Identifying a possible factor for the increased newborn size in singleton pregnancies after assisted reproductive technology using cryopreserved embryos, in comparison with fresh embryos

Abstract

PurposeTo determine whether the cycle regimens that are used for endometrial preparation are associated with the birthweight (BW) after assisted reproductive technology (ART) using frozen‐thawed embryo transfer (FET).MethodsThe BW of singletons who were born by ART using FET was compared retrospectively, according to whether a FET was conducted in a hormone replacement therapy cycle (HRT, n = 403) or an ovulatory cycle (OVL, n = 117). The BW after timed intercourse (NAT, n = 162) also was investigated.ResultsThere were no significant differences in the age of the mothers, percentage of primiparas, gestational periods, Body Mass Index, and sex ratio between the HRT and OVL cycles. The average BW from HRT was significantly greater than that of OVL. The BW from HRT was also greater, compared with NAT, while statistical significance was not achieved between OVL and NAT. The putative factors affecting the BW, such as ovarian stimulation protocols, endometrial thickness, and the stage and quality of embryos, could not explain the difference in the BW between the HRT and OVL cycles.ConclusionAn increased BW from ART using FET seems to be ascribable to conditions of the endometrium, but not cryopreservation procedures per se, which might provide a mechanistic framework for understanding heavier neonates who are born by FET.

Large-for-gestational age is male-gender dependent in artificial frozen embryo transfers cycles: a cohort study of 1295 singleton live births

“…In the present study, the reported LGA rate (13.28%) was at the lower end of the range, even though the evidence suggests that the procedures, conditions and manipulations, i.e. extended embryo cultures and artificial FET cycles used favour high birth weight outcomes (Zhu et al, 2014;Tsuji et al, 2017;Ishii et al, 2018;Ginström Ernstad et al, 2019;Zhang et al, 2019). Although increases in fetal growth of FET conceptions lessen the risk of LBW and SGA (Li et al, 2014;Spijkers et al, 2017), the increase in fetal growth also elevate the risk of HBW, LGA and macrosomia, compared with both fresh embryo transfer and spontaneous conceptions (Maheshwari et al, 2016;Litzky et al, 2018;Sha et al, 2018).…”

“…Moreover, most studies have found female infants to have lower birth weights and lower LGA risks, with multiple logistic regressions, including that of the present study, selecting infant gender as a significant independent predictor of fetal growth outcomes (Zhu et al, 2014;Kaartinen et al, 2015;Luke et al, 2017;Tsuji et al, 2017;Fang et al, 2018;Litzky et al, 2018;Ishii et al, 2018;Wei et al, 2019;Zhang et al, 2019). In the study by Litzky et al (2018), a significant interaction between infant gender and embryo transfer type was observed, with FET cycles having a greater effect on male infant birth weight.…”

“…i.e. natural versus artificial) in analyses and found that artificial FET cycles were associated with increased high infant birth weight outcomes (Tsuji et al, 2017;Ishii et al, 2018;Ginström Ernstad et al, 2019) and that infant birth weights were similar for natural FET and spontaneous conception cycles (Ishii et al, 2018). The evidence from these studies suggests that hormone-induced modifications to the endometrium may also contribute to differences in fetal growth.…”

“…Whether cryopreservation per se and embryo culture duration had an effect on fetal growth outcomes, however, could not be investigated in the present study because of the lack of reference variables. Moreover, the effects of cryopreservation (Pinborg et al, 2014;Galliano et al, 2015;Luke et al, 2017;Vidal et al, 2017) and embryo culture duration (Zhu et al, 2014;Ishihara et al, 2014;Kaartinen et al, 2015;Belva et al, 2016;Spijkers et al, 2017;Tsuji et al, 2017;Fang et al, 2018;Ishii et al, 2018;Zhang et al, 2019) reported have been inconsistent. Reasons for the inconsistent outcomes reported might include differences in the quality of procedures, conditions and manipulations at the different study centres, differences in study designs and differences in variable collinearity.…”

Authors’ reply Re: Supraphysiological estradiol level in ovarian stimulation cycles affects the birthweight of neonates conceived through subsequent frozen‐thawed cycles: a retrospective study

“…Although it is suspected that ‘lower embryo quality accounts for lower fetal growth potential’, the association is less clear. Some studies suggested that delayed or non‐grade‐A blastocysts may result in heavier singletons , …”