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3. Cumulative pregnancy rates of two strategies: Day 3 fresh embryo transfer followed by Day 3 or Day 5/6 vitrification and embryo transfer: a randomized controlled trial.

Author

Mengels, A, Muylder, A Van, Peeraer, K, Luyten, J, Laenen, A, Spiessens, C, and Debrock, S

Subjects
EMBRYO transfer, RANDOMIZED controlled trials, VITRIFICATION, PROPORTIONAL hazards models, PREGNANCY
Abstract

STUDY QUESTION Are cumulative pregnancy rates better if supernumerary embryos are vitrified on Day 5/6 instead of Day 3? SUMMARY ANSWER The results do not show a significant difference in cumulative pregnancy rates between the Day 3 and Day 5/6 vitrification groups. WHAT IS KNOWN ALREADY Pregnancy and live birth rates following IVF or ICSI treatment are higher after extended embryo culture and blastocyst transfer (Day 5/6) compared to cleavage-stage (Day 3) transfer. Cumulative pregnancy rates from one oocyte retrieval (OR) cycle show no significant difference after fresh and frozen embryo transfers, but only one study has used vitrification for the cryopreservation of supernumerary embryos while four studies have used a slow freezing protocol. STUDY DESIGN, SIZE, DURATION Our prospective randomized controlled trial was performed in an academic centre between January 2018 and August 2020. Patients were randomized into vitrification Day 3 (n = 80) or Day 5/6 (n = 81) groups. The primary outcome was the cumulative ongoing pregnancy rate (cOPR), considering only the first pregnancy for each couple. The power calculation revealed that 75 patients were required in each group, when assuming a 50% cOPR with four embryo transfers in the vitrification Day 3 group vs two transfers in the vitrification Day 5/6 group. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients <38 years undergoing their first or second OR cycles were randomized at the start of the first cycle. Up to two cycles were included in the analysis. A fresh embryo transfer was performed on Day 3. Supernumerary embryos (with ≥6 cells, <25% fragmentation, and equal blastomeres) or blastocysts (with expansion grade ≥2 with inner cell mass and trophectoderm score A/B) were vitrified on Day 3 or Day 5/6, respectively, and then transferred at a later date. A time-to-event analysis was performed with the patient's first ongoing pregnancy as the event of interest and the number of embryo transfers as the time component. The statistical comparison was performed by a Cox proportional hazards model. Cumulative costs of vitrification on Day 3 vs Day 5/6 were explored and compared using Mann–Whitney U tests. MAIN RESULTS AND THE ROLE OF CHANCE By December 2021, 233 transfers (96 fresh and 137 frozen) in 77 patients were performed in the vitrification Day 3 group and 201 transfers (88 fresh and 113 frozen) in 77 patients were performed in the vitrification Day 5/6 group. The time-to-event analysis did not show a difference between the two arms with regard to the patient's first ongoing pregnancy as the primary study outcome (hazard ratio [HR] 1.25, 95% CI 0.82; 1.92, P = 0.30). The cumulative ongoing pregnancy rate after eight transfers (from one or two ORs) was 57% in the vitrification Day 3 group vs 58% in the vitrification Day 5/6 group. The median number of embryo transfers until a pregnancy was achieved was five vs four, respectively, in the vitrification Day 3 group vs the Day 5/6 group. Similar results were found for the secondary study outcome, i.e. clinical pregnancy with foetal heart rate (HR 1.19, 95% CI 0.78; 1.80, P = 0.41). The cumulative clinical pregnancy rate (cCPR) after eight embryo transfers was 62% in the vitrification Day 3 group vs 59% in the vitrification Day 5/6 group. The median number of transfers until a pregnancy was achieved was four in both groups. The healthcare consumption pattern differed between the two groups and we observed higher costs for the vitrification Day 3 group compared to the vitrification Day 5/6 group, although these differences were not statistically significant. LIMITATIONS, REASONS FOR CAUTION Although our power calculation revealed that only 75 patients were needed in each study group (β = 0.87, α < 0.05), the numbers were low. Also, different numbers of single and double embryo transfers were performed between the two groups, which may have affected the results. The cost analysis was performed on a subset of the patients and is therefore exploratory. WIDER IMPLICATIONS OF THE FINDINGS Our study shows no difference in the cumulative pregnancy rate nor costs after fresh and frozen embryo transfers of at most two sequential OR cycles between the Day 3 and Day 5/6 vitrification groups; however, obstetric and perinatal outcomes should be taken into account to determine the best strategy. STUDY FUNDING/COMPETING INTEREST(S) This study was funded as an investigator-sponsored study of S.D. by Merck nv/sa Belgium, an affiliate of Merck KGaA, Darmstadt, Germany, and by Gedeon Richter Benelux (PA18-0162). The authors declare no conflict of interest related to this study. TRIAL REGISTRATION NUMBER NCT04196036. TRIAL REGISTRATION DATE 15 January 2018. DATE OF FIRST PATIENT'S ENROLMENT 15 January 2018. [ABSTRACT FROM AUTHOR]

Published
2024
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4. O-236 A multi-omics genome-plus-transcriptome single-cell atlas of human pre-implantation development reveals the impact of chromosome instability on cell function within the embryo

Author

Fernandez, E, primary, Sifrim, A, additional, Chappell, J, additional, Demeulemeester, J, additional, Van der Haegen, M, additional, Brown, D, additional, Theunis, K, additional, Van Herck, J, additional, Vandereyken, K, additional, Ponting, C, additional, Vermeesch, J, additional, Peeraer, K, additional, Debrock, S, additional, Pasque, V, additional, and Voet, T, additional

Published
2022
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25. How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice

Author

Vanhie, A., Fassbender, A., O, D., Tomassetti, C., Meuleman, C., Peeraer, K., Debrock, S., and D’Hooghe, Th.

Subjects
Article Subject
Abstract

Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women’s lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis.

Published
2015
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29. Low-dose human menopausal gonadotrophin versus clomiphene citrate in subfertile couples treated with intrauterine insemination: a randomized controlled trial

Author

Peeraer, K., primary, Debrock, S., additional, De Loecker, P., additional, Tomassetti, C., additional, Laenen, A., additional, Welkenhuysen, M., additional, Meeuwis, L., additional, Pelckmans, S., additional, Mol, B. W., additional, Spiessens, C., additional, De Neubourg, D., additional, and D'Hooghe, T. M., additional

Published
2015
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30. Replacement of FISH by genome-wide single cell array analysis for preimplantation genetic diagnosis of translocation carriers

Author

Vanneste, E., Melotte, Cindy, Ullmann, Urielle, Staessen, C., Liebaers, Ingeborg, Voet, Thierry, Debrock, S, D'hooghe, T., Vermeesch, Joris, Department of Embryology and Genetics, and Reproduction and Genetics

Subjects
PGD, IVF
Abstract

Preimplantation genetic diagnosis (PGD) is the genetic analysis of a single (or two) blastomere(s) from an in vitro fertilized embryo and is offered to couples to avoid the transmission of heritable genetic disorders to their potential offspring. Fluorescence in situ hybridization (FISH) is the current standard technique to detect chromosomal imbalances, however it requires a long, labor-intensive and indication-specific preparation. Moreover, the number of fluorescent labels is limited and couples carrying complex chromosomal aberrations cannot be helped. Array-based PGD can overcome all these shortcomings and will increase the accuracy. As proof-of-principle, we applied the genome-wide 1Mb resolution BAC array in the PGD-clinic for a couple that suffered multiple miscarriages and could not be helped using the current FISH technique since one of the partners carried a complex chromosomal aberration including a reciprocal translocation between chromosomes 6 and 14 and an insertion between chromosomes 2 and 3. In concurrence with the ethical committee, we decided to check only the copy number status of the chromosomes involved in the translocation and insertion. Consequently, whole chromosome or segmental imbalances of other autosomes did not affect the transfer policy. The chromosomal imbalances detected following array screening were confirmed on the remaining blastomeres using locus-specific FISH. Two array-based PGD cycles with single embryo transfer were performed, which resulted in a clinical pregnancy. The embryo that give rise to the pregnancy was normal diploid (or balanced) for both the translocation and the insertion region, but carried however a trisomy 8 and nullisomy 9 in one blastomere, while the second blastomere was completely normal diploid. Besides the successful implementation of single cell arrays into the fertility clinic, we thus proved that at least some mosaic embryos, which are currently all discarded, can result in a clinical pregnancy. Finally, the application of single cell arrays on human cleavage stage IVF embryos revealed new insights in the segregation patterns during early embryogenesis. Whereas mosaic FISH results would have been classified as potential FISH errors, whole-chromosome array analysis shows that despite the occurrence of meiotic aberrations, mosaic results can be explained by additional mitotic non-disjunctions. In conclusions, FISH can be replaced by genome-wide single cell array analysis in PGD for the detection of chromosomal imbalances as small as 10 Mb.

Published
2010

33. Intra- and interobserver analysis in the morphological assessment of early stage embryos during an IVF procedure: a multicentre study

Author

Paternot, G., Wetzels, A.M.M., Thonon, F., Vansteenbrugge, A., Willemen, D., Devroe, J., Debrock, S., D'Hooghe, T.M., Spiessens, C., Paternot, G., Wetzels, A.M.M., Thonon, F., Vansteenbrugge, A., Willemen, D., Devroe, J., Debrock, S., D'Hooghe, T.M., and Spiessens, C.

Abstract

Contains fulltext : 96031.pdf (publisher's version ) (Open Access)

Published
2011

36. Session 45: Clinical female infertility

Author

Tjon-Kon-Fat, R. I., primary, Bensdorp, A. J., additional, Maas, J., additional, Oosterhuis, G. J. E., additional, Hoek, A., additional, Hompes, P. G. A., additional, Broekmans, F. J., additional, Verhoeve, H. R., additional, de Bruin, J. P., additional, Repping, S., additional, Cohlen, B. J., additional, Groen, H., additional, Mol, B. W. J., additional, van der Veen, F., additional, Wely, M., additional, Peeraer, K., additional, Debrock, S., additional, De Loecker, P., additional, Laenen, A., additional, Welkenhuyzen, M., additional, Spiessens, C., additional, De Neubourg, D., additional, D'Hooghe, T. M., additional, Puri, S., additional, Mohan, B., additional, Herbemont, C., additional, Adda, E., additional, Hugues, J. N., additional, Sermondade, N., additional, Dupont, C., additional, Cedrin-Durnerin, I., additional, Poncelet, C., additional, Levy, R., additional, Sifer, C., additional, Bellver, J., additional, Pellicer, A., additional, Garcia-Velasco, J. A., additional, Ballesteros, A., additional, Remohi, J., additional, and Meseguer, M., additional

Published
2013
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39. S12 Chromosomal instability in the human preimplantation embryo

Author

Voet, T., primary, Van der Aa, N., additional, Esteki, M. Zamani, additional, Kumar, P., additional, Vanneste, E., additional, Melotte, C., additional, Konings, P., additional, Debrock, S., additional, Fryns, J.-P., additional, Moreau, Y., additional, D'Hooghe, T., additional, Stratton, M.R., additional, Campbell, P.J., additional, and Vermeesch, J.R., additional

Published
2012
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40. SELECTED ORAL COMMUNICATION SESSION, SESSION 26: PARAMEDICAL - LABORATORY, Monday 4 July 2011 17:00 - 18:00

Author

Speksnijder, J., primary, van de Werken, C., additional, de Jong, S. M., additional, Dons, A. J. A. M., additional, Laven, J. S. E., additional, Baart, E. B., additional, Yumoto, K., additional, Iwata, K., additional, Kawai, A., additional, Ueda, M., additional, Tsuchie, Y., additional, Imajo, A., additional, Miura, Y., additional, Mochida, T., additional, Iba, Y., additional, Mio, Y., additional, Velaers, A., additional, Paternot, G., additional, Debrock, S., additional, D'Hooghe, T. M., additional, Spiessens, C., additional, Janssens, R., additional, Souffreau, R., additional, Haentjens, P., additional, Van de Velde, H., additional, and Verheyen, G., additional

Published
2011
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41. SELECTED ORAL COMMUNICATION SESSION, SESSION 72: FEMALE FERTILITY AND ART Wednesday 6 July 201114:00 - 15:45

Author

Yarde, F., primary, Oudendijk, J. F., additional, Broekmans, F. J., additional, Broer, S. L., additional, Setti, A. S., additional, Braga, D. P. A. F., additional, Figueira, R. C. S., additional, Pasqualotto, F. F., additional, Iaconelli Jr., A., additional, Borges Jr., E., additional, Rittenberg, V., additional, Seshadri, S., additional, Sunkara, S., additional, Sobaleva, S., additional, Oteng-Ntim, E., additional, El-Toukhy, T., additional, Peeraer, K., additional, Debrock, S., additional, De Legher, C., additional, Laenen, A., additional, De Neubourg, D., additional, De Loecker, P., additional, Spiessens, C., additional, D'Hooghe, T. M., additional, Ochalski, M., additional, Wakim, K., additional, Wakim, A., additional, Nyboe Andersen, A., additional, Pellicer, A., additional, Devroey, P., additional, Arce, J. C., additional, Blockeel, C., additional, Polyzos, N., additional, Ermini, B., additional, Riva, A., additional, Stoop, D., additional, and Tournaye, H., additional

Published
2011
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42. INVITED SESSION, SESSION 42: PARAMEDICAL INVITED SESSION - EMERGING TECHNOLOGIES IN HUMAN IVF LABORATORIES, Tuesday 5 July 2011 14:00 - 15:00

Author

Voet, T., primary, Vanneste, E., additional, Zamani Esteki, M., additional, Van der Aa, N., additional, Melotte, C., additional, Jackmaert, S., additional, Konings, P., additional, Debrock, S., additional, Fryns, J. P., additional, Moreau, Y., additional, D'Hooghe, T., additional, Legius, E., additional, Campbell, P., additional, Stratton, M., additional, Vermeesch, J. R., additional, and Smith, G. D., additional

Published
2011
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45. Session 19: Reproduction and Genetics

Author

Elaimi, A. H., primary, Sabhnani, T. V., additional, Sultan, H., additional, Alduraihem, A., additional, Fitzharris, G., additional, Howe, K., additional, Harper, J., additional, Garcia, F., additional, Alvarez, J. G., additional, Velilla, E., additional, Fernandez, S., additional, Serra, O., additional, Lopez-Teijon, M., additional, Figueira, R. C. S., additional, Braga, D. P. A. F., additional, Queiroz, P., additional, Pasqualotto, F. F., additional, Iaconelli, A., additional, Borges, E., additional, Vanneste, E., additional, Voet, T., additional, Melotte, C., additional, Vandendael, T., additional, Declercq, M., additional, Vervoort, C., additional, Debrock, S., additional, Fryns, J. P., additional, D'Hooghe, T., additional, Vermeesch, J. R., additional, Choi, Y., additional, Park, M., additional, Song, S. H., additional, Won, H. J., additional, Kim, Y. S., additional, Ryu, S. W., additional, Lee, D. R., additional, Shim, S. H., additional, and Yoon, T. K., additional

Published
2010
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48. Surface tension propellant control for Viking 75 Orbiter

Author

Dowdy, M. W, Hise, R. E, Peterson, R. G, and Debrock, S. C

Subjects
Spacecraft Propulsion And Power
Abstract

The paper describes the selection, development and qualification of the surface tension system and includes results of low-g drop tower tests of scale models, 1-g simulation tests of low-g large ullage settling and liquid withdrawal, structural qualification tests, and propellant surface tension/contact angle studies. Subscale testing and analyses were used to evaluate the ability of the system to maintain or recover the desired propellant orientation following possible disturbances during the Viking mission. This effort included drop tower tests to demonstrate that valid wick paths exist for moving any displaced propellant back over the tank outlet. Variations in surface tension resulting from aging, temperature, and lubricant contamination were studied and the effects of surface finish, referee fluid exposure, aging, and lubricant contamination on contact angle were assessed. Results of movies of typical subscale drop tower tests and full scale slosh tests are discussed.

Published
1976

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