Publications by authors named "Fabienne Devreker"

14 Publications

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Higher estradiol levels are associated with lower neonatal birthweight after fresh and frozen embryo transfers. A cohort study of 3631 singleton IVF pregnancies.

Gynecol Endocrinol 2021 Jul 5;37(7):618-623. Epub 2020 Oct 5.

Hôpital Erasme - ULB, Fertility Clinic, Department of Obstetrics and Gynecology, Brussels, Belgium.

Aim: To assess the birthweight of neonates conceived after fresh and frozen embryo transfers (FET) and, if different, to investigate whether estradiol levels during the late follicular phase were associated with the observed difference.

Methods: Singleton pregnancies from fresh and FET transfers between January 1990 and December 2013 were compared retrospectively. A total of 2885 singleton pregnancies after fresh embryo transfer and 746 after FET were analyzed. Obstetric and neonatal outcomes were compared between fresh and FET cycles.

Results: The singletons born after FET were found to have a significantly higher birth weight (3313 g), compared to those born after fresh embryo transfer (3143 g); p < .001. The main predictor of this difference was found to be estradiol levels at the end of the follicular phase. The difference in birthweight was inversely correlated to estradiol levels considering all cycles together but also considering fresh and frozen cycles separately.

Conclusions: Our study demonstrates a link between high estradiol levels and low birth weight of singletons after IVF both in fresh and frozen-thawed embryo transfer cycles. It provides additional support to the involvement of hyperestrogenemia in the process of implantation and on the subsequent fetal development.
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http://dx.doi.org/10.1080/09513590.2020.1827383DOI Listing
July 2021

Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers.

Reprod Biol Endocrinol 2019 Jan 3;17(1). Epub 2019 Jan 3.

Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium.

Background: Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality.

Methods: In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups.

Results: FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa.

Conclusions: Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients.

Trial Registration: Clinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.
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http://dx.doi.org/10.1186/s12958-018-0443-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318989PMC
January 2019

What is the best predictor of severe ovarian hyperstimulation syndrome in IVF? A cohort study.

J Assist Reprod Genet 2017 Oct 14;34(10):1341-1351. Epub 2017 Jul 14.

Fertility Clinic, Department of Obstetrics and Gynecology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.

Purpose: The purpose of the present study is to study what is the best predictor of severe ovarian hyperstimulation syndrome (OHSS) in IVF.

Methods: This is a retrospective analysis of all consecutive IVF/intracytoplasmic injection cycles performed during a 5-year period (2009-2014) in a single university fertility centre. All fresh IVF cycles where ovarian stimulation was performed with gonadotrophins and GnRH agonists or antagonists and triggering of final oocyte maturation was induced with the administration of urinary or recombinant hCG were analyzed (2982 patients undergoing 5493 cycles). Because some patients contributed more than one cycle, the analysis of the data was performed with the use of generalized estimating equation (GEE).

Results: Severe OHSS was diagnosed in 20 cycles (0.36%, 95% CI 0.20-0.52). The number of follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles. The cutoff in the number of follicles ≥10 mm with the best capacity to discriminate between women that will and will not develop severe OHSS was ≥15.

Conclusion: The presence of more than 15 follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles.
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http://dx.doi.org/10.1007/s10815-017-0990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633577PMC
October 2017

Outcomes of immature oocytes collected from ovarian tissue for cryopreservation in adult and prepubertal patients.

Reprod Biomed Online 2017 Jun 20;34(6):575-582. Epub 2017 Mar 20.

Research Laboratory on Human Reproduction, Campus Erasme, Université Libre de Bruxelles (ULB), Belgium; Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium.

The efficiency of oocyte in-vitro maturation (IVM) and vitrification procedures after ex-vivo collection from ovarian tissue were assessed according to patient age, number of retrieved oocytes and tissue transport conditions. The combined procedure was performed in 136 patients: 130 adults (mean 27.6 ± 5.6 years) and six prepubertal girls (mean 8.7 ± 2.3 years). A higher mean number of oocytes were collected in girls compared with adults (11.5 ± 8.0 versus 3.8 ± 4.2, respectively, P < 0.001) but the percentage of degenerated oocytes was significantly higher in girls (35.5% versus 17.1%, respectively, P < 0.001). IVM rates were significantly lower in prepubertal than postpubertal population (10.3% versus 28.1%, P = 0.002). In adults, a negative correlation was observed between number of retrieved oocytes and age (P = 0.002; r = -0.271); the correlation was positive between anti-Müllerian hormone (AMH) and number of collected oocytes (P = 0.002; r = 0.264). IVM rates were not correlated with AMH levels (r = 0.06) or age (r = -0.033). At present, nine oocytes and one embryo have been warmed in four patients and one biochemical pregnancy obtained. This suggests the combined procedure could be an additional option for fertility preservation.
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http://dx.doi.org/10.1016/j.rbmo.2017.03.007DOI Listing
June 2017

Live birth after autograft of ovarian tissue cryopreserved during childhood.

Hum Reprod 2015 Sep 9;30(9):2107-9. Epub 2015 Jun 9.

Department of Hematology-Oncology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), 1020 Brussels, Belgium.

Ovarian insufficiency is a major long-term adverse event, following the administration of a myeloablative conditioning regimen, and occurring in >80% of children and adolescents receiving such treatment for malignant or non-malignant disease. Cryopreservation of ovarian tissue is currently offered to preserve the fertility of these young patients. At least 35 live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age. We report here the first live birth after autograft of cryopreserved ovarian tissue in a woman with primary ovarian failure after a myeloablative conditioning regimen as part of a hematopoietic stem cell transplantation performed for homozygous sickle-cell anemia at age 14 years. This first report of successful fertility restoration after the graft of ovarian tissue cryopreserved before menarche offers reassuring evidence for the feasibility of the procedure when performed during childhood.
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http://dx.doi.org/10.1093/humrep/dev128DOI Listing
September 2015

A randomized controlled trial comparing two vitrification methods versus slow-freezing for cryopreservation of human cleavage stage embryos.

J Assist Reprod Genet 2014 Feb 8;31(2):241-7. Epub 2013 Dec 8.

Research Laboratory on Human Reproduction, Faculty of Medicine, Université Libre de Bruxelles, Campus Erasme, Bruxelles, Belgium,

Purpose: To compare two different vitrification methods to slow freezing method for cryopreservation of human cleavage stage embryos.

Design: Prospective randomised trial.

Setting: University assisted reproduction centre.

Patient(s): 568 patients (mean age 33.4 ± 5.2) from April 2009 to April 2011.

Methods: 1798 supernumerary good-quality cleavage stage embryos in 645 IVF cycles intended to be cryopreserved were randomly allocated to three groups: slow freezing, vitrification with the Irvine® method, vitrification with the Vitrolife® method.

Main Outcome Measure(s): Embryo survival and cleavage rates, implantation rate.

Results: A total of 1055 embryos were warmed, 836 (79.2%) survived and 676 were finally transferred (64.1%). Post-warming embryos survival rate was significantly higher after vitrification (Irvine: 89.4%; Vitrolife: 87.6%) than after slow freezing (63.8%) (p < 0.001). No differences in survival rates were observed between the two vitrification methods, but a significant higher cleavage rate was observed using Irvine compared to Vitrolife method (p < 0.05). Implantation rate (IR) per embryo replaced and per embryo warmed were respectively 15.8% (41/259) and 12.4% (41/330) for Irvine, 17.0% (40/235) and 12.1% (40/330) for Vitrolife, 21.4% (39/182) and 9.9% (39/395) for slow-freezing (NS).

Conclusions: Both vitrification methods (Irvine and Vitrolife) are more efficient than slow freezing for cryopreservation of human cleavage stage embryos in terms of post-warming survival rate. No significant difference in the implantation rate was observed between the three cryopreservation methods.
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http://dx.doi.org/10.1007/s10815-013-0145-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933602PMC
February 2014

A specific increase in inositol 1,4,5-trisphosphate 3-kinase B expression upon differentiation of human embryonic stem cells.

Cell Signal 2012 Jul 13;24(7):1461-70. Epub 2012 Mar 13.

Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium.

Human embryonic stem cells (hESCs) are of great hope for regenerative medicine due to their dual pluripotency and self-renewal properties. We report a comparison of inositol phosphate (InsP(s)) production in undifferentiated, differentiated hESCs and in two cancer cell lines, Ntera2 cells, a human embryonal carcinoma cell (hECC) line and HeLa cells. To evaluate the potential impact of InsP(s) in differentiation, hESCs were spontaneously differentiated in culture for two weeks. The distribution of the different InsP(s) was affected upon differentiation: the level of highly phosphorylated InsP(s) was decreased. In contrast, the total level of phosphoinositides (PI) was increased. Using real time quantitative PCR (qPCR), the mRNA expression of several enzymes of the metabolism of InsP(s) was determined: a specific increase in inositol 1,4,5-trisphosphate 3-kinase A and B (ITPKA and ITPKB) was observed upon hESCs spontaneous differentiation. Ins(1,4,5)P(3) 3-kinase activity, undetectable in undifferentiated hESCs, increased upon differentiation. The same observation was made by Western blotting using an antibody directed against human ITPKB. This is the first report showing the potential implication of soluble InsP(s) in hESCs and possible function of isoenzymes of the inositol trisphosphate 3-kinase family in differentiation.
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http://dx.doi.org/10.1016/j.cellsig.2012.03.006DOI Listing
July 2012

Contribution of cryopreservation in a mandatory SET policy: analysis of 5 years of application of law in an academic IVF center.

J Assist Reprod Genet 2011 Nov 1;28(11):1059-66. Epub 2011 Oct 1.

Fertility Clinic, department obstetrics/gynecology, hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.

Objective: To analyse treatment outcomes after SET law enforcement and to evaluate the contribution of cryopreservation in a SET policy.

Material: Embryo transfer cycles performed after the law enforcement (SET period) was retrospectively compared to the cycles performed before the law enforcement (DET period).

Results: Pregnancy and delivery rates after fresh transfer of SET and DET periods were comparable (31.7% versus 33.3% and 24.5% versus 26.2%, respectively, NS). Overall twin delivery rate is significantly decreased after the law enforcement (11.3% versus 22.4%, p < 0.001) but not in patients aged 36 to 39 years (20.3% versus 24%, NS). Frozen-thawed embryo cycles allowed similar cumulative pregnancy rate (30.6%, NS). Taking into account all frozen embryos still to be transferred, SET period offers a better overall pregnancy rate than the DET period (36.1% versus 32.3%, p < 0.01).

Conclusions: The Belgian law allowed a dramatic reduction of twin deliveries especially for patients under 39 years. Cryopreservation maintains a similar cumulative pregnancy rate.
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http://dx.doi.org/10.1007/s10815-011-9642-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224168PMC
November 2011

Nucleoside analog stavudine depletes mitochondrial DNA with no organelle loss in mouse oocytes.

Curr HIV Res 2010 Mar;8(2):127-33

Human Reproduction Research Laboratory, Université Libre de Bruxelles, Campus Erasme, GE 2.2.214, Route de Lennik 808, 1070 Brussels, Belgium.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the basis of antiretroviral treatment of HIV-positive patients. Several studies have shown decreased fertility and fecundity among HIV-positive women under antiretroviral treatment. Oocyte impaired competence has been hypothesized to be one of the main mechanisms underlying of this decreased fertility. NRTI side effects are thought to be due to the induced mitochondrial dysfunction. Stavudine, a widely used NRTI, causes persistent mitochondrial damage in various tissues. In order to gain insights into possible mechanisms of HIV-related diminished fertility, we studied the effects of stavudine on mouse oocyte mitochondria. Mitochondrial volume, protein assay and ATP contents were unaltered by stavudine treatment, but we found mitochondrial Cox I depletion in liver and oocytes. Our findings suggest that stavudine induces mtDNA depletion without organelle loss in mouse oocytes. The decrease in Cox I DNA in treated oocytes likely points to mitochondrial dysfunction, which can impair chances of pregnancy and embryo viability. We propose that the competence of oocytes depends primarily on functional capacity of mitochondria and less on their number.
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http://dx.doi.org/10.2174/157016210790442678DOI Listing
March 2010

Impaired ovarian stimulation during in vitro fertilization in women who are seropositive for hepatitis C virus and seronegative for human immunodeficiency virus.

Fertil Steril 2007 Sep 22;88(3):607-11. Epub 2007 Feb 22.

Laboratory for Human Reproduction Research, Faculty of Medicine, Campus Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Objective: To analyze the impact of seropositivity with hepatitis C virus (HCV) on in vitro fertilization (IVF) outcomes.

Design: Retrospective, case-controlled study.

Setting: Fertility clinic of academic hospital.

Patient(s): 42 IVF/intracytoplasmic sperm injection cycles in HCV-seropositive women and 84 matched control cycles.

Intervention(s): IVF/intracytoplasmic sperm injection treatment for infertility.

Main Outcome Measure(s): Ovarian response to stimulation, laboratory findings, and implantation and pregnancy rates.

Result(s): Absence of ovarian response was statistically significantly higher for HCV-seropositive women compared with controls (10/42 vs 5/84 cycles, respectively). For cycles with oocyte retrieval, HCV-seropositive women required more gonadotropin units compared with controls. The maximum estradiol levels and number of collected oocytes were similar, but HCV-seropositive women had statistically significantly fewer embryos available compared with controls. Embryo morphologic features, number of transferred embryos, and rates of implantation and pregnancy were similar for HCV-seropositive women and controls.

Conclusion(s): When compared with matched uninfected controls, HCV-seropositive women display a decreased ovarian response.
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http://dx.doi.org/10.1016/j.fertnstert.2006.11.177DOI Listing
September 2007

Ovarian clear cell carcinoma occurring in a young patient with endometriosis and long-term ovulation stimulations.

Acta Obstet Gynecol Scand 2006 ;85(12):1506-7

Department of Gynaecology and Obstetrics, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.

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http://dx.doi.org/10.1080/00016340600603577DOI Listing
February 2007

Impact of the assessment of early cleavage in a single embryo transfer policy.

Reprod Biomed Online 2006 Aug;13(2):255-60

Fertility Clinic Erasmus Hospital, Free University of Brussels, French Speaking, Route de Lennik 808, 1070 Brussels Belgium.

The policy of single embryo transfer (SET) adopted for women <36 years old since 1 July 2003, strongly calls for improvement of embryo selection. A total of 196 cycles in which SET was performed were randomly allocated to two groups. In the first group, early cleavage was assessed (ECA) 25 h after insemination. The embryo with the best score that cleaved early, if present, was selected for transfer. In the second group, early cleavage was not assessed (ECNA) and embryo selection was based solely on the embryo score. Ninety-eight cycles were allocated in the ECA and ECNA group respectively. Early cleavage occurred in 64% of cycles and 32.2% of embryos. Patient population and embryo morphology were similar between the two groups, and similar delivery rates were observed (27.6 versus 24.5% respectively in the ECA and ECNA groups). The assessment of early cleavage as additional parameter did not improve the delivery rate in the single embryo transfer policy.
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http://dx.doi.org/10.1016/s1472-6483(10)60623-2DOI Listing
August 2006

Embryo-maternal interactive factors regulating the implantation process: implications in assisted reproductive.

Reprod Biomed Online 2005 Apr;10(4):527-40

Fertility Clinic, Erasmus Hospital, Belgium.

The embryo-maternal dialogue that starts very early in the life of the embryo is crucial for its own implantation. A disturbance in this dialogue is the major reason for which 60% of all pregnancies are terminated at the end of the periimplantation period. Many studies have been performed to improve the understanding of the molecular mechanisms involved in this dialogue. Both partners, the mother and the embryo, are equally involved in this exchange of signals. Much progress has been done in understanding the role of (i) chorionic gonadotrophin, (ii) growth factors and cytokines, and (iii) steroid hormones and other mediators, produced either by the embryo, by the mother, or by both, during the peri-implantation period. Today it is clear that their production dictates changes in the endometrium, in the immunological system of the mother and in embryo metabolism, that enable the embryo to implant. Knowledge of the molecular mechanisms involved in the embryo-maternal interaction are reviewed in this article.
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http://dx.doi.org/10.1016/s1472-6483(10)60831-0DOI Listing
April 2005

Similar delivery rates in a selected group of patients, for day 2 and day 5 embryos both cultured in sequential medium: a randomized study.

Hum Reprod 2003 Oct;18(10):2145-50

Fertility Clinic, Erasme Hospital, Free University of Brussels, French Speaking, 808, Route de Lennik, B-1070 Brussels, Belgium.

Background: The existence of a real benefit of blastocyst transfer is still a matter of debate. The aim of this study was to compare, in a prospective randomized trial, the outcome of day 2 and day 5 transfer of human embryos cultured in an 'in-house' sequential medium.

Methods: A total of 193 cycles from 171 patients with less than four previous IVF cycles, <39 years old and with four or more zygotes on day 1, were randomly allocated to day 2 (94 cycles) or day 5 (99 cycles) transfer. Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a 'glucose-free' cleavage medium. Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization. Two or three embryos were replaced according to the morphology.

Results: A mean (+/- SEM) number of 2.1 +/- 0.4 and 1.9 +/- 0.3 embryos were replaced on day 2 and day 5 (P < 0.001) respectively. Delivery rates per transfer were 44.1 and 37.1% [P = not significant (NS)], implantation rates were 31.4 and 29.4% (NS) and multiple delivery rates 22 and 36% (NS) for day 2 and day 5 groups respectively. Ten patients (10.1%) had no blastocysts available for transfer.

Conclusions: No clear benefits were observed using blastocyst transfer for patients aged <39 years who had had less than four previous IVF cycle attempts.
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http://dx.doi.org/10.1093/humrep/deg394DOI Listing
October 2003
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