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. 2019 Dec;98(12):1575-1584.
doi: 10.1111/aogs.13691. Epub 2019 Aug 11.

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

Alexandra S Kohl Schwartz  1 , Vera R Mitter  1 , Sofia Amylidi-Mohr  2 , Pascale Fasel  1 , Mirja A Minger  1 , Costanzo Limoni  3 , Marcel Zwahlen  4 , Michael von Wolff  1
Affiliations

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

Alexandra S Kohl Schwartz et al. Acta Obstet Gynecol Scand. 2019 Dec.

Abstract

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.

Keywords: gonadotropin; high-risk pregnancy; in vitro fertilization; infertility; pregnancy; reproductive endocrinology.

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Conflict of interest statement

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Figures

Figure 1
Figure 1
Boxplot of birthweight percentiles of conventional gonadotropin‐stimulated in vitro fertilization (c‐IVF) vs natural cycle in vitro fertilization (NC‐IVF) [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 2
Figure 2
Boxplot of birthweight percentiles estradiol (E2) level <10 000 pmol/L vs ≥10 000 pmol/L E2 level [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 3
Figure 3
Birthweight percentile with higher estradiol (E2) level (in maternal serum, pmol/L) on ovulation trigger day in natural cycle in vitro fertilization [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 4
Figure 4
Birthweight percentile with higher estradiol (E2) level (in maternal serum, pmol/L) on ovulation trigger day in conventional gonadotropin‐stimulated in vitro fertilization [Color figure can be viewed at http://www.wileyonlinelibrary.com]
See this image and copyright information in PMC

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