Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer

Pereira, Nigel; Elias, Rony T.; Christos, Paul J.; Petrini, Allison C.; Hancock, Kolbe; Lekovich, Jovana P.; Rosenwaks, Zev

doi:10.1093/humrep/dex095

Cited by 154 publications

(122 citation statements)

References 49 publications

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“…The high estrogen levels on the decidua, implantation, and early events in pregnancy are assumed to be of paramount importance for determining some features of newborns . In comparison with previous studies showing a dramatic increase in LBW incidence with elevating estradiol level in fresh embryo transfer cycles, the present study found that the change magnitude of birthweight across estradiol categories was relatively moderate. This suggests that any effect of superovulation on gametes and embryos might be easily overwhelmed by the effect of intrauterine supraphysiological estradiol exposure in fresh embryo transfer cycles.…”

Section: Discussioncontrasting

confidence: 64%

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

Cai

Liu

et al. 2019

BJOG

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Objective To investigate whether supraphysiological estradiol (E2) in controlled ovarian stimulation (COS) cycles affects the subsequent frozen‐thawed embryo transfer (FET) in terms of the neonatal birthweight. Design Retrospective cohort study. Setting University affiliated hospital. Population In all, 2066 patients undergoing FET cycles that resulted in live singleton births between July 2011 and Dec 2016. Interventions None. Methods Multivariable linear regression and logistic regression was used to evaluate the association between peak E2 and birthweight outcomes. Main outcome measures Birthweight, z‐score adjusted for gender and gestational age, and incidence of small‐for‐gestational‐age (SGA) and low birthweight (LBW) in singleton neonates derived from FET cycles. Results Adjusted for confounding factors, both the absolute birthweight and the z‐score of singletons following FET were negatively associated with peak E2 levels in COS. In comparison with the referent category (E2 ≤1500 pg/ml), the categories with E2 >3000 pg/ml had a significantly lower z‐score. The difference (95% CI) in estimated marginal mean of birthweights between referent category and highest E2 (>8000 pg/ml) category was 104.57 g (18.13–181.06). Multiple logistic regression analyses showed that the adjusted odds ratio (95% CI) for SGA and LBW in term singletons comparing patients with E2 >3000 pg/ml with those with E2 ≤3000 pg/ml was 2.44 (1.37–4.34) and 2.32 (1.01–5.40), respectively. Conclusions Peak E2 levels in COS cycles are negatively associated with the birthweight of singletons conceived through subsequent FET cycles. Tweetable abstract The birthweight following FET is affected by previous COS cycle.

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Section: Discussioncontrasting

confidence: 64%

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

Cai

Liu

et al. 2019

BJOG

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“…Lastly, various factors have been implicated in association with low neonatal birthweight, including maternal age, maternal education level, socio‐economic status, physical and dietary habits, and anthropometric parameters. As several studies have shown a lack of negative effect of sustained supraphysiological E 2 levels on oocyte and embryo quality, and given the retrospective design of the current and other studies reporting a similar association, we suggest that the authors should be more careful in their conclusions. Moreover, using birthweight as a surrogate measure for oocyte quality is highly questionable.…”

mentioning

confidence: 59%

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

Rottenstreich

2019

BJOG

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“…Our results suggest that the stimulation is detrimental if a supraphysiological estradiol level is reached. Measures of intensive ovarian hyperstimulation, such as supraphysiological E2 levels on ovulation trigger day and a high number of oocytes retrieved, have been identified previously as independent risk factors for lower birthweight in IVF therapy. Supraphysiological E2 levels are also associated with a higher risk of preeclampsia (18).…”

Section: Discussionmentioning

confidence: 99%

“…We also used supraphysiological E2 levels (>10 000 pmol/L) as a binary exposure. The E2 cut‐off levels in previous studies ranged between 9178 and 12 665 pmol/L . We considered E2 >10 000 pmol/L to be supraphysiological, “because this E2 level is higher than that of 10 mature follicles and lower than that of high‐risk ovarian hyperstimulation syndrome” and it comprises median and mean E2 levels of our c‐IVF patients (9590 pmol/L; 10 459 pmol/L).…”

Section: Methodsmentioning

confidence: 99%

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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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Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer

Abstract: N/A.

Cited by 154 publications

References 49 publications

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

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

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

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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