group, OPTIMIST, van Tilborg, T C, and OPTIMIST group

Subjects
FERTILIZATION in vitro, CUMULATIVE instruction, CHILDBIRTH, EMBRYO transfer, OVARIAN atresia
Abstract

Study Question: Are the published pre-treatment and post-treatment McLernon models, predicting cumulative live birth rates (LBR) over multiple complete IVF cycles, valid in a different context?Summary Answer: With minor recalibration of the pre-treatment model, both McLernon models accurately predict cumulative LBR in a different geographical context and a more recent time period.What Is Known Already: Previous IVF prediction models have estimated the chance of a live birth after a single fresh embryo transfer, thereby excluding the important contribution of embryo cryopreservation and subsequent IVF cycles to cumulative LBR. In contrast, the recently developed McLernon models predict the cumulative chance of a live birth over multiple complete IVF cycles at two certain time points: (i) before initiating treatment using baseline characteristics (pre-treatment model) and (ii) after the first IVF cycle adding treatment related information to update predictions (post-treatment model). Before implementation of these models in clinical practice, their predictive performance needs to be validated in an independent cohort.Study Design, Size, Duration: External validation study in an independent prospective cohort of 1515 Dutch women who participated in the OPTIMIST study (NTR2657) and underwent their first IVF treatment between 2011 and 2014. Participants underwent a total of 2881 complete treatment cycles, with a complete cycle defined as all fresh and frozen thawed embryo transfers resulting from one episode of ovarian stimulation. The follow up duration was 18 months after inclusion, and the primary outcome was ongoing pregnancy leading to live birth.Participants/materials, Setting, Methods: Model performance was externally validated up to three complete treatment cycles, using the linear predictor as described by McLernon et al. to calculate the probability of a live birth. Discrimination was expressed by the c-statistic and calibration was depicted graphically in a calibration plot. In contrast to the original model development cohort, anti-Müllerian hormone (AMH), antral follicle count (AFC) and body weight were available in the OPTIMIST cohort, and evaluated as potential additional predictors for model improvement.Main Results and the Role Of Chance: Applying the McLernon models to the OPTIMIST cohort, the c-statistic of the pre-treatment model was 0.62 (95% CI: 0.59-0.64) and of the post-treatment model 0.71 (95% CI: 0.69-0.74). The calibration plot of the pre-treatment model indicated a slight overestimation of the cumulative LBR. To improve calibration, the pre-treatment model was recalibrated by subtracting 0.35 from the intercept. The post-treatment model calibration plot revealed accurate cumulative LBR predictions. After addition of AMH, AFC and body weight to the McLernon models, the c-statistic of the updated pre-treatment model improved slightly to 0.66 (95% CI: 0.64-0.68), and of the updated post-treatment model remained at the previous level of 0.71 (95% CI: 0.69-0.73). Using the recalibrated pre-treatment model, a woman aged 30 years with 2 years of primary infertility who starts ICSI treatment for male factor infertility has a chance of 40% of a live birth from the first complete cycle, increasing to 72% over three complete cycles. If this woman weighs 70 kg, has an AMH of 1.5 ng/mL and an AFC of 10 measured at the beginning of her treatment, the updated pre-treatment model revises the estimated chance of a live birth to 30% in the first complete cycle and 59% over three complete cycles. If this woman then has five retrieved oocytes, no embryos cryopreserved and a single fresh cleavage stage embryo transfer in her first ICSI cycle, the post-treatment model estimates the chances of a live birth at 28 and 58%, respectively.Limitations, Reasons For Caution: Two randomized controlled trials (RCT) evaluating the effectiveness of gonadotropin dose individualization on basis of the AFC were nested within the OPTIMIST study. The strict dosing regimens, the RCT in- and exclusion criteria and the limited follow up time of 18 months might have influenced model performance in this independent cohort. Also, consistent with the original model development study, external validation was performed using the optimistic assumption that the cumulative LBR in couples who discontinue treatment without a live birth would have been equal to that of those who continue treatment.Wider Implications Of the Findings: After national recalibration to account for geographical differences in IVF treatment, the McLernon prediction models can be introduced as new counselling tools in clinical practice to inform patients and to complement clinical reasoning. These models are the first to offer an objective and personalized estimate of the cumulative probability of a live birth over multiple complete IVF cycles.Study Funding/competing Interest(s): No external funds were obtained for this study. M.J.C.E., D.J.M. and S.B. have nothing to disclose. J.A.L, S.C.O, T.C.v.T. and H.LT. received an unrestricted personal grant from Merck BV. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for ObsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Merck BV (the Netherlands) and Ferring pharmaceutics BV (the Netherlands), for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development, and for a research cooperation with Ansh Labs (USA).Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Published
2018
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43. Cumulative live birth rates following lVF in 41-to 43-year-old women presenting with favourable ovarian reserve characteristics

Author

van Disseldorp, J., Eijkemans, M. J. C., Klinkert, E. R., Velde, E. R. te, Fauser, B. C., and Broekmans, F. J. M.

Subjects
antral follicle count, OLDER, INHIBIN-B, ANTI-MULLERIAN HORMONE, ONGOING PREGNANCY, FOLLICLE-STIMULATING-HORMONE, live birth, POOR RESPONSE, AGE, cost analysis, IVF, IN-VITRO FERTILIZATION, basal FSH, NORMAL MENSTRUAL-CYCLE
Abstract

For women aged 41-43 years old, success rates in IVF are generally poor. This study aimed to assess cumulative live birth rate related to treatment costs over a maximum of three IVF cycles in selected women who were considered to still have adequate ovarian reserve. Fifty-five patients (38% of the total cohort, n = 144) were excluded from IVF treatment based on low antral follicle count ( 15 IU/l). Of those admitted, 66 (74%) actually started and completed a total of 125 IVF/intracytoplasmic sperm injection cycles. Treatment resulted in 10 live births (8% per cycle). Kaplan-Meier survival analysis revealed a realistic cumulative live birth rate after three cycles of 17%. The direct medical costs per live birth were calculated to be approximately E44,000. These results show that selection towards favourable ovarian reserve status in the female age group 41-43 years yielded disappointing results in terms of cumulative live birth rates after IVF. In view of the costs raised per live birth, improvement of selection parameters for treatment in this age group is warranted.

Published
2007

44. Prevention of multiple pregnancies after IVF in women 38 and older: a randomized study

Author

Heijnen, E. M. E. W., Klinkert, E. R., Schmoutziguer, A. P. E., Eijkemans, M. J. C., te Velde, E. R., and Broekmans, F. J. M.

Subjects
ASSISTED REPRODUCTION, LEGISLATION, AGE, cumulative pregnancy rates, IVF, QUALITY EMBRYOS, multiple pregnancy, CYCLES, SINGLE-EMBRYO-TRANSFER, IN-VITRO FERTILIZATION, CONTROLLED-TRIAL, TWIN PREGNANCIES, INFERTILITY
Abstract

The objective of this study was to answer the question of whether a double instead of triple embryo transfer strategy in patients over 38 years would substantially reduce the number of multiple pregnancies while maintaining the chance of a term live birth at an acceptable level. A randomized controlled two-centre trial was performed. Forty-five patients, 38 years or older, were randomized. Double embryo transfer over a maximum of four cycles (DET group) or triple embryo transfer over a maximum of three cycles JET group) was performed. The cumulative term live birth rate was 47.3% after four cycles in the DET group and 40.5% after three cycles in the TET group. The difference between the DET and the TET group was 6.8% in favour of the DET group (95% CI -25 to 38). The multiple pregnancy rates in the DET and TET group were 0% (95% CI 0 to 24) and 30% (95% CI 7 to 65) respectively (P = 0.05). In the DET patients, the mean number of treatment cycles was 2.9 compared with 2.1 in the TET group (P = 0.01). In women of 38 years and older, double embryo transfer after IVF may result in similar cumulative term live birth rates compared with triple embryo transfer, provided that a higher number of treatment cycles is accepted.

Published
2006

45. Implementing targeted expectant management in fertility care using prognostic modelling: a cluster randomized trial with a multifaceted strategy.

Author

Kersten, F A M, Nelen, W L D M, van den Boogaard, N M, van Rumste, M M, Koks, C A, IntHout, J, Verhoeve, H R, Pelinck, M J, Boks, D E S, Gianotten, J, Broekmans, F J M, Goddijn, M, Braat, D D M, Mol, B W J, Hermens, R P G M, and Improvement study group

Subjects
HUMAN fertility, FERTILITY, HUMAN reproduction, HUMAN physiology, REPRODUCTION, INFERTILITY treatment, HUMAN artificial insemination, BIRTH rate, COMPARATIVE studies, FERTILIZATION in vitro, MATHEMATICAL models, RESEARCH methodology, MEDICAL cooperation, INDUCED ovulation, PROGNOSIS, RESEARCH, THEORY, EVALUATION research, RANDOMIZED controlled trials, TREATMENT effectiveness
Abstract

Study Question: What is the effectiveness of a multifaceted implementation strategy compared to usual care on improving the adherence to guideline recommendations on expectant management for couples with unexplained infertility?Summary Answer: The multifaceted implementation strategy did not significantly increase adherence to guideline recommendations on expectant management compared to care as usual.What Is Known Already: Intrauterine insemination (IUI) with or without ovarian hyperstimulation has no beneficial effect compared to no treatment for 6 months after the fertility work-up for couples with unexplained infertility and a good prognosis of natural conception. Therefore, various professionals and policy makers have advocated the use of prognostic profiles and expectant management in guideline recommendations.Study Design, Size, Duration: A cluster randomized controlled trial in 25 clinics in the Netherlands was conducted between March 2013 and May 2014. Clinics were randomized between the implementation strategy (intervention, n = 13) and care as usual (control, n = 12). The effect of the implementation strategy was evaluated by comparing baseline and effect measurement data. Data collection was retrospective and obtained from medical record research and a patient questionnaire.Participants/materials, Setting, Methods: A total of 544 couples were included at baseline and 485 at the effect measurement (247 intervention group/238 control group).Main Results and the Role Of Chance: Guideline adherence increased from 49 to 69% (OR 2.66; 95% CI 1.45-4.89) in the intervention group, and from 49 to 61% (OR 2.03; 95% CI 1.38-3.00) in the control group. Multilevel analysis with case-mix adjustment showed that the difference of 8% was not statistically significant (OR 1.31; 95% CI 0.67-2.59). The ongoing pregnancy rate within six months after fertility work-up did not significantly differ between intervention and control group (25% versus 27%: OR 0.72; 95% CI 0.40-1.27).Limitations Reasons For Caution: There is a possible selection bias, couples included in the study had a higher socio-economic status than non-responders. How this affects guideline adherence is unclear. Furthermore, when powering for this study we did not take into account the unexpected improvement of adherence in the control group.Wider Implications Of the Findings: Generalization of our results to other countries with recommendations on expectant management might be questionable because barriers for expectant management can be very different in other countries. Furthermore, due to a large variation in improved adherence rate in the intervention group it will be interesting to further analyse the process of implementation in each clinic with a process evaluation on professionals and couples' exposure to and experiences with the strategy.Study Funding/competing Interest(s): Supported by Netherlands Organisation for Health Research and Development (ZonMW, project number 171203005). No competing interests.Trial Registration Number: Dutch trial Register, www.trialregister.nl NTR3405.Trial Registration Date: 19 April 2012.Date Of First Patient's Enrolment: 10 July 2012. [ABSTRACT FROM AUTHOR]

Published
2017
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46. The SUPER study: protocol for a randomised controlled trial comparing follicle-stimulating hormone and clomiphene citrate for ovarian stimulation in intrauterine insemination.

Author

Danhof, N. A., van Wely, M., Koks, C. A. M., Gianotten, J., de Bruin, J. P., Cohlen, B. J., van der Ham, D. P., Klijn, N. F., van Hooff, M. H. A., Broekmans, F. J. M., Fleischer, K., Janssen, C. A. H., van Weert, J. M. Rijn, van Disseldorp, J., Twisk, M., Traas, M., Verberg, M. F. G., Pelinck, M. J., Visser, J., and Perquin, D. A. M.

Abstract

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]

Published
2017
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48. Reproductive endocrinology

Author

Nazzaro, A., primary, Salerno, A., additional, Di Iorio, L., additional, Landino, G., additional, Marino, S., additional, Pastore, E., additional, Fabregues, F., additional, Iraola, A., additional, Casals, G., additional, Creus, M., additional, Peralta, S., additional, Penarrubia, J., additional, Manau, D., additional, Civico, S., additional, Balasch, J., additional, Lindgren, I., additional, Giwercman, Y. L., additional, Celik, E., additional, Turkcuoglu, I., additional, Ata, B., additional, Karaer, A., additional, Kirici, P., additional, Berker, B., additional, Park, J., additional, Kim, J., additional, Rhee, J., additional, Krishnan, M., additional, Rustamov, O., additional, Russel, R., additional, Fitzgerald, C., additional, Roberts, S., additional, Hapuarachi, S., additional, Tan, B. K., additional, Mathur, R. S., additional, van de Vijver, A., additional, Blockeel, C., additional, Camus, M., additional, Polyzos, N., additional, Van Landuyt, L., additional, Tournaye, H., additional, Turhan, N. O., additional, Hizli, D., additional, Kamalak, Z., additional, Kosus, A., additional, Kosus, N., additional, Kafali, H., additional, Lukaszuk, A., additional, Kunicki, M., additional, Liss, J., additional, Bednarowska, A., additional, Jakiel, G., additional, Lukaszuk, K., additional, Lukaszuk, M., additional, Olszak-Sokolowska, B., additional, Wasniewski, T., additional, Neuberg, M., additional, Cavalcanti, V., additional, Peluso, C., additional, Lechado, B. L., additional, Cordts, E. B., additional, Christofolini, D. M., additional, Barbosa, C. P., additional, Bianco, B., additional, Venetis, C. A., additional, Kolibianakis, E. M., additional, Bosdou, J., additional, Tarlatzis, B. C., additional, Onal, M., additional, Gungor, D. N., additional, Acet, M., additional, Kahraman, S., additional, Kuijper, E., additional, Twisk, J., additional, Caanen, M., additional, Korsen, T., additional, Hompes, P., additional, Kushnir, M., additional, Rockwood, A., additional, Meikle, W., additional, Lambalk, C. B., additional, Yan, X., additional, Dai, X., additional, Wang, J., additional, Zhao, N., additional, Cui, Y., additional, Liu, J., additional, Yarde, F., additional, Maas, A. H. E. M., additional, Franx, A., additional, Eijkemans, M. J. C., additional, Drost, J. T., additional, van Rijn, B. B., additional, van Eyck, J., additional, van der Schouw, Y. T., additional, Broekmans, F. J. M., additional, Martyn, F., additional, Anglim, B., additional, Wingfield, M., additional, Fang, T., additional, Yan, G. J., additional, Sun, H. X., additional, Hu, Y. L., additional, Chrudimska, J., additional, Krenkova, P., additional, Macek, M., additional, Teixeira da Silva, J., additional, Cunha, M., additional, Silva, J., additional, Viana, P., additional, Goncalves, A., additional, Barros, N., additional, Oliveira, C., additional, Sousa, M., additional, Barros, A., additional, Nelson, S. M., additional, Lloyd, S. M., additional, McConnachie, A., additional, Khader, A., additional, Fleming, R., additional, Lawlor, D. A., additional, Thuesen, L., additional, Andersen, A. N., additional, Loft, A., additional, Smitz, J., additional, Abdel-Rahman, M., additional, Ismail, S., additional, Silk, J., additional, Abdellah, M., additional, Abdellah, A. H., additional, Ruiz, F., additional, Cruz, M., additional, Piro, M., additional, Collado, D., additional, Garcia-Velasco, J. A., additional, Requena, A., additional, Kollmann, Z., additional, Bersinger, N. A., additional, McKinnon, B., additional, Schneider, S., additional, Mueller, M. D., additional, von Wolff, M., additional, Vaucher, A., additional, Weiss, B., additional, Stute, P., additional, Marti, U., additional, Chai, J., additional, Yeung, W. Y. T., additional, Lee, C. Y. V., additional, Li, W. H. R., additional, Ho, P. C., additional, Ng, H. Y. E., additional, Kim, S. M., additional, Kim, S. H., additional, Jee, B. C., additional, Ku, S., additional, Suh, C. S., additional, Choi, Y. M., additional, Kim, J. G., additional, Moon, S. Y., additional, Lee, J. H., additional, Kim, S. G., additional, Kim, Y. Y., additional, Kim, H. J., additional, Lee, K. H., additional, Park, I. H., additional, Sun, H. G., additional, Hwang, Y. I., additional, Sung, N. Y., additional, Choi, M. H., additional, Cha, S. H., additional, Park, C. W., additional, Kim, J. Y., additional, Yang, K. M., additional, Song, I. O., additional, Koong, M. K., additional, Kang, I. S., additional, Kim, H. O., additional, Haines, C., additional, Wong, W. Y., additional, Kong, W. S., additional, Cheung, L. P., additional, Choy, T. K., additional, Leung, P. C., additional, Fadini, R., additional, Coticchio, G., additional, Renzini, M. M., additional, Guglielmo, M. C., additional, Brambillasca, F., additional, Hourvitz, A., additional, Albertini, D. F., additional, Novara, P., additional, Merola, M., additional, Dal Canto, M., additional, Iza, J. A. A., additional, DePablo, J. L., additional, Anarte, C., additional, Domingo, A., additional, Abanto, E., additional, Barrenetxea, G., additional, Kato, R., additional, Kawachiya, S., additional, Bodri, D., additional, Kondo, M., additional, Matsumoto, T., additional, Maldonado, L. G. L., additional, Setti, A. S., additional, Braga, D. P. A. F., additional, Iaconelli, A., additional, Borges, E., additional, Iaconelli, C., additional, Figueira, R. C. S., additional, Kitaya, K., additional, Taguchi, S., additional, Funabiki, M., additional, Tada, Y., additional, Hayashi, T., additional, Nakamura, Y., additional, Snajderova, M., additional, Zemkova, D., additional, Lanska, V., additional, Teslik, L., additional, Calonge, R. N. -, additional, Ortega, L., additional, Garcia, A., additional, Cortes, S., additional, Guijarro, A., additional, Peregrin, P. C., additional, Bellavia, M., additional, Pesant, M. H., additional, Wirthner, D., additional, Portman, L., additional, de Ziegler, D., additional, Wunder, D., additional, Chen, X., additional, Chen, S. H. L., additional, Liu, Y. D., additional, Tao, T., additional, Xu, L. J., additional, Tian, X. L., additional, Ye, D. S. H., additional, He, Y. X., additional, Carby, A., additional, Barsoum, E., additional, El-Shawarby, S., additional, Trew, G., additional, Lavery, S., additional, Mishieva, N., additional, Barkalina, N., additional, Korneeva, I., additional, Ivanets, T., additional, Abubakirov, A., additional, Chavoshinejad, R., additional, Hartshorne, G. m., additional, Marei, W., additional, Fouladi-nashta, A. a., additional, Kyrkou, G., additional, Trakakis, E., additional, Chrelias, C. H., additional, Alexiou, E., additional, Lykeridou, K., additional, Mastorakos, G., additional, Bersinger, N., additional, Ferrero, H., additional, Gomez, R., additional, Garcia-Pascual, C. M., additional, Simon, C., additional, Pellicer, A., additional, Turienzo, A., additional, Lledo, B., additional, Guerrero, J., additional, Ortiz, J. A., additional, Morales, R., additional, Ten, J., additional, Llacer, J., additional, Bernabeu, R., additional, De Leo, V., additional, Focarelli, R., additional, Capaldo, A., additional, Stendardi, A., additional, Gambera, L., additional, Marca, A. L., additional, Piomboni, P., additional, Kim, J. J., additional, Kang, J. H., additional, Hwang, K. R., additional, Chae, S. J., additional, Yoon, S. H., additional, Ku, S. Y., additional, Iliodromiti, S., additional, Kelsey, T. W., additional, Anderson, R. A., additional, Lee, H. J., additional, Weghofer, A., additional, Kushnir, V. A., additional, Shohat-Tal, A., additional, Lazzaroni, E., additional, Barad, D. H., additional, Gleicher, N. N., additional, Shavit, T., additional, Shalom-Paz, E., additional, Fainaru, O., additional, Michaeli, M., additional, Kartchovsky, E., additional, Ellenbogen, A., additional, Gerris, J., additional, Vandekerckhove, F., additional, Delvigne, A., additional, Dhont, N., additional, Madoc, B., additional, Neyskens, J., additional, Buyle, M., additional, Vansteenkiste, E., additional, De Schepper, E., additional, Pil, L., additional, Van Keirsbilck, N., additional, Verpoest, W., additional, Debacquer, D., additional, Annemans, L., additional, De Sutter, P., additional, Von Wolff, M., additional, Bersinger, N. a., additional, Verit, F. F., additional, Keskin, S., additional, Sargin, A. K., additional, Karahuseyinoglu, S., additional, Yucel, O., additional, Yalcinkaya, S., additional, Comninos, A. N., additional, Jayasena, C. N., additional, Nijher, G. M. K., additional, Abbara, A., additional, De Silva, A., additional, Veldhuis, J. D., additional, Ratnasabapathy, R., additional, Izzi-Engbeaya, C., additional, Lim, A., additional, Patel, D. A., additional, Ghatei, M. A., additional, Bloom, S. R., additional, Dhillo, W. S., additional, Colodron, M., additional, Guillen, J. J., additional, Garcia, D., additional, Coll, O., additional, Vassena, R., additional, Vernaeve, V., additional, Pazoki, H., additional, Bolouri, G., additional, Farokhi, F., additional, Azarbayjani, M. A., additional, Alebic, M. S., additional, Stojanovic, N., additional, Abali, R., additional, Yuksel, A., additional, Aktas, C., additional, Celik, C., additional, Guzel, S., additional, Erfan, G., additional, Sahin, O., additional, Zhongying, H., additional, Shangwei, L., additional, Qianhong, M., additional, Wei, F., additional, Lei, L., additional, Zhun, X., additional, Yan, W., additional, De Baerdemaeker, A., additional, Tilleman, K., additional, Vansteelandt, S., additional, Oliveira, J. B. A., additional, Baruffi, R. L. R., additional, Petersen, C. G., additional, Mauri, A. L., additional, Nascimento, A. M., additional, Vagnini, L., additional, Ricci, J., additional, Cavagna, M., additional, Massaro, F. C., additional, Pontes, A., additional, Franco, J. G., additional, El-khayat, W., additional, Elsadek, M., additional, Foroozanfard, F., additional, Saberi, H., additional, Moravvegi, A., additional, Kazemi, M., additional, Gidoni, Y. S., additional, Raziel, A., additional, Friedler, S., additional, Strassburger, D., additional, Hadari, D., additional, Kasterstein, E., additional, Ben-Ami, I., additional, Komarovsky, D., additional, Maslansky, B., additional, Bern, O., additional, Ron-El, R., additional, Izquierdo, M. P., additional, Araico, F., additional, Somova, O., additional, Feskov, O., additional, Feskova, I., additional, Bezpechnaya, I., additional, Zhylkova, I., additional, Tishchenko, O., additional, Oguic, S. K., additional, Baldani, D. P., additional, Skrgatic, L., additional, Simunic, V., additional, Vrcic, H., additional, Rogic, D., additional, Juras, J., additional, Goldstein, M. S., additional, Garcia De Miguel, L., additional, Campo, M. C., additional, Gurria, A., additional, Alonso, J., additional, Serrano, A., additional, Marban, E., additional, Shalev, L., additional, Yung, Y., additional, Yerushalmi, G., additional, Giovanni, C., additional, Has, J., additional, Maman, E., additional, Monterde, M., additional, Marzal, A., additional, Vega, O., additional, Rubio, J. m., additional, Diaz-Garcia, C., additional, Eapen, A., additional, Datta, A., additional, Kurinchi-selvan, A., additional, Birch, H., additional, Lockwood, G. M., additional, Ornek, M. C., additional, Ates, U., additional, Usta, T., additional, Goksedef, C. P., additional, Bruszczynska, A., additional, Glowacka, J., additional, Jaguszewska, K., additional, Oehninger, S., additional, Nelson, S., additional, Verweij, P., additional, Stegmann, B., additional, Ando, H., additional, Takayanagi, T., additional, Minamoto, H., additional, Suzuki, N., additional, Rubinshtein, N., additional, Saltek, S., additional, Demir, B., additional, Dilbaz, B., additional, Demirtas, C., additional, Kutteh, W., additional, Shapiro, B., additional, Witjes, H., additional, Gordon, K., additional, Lauritsen, M. P., additional, Pinborg, A., additional, Freiesleben, N. L., additional, Mikkelsen, A. L., additional, Bjerge, M. R., additional, Chakraborty, P., additional, Goswami, S. K., additional, Chakravarty, B. N., additional, Mittal, M., additional, Bajoria, R., additional, Narvekar, N., additional, Chatterjee, R., additional, Bentzen, J. G., additional, Johannsen, T. H., additional, Scheike, T., additional, Friis-Hansen, L., additional, Sunkara, S., additional, Coomarasamy, A., additional, Faris, R., additional, Braude, P., additional, Khalaf, Y., additional, Makedos, A., additional, Masouridou, S., additional, Chatzimeletiou, K., additional, Zepiridis, L., additional, Mitsoli, A., additional, Lainas, G., additional, Sfontouris, I., additional, Tzamtzoglou, A., additional, Kyrou, D., additional, Lainas, T., additional, Fermin, A., additional, Crisol, L., additional, Exposito, A., additional, Prieto, B., additional, Mendoza, R., additional, Matorras, R., additional, Louwers, Y., additional, Lao, O., additional, Kayser, M., additional, Palumbo, A., additional, Sanabria, V., additional, Rouleau, J. P., additional, Puopolo, M., additional, Hernandez, M. J., additional, Rubio, J. M., additional, Ozturk, S., additional, Sozen, B., additional, Yaba-Ucar, A., additional, Mutlu, D., additional, Demir, N., additional, Olsson, H., additional, Sandstrom, R., additional, Grundemar, L., additional, Papaleo, E., additional, Corti, L., additional, Rabellotti, E., additional, Vanni, V. S., additional, Potenza, M., additional, Molgora, M., additional, Vigano, P., additional, Candiani, M., additional, Fernandez-Sanchez, M., additional, Bosch, E., additional, Visnova, H., additional, Barri, P., additional, Fauser, B. J. C. M., additional, Arce, J. C., additional, Peluso, P., additional, Trevisan, C. M., additional, Fonseca, F. A., additional, Bakas, P., additional, Vlahos, N., additional, Hassiakos, D., additional, Tzanakaki, D., additional, Gregoriou, O., additional, Liapis, A., additional, Creatsas, G., additional, Adda-Herzog, E., additional, Steffann, J., additional, Sebag-Peyrelevade, S., additional, Poulain, M., additional, Benachi, A., additional, Fanchin, R., additional, Zhang, D., additional, Aybar, F., additional, Temel, S., additional, Hamdine, O., additional, Macklon, N. S., additional, Laven, J. S., additional, Cohlen, B. J., additional, Verhoeff, A., additional, van Dop, P. A., additional, Bernardus, R. E., additional, Oosterhuis, G. J. E., additional, Holleboom, C. A. G., additional, van den Dool-Maasland, G. C., additional, Verburg, H. J., additional, van der Heijden, P. F. M., additional, Blankhart, A., additional, Fauser, B. C. J. M., additional, Broekmans, F. J., additional, Bhattacharya, J., additional, Mitra, A., additional, Dutta, G. B., additional, Kundu, A., additional, Bhattacharya, M., additional, Kundu, S., additional, Pigny, P., additional, Dassonneville, A., additional, Catteau-Jonard, S., additional, Decanter, C., additional, Dewailly, D., additional, Pouly, J., additional, Olivennes, F., additional, Massin, N., additional, Celle, M., additional, Caizergues, N., additional, Gaudoin, M., additional, Messow, M., additional, Vanhove, L., additional, Peigne, M., additional, Thomas, P., additional, and Robin, G., additional

Published
2013
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49. Female (in)fertility

Author

Saad, H., primary, Khalil, E., additional, Bora, S. A., additional, Parikh, J., additional, Abdalla, H., additional, Thum, M. Y., additional, Bina, V., additional, Roopa, P., additional, Shyamala, S., additional, Anupama, A., additional, Tournaye, H., additional, Polyzos, N. P., additional, Guzman, L., additional, Nelson, S. M., additional, Lourenco, B., additional, Sousa, A. P., additional, Almeida-Santos, T., additional, Ramalho-Santos, J., additional, Okhowat, J., additional, Wirleitner, B., additional, Neyer, T., additional, Bach, M., additional, Murtinger, M., additional, Zech, N. H., additional, Nwoye, M., additional, Corona, R., additional, Blockeel, C., additional, Stoop, D., additional, Camus, M., additional, Rajikin, M. H., additional, Kamsani, Y. S., additional, Chatterjee, A., additional, Nor-Ashikin, M. N. K., additional, Nuraliza, A. S., additional, Scaravelli, G., additional, D'Aloja, P., additional, Bolli, S., additional, De Luca, R., additional, Spoletini, R., additional, Fiaccavento, S., additional, Speziale, L., additional, Vigiliano, V., additional, Farquhar, C., additional, Brown, J., additional, Arroll, N., additional, Gupta, D., additional, Boothroyd, C., additional, Al Bassam, M., additional, Moir, J., additional, Johnson, N., additional, Pantasri, T., additional, Robker, R. L., additional, Wu, L. L., additional, Norman, R. J., additional, Buzaglo, K., additional, Velez, M., additional, Shaulov, T., additional, Sylvestre, C., additional, Kadoch, I. J., additional, Krog, M., additional, Prior, M., additional, Carlsen, E., additional, Loft, A., additional, Pinborg, A., additional, Andersen, A. N., additional, Dolleman, M., additional, Verschuren, W. M. M., additional, Eijkemans, M. J. C., additional, Dolle, M. E. T., additional, Jansen, E. H. J. M., additional, Broekmans, F. J. M., additional, Van der Schouw, Y. T., additional, Fainaru, O., additional, Pencovich, N., additional, Hantisteanu, S., additional, Barzilay, I., additional, Ellenbogen, A., additional, Hallak, M., additional, Cavagna, M., additional, Baruffi, R. L. R., additional, Petersen, C. G., additional, Mauri, A. L., additional, Massaro, F. C., additional, Ricci, J., additional, Nascimento, A. M., additional, Vagnini, L. D., additional, Pontes, A., additional, Oliveira, J. B. A., additional, Franco, J. G., additional, Canas, M. C. T., additional, Nicoletti, A., additional, Martins, A. M. V. C., additional, Lichtblau, I., additional, Olivennes, F., additional, Aubriot, F. A., additional, Junca, A. M., additional, Belloc, S., additional, Cohen-Bacrie, M., additional, Cohen-Bacrie, P., additional, de Mouzon, J., additional, Nandy, T., additional, Caragia, A., additional, Balestrini, S., additional, Zosmer, A., additional, Sabatini, L., additional, Al-Shawaf, T., additional, Seshadri, S., additional, Khalaf, Y., additional, Sunkara, S. K., additional, Joy, J., additional, Lambe, M., additional, Lutton, D., additional, Nicopoullos, J., additional, Faris, R., additional, Behre, H. M., additional, Howles, C. M., additional, Longobardi, S., additional, Chimote, N., additional, Mehta, B., additional, Nath, N., additional, Chimote, N. M., additional, Mine, K., additional, Yoshida, A., additional, Yonezawa, M., additional, Ono, S., additional, Abe, T., additional, Ichikawa, T., additional, Tomiyama, R., additional, Nishi, Y., additional, Kuwabara, Y., additional, Akira, S., additional, Takeshita, T., additional, Shin, H., additional, Song, H. S., additional, Lim, H. J., additional, Hauzman, E., additional, Kohls, G., additional, Barrio, A., additional, Martinez-Salazar, J., additional, Iglesias, C., additional, Velasco, J. A. G., additional, Tejada, M. I., additional, Maortua, H., additional, Mendoza, R., additional, Prieto, B., additional, Martinez-Bouzas, C., additional, Diez-Zapirain, M., additional, Martinez-Zilloniz, N., additional, Matorras, R., additional, Amaro, A., additional, Bianco, B., additional, Christofolini, J., additional, Mafra, F. A., additional, Barbosa, C. P., additional, Christofolini, D. M., additional, Pesce, R., additional, Gogorza, S., additional, Ochoa, C., additional, Gil, S., additional, Saavedra, A., additional, Ciarmatori, S., additional, Perman, G., additional, Pagliardini, L., additional, Papaleo, E., additional, Corti, L., additional, Vanni, V. S., additional, Ottolina, J., additional, de Michele, F., additional, Marca, A. L., additional, Vigano, P., additional, Candiani, M., additional, Li, L., additional, Yin, Q., additional, Huang, L., additional, Huang, J., additional, He, Z., additional, Yang, D., additional, Tiplady, S., additional, Ledger, W., additional, Godbert, S., additional, Hart, S., additional, Johnson, S., additional, Wong, A. W. Y., additional, Kong, G. W. S., additional, Haines, C. J., additional, Franik, S., additional, Nelen, W., additional, Kremer, J., additional, Gillett, W. R., additional, Lamont, J. M., additional, Peek, J. C., additional, Herbison, G. P., additional, Sung, N. Y., additional, Hwang, Y. I., additional, Choi, M. H., additional, Song, I. O., additional, Kang, I. S., additional, Koong, M. K., additional, Lee, J. S., additional, Yang, K. M., additional, Celtemen, M. B., additional, Telli, P., additional, Karakaya, C., additional, Bozkurt, N., additional, Gursoy, R. H., additional, Younis, J. S., additional, Ben-Ami, M., additional, Pundir, J., additional, Pundir, V., additional, Omanwa, K., additional, and El-Toukhy, T., additional

Published
2013
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50. The association of low ovarian reserve with cardiovascular disease risk: a cross-sectional population-based study.

Author

de Kat, A. C., Verschuren, W. M. M., Eijkemans, M. J. C., van der Schouw, Y. T., and Broekmans, F. J. M.

Subjects
CARDIOVASCULAR diseases risk factors, PERIMENOPAUSE, CROSS-sectional method, SYSTOLIC blood pressure, CONFIDENCE intervals, CARDIOVASCULAR disease diagnosis, AGE distribution, CARDIOVASCULAR diseases, SEX hormones, MENOPAUSE, OVARIAN reserve
Abstract

Study Question: Is there a relationship between serum anti-Müllerian hormone (AMH) level and cardiovascular disease (CVD) risk in premenopausal women?Summary Answer: There are indications that premenopausal women with very low ovarian reserve may have an unfavorable CVD risk profile.What Is Known Already: Age at menopause is frequently linked to CVD occurrence. AMH is produced by ovarian antral follicles and provides a measure of remaining ovarian reserve Literature on whether AMH is related to CVD risk is still scarce and heterogeneous.Study Design, Size, Duration: Cross-sectional study in 2338 women (age range of 20-57 years) from the general population, participating in the Doetinchem Cohort Study between 1993 and 1997.Participants/materials, Setting, Methods: CVD risk was compared between 2338 premenopausal women in different AMH level-categories, with adjustment for confounders. CVD risk was assessed through levels of systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and glucose, in addition to a summed score of CVD risk factors. Among other factors, analyses were corrected for smoking, oral contraceptive use and BMI.Main Results and the Role Of Chance: The relationship of serum AMH levels with CVD risk factor outcomes was nonlinear. Women with AMH levels <0.16 µg/l had 0.11 (95% confidence intervals (CIs) 0.01; 0.21) more metabolic risk factors compared with women with AMH levels ≥0.16 µg/l. There was no association of individual risk factor levels with AMH levels, besides a tendency towards lower total cholesterol levels of 0.11 mmol/l (95% CI -0.23; 0.01) in women with AMH levels <0.002 µg/l compared with women with AMH levels ≥0.16 µg/l. Although not statistically significant, these effect sizes were larger in women below 40 years of age.Limitations, Reasons For Caution: Causality and temporality of the studied association cannot be addressed here. Moreover, the clinical and statistical significance of the results of this exploratory study should be interpreted with caution due to the absence of adjustment for multiple statistical testing.Wider Implications Of the Findings: This population-based study supports previous findings that premenopausal women with very low AMH levels may have an increased CVD risk. It lays the groundwork for future research to focus on this group of women. Longitudinal studies with more sensitive AMH assays may furthermore help better understand the implications of these results.Study Funding/competing Interest: No financial support was received for this research or manuscript. The Doetinchem Cohort Study is conducted and funded by the Dutch National Institute for Public Health and the Environment F.J.M.B. has received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and Roche.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Published
2016
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