المؤلفون: Vos, E S De¹ (AUTHOR), Mulders, A G M G J¹ (AUTHOR) a.mulders@erasmusmc.nl, Koning, A H J² (AUTHOR), Willemsen, S P^1,3 (AUTHOR), Rousian, M¹ (AUTHOR), Rijn, B B Van¹ (AUTHOR), Steegers, E A P¹ (AUTHOR), Steegers-Theunissen, R P M¹ (AUTHOR)

المصدر: Human Reproduction. May2024, Vol. 39 Issue 5, p923-935. 13p.

مصطلحات موضوعية: *FETAL development, *FETAL growth retardation, *EMBRYOLOGY, *BLOOD vessels, *BIRTH weight, *VIRTUAL reality therapy

مصطلحات جغرافية: ROTTERDAM (Netherlands), NETHERLANDS

مستخلص: STUDY QUESTION Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints β  = 0.017, 95% CI [0.009; 0.025], bifurcation points β  = 0.012, 95% CI [0.006; 0.018], crossing points β  = 0.017, 95% CI [0.008; 0.025], vessel points β  = 0.01, 95% CI [0.002; 0.008], and total vascular length β  = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P -values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = −94.972, 95% CI [−185.245; −3.698], bifurcation points: uPVV β = −192.601 95% CI [−360.532; −24.670]) and birth weight percentiles (endpoints: uPVV β = −20.727, 95% CI [−32.771; −8.683], bifurcation points: uPVV β −51.097 95% CI [−72.257; −29.937], and crossing points: uPVV β = −48.604 95% CI [−74.246; −22.961])), all P -values < 0.05. After stratification, the associations were observed in natural conceptions specifically. LIMITATION, REASONS FOR CAUTION Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER Registered at the Dutch Trial Register (NTR6854). [ABSTRACT FROM AUTHOR]

المؤلفون: Boudry, L, Mateizel, I, Wouters, K, Papaleo, E, Mackens, S, Vos, M De, Racca, A, Adriaenssens, T, Tournaye, H, Blockeel, C

المصدر: Human Reproduction; Mar2024, Vol. 39 Issue 3, p538-547, 10p

مصطلحات موضوعية: INDUCED ovulation, OOCYTE retrieval, OVARIAN follicle, RANDOMIZED controlled trials, OVUM, OVARIAN reserve

الشركة/الكيان: MERCK KGaA

مستخلص: STUDY QUESTION Is there an increase in the total number of metaphase II (MII) oocytes between a conventional ovarian stimulation (OS) and a double uninterrupted stimulation? SUMMARY ANSWER There is no increase in the total number of MII oocytes when comparing one conventional OS to a continuous stimulation with double oocyte aspiration. WHAT IS KNOWN ALREADY Based on the concept of multiple follicular waves, the combination of two stimulations in the same ovarian cycle has gained interest in patients with a low ovarian reserve. This so-called dual stimulation approach is usually characterized by a discontinuation of FSH administration for ∼5 days and appears to have a favourable impact on the number of retrieved oocytes without affecting the embryo quality or ploidy status. The outcomes of dual uninterrupted OS have not yet been studied. STUDY DESIGN, SIZE, DURATION This was an open-label randomized controlled trial (RCT) with superiority design, performed in a single tertiary centre. Subjects were randomized with a 1:1 allocation into two groups between October 2019 and September 2021. All patients underwent a conventional stimulation with recombinant FSH. When two or more follicles of 17 mm were present, the final inclusion criterion was assessed; randomization occurred only in the presence of ≤9 follicles of ≥11 mm. In Group A, ovulation was triggered with hCG, and oocyte retrieval (OR) was performed 34–36 h later, followed by a fresh single or double embryo transfer (SET or DET) on Day 3/5. In Group B, ovulation was triggered with GnRH agonist, followed by another OS, without discontinuation of the FSH administration. In the presence of one or more follicles of ≥17 mm, the second stimulation was completed with hCG. A freeze-all strategy (Day 3/5) was applied for both retrievals, followed by transfer of one or two embryos in an artificially prepared frozen-thawed cycle. In the absence of one or more follicles of ≥17 mm after 13 additional days of stimulation, the second cycle was cancelled. All ORs were executed by a senior fertility specialist who was blinded for the first treatment, and all follicles >10 mm were aspirated, according to routine clinical practice. The primary outcome was the total number of MII oocytes. Patients were followed up until all embryos were transferred, or until live birth was achieved. Other secondary outcomes included the number of cumulus–oocyte complexes (COCs), the number of good quality embryos (Day 3/5), the ongoing pregnancy rate, and gonadotropin consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients between 25 and 40 years old, with an anti-Müllerian hormone level of ≤1.5 ng/ml, antral follicle count of ≤6, or ≤5 oocytes after a previous stimulation, were included. At the start, 70 patients were eligible for participation in the trial, of whom 48 patients fulfilled the final inclusion criterium and were randomized. After drop-out of two patients, 23 patients were randomized to a single round of OS (Group A), and 23 patients were randomized to two uninterrupted rounds of OS (Group B). MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics were similar between both groups. The cumulative number of COCs and MII oocytes after completion of the second OR was similar in Group A and Group B [5.3 ± 2.7 versus 5.3 ± 3.0 (P  = 0.95); 4.1 ± 2.4 versus 4.3 ± 2.7 (P  = 0.77)]. Likewise, a comparable number of excellent and good quality embryos was available on Day 3 (3.0 ± 2.0 versus 2.7 ± 2.0; P  = 0.63). In Group B, the cancellation rate due to insufficient response to the second round of stimulation was 39.1% (9/23). When focusing on the first stimulation in both groups, there were no significant differences regarding basal FSH, gonadotropin consumption, and the number of preovulatory follicles. After the first OR, the mean number of COC and MII oocytes was significantly higher in Group A (who had hCG triggering), compared to Group B (who had GnRH agonist triggering) [5.3 ± 2.7 versus 3.3 ± 2.2; difference 95% CI (0.54 to 3.45), P  = 0.004 and 4.1 ± 2.4 versus 3.0 ± 2.2; difference 95% CI (−0.15 to 2.6), P  = 0.05, respectively]. Likewise, the number of excellent and good quality embryos on Day 3 was significantly higher (3.0 ± 2.0 versus 1.9 ± 1.7; P  = 0.02) in Group A. LIMITATIONS, REASONS FOR CAUTION This study was powered to demonstrate superiority for the number of MII oocytes after dual stimulation. Investigating the impact of dual stimulation on pregnancy rates would have required a larger sample size. Furthermore, the heterogeneity in embryo vitrification and transfer policies precluded a correct comparison of embryologic outcomes between both groups. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT investigating the role of continuous stimulation with double aspiration in low responders. Our results show no statistically significant differences in the cumulative number of MII oocytes between one conventional stimulation with fresh ET and two consecutive stimulations with a freeze-only approach. Furthermore, the observed suboptimal oocyte yield after agonist ovulation triggering in low responders in the dual uninterrupted OS group is a reason for concern and further scrutiny, given that previous RCTs have shown similar outcomes in normal and high responders after hCG and GnRH agonist triggers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by a research grant from Organon. H.T. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, Cook, Goodlife, and Ferring. L.B. received fees for lectures from Merck & Organon and support for attending ESHRE 2023. M.D.V. reports fees for lectures from Ferring, Merck, Organon, IBSA, Gedeon Richter, and Cooper Surgical and support for attending ASRM 2023. S.M. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. C.B. was on the Advisory board and received consulting fees from Theramex and received honoraria for lectures and presentations from Abbott, Ferring, Gedeon-Richter, IBSA, and Merck. TRIAL REGISTRATION NUMBER NCT03846544 TRIAL REGISTRATION DATE 19 February 2019 DATE OF FIRST PATIENT'S ENROLMENT 28 October 2019 [ABSTRACT FROM AUTHOR]

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المؤلفون: Mostinckx, L, Goyens, E, Mackens, S, Roelens, C, Boudry, L, Uvin, V, Segers, I, Schoemans, C, Drakopoulos, P, Blockeel, C, Vos, M De

المصدر: Human Reproduction; Mar2024, Vol. 39 Issue 3, p586-594, 9p

مصطلحات موضوعية: INDUCED ovulation, FROZEN human embryos, FERTILIZATION in vitro, OVARIAN follicle, OVARIAN reserve, INTRACYTOPLASMIC sperm injection, OVUM

مصطلحات جغرافية: ROTTERDAM (Netherlands)

الشركة/الكيان: MERCK KGaA

مستخلص: STUDY QUESTION Do ongoing pregnancy rates (OPRs) differ in predicted hyperresponders undergoing ART after IVM of oocytes compared with conventional ovarian stimulation (OS) for IVF/ICSI? SUMMARY ANSWER One cycle of IVM is non-inferior to one cycle of OS in women with serum anti-Müllerian hormone (AMH) levels ≥10 ng/ml. WHAT IS KNOWN ALREADY Women with high antral follicle count and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of OS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to OS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and OS may differ depending on the extent of AMH elevation. STUDY DESIGN, SIZE, DURATION This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified hMG (HP-hMG) primed, non-hCG-triggered IVM or OS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Predicted hyperresponse was defined as a serum AMH level ≥3.25 ng/ml (Elecsys^® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate assessed 10–11 weeks after embryo transfer (ET). The predefined non-inferiority limit was −10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy, defined as the number of ET cycles until ongoing pregnancy was achieved, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Data from 463 IVM cycles were compared with those from 1244 OS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing OS (522/1193, 43.8%), were significantly younger (29.5 years versus 30.5 years, P  ≤ 0.001), had a higher BMI (25.7 kg/m² versus 25.1 kg/m², P  ≤ 0.01) and higher AMH (11.6 ng/ml versus 5.3 ng/ml, P  ≤ 0.001). Although IVM cycles yielded more cumulus–oocyte complexes (COCs) (24.5 versus 15.0 COC, P  ≤ 0.001), both groups had similar numbers of mature oocytes (metaphase II (MII)) (11.9 MII versus 10.6 MII, P  = 0.9). In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to OS (794/1244, 63.8%), P  ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to OS from serum AMH levels >10 ng/ml onwards (113/221, 51.1% (IVM); 29/48, 60.4% (OS)). The number of ETs needed to reach an ongoing pregnancy was comparable in both the IVM and the OS group (1.6 versus 1.5 ET's, P  = 0.44). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number, and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. WIDER IMPLICATIONS OF THE FINDINGS Among subfertile women who are eligible for ART, IVM, and OS resulted in comparable reproductive outcomes in a subset of women with a serum AMH ≥10 ng/ml. These findings should be corroborated by a randomised controlled trial (RCT) comparing both treatments in selected patients with elevated AMH. STUDY FUNDING/COMPETING INTEREST(S) There was no external funding for this study. P.D. has been consultant to Merck Healthcare KGaA (Darmstadt, Germany) from April 2021 till June 2023 and is a Merck employee (Medical Director, Global Medical Affairs Fertility) with Merck Healthcare KGAaA (Darmstadt, Germany) since July 2023. He declares honoraria for lecturing from Merck KGaA, MSD, Organon, and Ferring. The remaining authors declared no conflict of interest pertaining to this study. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

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المؤلفون: Loreti, S, Darici, E, Nekkebroeck, J, Drakopoulos, P, Landuyt, L Van, Munck, N De, Tournaye, H, Vos, M De

المصدر: Human Reproduction; Feb2024, Vol. 39 Issue 2, p355-363, 9p

مصطلحات موضوعية: REPRODUCTIVE health, OVUM, INDUCED ovulation, ANTI-Mullerian hormone, ARTIFICIAL insemination

مستخلص: STUDY QUESTION Which reproductive treatment outcomes are observed in women who underwent elective oocyte cryopreservation (EOC) and who returned to the clinic with a desire for a child? SUMMARY ANSWER Whether to warm oocytes or to first use fresh own oocytes for ART depends on age upon returning, but both strategies result in favorable reproductive outcomes. WHAT IS KNOWN ALREADY Most affluent countries have observed a trend toward postponement of childbearing, and EOC is increasingly used based on the assumption that oocytes cryopreserved at a younger age may extend a woman's reproductive lifespan and mitigate her age-related fertility decline. Although most follow-up studies after EOC have focused on women who requested oocyte warming, a substantial proportion of women who do not conceive naturally will embark on fertility treatment without using their cryopreserved oocytes. Reports on reproductive outcomes in past EOC users are scarce, and the lack of reproductive treatment algorithms in this group of women hampers counseling toward the most efficient clinical strategy. STUDY DESIGN, SIZE, DURATION This retrospective observational single-center study encompasses 843 women who had elective oocyte vitrification between 2009 and 2019 at our fertility clinic. Women who underwent fertility preservation for medical or oncological reasons were excluded. This study describes the outcomes of the diverse reproductive treatment strategies performed until May 2022 in women returning to our clinic to attempt motherhood. PARTICIPANTS/MATERIALS, SETTING, METHODS Using descriptive statistics, patient characteristics and data of ovarian stimulation (OS) of EOC cycles were analyzed, as well as data related to OS and laboratory data of ART in women who pursued fertility treatment with and/or without using their cryopreserved oocytes. The primary outcome was live birth rate (LBR) per patient after oocyte warming and after ART using fresh oocytes. Secondary outcomes were return rate, utilization rate of the cryopreserved oocytes, laboratory outcomes upon return, and LBR per embryo transfer. A multivariable regression model was developed to identify factors associated with the decision to thaw oocytes as the primary strategy and factors associated with ongoing pregnancy upon return to the clinic. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1353 EOC cycles (mean ± SD, 1.6 ± 0.9 per patient) were performed. At the time of EOC, the mean age was 36.5 ± 2.8 years, mean anti-Müllerian hormone (AMH) was 2.3 ± 2.0 ng/ml, and 174 (20.6%) women had a partner. On average, 13.9 ± 9.2 mature oocytes were cryopreserved. Two hundred thirty-one (27.4%) women returned to the clinic, an average of 39.9 ± 23.4 months after EOC. Upon returning, their mean age was 40.4 ± 3.1 years, mean AMH was 1.5 ± 1.5 ng/ml, and 158/231 (68.3%) patients had a partner. As a primary approach, 110/231 (47.6%) past EOC users embarked on oocyte warming, 50/231 (21.6%) had intrauterine insemination, and 71/231 (30.7%) had ART using fresh own oocytes. Cumulative LBR (CLBR) was 45.9% (106/231) notwithstanding a miscarriage rate (MR) of 30.7% (51/166) in the entire cohort. In total, 141 women performed oocyte warming at some stage in their treatment trajectory. A subset of 90/231 (39.0%) patients exclusively had oocyte warming (41.6 ± 3.0 years, with 10.0 ± 5.2 oocytes warmed per patient). 52/231 (22.5%) patients exclusively had ART using fresh own oocytes (mean age of 39.0 ± 2.8 years, with 9.9 ± 7.4 mature oocytes retrieved per patient). CLBR was 37/90 (41.1%) in the oocyte warming-only group and 25/52 (48.1%) in the OS-only group. MR/transfer was 25.0% and 29.3% in the oocyte warming-only group and the OS-only group, respectively. LIMITATIONS, REASONS FOR CAUTION Both sample size and the retrospective design are limitations of this study. The decision to embark on a specific reproductive treatment strategy was based on patient preference, after counseling on their treatment options. This precludes direct comparison of the efficiency of reproductive treatment options in past EOC users in this study. WIDER IMPLICATIONS OF THE FINDINGS Reporting on clinical outcomes of women who underwent EOC and returned to the clinic to embark on divergent reproductive treatment strategies is mandatory to establish guidelines for best clinical practice in this growing patient population. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

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المؤلفون: Sterckx, Johan, Wouters, Koen, Mateizel, Ileana, Segers, Ingrid, Vos, Anick De, Landuyt, Lisbet Van, Velde, Hilde Van de, Tournaye, Herman, Munck, Neelke De

المصدر: Human Reproduction; Aug2023, Vol. 38 Issue 8, p1529-1537, 9p

مصطلحات موضوعية: REPRODUCTIVE technology, INTRACYTOPLASMIC sperm injection, OOCYTE retrieval, EMBRYO transfer, ELECTRONIC systems

مستخلص: STUDY QUESTION What have we learnt after 10 years of electronic witnessing? SUMMARY ANSWER When applied correctly, an electronic witnessing system can replace manual witnessing in the medically assisted reproduction lab to prevent sample mix-up. WHAT IS KNOWN ALREADY Electronic witnessing systems have been implemented to improve the correct identification, processing, and traceability of biological materials. When non-matching samples are simultaneously present in a single workstation, a mismatch event is generated to prevent sample mix-up. STUDY DESIGN, SIZE, DURATION This evaluation investigates the mismatch and administrator assign rate over a 10-year period (March 2011–December 2021) with the use of an electronic witnessing system. Radiofrequency identification tags and barcodes were used for patient and sample identification. Since 2011, IVF and ICSI cycles and frozen embryo transfer cycles (FET) were included; IUIs cycles were included since 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS The total number of tags and witnessing points were recorded. Witnessing points in a particular electronic witnessing system represent all the actions that have been performed from gamete collection through embryo production, to cryopreservation and transfer. Mismatches and administrator assigns were collected and stratified per procedure (sperm preparation, oocyte retrieval, IVF/ICSI, cleavage stage embryo or blastocyst embryo biopsy, vitrification and warming, embryo transfer, medium changeover, and IUI). Critical mismatches (such as mislabelling or non-matching samples within one work area) and critical administrator assigns (such as samples not identified by the electronic witnessing system and unconfirmed witnessing points) were selected. MAIN RESULTS AND THE ROLE OF CHANCE A total of 109 655 cycles were included: 53 023 IVF/ICSI, 36 347 FET, and 20 285 IUI cycles. The 724 096 used tags, led to a total of 849 650 witnessing points. The overall mismatch rate was 0.251% (2132/849 650) per witnessing point and 1.944% per cycle. In total, 144 critical mismatches occurred over the different procedures. The yearly mean critical mismatch rate was 0.017 ± 0.007% per witnessing point and 0.129 ± 0.052% per cycle. The overall administrator assign rate was 0.111% (940/849 650) per witnessing point and 0.857% per cycle, including 320 critical administrator assigns. The yearly mean critical administrator assign rate was 0.039 ± 0.010% per witnessing point and 0.301 ± 0.069% per cycle. Overall mismatch and administrator assign rates remained fairly stable during the evaluated time period. Sperm preparation and IVF/ICSI were the procedures most prone to critical mismatch and administrator assigns. LIMITATIONS, REASONS FOR CAUTION The procedures and methods of integration of an electronic witnessing system may vary from one laboratory to another and result in differences in the potential risks related to sample identification. Individual embryos cannot (yet) be identified by such a system; this makes extra manual witnessing indispensable at certain critical steps where potential errors are not recorded. The electronic witnessing system still needs to be used in combination with manual labelling of both the bottom and lid of dishes and tubes to guarantee correct assignment in case of malfunction or incorrect use of radiofrequency identification tags. WIDER IMPLICATIONS OF THE FINDINGS Electronic witnessing is considered to be the ultimate tool to safeguard correct identification of gametes and embryos. But this is only possible when used correctly, and proper training and attention of the staff is required. It may also induce new risks, i.e. blind witnessing of samples by the operator. STUDY FUNDING/COMPETING INTEREST(s) No funding was either sought or obtained for this study. J.S. presents webinars on RIW for CooperSurgical. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

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المؤلفون: Vos, Eline S de¹ (AUTHOR), Koning, Anton H J² (AUTHOR), Steegers-Theunissen, Régine P M¹ (AUTHOR), Willemsen, Sten P^1,3 (AUTHOR), Rijn, Bas B van¹ (AUTHOR), Steegers, Eric A P¹ (AUTHOR), Mulders, Annemarie G M G J¹ (AUTHOR) a.mulders@erasmusmc.nl, de Vos, Eline S⁴ (AUTHOR), van Rijn, Bas B⁴ (AUTHOR)

المصدر: Human Reproduction. Nov2022, Vol. 37 Issue 11, p2532-2545. 14p.

مصطلحات موضوعية: *PLACENTA, *DOPPLER ultrasonography, *RESEARCH funding, *SEX distribution, *FETAL ultrasonic imaging, *ULTRASONIC imaging, *LONGITUDINAL method, *FIRST trimester of pregnancy, *ALGORITHMS

مستخلص: Study Question: Can three-dimensional (3D) Power Doppler (PD) ultrasound and a skeletonization algorithm be used to assess first-trimester development of the utero-placental vascular morphology?Summary Answer: The application of 3D PD ultrasonography and a skeletonization algorithm facilitates morphologic assessment of utero-placental vascular development in the first trimester and reveals less advanced vascular morphologic development in pregnancies with placenta-related complications than in pregnancies without placenta-related complications.What Is Known Already: Suboptimal development of the utero-placental vasculature is one of the main contributors to the periconceptional origin of placenta-related complications. The nature and attribution of aberrant vascular structure and branching patterns remain unclear, as validated markers monitoring first-trimester utero-placental vascular morphologic development are lacking.Study Design, Size, Duration: In this prospective observational cohort, 214 ongoing pregnancies were included before 10 weeks gestational age (GA) at a tertiary hospital between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception Cohort study.Participants/materials, Setting, Methods: By combining 3D PD ultrasonography and virtual reality, utero-placental vascular volume (uPVV) measurements were obtained at 7, 9 and 11 weeks GA. A skeletonization algorithm was applied to the uPVV measurements to generate the utero-placental vascular skeleton (uPVS), a network-like structure containing morphologic characteristics of the vasculature. Quantification of vascular morphology was performed by assigning a morphologic characteristic to each voxel in the uPVS (end-, vessel-, bifurcation- or crossing-point) and calculating total vascular network length. A Mann-Whitney U test was performed to investigate differences in morphologic development of the first-trimester utero-placental vasculature between pregnancies with and without placenta-related complications. Linear mixed models were used to estimate trajectories of the morphologic characteristics in the first trimester.Main Results and the Role Of Chance: All morphologic characteristics of the utero-placental vasculature increased significantly in the first trimester (P < 0.005). In pregnancies with placenta-related complications (n = 54), utero-placental vascular branching was significantly less advanced at 9 weeks GA (vessel points P = 0.040, bifurcation points P = 0.050, crossing points P = 0.020, total network length P = 0.023). Morphologic growth trajectories remained similar after adjustment for parity, conception mode, foetal sex and occurrence of placenta-related complications.Limitations, Reasons For Caution: The tertiary setting of this prospective observational study provides high internal, but possibly limited external, validity. Extrapolation of the study's findings should therefore be addressed with caution.Wider Implications Of the Findings: The uPVS enables assessment of morphologic development of the first-trimester utero-placental vasculature. Further investigation of this innovative methodology needs to determine its added value for the assessment of (patho-) physiological utero-placental vascular development.Study Funding/competing Interest(s): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest.Trial Registration Number: Registered at the Dutch Trial Register (NTR6854). [ABSTRACT FROM AUTHOR]

المؤلفون: T Adriaenssens, I Van Vaerenbergh, M Reis, L Van Landuyt, G Verheyen, M Debrucker, M Camus, P Platteau, M De Vos, W Coucke, E Vanhecke, A Rosenthal, J Smitz

المصدر: Human Reproduction. 37

مصطلحات موضوعية: Reproductive Medicine, Rehabilitation, Obstetrics and Gynecology

الوصف: Study question Can non-invasive gene expression analysis of cumulus cells (CC) improve efficiency in ART by prioritizing oocytes for further culture and fresh single embryo transfer? Summary answer CC analysis can be used for the selective processing of oocytes. This may reduce culture work and improve the outcome in ICSI elective SETs (eSET). What is known already In an interventional, blinded, prospective cohort study (Van Vaerenbergh et al. 2021), 113 patients underwent a fresh Day3 eSET with embryos ranked and transferred based on morphology and CC gene expression (Aurora Test), while 520 control patients underwent a Day3 eSET without the Aurora Test. This resulted in a significant higher clinical pregnancy of 61% in the patients with eSET based on CC ranking applied on good morphology embryos, compared to 29% in the controls with eSET based on embryo morphology only. Live birth rate was also significantly increased, while time-to-pregnancy was significantly reduced with 3 transfer cycles. Study design, size, duration In a retrospective analysis, in a subset of patients with at least 6 growing follicles and at least five 2PN oocytes (n = 80), it was investigated whether the Aurora Test, used to select transferrable Day3-embryos, could also be applied to select oocytes on Day0/1. The effect of processing only the three highest ranked oocytes (based on the Aurora Test) on embryo development and clinical pregnancy was studied compared to processing all oocytes. Participants/materials, setting, methods Patients included in this single centre study had their first or second GnRH-antagonist ICSI cycle, were younger than 40y, had normal BMI, were stimulated with HP-hMG and scheduled for Day3 eSET. Two-sided statistical analysis (p Main results and the role of chance On average, 8 MII oocytes were obtained per patient and the average fertilization rate was 83%. In total, 407 good quality embryos (GQE) on Day3 were generated from these 80 patients when utilising all 639 oocytes. Processing the three top-ranked oocytes only (240/639 oocytes) would have reduced the number of embryos to 169 GQE and would have resulted in 2.1 GQE on average on Day3 per patient; 75/80 (94%) patients would have had a fresh Day3 transfer resulting in a 63% clinical pregnancy rate. Processing all 639 available 2PN oocytes (standard of care) resulted in a fresh Day3 transfer in all 80 patients and a similar 64% clinical pregnancy rate (ns). However, 399 more oocytes would need to be processed. The strategy of restricting the number of oocytes to be processed would not have compromised cumulative cycle outcome. Considering all subsequent freeze/thawing cycles the cumulative clinical pregnancy rate calculated per all 80 patients would increase to 90%. Limitations, reasons for caution The limitation of this approach is that the Aurora Test requires individual oocyte denudation and individual oocyte vitrification. Secondly, this new strategy should be validated in a prospective study. Wider implications of the findings By applying this oocyte selection strategy patients would benefit from a high pregnancy rate in the fresh transfer cycle, while the lab would see reduction in embryo culture work, because freeze/thawing cycles and culture of embryos with lower competence would be prevented. Trial registration number NA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0ac7a836059dad0baf52554b8b72980eTest
https://doi.org/10.1093/humrep/deac107.241Test

المؤلفون: S Hendrickx, P Drakopoulos, N De Munck, S Ruttens, H Tournaye, M De Vos, C Blockeel

المصدر: Human Reproduction. 37

مصطلحات موضوعية: Reproductive Medicine, Rehabilitation, Obstetrics and Gynecology

الوصف: Study question Does progestin primed ovarian stimulation (PPOS) with dydrogesterone starting from stimulation day 6 yield similar outcomes compared with a GnRH antagonist protocol in oocyte donors? Summary answer The number of retrieved oocytes and metaphase II oocytes was similar in both stimulation protocols. What is known already The use of progestins in the follicular phase to suppress a premature LH surge as an alternative to the GnRH analogue is an emerging regimen for ovarian stimulation. There is robust evidence of the safety and efficacy of PPOS compared to conventional ovarian stimulation regimens in oocyte donation cycles. Progestins and gonadotropins are typically administered simultaneously from day 2 or day 3 of the cycle onwards. Reports on initiation of progestins at a later stage, from day 6 of stimulation, are scarce. Study design, size, duration This is a retrospective longitudinal cohort study comparing two strategies of ovarian stimulation in the same oocyte donors. Oocyte donors who had a PPOS protocol between January 2021 and December 2021 and who had another ovarian stimulation cycle using a GnRH antagonist protocol within the same year were included in the analysis. Dydrogesterone 10 mg twice daily was started on day 6 of stimulation onwards. In total, 68 cycles from 34 oocyte donors were Included. Participants/materials, setting, methods All oocyte donors had the same type of gonadotropin and daily dose in both stimulation cycles. The primary outcome was the number of retrieved cumulus oocyte complexes (COC) and the number of metaphase II oocytes. Secondary outcomes were the duration of stimulation, the total dose of gonadotropins, the occurrence of premature ovulation and the difference in total cost between the two stimulation protocols. Main results and the role of chance The average female age was 28.3 years (SD 4.3), BMI 24.0 kg/m2 (SD 2.9) and AMH 2.9 µg/l (SD 1.5). When comparing the PPOS cycle with the GnRH antagonist cycle, the mean number of retrieved COCs was 20.0 ± 9.9 and 20.2 ± 9.3, respectively (p = 0.33) and the number of metaphase II oocytes was also similar (15.6 ± 7.9 and 16.9 ± 8.0, respectively; p = 0.35). The duration of stimulation (10.6 ± 1.7 days versus 10.9 ± 1.7 days; p = 0.26) and cumulative dose of gonadotropins (2284.6 ± 494.9 IU versus 2338.2 ± 462.1 IU; p = 0.25) were comparable in the PPOS and the GnRH antagonist group. No events of premature ovulation were observed in both groups. There was a significant difference in total medication cost per cycle between both protocols, 903.3 ± 195.7 € for PPOS versus 1205.3 ± 243.9 € (p Limitations, reasons for caution The small sample and the retrospective design are limitations of this study. Wider implications of the findings PPOS is a patient friendly and well-tolerated protocol. A simplified protocol of ovarian stimulation with the advantage of cost reduction. The protocol can easily be applied in oocyte donation and cycles with elective freeze all. Adequately powered RCTs should be performed to confirm our results. Trial registration number not applicable

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::8b701afe5afb2f64ea73933706f9b144Test
https://doi.org/10.1093/humrep/deac107.620Test

المؤلفون: K Wouters, M Regin, I Segers, A De Vos, L Van Landuyt, H Tournaye, G Verheyen, H Van de Velde, N De Munck

المصدر: Human Reproduction. 37

مصطلحات موضوعية: Reproductive Medicine, Rehabilitation, Obstetrics and Gynecology

الوصف: Study question Is the duration of compaction, KID- (Known Implantation Data) and iDAScore (Intelligent Data Analysis for embryo evaluation) associated to clinical pregnancy rate? Summary answer Duration of compaction, KID- or iDAScore can be used to select the best embryo for transfer to increase clinical pregnancy rate. What is known already The development of human preimplantation embryos follows a programmed timeline in which a series of critical events occur. Compaction is a typical event at 3 to 4 days post fertilisation that is characterised by flattening of the blastomeres and the formation of tight junctions between the blastomeres. It is considered the first morphological event in the differentiation process of the embryo. Time-lapse technology introduced continuous monitoring of the embryo throughout development in the IVF laboratory. Evaluation of the developmental events combined with calculating KID- and iDAScore can optimise the selection of the most competent embryos for transfer and/or cryopreservation. Study design, size, duration This single-centre retrospective observational study included 158 IVF/ICSI cycles with fresh single embryo transfer (SET) was performed between December 2018 and November 2021. Embryos were cultured during 5 days in cleavage/blastocyst medium (Coopersurgical) in the EmbryoScope + (Vitrolife). Transferred embryos were evaluated for start of compaction, time to full compaction and duration of compaction. Embryo quality was calculated using KID- and iDAScore. These parameters were compared between the clinically pregnant and non-pregnant group (primary outcome). Participants/materials, setting, methods Only IVF/ICSI cycles with ejaculated sperm and fresh SET on day 5 were included. MNC, IVM and PGT cycles were excluded. Time zero was the start of injection or insemination. Pregnancy was confirmed by hCG and clinical pregnancy was defined by gestational sac visualisation at ultrasound. GraphPad Prism and R-studio were used for statistical analysis. For prediction of clinical pregnancy, univariate logistic regression was used. Other significant differences were determined using t-test. Main results and the role of chance Out of 158 fresh ET, 101 (63.9%) had a positive hCG, of which 88 (55.6%) achieved clinical pregnancy. All 158 transferred blastocysts were annotated to calculate KID- and iDAScore. There was no statistical difference in age between the two groups (34.7 years vs 35.0 years; p = 0.69). Start of compaction was heterogeneous (between 50.9 and 98.3 hours post injection/insemination; mean=76.5±7.7), as well as the blastomere number at its initiation (between 4 and 16 blastomeres; mean=11.8±2.1). Univariate logistic regression showed that each individual parameter, i.e. duration of compaction (p = 0.02), KID-score (p = 0.001) and iDAScore (p = 0.0006) was different between the clinically pregnant and non-pregnant group. The total duration of compaction was significantly shorter in the clinical pregnant group (mean=8.6±3.4 hours vs 10.2±4.7 hours; p = 0.01; t-test). In the pregnant group the KIDscore (mean=7.7±1.4 vs 6.7±2.3; p = 0.0007) and iDAScore (mean=8.9±0.7 vs 8.3±1.3; p = 0.0002) were significantly higher. During partial compaction, cells were rather excluded (93%) than extruded from the process; 17 embryos underwent this process, 10 of which resulted in a clinical pregnancy. Limitations, reasons for caution As this is a retrospective study, the influence of uncontrolled variables cannot be excluded. In the future, different models will be applied that can combine duration of compaction, KID- and iDAScore in a larger study. Wider implications of the findings Our analysis confirms previous findings that KID- and iDAScore are good predictors of clinical pregnancy. We also show that duration of compaction can be used as a potential predictor for pregnancy, especially in IVF clinics that have no access to KID- or iDAScore. Trial registration number not applicable

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::05f06b7ed98edd994b114aa644d6cffdTest
https://doi.org/10.1093/humrep/deac107.243Test

المؤلفون: M Vromman, S Mackens, M De Vos, H Tournaye, N De Munck, C Blockeel, P Drakopoulos

المصدر: Human Reproduction. 37

مصطلحات موضوعية: Reproductive Medicine, Rehabilitation, Obstetrics and Gynecology

الوصف: Study question Does female age affect reproductive outcomes in a vitrified/warmed OD program with fresh embryo transfer? Summary answer Oocyte donation performed below the age of 40 was associated with less favorable reproductive outcomes. What is known already It is well established that oocyte and embryo aneuploidy are mainly responsible for the age-related decline in female fertility. Previous studies evaluating the effect of maternal age on implantation potential in OD cycles generated controversial results. It remains unclear whether female age affects reproductive outcome independent of embryo quality. Study design, size, duration This is a retrospective, single tertiary center, cohort study analyzing a vitrified/warmed OD program over a ten-years period (February 2010-February 2020). More specifically, data from 491 unique oocyte recipients were included who performed a fresh embryo transfer after sharing (with at least two recipients) sibling oocytes from the same donor stimulation cycle. For all treatments ICSI was performed without preimplantation genetic testing. Participants/materials, setting, methods The association between recipient’s age and reproductive outcomes was investigated according to three age categories (40 years old). The primary outcome was live birth rate (LBR), while the secondary outcome was biochemical pregnancy rate (BPR). A multivariate regression model was developed adjusting for the following covariates (entered simultaneously): recipient’s BMI, recipient’s endometrial thickness, age of the oocyte donor, number of mature oocytes used for ICSI, embryo transfer stage and number of embryos transferred. Main results and the role of chance Mean age of donors was 28.6 years old(±4.1). Mean starting dose was 192.6 IU(±139.9) and duration of stimulation 11.0 days (±1.7). Mean number of collected cumulus oocyte complexes was 25.6(±9.6) and sibling oocytes were assigned to 2, 3 or more recipients in, respectively, 83.1%, 12.4% and 4.5% of cases. Mean age of recipients was 38.6 years old(±5.1), BMI 24.3 kg/m²(±4.1) and endometrial thickness 8.9mm(±2.1). ICSI was performed on a mean number of 6.5 (±2.0) warmed, intact, mature oocytes with a fertilization rate of 68.2% (±22.5). Cleavage-stage embryos were transferred in 91.0% of the recipients, with a double embryo transfer in 42.6%. 81.3% of embryos were scored as top-quality and a mean of 1.4 (±1.4) surplus embryos were available for additional vitrification. Overall BPR was 44.2%, clinical pregnancy rate 39.3% and LBR 31.0%. Categorizing according to recipient’s age showed a LBR of 24.3%,26.7% and 37.0% for, respectively, the group 40 years old (p = 0.02). The multivariate GEE regression model confirmed the crude data showing that the age was a significant positive predictor of LBR [coefficient (-), 0.01,0.11, for group40 years old, p = 0.05] and BPR [coefficient (-),0.008,0.15, for group 40 years old, p = 0.006]. Limitations, reasons for caution Sibling donor oocytes were used, but the retrospective nature of the study remains a reason for caution. Also, the fact that the majority of embryos were transferred at the cleavage stage is a limitation. Wider implications of the findings The observation that recipients below the age of 40 have lower reproductive success rates following oocyte donation deserves further attention. The need for oocyte donation at younger age might be associated with a less performant uterine/endometrial function due to underlying conditions of genetic and/or endocrine nature. Trial registration number B1432020000146

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e27dcf7fe3caa80a721c30eab0745f9aTest
https://doi.org/10.1093/humrep/deac107.378Test