Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial

Wei, Daimin; Liu, Jia Yin; Sun, Yun; Shi, Yuhua; Zhang, Bo; Liu, Jianqiao; Tan, Jichun; Liang, Xiaoyan; Cao, Yunxia; Wang, Ze; Qin, Yingying; Zhao, Han; Zhou, Yi; Ren, Haiqin; Hao, Guimin; Ling, Xiufeng; Zhao, Junzhao; Zhang, Yunshan; Qi, Xiujuan; Zhang, Lin; Deng, Xiaohui; Chen, Xiaoli; Zhu, Yimin; Wang, Xiaohong; Tian, Li; Lv, Qun; Ma, Xiang; Zhang, Heping; Legro, Richard S.; Chen, Zi‐Jiang

doi:10.1016/s0140-6736(18)32843-5

Cited by 371 publications

(312 citation statements)

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“…Though the risks of hospital admission in FET-conceived children and asthma medication in ART-conceived children have been reported to be higher than CTRL conceived children 32,33 , direct evidence regarding the effects of ART on the immune system is lacking so far and long-term follow-up studies are required. Previous studies have revealed elevated rates of preeclampsia in women who have undergone FET 34 . GTPases, especially Rho kinases, play essential roles in extravillous trophoblast cell (EVT) invasion 35 , and limited EVT invasion following poor remodeling of arteries is widely observed in preeclampsia 36 .…”

Section: Discussionmentioning

confidence: 94%

Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

Chen

Peng

et al. 2019

Preprint

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19The births of more than 8 million infants have been enabled globally through assisted 20 reproductive technologies (ARTs), including conventional in vitro fertilization (IVF) and 21 intracytoplasmic sperm injection (ICSI) with either fresh embryo transfer (ET) or frozen embryo 22 transfer (FET). However, the potential for elevated risks of ART-related disorders persists in adult 23 life, and the underlying epigenetic mechanisms are largely uncharacterized. Here, we recruited 100 24 nuclear families and profiled the DNA methylomes, genome-wide histone modifications and 25 transcriptomes to clarify the inherent extra risks attributable to specific ART procedures. We 26 discovered that IVF-ET seemed to introduce less disturbance into the infant epigenome than IVF-27 FET or ICSI-ET did. Furthermore, we noted approximately half of the DNA methylomic changes 28 in ART-conceived offspring could be explained by parental background biases. Through removal 29 of the parental effect, we confirmed that ART per se would introduce minor DNA methylation 30 changes locally. More importantly, we found that ART-induced epigenomic alterations were highly 31 enriched in the processes which might contribute to increased incidence of preeclampsia during 32 pregnancy and metabolic syndrome in offspring. Overall, our study provides an epigenetic basis 33 for the potential long-term health risks in ART-conceived offspring that reinforces the need to 34 review all methods of human ART. 35 Introduction 36Assisted reproductive technology (ART) has become routine in infertile treatment; indeed, 37 more than eight million ART-conceived infants have been born worldwide 1 . However, 38 conventional in vitro fertilization and fresh embryo transfer (IVF-ET) will introduce extraordinary 39 changes in the environment where oocytes mature and the early embryo develops 2 . Moreover, 40 intracytoplasmic sperm injection (ICSI), which was initially used to address severe male infertility, 41 has replaced IVF as the most commonly used method for ART-mediated fertilization in many 42 countries 3 . This more invasive fertilization procedure introduces additional mechanical damage, 43 bypasses the complicated process of sperm-egg recognition and alters a series of downstream 44 reactions 4 . Embryo cryopreservation enables embryos to be preserved for further transplantation, 45 but both cryogens and freeze-thawing operation may cause damage to embryos 5 . All those 46 unfavorable factors have raised concerns regarding the long-term health of ART-conceived 47 children in recent years 6 . Despite claims to the contrary 7-9 , accumulating evidences have linked 48 ART with potentially increased risks of neurodevelopmental disorders, cardiovascular dysfunction 49 and metabolic abnormity in offspring and preeclampsia during pregnancy 10,11 . 50 Epigenetic modifications, such as DNA methylation and histone modifications, play key roles 51 in regulating gene expression and are relatively sensitive to environmental factors 12 . 52 Preimplantation embry...

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Section: Discussionmentioning

confidence: 94%

Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

Chen

Peng

et al. 2019

Preprint

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“…(Chen et al,2016;Shapiro et al,2011;Aflatoonian et al, 2010). However, results remain contradictory when applying the FA strategy to a normo-responsive population (Roque et al, 2018;Shi et al,2018, Wei et al, 2019. This study has analysed retrospectively a cohort of patients having undergone an FA strategy compared to a control group having benefitted from a fresh transfer with remaining frozen embryos, in a "real life" study situation, the first end point being the cumulative live birth rate.…”

Section: Discussionmentioning

confidence: 99%

“…His results show a cumulative pregnancy rate of 50.74% but this study does not benefit from control group results. Finally, a multicentric randomised controlled trial showed that frozen single blastocyst transfer resulted in a higher singleton live birth rate than did fresh single blastocyst transfer in ovulatory women (Wei et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Does the Freeze-all strategy improve the cumulative live birth rate and the time to become pregnant in IVF cycles?

Johnson¹,

Vandromme

Larbuisson³

et al. 2020

Preprint

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IntroductionFreezing of all good quality embryos and their transfer in subsequent cycles, named the freeze-all strategy (FAS), is widely used for ovarian hyperstimulation syndrome (OHSS) prevention. Indeed, it increases live birth rates among high responders and prevents preterm birth and small for gestational age. Consequently, why shouldn’t we extend it to all?Materials and methodsA retrospective and monocentric study was conducted between January 2008 and January 2018 comparing the cumulative live birth rates (CLBR) between patients having undergone FAS and a control group using fresh embryo transfer (FET) and having at least one frozen embryo available. Analyses were made for the entire cohort (population 1) and for different subgroups according to confounding factors selected by a logistic regression (population 3), and to the BELRAP (Belgian Register for Assisted Procreation) criteria (population 2).Results2216 patients were divided into two groups: Freeze all (FA), 233 patients and control (C), 1983 patients. The CLBR was 50.2% vs 58.1% P=0.021 for population 1 and 53.2% vs 63.3% P=0.023 for population 2, including 124 cases and 1241 controls. The CLBR stayed in favour of the C group: 70.1% vs 55.9% P=0.03 even when confounding variables were excluded (FA and C group respectively 109 and 770 patients). The median time to become pregnant was equally in favour of the C group with a median of 5 days against 61 days.ConclusionsCLBR is significantly lower in the FA group compared to the C group with a longer time to become pregnant. Nevertheless, the CLBR in the FA group remains excellent and superior to that observed in previous studies with similar procedures and population. These results confirm the high efficiency of FAS but underline the necessity to restrict the strategy to selected cases.

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“…However, while we cannot alter many factors in IVF therapy to achieve acceptable pregnancy outcomes, we can reduce the use of gonadotropin and the dosage when it is used. Furthermore, the risk of SGA can be reduced by frozen embryo transfer cycles, but there instead a higher risk of large‐for‐gestational‐age (LGA), and preeclampsia has been described recently. In NC‐IVF, the serum E2 milieu remains within physiologic limits, whereas gonadotropin stimulation in c‐IVF alters it.…”

Section: Discussionmentioning

confidence: 99%

The greater incidence of small‐for‐gestational‐age newborns after gonadotropin‐stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day

Schwartz

Mitter

Amylidi-Mohr

et al. 2019

Acta Obstet Gynecol Scand

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Introduction Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin‐stimulated in vitro fertilization compared with spontaneously conceived children: parental factors (age, health, duration of subfertility and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn being small‐for‐gestational‐age. Material and methods We conducted a cohort study (2010‐2016) of singletons (n = 155) born either after conventional gonadotropin‐stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, adjusted for gestational age and sex. Results The proportion of small‐for‐gestational‐age was 11.8% following conventional gonadotropin‐stimulated in vitro fertilization and 2.9% after natural cycle in vitro fertilization (P = 0.058). The odds of small‐for‐gestational‐age were significantly higher with supraphysiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35‐15.55; P = 0.015). It remained significant after adjusting for maternal height, age and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06‐13.82; P = 0.041). Conclusions We found an associated risk of children being born small‐for‐gestational‐age after conventional gonadotropin‐stimulated in vitro fertilization compared with natural cycle in vitro fertilization. This higher risk is significantly associated with supraphysiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small‐for‐gestational‐age and future health consequences.

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Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial

Cited by 371 publications

References 28 publications

Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

Does the Freeze-all strategy improve the cumulative live birth rate and the time to become pregnant in IVF cycles?

The greater incidence of small‐for‐gestational‐age newborns after gonadotropin‐stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day

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