SELECTED ORAL COMMUNICATION SESSION, SESSION 60: CHILDREN’S HEALTH Wednesday 6 July 2011 10:00 – 11:45

Human Reproduction, Jan 2011

Introduction: The number of children born after frozen/thawed embryo transfer (FET) is steadily rising, as well as questions about their neonatal health and development. However, large studies on neonatal outcomes are limited. The main objective of this based controlled prospective study was to assess neonatal outcome of “cryo” singletons conceived with In Vitro Fertilization (IVF) or Intra Cytoplamic Sperm Injection (ICSI) born from FET, and to compare them with that of singleton controls conceived with IVF or ICSI and fresh transfer, as a reference, inside the very large French cohort “Follow Up”, which provides long term follow-up of children conceived with ART. Medical data are collected from sequential parental questionnaires administered from birth to age 5. The second objective was to establish a cohort for further evaluations of health of these infants during childhood. Material and Methods: This current prospective survey was carried out for 16 002 singletons born after ART and recruited at birth from 1998 to 2008. Thirty ART centers were involved in this survey. We report here birth questionnaire data. Among the total cohort of 16002 singletons, the cryo population was 2 140 (13.3%); 6.1% were initially conceived with IVF (cryo–IVF), and 7.3% with ICSI (cryo-ICSI). The control group was 13 862 singletons (86.6%), 34.1% born after IVF and fresh transfer, 52.5% after ICSI. IVF/ICSI ratio was higher in cryo cohort than in the fresh one (84% versus 65%, p < 0.0001). Main outcome measures were demographic parental data and neonatal data (mode of delivery, gestational age and preterm birth rate (PTB) < 37 weeks of amenorrhea (WA), mean child measurements and low birth weight (LBW). Results: Maternal and paternal ages were not statistically different in fresh and cryo groups (33.3 ± 4 & 33.2 ± 4/36 ± 5.7 & 36 ± 5.6 years). The primiparous/multiparous maternal status ratio appeared 1.6 higher (p < 0.0001) in fresh sample. The caesarean section/vaginal delivery ratio was the same in both populations (28%). The boys/girls ratio was 1.05 higher in the cryo population (NS).The PTB rates p = 0.64), although the gestational age was slightly lower in cryo (39.1 WA, SD 1.95) than in fresh (39.3 WA, SD 1.99). The mean birth weight was 102g higher in the cryo singletons versus the fresh ones. When considering term-born children ( > 37WA), the low birth weight (LBW) < 2500 g rate was significantly higher in fresh cohort. LBW/normal BW ratio was twice higher in fresh population than in cryo (3.6%/1.8%, p < 0.0001). Babies mean height (49.7 ± 4 and 50.1 ± 2 cms) and head circumference (34.5 ± 1.7 and 34.7 ± 1.7cms) were both in favor of cryo cohort (p < 0.0001). The mortality rate was not different between the two groups (0.19%/0.22%, OR = 0.84). When considering the initial ART in both cryo and fresh groups, we did not find any significant difference in neonatal outcomes, although maternal age was in both groups lower in ICSI versus IVF children. Conclusions: This survey is one of the largest on FET pregnancies. We observed that embryo freezing does not adversely affect neonatal outcome. Our results show that the outcome is similar or even better after FET compared with fresh transfer, particularly regarding fetal growth. These findings are not modified as the initial technique was IVF or ICSI. “Follow-up” survey at older ages will provide further evaluations of the congenital malformations, health and development of cryo children among the ART cohort. We wish to thank all the parents and ART centers medical teams who participated in this study.

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SELECTED ORAL COMMUNICATION SESSION, SESSION 60: CHILDREN’S HEALTH Wednesday 6 July 2011 10:00 – 11:45

Abstracts of the 27th Annual Meeting of ESHRE, Stockholm, Sweden, 3 July – 6 July, 2011 Results: Interestingly neither AD, nor T resulted to be statistically lower on YLR and ALR patients when compared with the control group of egg donors (AD = 198.5 ± 171.8, 157.9 ± 218.9, and 224.6 ± 312.7 nM, (T = 20.6 ± 9.7, 20.2 ± 9.3, and 29.8 ± 31.8 nM), respectively. On the contrary in the group of ALR patients, lower intrafollicular E2 concentration (1298 ± 963, 1927 ± 960 and 2071 ± 1275 nM) and higher FSH level (6.1 ± 4.0, 3.6 ± 1.7, and 4.6 ± 2.6 mIU/ml) were found when compared to control and YLR groups respectively. Conclusions: With the exception of FSH and E2, the intrafollicular androgenic levels in low responder patients were not different with regards to the control group. These results may support the idea that more than an insufficiency on androgen substrate, low responder patients, specially the aged subgroup, may have an inferior aromatase activity as is shown by the significant lower E2 concentration observed in this subgroup. Also, the supposed lower number of FSH receptors on the granulosa cells of low responder women may explain the higher concentration of free FSH detected in the preovulatry follicles of ALR patients. Research supported by IMPIVA IMIDTG/2008/26. O-227 High AMH-values do not correlate with the risk of ovarian hyperstimulation syndrome after IVF-treatments Introduction: Anti-Müllerian Hormone (AMH) is considered a marker for ovarian reserve, and is used to estimate the response to ovarian stimulation in an IVF/ICSI-treatment. By using the AMH-value as a guide to adjust the dose of gonadotropins used in the stimulation, one can try to minimize the risk of complications, especially Ovarian Hyperstimulation Syndrome (OHSS). In our department, the starting dose is reduced to 112.5 IU per day instead of the standard dose (150 IU/day) when AMH is higher than 4 μg/L. The aim of the present study is to evaluate whether this policy succeeds in reducing the incidence of severe OHSS. Materials and Methods: A retrospective observational study was carried out based on the database of the Department of Reproductive Medicine of the University Hospital of Ghent. The following parameters were extracted from the database: date of birth of the patient, AMH-value, outcome of the treatment cycle, including a positive pregnancy test, the need for coasting, the occurrence of OHSS and cancelling of the cycle. Results: A total of 1654 treatment cycles was evaluated. Three groups could be distinguished: serum AMH ≤ 2 μg/L, 2 - 4 μg/L, and > 4 μg/L. AMH-values in the high ranges were additionally subdivided into smaller groups ( > 4 and ≤ 6, > 6 and ≤ 8, > 8 and ≤ 10, > 10 and ≤ 12, > 12 μg/L). Furthermore, stratification based on age was performed ( ≤ 35, between 35 and 40 en ≥ 40 years of age). The global risk of severe OHSS (including admission to hospital) was 0.6 % in the population studied (10/1654). 60% of all cases occurred in patients with AMH-values between 8 and 10 μg/L. Nine out of 10 cases were reported in women at the age of 35 or younger, in whom the starting dose of gonadotropins was reduced according to protocol. In this subgroup, the risk of OHSS appeared to be the highest at an AMH between 4 and 6 (1.24%) and between 8 and 10 μg/L (6.59%). Coasting was considered necessary mainly in the group of patients with AMH values ranging from 4 to 6 μg/L, from 8 to 10 μg/L and higher than 12μg/L, regardless of age. Conclusions: The data seem to suggest that there is no clear linear correlation between high serum AMH-values and the risk of ovarian hyperstimulation syndrome. Although AMH is a meaningful marker in estimating which patients can be considered as “poor responders”, it has little predictive value in the high ranges. Additionally, in this series of patients, reduction of the starting dose of gonadotropins from a normal starting dose of 150 IU per day to a slightly decreased dose of 112.5 IU/day in patients with high AMH-values does not seem to be able to prevent OHSS. O-228 Role of vascular endothelial cell growth factor (VEGF) and angiopoietins (ANGPTs) in ovarian hyperstimulation syndrome (OHSS) I. de Zúñiga1, D. Colaci1, F. Sobral1, C. Bisioli1, L. Scotti2, D. Abramovich2, M. Tesone2, F. Parborell2 1 PREGNA, Reproductive Medicine, Buenes Aires, Argentina Introduction: Moderate to severe OHSS has been calculated to occur in 0.2% to 2% of all ovarian stimulation cycles. Risk factors include low body weight, high follicle count, polycystic ovary syndrome, previous OHSS and elevated serum estradiol. VEGF is clearly implicated in the pathogenesis of OHSS, and it seems to be the principal mediator of the action of hCG. In women who develop OHSS, VEGF is expressed and produced by granulosa-lutein cells, released into the follicular fluid in response to hCG, and in turn, it induces capillary permeability. The ANGPTs/Tie-2 system acts in concert with VEGF. ANGPT1 is necessary to stabilize blood vessels and ANGPT2 acts as a natural antagonist for ANGPT1. The balance between the ANGPT1/ANGPT2 ratio and VEGF expression is important for angiogenesis in the ovary. However, up to now, the possible involvement of ANGPTs in OHSS is unknown. Our objectives were to analyze: 1) the effect of VEGF inhibition in a rat model of OHSS on follicular and luteal development and 2) a possible involvement of ANGPTs in this model and in patients with high probability of developing OHSS when undergo ART. Material and Methods: OHSS group (hyperstimulated immature Sprague Dawley rats) received excessive doses of pregnant mare serum gonadotropin (PMSG, 50 UI/day) injected for 4 consecutive days (from 21 to 24 days old), followed by human chorionic gonadotropin (hCG, 25 UI, on the 25 days old). OHSS + TRAP group (TRAP-treated hyperstimulated immature rats) received the same doses of gonadotropins as OHSS group and then received 1 ug Trap (recombinant mouse-soluble VEGF receptor 1/Fc Chimera) in 5 ul of PBS with 0.1% BSA under the ovarian bursa at the same day of hCG. Rats were sacrificed 48 hs post hCG. Histological features of sectioned ovaries were assessed in hematoxilin and eosin stained slides. Corpora lutea (CLs) were isolated by microdissection under the microscope and then proteins were extracted for western blot. In addition, levels of ANGPT1 and Tie-2 were measured by ELISA assay in follicular fluid (FF) of control and OHSS women. Results: In the OHSS group, TRAP increased the number of atretic follicles (OHSS: 0.39 ± 0.25 vs OHSS + TRAP: 9.18 ± 1.39, %FAtr/ovary; p < 0.001) and decreased the number of CLs (OHSS: 72.10 ± 4.33 vs OHSS + TRAP: 55.26 ± 3.85, %CL/ovary; p < 0.05) and cysts (OHSS: 7.36 ± 0.66 vs OHSS + TRAP: 3.64 ± 1.29, %Cyst/ovary; p < 0.01). In addition, TRAP decreased the ovarian weight in OHSS group respect to the OHSS group without treatment (OHSS: 0.22 ± 0.01 vs OHSS + TRAP: 0.19 ± 0.01, g.; p < 0.05). In isolated CLs from OHSS group, the ratio ANGPT1/A (...truncated)


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S. Epelboin, E. Devouche, H. Pejoan, G. Viot, G. Apter Danon, F. Olivennes, A. Follow Up ART Network, A. Pinborg, A. Loft, L. Noergaard, A.A Henningsen, S. Rasmussen, A. Nyboe Andersen, M.J Davies, V.M Moore, K. Willson, P. Van Essen, H. Scott, K. Priest, E.A Haan, A. Chan, A. Sazonova, K. Källen, A. Thurin-Kjellberg, U.B Wennerholm, C. Bergh, D. Wunder, E.M Neurohr, M. Faouzi, M. Birkhäuser, M. Garcia Cabrera, M.J Zurit, J.A Sainz, E. De la Hoz, V. Caballero, R. Garrido, M. Guo, M. Richardson, N.S Macklon. SELECTED ORAL COMMUNICATION SESSION, SESSION 60: CHILDREN’S HEALTH Wednesday 6 July 2011 10:00 – 11:45, Human Reproduction, 2011, pp. i91-i94, 26/suppl 1, DOI: 10.1093/humrep/26.s1.60