{"paper_id":"754804f6-b842-4a7b-9196-6c8fb152fd91","body_text":"Obesity is a major global health issue, and its severity is increasing in recent\nyears. The worldwide proportion of women with a body mass index (BMI) of above 25\nkg/m 2  has increased from 29.8% in 1980 to 38% in 2013, which is\nlargely driven by new cases from Asia [ 1 ]. In Asia, the prevalence of obesity is very\nlow previously, while it is increasing at an alarming rate recently, especially in\nChina, Japan and India [ 2 ].\nThe number of Chinese obese people is below 0.1 million in 1975, while such number\nhas reached 43.2 million in 2014, accounting for 16.3% of worldwide obesity [ 3 ]. As obesity and overweight\nhave become one of the most important threats to human health in general, it has\nalso become one of the most common medical conditions complicating pregnancies of\nwomen of reproductive age. Now it is not uncommon for overweight and obese women to\nseek fertility treatment, such as in vitro fertilization (IVF) [ 4 ]. Previous studies have found\nthat the presence of excessive maternal adipose tissue is linked to a number of\nimportant adverse outcomes in spontaneous pregnancies. However, the effects of\nobesity on risks of maternal and fetal adverse outcomes in pregnancies following\nsuccessful IVF remain largely unexplored.\nThe 2013 American College of Obstetricians and Gynecologists strongly recommends\npreconception counseling for overweight and obese women about maternal and fetal\nrisks in pregnancy and encourage them to undertake a weight-loss program [ 5 ]. Until now, there is\ninsufficient data regarding the effects of weight loss on the risks of perinatal\ncomplications. The gold standard evidence to inform this counseling would come from\nrandomized trials of preconceptional weight-loss interventions. However, such\nstudies are difficult to conduct in IVF pregnancies. Therefore, population-based\nstudies comparing the pregnancy outcomes of different women based on their pre-IVF\nBMI are important to provide weight-loss goals prior to conception with the aim to\nreduce perinatal complications.\nThe aim of this study was to evaluate whether pre-IVF obesity independently predicts\nincreased pregnancy complications after adjusting for important confounders. We also\naimed to provide recommendations for Chinese women about the magnitude of weight\nloss prior to IVF for better perinatal outcomes.\n\nThis retrospective cohort study was carried out at the Reproductive Medical\nCenter affiliated to Shandong University. The Centre routinely collects\npregnancy and delivery information from postpartum patients. Women who underwent\ntheir first IVF cycle and delivered a single live infant (vanishing twin and\nselective reduction were excluded) at ≥28 weeks of gestation were enrolled in\nthe cohort. Those who had internal medical conditions, especially pre-IVF\nhypertension and mellitus diabetes, recurrent spontaneous abortion (defined as\nthree or more previous spontaneous miscarriages), cervical incompetence or\nchromosomal abnormality were excluded from the present study. To eliminate age\nas an independent variable for IVF pregnancy, women aged 38 years or older were\nexcluded from this study. Of the 4,670 charts identified with a singleton live\nbirth, 356 subjects used donor sperm, 204 women were over 38 years of age, 42\nwomen had internal medical conditions, 56 cases had chromosomal abnormality and\nunderwent preimplantation genetic diagnosis, and 50 births did not meet\ninclusion criteria or contained insufficient information The flow chart was\npresented in  Fig 1 .\nEventually, a total of 3,962 women were included in the final analysis. Of these\nenrolled women, 584 subjects had polycystic ovary syndrome (PCOS), and 3,378\nwomen did not. They were categorized into three groups according to their BMI,\nwhich was measured at the initial IVF consultation (weight [kilograms]/height\n[meters] 2 ). The WHO expert consultation has reviewed scientific\nevidence and suggested that Asian populations have different associations\nbetween BMI, percentage of body fat, and health risks compared with European\npopulations. They conclude that the proportion of Asian people with a high risk\nof type 2 diabetes and cardiovascular disease is substantial at BMI lower than\nthe existing WHO cut-off point for overweight (> or = 25 kg/m 2 )\n[ 6 ]. Since only Asian\nwomen were included in the present study, it might be more reasonable to\nclassify them according to the BMI definitions of the Working Group on Obesity\nin China (WGOC). BMI groups were defined as follows: normal weight (BMI<24.00\nkg/m 2 ), overweight (BMI 24.00–27.99 kg/m 2 ) and obese\n(BMI≥28.00 kg/m 2 ).\nMost of the studies on effects of BMI on perinatal outcomes have focused on\nspontaneous pregnancies. Therefore, PCOS is often a confounding factor being\nomitted. However, it remains unclear whether the reported effects of obesity on\npregnancy outcome are independent of the effects of PCOS. We therefore performed\ntwo subgroup analyses to isolate the effect of obesity from PCOS on pregnancy\noutcomes.\nFor those outcomes significantly associated with pregravid obesity or overweight,\nadditional analyses were carried out to compare the target BMI group and\ncorresponding BMI reduction group. Because the National Institutes of Health\n(NIH) recommends a 10% reduction in body weight to confer health benefits\noutside of pregnancy [ 7 ],\na 10% reduction in prepregnancy BMI was defined as the BMI reduction goal to\nmake the weight-loss model. For example, the risks among women with a\nprepregnancy BMI of 30–32 were compared with risks among women with a BMI of\n27–29, which represents approximately a 10% reduction in BMI. Four models were\nconducted as follows: group with a BMI of 30–32 vs. group with a BMI of 27–29;\ngroup with a BMI of 28–29 vs. group with a BMI of 25–26; group with a BMI of\n26–27 vs. group with a BMI of 23–24; group with a BMI of 24–25 vs. group with a\nBMI of 21–22, and the BMI reduction group was approximately a 10% reduction of\nthe target BMI group. Logistic regressions were performed between the target BMI\ngroup and BMI reduction group (the control group) separately. If there was a\nstatistically significant increase in the risks of poor pregnancy outcomes\nbetween the target BMI group and BMI reduction group, the target BMI group was\ncontinuously compared with a smaller BMI reduction group, which presents only a\n5% difference in prepregnancy BMI. For example, group with a BMI of 26–27 vs.\ngroup with a BMI of 24–25; group with a BMI of 24–25 vs. group with a BMI of\n22–23; the BMI reduction group was approximately a 5% reduction of the target\nBMI group. On the contrary, if there was no statistically significant difference\nbetween the target BMI group and the control group, a stricter group which\npresents a greater magnitude of weight loss (a 15% difference in pre-IVF BMI)\nwas defined as the control group. For example, group with a BMI of 30–32 vs.\ngroup with a BMI of 25–27; group with a BMI of 28–29 vs. group with a BMI of\n24–25.\nThe following adverse maternal and perinatal outcomes were examined: 1)\ngestational diabetes mellitus (GDM) was diagnosed via the oral glucose tolerance\ntest (75 g, 2 h) [ 8 ], 2)\nhypertensive disorders of pregnancy (HDP), including gestational hypertension\n(GH) and pre-eclampsia (PE) as per the International Society for the Study of\nHypertension in Pregnancy guidelines [ 9 ], 3) polyhydramnios was defined as\namniotic fluid index (AFI) >24 cm, whereas oligohydramnios was defined as AFI\n<8 cm, 4) placenta previa (PP) refers to that the placenta partially or\ncompletely obstructs the internal orifice of the cervix by lying the lower\nuterine segment, 5) placental abruption was defined as the premature detachment\nof the placenta from the uterine wall before birth and after 20 weeks’\ngestation, 5) postpartum hemorrhage (PPH) was defined as blood loss of more than\n500 mL within 24 h after vaginal delivery or more than 1,000 mL after caesarean\nsection (CS), 6) PPROM, and 7) mode of delivery (rate of CS).\nBirth outcome variables included gestational age (GA) at delivery (week), birth\nweight (g), birth height (cm), preterm birth (PTB)<32 and <37 weeks, low\nbirth weight (LBW<1,500 and <2,500 g), macrosomia (>4,000 g), small for\ngestational age and large for gestational age (SGA and LGA; <10th and\n>90th percentiles, respectively, according to Fenton 2013 growth curves\n[ 10 ]), neonatal\nrespiratory distress syndrome (NRDS) (defined as one or more signs of increased\nwork of breathing, such as tachypnea, nasal flaring, chest retractions and\ngrunting), congenital malformations, and perinatal mortality (≤28 days).\nStatistical analysis was performed with SPSS 20.0. Descriptive statistical\nmethods were used to summarize the study population. Participant characteristics\nwere summarized using median and interquartile range (IQR) for continuous\nvariables, and counted with percentages (%) for categorical variables. The\nWilcoxon rank-sum test was used to evaluate differences between continuous\nvariables, and Fisher’s exact test and X 2  were performed for\ncategorical variables to compare data of the three BMI categories. For each\noutcome, logistic regression was used to estimate odds ratio (OR) and 95%\nconfidence interval (CI). Initially, unadjusted ORs were calculated for all\noutcomes by fitting univariable logistic regression models. Then, multiple\nlogistic regression models were constructed to examine the magnitude and\nsignificance of the independent effect of BMI by adjusting maternal age, parity,\nPCOS, and type of controlled ovarian hyperstimulation (COH). To demonstrate how\nobesity affected neonatal outcomes, PTB was also adjusted (in addition to age,\nparity, PCOS and type of COH) in logistic regression analyses. A P value of\n<0.05 was considered as statistically significant.\n\nA total of 3,962 singleton births were assessed for selected adverse pregnancy\nand birth outcomes.  Table\n1  lists the baseline characteristics of all participants. The obese\npopulation was significantly older than the normal-weight population and less\nfrequently diagnosed with tubal factor. The proportion of women with PCOS in the\nobese population was significantly higher compared with the normal-weight group.\nThe rate of “long agonist protocol” used in COH was significantly lower in\noverweight women compared with the other two groups. Parity was not\nsignificantly different across groups.\nData were presented as median and interquartile range (IQR) or n\n(%).\na. Pairwise comparisons revealed a statistically significant\ndifference between the first and second BMI categories.\nb. Pairwise comparisons revealed a statistically significant\ndifference between the first and third BMI categories.\nc. Pairwise comparisons revealed a statistically significant\ndifference between the second and third BMI categories.\nIn the unadjusted analyses ( Table\n2 ), obesity was associated with increased risks of GDM, HDP, PPROM,\nplacental abruption, PTB <37 weeks, CS, fetal macrosomia, LGA, LBW<2,500\ng, NRDS, neonatal intensive care unit (NICU) admission and congenital anomalies.\nIn the adjusted analyses ( Table\n3 ), the significantly increased risk of LBW<2,500 g disappeared,\nwhereas the following pregnancy complications remained significant after\nadjustment of age, parity, PCOS, and type of COH: GDM (aOR: 2.32, 95% CI:\n1.58–3.40), GH (aOR: 3.08, 95% CI: 2.11–4.50), PE (aOR: 2.92, 95% CI:\n1.19–7.20), polyhydramnios (aOR: 2.25, 95% CI: 1.14–4.47), PPROM (aOR: 2.92, 95%\nCI: 0.94–2.77), placental abruption (aOR: 4.51, 95% CI: 1.30–15.60), PTB <37\nweeks (aOR: 1.68, 95% CI: 1.18–2.37), CS (aOR: 2.19, 95% CI: 1.63–2.95), fetal\nmacrosomia (aOR: 2.19, 95% CI: 1.63–2.95), NRDS (aOR: 3.17, 95% CI: 1.23–8.19),\nLGA (aOR: 2.33, 95% CI: 1.85–2.94), NICU admission (aOR: 1.51, 95% CI:\n1.04–2.29) and congenital anomalies (aOR: 1.63, 95% CI: 1.04–2.56). The risks of\nGDM, CS, LGA, fetal macrosomia and NICU admission were considerably increased in\nthe overweight and obese women compared with the normal-weight ones, whereas the\nremaining selected adverse pregnancy and birth outcomes appeared to be\nsignificantly increased only in the obese women. In the subgroup analysis of\norgan specific malformations, there was a statistically significant increase for\nmalformations of the urogenital system and congenital heart defects in the obese\npopulation. Compared with offspring of normal-weight mothers, the aOR for\nurogenital system malformations was 2.48 (95% CI: 1.13–7.14) for obese mothers,\nand that for congenital heart defects was 2.30 (95% CI: 0.64–8.27). The results\nwere presented in  Fig 2 .\n(adjusted for age, PCOS, parity and type of COH).\nPTB<37 weeks and PPH seemed to have a less significant association with BMI in\nthe present study. We observed that obese women had a slightly higher rate of\nLBW<2,500g, but a lower rate of LBW<1,500 g. Even though both of them were\nnot statistically significant between the obese group and reference group (REF),\nGA at birth was significantly lower in obese pregnancies not only compared with\nthe normal-weight group but also the overweight group. There were no significant\ndifferences in rates of SGA, PP or perinatal mortality.\nTo assess whether the increased risk of perinatal complications might be mediated\nby development of GDM and HDP, we performed logistic regressions for those\noutcomes with a significant association with pre-IVF BMI that was adjusted for\ndevelopment of GDM and HDP separately (in addition to age, PCOS, parity and type\nof COH) ( Table 4 ). There\nwere no longer increased risks of PPROM (aOR: 1.94, 95% CI: 0.97–3.85, P =\n0.060), NRDS (aOR: 2.59, 95% CI: 0.96–7.01, P = 0.061) and congenital anomalies\n(aOR: 1.54, 95% CI: 0.98–2.43, P = 0.061) once the development of GDM for obese\nwomen was adjusted when compared with the normal-weight women. The increased\nrisk of NRDS was eliminated after adjustment of HDP development (aOR: 2.58, 95%\nCI: 0.95–7.01, P = 0.063).\nIn the group of women without PCOS, GDM, GH, PE, polyhydramnios, placental\nabruption, CS, fetal macrosomia, LGA, NRDS and NICU admission were\nsignificantly more common in the obese group compared with the normal-weight\ngroup ( Table 5 ).\nHowever, the increased risks of PTB <37 weeks and placental abruption\nwere no longer observed after adjustment of HDP.\nIn patients with PCOS, GDM, HDP, PPROM, CS, fetal macrosomia and LGA were the\noutcomes that were significantly changed with the increase of BMI ( Table 6 ).\nTables  7 – 10  show the comparisons of\nadverse perinatal outcomes between the target BMI group and BMI reduction group.\nThere was a statistically significant difference for congenital anomalies\nbetween the group with a BMI of 30–32 and the group with a BMI of 27–29,\nrepresenting a 10% reduction in BMI. Apart from congenital anomalies, there was\nno statistically significant difference regarding other pregnancy outcomes\nbetween the two groups. In contrast, women with a BMI of 30–32 were associated\nwith higher risks of GH, fetal macrosomia and LGA when compared with the women\nwith a BMI of 25–27, representing a 15% reduction in BMI. No significant\ndifference was observed regarding the perinatal complications between the group\nwith a BMI of 28–29 and group with a BMI of 25–26, representing approximately a\n10% reduction in BMI. Rates of GH, CS and fetal macrosomia were significantly\ndifferent between the group with a BMI of 28–29 and group with a BMI of 24–25,\nrepresenting a 15% reduction in BMI. Pregravid BMI in the overweight range was\nassociated with higher rates of GDM, CS, fetal macrosomia, LGA and NICU\nadmission. BMI of 26–27 resulted in increased rates of CS, fetal macrosomia, and\nLGA when compared with BMI of 23–24, representing a 10% reduction in BMI. The\nsame results were seen between BMI of 26–27 and BMI of 24–25, representing a 5%\nreduction in BMI. Rates of GDM, LGA and NICU admission were significantly higher\namong women with a BMI of 24–25 compared with those with a BMI of 21–22,\nrepresenting a 10% reduction in BMI. Meanwhile, the rates of GDM and NICU\nadmission in women with a BMI of 24–25 were still significantly higher than\nthose in women with a BMI of 22–23, representing a 5% reduction in BMI.\n\nTo the best of our knowledge, we, for the first time, evaluated the association\nbetween pre-IVF BMI and the risks of negative pregnancy outcomes in Chinese\npopulation. Moreover, we assessed the effect of obesity on some particular pregnancy\noutcomes, such as PPROM and PP, which have not been recognized previously. In the\npresent study, we found that pre-IVF obesity was independently associated with\nabsolute risks of many important obstetric outcomes, including GDM, GH, PE,\npolyhydramnios, PPROM, placental abruption, PTB<32 weeks, macrosomia, LGA,\ncesarean delivery rate, NRDS, NICU admission and congenital anomalies. In general,\nour findings were consistent with previous studies on spontaneous pregnancies [ 11 – 17 ].\nThe present study reported that pre-IVF obesity was related to a significantly\nincreased risk of polyhydramnios, which has not been well-documented in previous\nstudies. It may occur through the development of GDM. Unexpectedly, the increased\nrisk of polyhydramnios remained significant after adjustment of GDM status,\nsuggesting that female obesity was an independent predictor of polyhydramnios, while\nits underlying mechanism remained largely unexplored. Maternal obesity seems to be\nprotective from PP, while the potential mechanism remains unclear. According to the\npresent study, PTB<32 weeks and PPH seemed to have a less significant association\nwith BMI in IVF pregnancies. As a matter of fact, there is a notable lack of clarity\nin the association between BMI and PPH reported in observational studies. However,\nsome studies [ 18 – 20 ] have suggested that\nmaternal obesity is an important risk factor for PPH, while others [ 21 – 23 ] fail to find any effect of BMI on PPH.\nSeveral potential explanations can be offered for such conflicting results. On the\none hand, different criteria for PPH definition (either blood loss> 500 mL or\n> 1,000 mL) can be advocated. On the other hand, it is clinically difficult to\naccurately estimate blood loss, particularly in obstetric scenarios. We observed\nthat obesity was related to PTB<37 weeks, while there was no significant change\nbetween obesity and PTB<32 weeks. Such finding was consistent with many previous\nreports [ 21 – 23 ], while its underlying\nmechanism remained unknown. In contrast with many previous reports [ 24 – 26 ], we did not find statistically significant\ndifference of neonatal mortality among all BMI groups, even though the obese group\nexhibited a higher risk. Such discrepancy might be partly attributed to the small\nsample size and the low number of deaths, and it was also possibly caused by the\nfact that only severe obesity (BMI≥35 kg/m 2 ) had relationship with\nneonatal mortality.\nEvidence suggests that GDM and HDP are associated with adverse outcomes for mother\nand offspring [ 27 – 28 ]. To assess whether the\nincreased risk of perinatal complications was mediated by development of GDM/HDP, we\nperformed a sensitivity analysis by conducting logistic regressions after adjustment\nfor development of GDM/HDP (in addition to age, parity, PCOS, and type of COH) for\nthose outcomes with a significant association with pre-IVF obesity. The observed\nincreased risks in PPROM, NRDS and congenital anomalies were no longer seen after\nadjustment of GDM, suggesting that these complications occurred through development\nof GDM. NRDS is a common complication of GDM, which adversely affects the formation\nof alveolar surfactants in neonates. Therefore, GDM might be the potential mechanism\nthat obesity potentiated the risk of respiratory distress.\nA number of previous studies have reported that there is a statistically significant\nincrease in risks of congenital malformations in offspring of women with\npregestational diabetes [ 29 – 31 ], and such\nrisks are increased with degree of maternal hyperglycemia [ 32 ]. GDM was also found to be related to\ncongenital malformations in our study. We could not conclude that congenital\nanomalies occurred through development of GDM, while it might play an important role\nin the mechanism. Unfortunately, our study was restricted to live births. A part of\nsevere congenital malformations during pregnancies ended in spontaneous miscarriages\nor stillbirths, which is a process of natural selection. Besides, some malformations\ncould be diagnosed prenatally, leading to induced abortions. Therefore, we might\nunderestimate the magnitude of the problem. When HDP was controlled, NRDS was the\nonly outcome showing a statistically significant change with the increase of BMI. It\nmight be related to the scientific fact that HDP is associated with intrauterine\ngrowth restriction and preterm delivery [ 33 ].\nIn patients without PCOS, PPROM and congenital anomalies were not significantly\nchanged with the increase of BMI, although the trends for outcomes were also\nworsened with the increase of BMI. These results suggested that PCOS was also the\nunderlying pathologies that contributed to the outcomes. PCOS might have underlying\nmetabolic and endocrine influences associated with GDM that contributed to PPROM and\ncongenital anomalies. For patients with PCOS, the risk of PPROM was significantly\nchanged in obese women, further confirming the association between PCOS and PPROM.\nApart from PPROM, the risks of GDM, HP, CS, fetal macrosomia and LGA were\nsignificantly increased. Further studies are needed to estimate whether there is a\nsynergistic risk of perinatal outcomes in overweight/obese women with PCOS.\nThe effect of obesity on poor perinatal outcomes has been widely studied. However,\nthe etiology of such influence remains unknown. Recently, emerging novel evidence\nsuggests a potential association among epigenetics, microRNAs (miRNAs) and pregnancy\ncomplications [ 34 ]. Numerous\ndata have proved that the placenta responds to the maternal obesogenic environment\nby expressing specific miRNAs. There have been eight miRNAs (miR-100, miR-1269,\nmiR-1285, miR-181, miR-185, miR-214, miR-296 and miR487), which are confirmed to be\nassociated with obesity. Among these miRNAs, five of them (miR-100, miR-181,\nmiR-185, miR-214 and miR-296) are related to type 2 diabetes. Four miRNAs (miR-100,\nmiR-1285, miR-296 and miR-487) are associated with LBW. In addition, miR-296 has\nbeen found to be dysregulated in placenta with PE and PTB [ 35 – 37 ]. The dysregulation of placental\nobesity-associated miRNAs may participate in the mediation of adverse effects of\nmaternal obesity on the offspring. Moreover, Laganà et al. have concluded that\nseveral miRNAs are also dysregulated in the sera of women affected by PE,\nfacilitating the miRNA evaluation and thus offering early diagnosis of PE [ 38 ]. It is worthwhile to\nperform large cohort studies to further identify the role of obesity-associated\nmiRNAs to improve early diagnosis and management of the disease.\nMost of the studies have focused on the effects of obesity on periantal outcomes and\nstrongly recommended that obese women should take efforts to lose weight\npre-conception or pre-IVF. However, weight loss to decrease the risk of poor\nperinatal complications has been rarely studied. In our present study, we\nestablished the weight-loss models to evaluate the effects of weight loss on the\nrisk of poor perinatal outcomes. We found that a 10% reduction in pre-IVF BMI was\nassociated with reduced risk of congenital anomalies for women with a BMI of 30–32.\nIn contrast, larger differences in prepregnancy BMI (15% differences, or more) would\nbe necessary to see meaningfully risk differences for GH, fetal macrosomia and LGA.\nOur study also found that for women with a BMI of 28–29, a 10% reduction in\nprepregnancy BMI did not improve the perinantal outcomes. A stricter weight\nreduction of 15% in pre-IVF BMI might lower the risks of GH, CS and fetal\nmacrosomia. For women with a BMI of 26–27, only a 5% reduction in BMI could\nsignificantly reduce the risks of GDM, CS and fetal macrosomia. As to women with a\nBMI of 24–25, a 5% reduction in pre-IVF BMI might result in reduced rates of GDM and\nNICU admission. If this target group could fulfill the goal to lose weight with a\n10% difference in pre-IVF BMI, they could have their babies at decreased risk of\nLGA, in addition to reduced rates of GDM and NICU admission.\nIt is very hard for obese population to lose enough weight to become normal-weight\nwomen. Based on this conclusion, a 10%-15% reduction in pregravid BMI was\nrecommended as a weight-loss target to reduce perinatal outcomes for the obese\npopulation. In overweight population, just a 5% reduction in pregravid BMI was\nhelpful for the health of both mother and baby, which is such inspiring news for\nobese people. Therefore, clinicians and patients in China could determine what\nmagnitude of expected reduction in risk was meaningful at an individual level.\nThe Chinese population is quite different from Western populations in the prevalence\nof overweight and obesity. Moreover, large differences exist in dietary structure\nand lifestyle habits. There were only 39 women (39/3,962, 0.98%) with a BMI of 33 or\nhigher in the present study. Therefore, we could not conduct a weight reduction\nmodel for the target BMI group with a BMI of 33 or higher. Fortunately, the current\nprevalence of severe obesity in China is relatively low. Therefore, we do not need\nto offer the weight-loss goals for the severe obesity group.\nThis study has several limitations. First, the between-woman differences in\nprepregnancy BMI were not equal to the same magnitudes of BMI loss for individual\nwomen. The lack of controlled trials and sufficient data regarding prepregnancy\nweight loss, studies that compare the outcomes of different women by prepregnancy\nBMIs provide clinicians available evidence to offer weight loss counseling. In the\nabsence of data from randomized trials of weight loss interventions, studies that\ncompare the outcomes of different women by prepregnancy BMIs provide clinicians\navailable evidence to offer weight loss counseling. Second, despite a very high\nresponse rate, our data on obstetric outcomes were self-reported. Therefore, it\nmight underestimate the magnitude of the problem. Third, our study was restricted to\nlive births. A part of severe congenital malformations during pregnancies ended in\nspontaneous miscarriages or stillbirths. Besides, some malformations could be\ndiagnosed prenatally, leading to induced abortions. Therefore, we might\nunderestimate the magnitude of association between pre-IVF obesity and congenital\nanomalies. The last but not the least, although single-center studies had limited\nsize and statistical power, they could also ensure homogeneity in clinical\npractice.\n\nCollectively, pregravid obesity served as an independent predictor of adverse birth\noutcomes in IVF pregnancies. Our results suggested that some risks could occur\nthrough development of HDP and GDM. It is hard for obese women to lose enough weight\nto normal BMI categories. We encouraged obese women to lose weight to a 10–15%\nreduction in pregravid BMI, which was useful to reduce the risks of some perinatal\ncomplications. For overweight women, just a 5% reduction in pregravid BMI was\nhelpful. However, we used BMI definitions of WGOC in the present study, making the\nrecommendations less applicable to general international population. Prospective\nstudies are required to further demonstrate the weight-loss goals to reduce the\nrisks of poor perinatal outcomes for women with high BMI.\nThe study was approved by the institutional review board of the Reproductive\nHospital Affiliated to Shandong University. The ethics board approval number is\n201424. The data were anonymously analyzed, so no consent was required.\n\n(XLS)\nClick here for additional data file.","source_license":"CC-BY-4.0","license_restricted":false}