P–380 Differential concentrations of maternal and fetal hemopexin and α1-microglobulin in preeclampsia from IVF pregnancies depending on the presence of corpus luteum at embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M L Boutet ◽  
L Youssef ◽  
L Erlandsson ◽  
E Hansson ◽  
D Manau ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Donation ◽  
Severe Preeclampsia ◽  
Fresh Embryo Transfer ◽  
Gestational Age At Birth ◽  
Age At Birth

Abstract Study question Does the presence of corpus luteum (CL) in in vitro fertilization (IVF) treatments affect maternal and fetal concentrations of hemopexin and α1-microglobulin in preeclampsia? Summary answer Decreased hemopexin and increased α1-microglobulin levels in maternal and fetal blood in IVF pregnancies with absence of CL particularly in pregnancies complicated by preeclampsia. What is known already: Pregnancies after frozen embryo transfer (FET) in programmed cycles have higher rates of hypertensive disorders of pregnancy, suggesting a link between the absence of CL in programmed cycles and adverse maternal outcomes.Cardiovascular function is impaired early in pregnancy in women conceiving by IVF treatments in the absence of CL.Plasma relaxin–2, a potent vasodilator and stimulus of decidualization, has been reported to be undetectable in a non-CL cohort, but markedly elevated in a multiple-CL cohort through pregnancy.Hemopexin and α1-microglobulin act as scavengers that eliminate free heme-groups responsible for hemoglobin-induced oxidative stress known to contribute to preeclampsia development. Study design, size, duration A case-control study of 160 singleton pregnancies recruited from 2016 to 2020, including 54 spontaneous pregnancies from fertile couples, 50 conceived by IVF following fresh embryo transfer (ET) and FET in natural cycle (presence of CL) and 56 IVF after fresh oocyte-donation or FET in programmed cycles (absence of CL). Pregnancies were subclassified according to the presence of preeclampsia in uncomplicated, preeclampsia and severe preeclampsia cases. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. Spontaneous pregnancies from fertile couples were randomly selected from our general population and matched to IVF by gestational age at birth. Hemopexin and α1-microglobulin concentrations were measured by ELISA in maternal and cord plasma collected at delivery. All comparisons were adjusted for age, ethnicity, prematurity, birthweight centile, oocyte-donation and FET cycles. Main results and the role of chance Parental ethnicity, body mass index, exposure to aspirin and corticoids during pregnancy, mean gestational age at birth and birthweight were similar in all study groups. While maternal hemopexin levels were lower in treatments without CL, the IVF group with one or several CL showed significantly increased hemopexin concentrations, both in uncomplicated and preeclampsia cases (uncomplicated: spontaneous conceptions median 1520 ug/ml [interquartile range 1054–1746], IVF with CL 1554 [1315–1778], IVF without CL 1401 [1130–1750]; Preeclampsia: spontaneous conceptions 1362 [1121–1667], IVF with CL 1372 [403–2558], IVF without CL 1215 [971–1498]). Maternal α1-microglobulin was significantly higher in the absence of CL in severe preeclamptic cases as compared to spontaneous pregnancies and IVF with CL (spontaneous conceptions median 23 ug/ml [interquantile range 20–24], IVF with CL 24 [24–26], IVF without CL 26 [25–28]). The cord blood profiles were identical to the maternal for both biomarkers. Overall, and in line with previous studies, preeclamptic pregnancies independently of the mode of conception, showed decreased concentrations of hemopexin and increased concentrations of α1-microglobulin both in maternal and fetal plasma, with more pronounced changes in severe preeclampsia cases. Limitations, reasons for caution Infertility factors contribution to the outcome cannot be unraveled from the assisted reproductive technologies procedure itself as we have only included spontaneous pregnancies from fertile couples. Adjustments for oocyte-donation and FET modalities were performed due to the higher proportion of these features in the ET in programmed cycles group. Wider implications of the findings: These findings acknowledge physiological differences between pregnancies following ET in stimulated and natural versus programmed cycles, supporting the hypothesis that the CL activity could influence perinatal results. This approach to perinatal outcomes in IVF patients could lead to changes in ET protocols in order to develop a CL if possible. Trial registration number Not applicable

Effectiveness and outcomes of embryo cryopreservation programs in assisted reproductive technologies

2014 ◽  
Vol 63 (4) ◽  
pp. 39-46 ◽  
Author(s):  
Yana Nikolayevna Kravchuk ◽  
Alla Stanislavovna Kalugina ◽  
Olga Vladimirovna Bystrova ◽  
Svetlana Aleksandrovna Shlykova
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Negative Impact ◽  
Perinatal Outcomes ◽  
Reproductive Technologies ◽  
Embryo Cryopreservation ◽  
Control Group ◽  
Fresh Embryo Transfer ◽  
Art Programs ◽  
Thawed Embryo Transfer

Background. Embryo cryopreservation is an essential part of ART programs today. In recent years vitrification method is used increasingly widely. Purposes and tasks. To compare the effectiveness of ART programs using vitrified and fresh embryos, as well as different endometrial preparation regimes for frozen\thawed embryo transfer (modified natural cycle (MNC) and the preparatory hormone therapy(PHT)). To analyze the course of pregnancy and perinatal outcomes after vitrified embryo transfer. Materials and methods. We prospectively assessed the ART programs effectiveness and perinatal outcomes in 153 patients (I group), who underwent vitrified embryo transfer in 2011-2013 year. To prepare the endometrium for thawed embryo transfer in 83 patients PHT (Ia subgroup) and MNC in 70 patients (Ib subgroup) were used. Control group consisted of 70 patients, who underwent fresh embryo transfer. Results. The clinical pregnancy rate, birth rate and “take home baby” rate were not significantly different between the I (47,5 %; 30,9 %; 30,9 %) and II (53,0 %; 34,9 %; 32,5 %) groups, and between Ia (48,3 %; 28,4 %; 28,4 %) and IIb (46,6 %; 34,1 %; 34,1 %) subgroups. Complications during pregnancy and delivery, birthweight, length, Apgar score, congenital malformation rate did not differ significantly after vitrified and fresh embryo transfer. Conclusion. Vitrification is an effective method to achieve clinical results, comparable to native cycles. Application of PHT and MNC results in similar clinical outcomes. Transfer Vitrified embryo transfer does not have a negative impact on obstetric and perinatal outcomes when compared with native cycles.

scholarly journals Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies

2013 ◽  
Vol 304 (2) ◽  
pp. R69-R72 ◽  
Author(s):  
Kirk P. Conrad ◽  
Valerie L. Baker
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Plasma Osmolality ◽  
Reproductive Technologies ◽  
Fresh Embryo Transfer ◽  
Pregnant Rats ◽  
Infertile Women ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
Donor Eggs

Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these findings in pregnant rats and women, we hypothesize that infertile women conceiving through donor eggs will have overall subdued circulatory changes (e.g., attenuated reduction in systemic vascular resistance and subdued increase in cardiac output) particularly during early pregnancy when CL hormones predominate before the full development and maturation of the placenta. In contrast, infertile women conceiving by autologous eggs retrieved after ovarian stimulation and fresh embryo transfer may have a relatively hyperdynamic circulation due to the presence of many CL (up to 20 or more) and higher circulating levels of vasodilatory ovarian hormones such as relaxin. Emerging evidence suggests that women undergoing Assisted Reproductive Technologies (ART) have increased risk for adverse pregnancy outcomes such as preeclampsia and small for gestational-age babies. This increased risk may be partly caused by the maternal milieu, which is not physiological in ART pregnancies due to the abnormal status of the CL.

scholarly journals Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

2019 ◽  
Author(s):  
Wei Chen ◽  
Yong Peng ◽  
Xinyi Ma ◽  
Siming Kong ◽  
Shuangyan Tang ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Adult Life ◽  
Reproductive Technologies ◽  
Fresh Embryo Transfer ◽  
Vitro Fertilization ◽  
Nuclear Families ◽  
Genome Wide ◽  
Parental Background

AbstractThe births of more than 8 million infants have been enabled globally through assisted reproductive technologies (ARTs), including conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with either fresh embryo transfer (ET) or frozen embryo transfer (FET). However, the potential for elevated risks of ART-related disorders persists in adult life, and the underlying epigenetic mechanisms are largely uncharacterized. Here, we recruited 100 nuclear families and profiled the DNA methylomes, genome-wide histone modifications and transcriptomes to clarify the inherent extra risks attributable to specific ART procedures. We discovered that IVF-ET seemed to introduce less disturbance into the infant epigenome than IVF-FET or ICSI-ET did. Furthermore, we noted approximately half of the DNA methylomic changes in ART-conceived offspring could be explained by parental background biases. Through removal of the parental effect, we confirmed that ART per se would introduce minor DNA methylation changes locally. More importantly, we found that ART-induced epigenomic alterations were highly enriched in the processes which might contribute to increased incidence of preeclampsia during pregnancy and metabolic syndrome in offspring. Overall, our study provides an epigenetic basis for the potential long-term health risks in ART-conceived offspring that reinforces the need to review all methods of human ART.

P–766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M L Boutet ◽  
E Eixarch ◽  
P Ahumada-Droguett ◽  
F Crovetto ◽  
M S Cívico ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Maternal Age ◽  
Assisted Reproductive Technologies ◽  
Cortical Development ◽  
Multiple Pregnancy ◽  
Fetal Brain ◽  
Reproductive Technologies ◽  
Fine Motor ◽  
Problem Solving Skills

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages & Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2–7.4] vs FET 5.8 [4.1–7.5] vs SC 6.5 [4.8–7.8]) and calcarine (fresh ET 13.5 [IQR 10.1–16.1] vs FET 14.5 [12.1–15.8] vs SC 16.4 [14.3–17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings: Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number Not applicable

P-766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M L Boutet ◽  
E Eixarch ◽  
P Ahumada-Droguett ◽  
F Crovetto ◽  
M S Cívico ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Maternal Age ◽  
Assisted Reproductive Technologies ◽  
Cortical Development ◽  
Multiple Pregnancy ◽  
Fetal Brain ◽  
Reproductive Technologies ◽  
Fine Motor ◽  
Problem Solving Skills

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages & Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2-7.4] vs FET 5.8 [4.1-7.5] vs SC 6.5 [4.8-7.8]) and calcarine (fresh ET 13.5 [IQR 10.1-16.1] vs FET 14.5 [12.1-15.8] vs SC 16.4 [14.3-17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number not applicable

scholarly journals Effectiveness of elective single versus double frozen embryo transfer in good prognosis IVF patients

2021 ◽  
Vol 8 (1) ◽  
pp. 4203-4213
Author(s):  
Tran Ha Lan Thanh ◽  
Pham Hoang Huy ◽  
Do Thi Linh ◽  
Nguyen Minh Tai Loc ◽  
Nguyen Huu Duy ◽  
...  
Keyword(s):  
Birth Weight ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Good Prognosis ◽  
Frozen Embryo Transfer ◽  
Multiple Birth ◽  
Birth Rates ◽  
Gestational Age At Birth ◽  
Age At Birth ◽  
Double Embryo Transfer

Objective: This study aimed to evaluate the effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) in frozen embryo transfer cycles following in vitro fertilization (IVF) treatment in good prognosis patients. The outcome would provide medical data for the multiple pregnancy rate reduction in IVF treatment. Methods: This multicenter retrospective cohort study was performed in patients undergoing the first frozen embryo transfer (FET) cycles at IVF centers which belonged to the IVFMD Group, Vietnam, from January 2018 to May 2020. Patients were divided into four groups, based on the number of embryos transferred, as follows: Group 1: one good quality day-3 embryo (eSET D3), Group 2: one good quality day-5 embryo (eSET D5), Group 3: two good quality day-3 embryos (DET D3), and Group 4: two good quality day-5 embryos (DET D5). The primary outcome of the study was live birth rates (LBR) after the first FET. Secondary outcomes were also analyzed, including pregnancy outcomes (β-hCG positive, clinical pregnancy, miscarriage < 12 weeks, ongoing pregnancy 12 weeks, miscarriage < 20 weeks, and multiple birth rates [MBR]), as well as neonatal outcomes (birth weight and gestational age at birth). Results: There were 819 patients, of which 819 FET cycles were analyzed, including 132 eSET D3, 278 eSET D5, 140 DET D3, and 269 DET D5. LBR and MBR values were significantly lower in the eSET D3 group than in the DET D3 group (LBR: 22.7% vs 39.3%, p = 0.002; MBR: 3.3% vs 29.1%, p < 0.001, respectively). MBR was also significantly lower in eSET D5 compared with DET D5 (9.6% vs 38.3%, p < 0.001), while LBR was comparable between the two groups (41.4% vs 42.8%, p < 0.74). Birth weight and gestational age at birth were similar between eSET and DET, regardless of day-3 or day-5 embryo transfer. Conclusions: Among infertile, good prognosis women undergoing FET, the eSET significantly decreased multiple birth rates compared with double embryo transfer, while still sustaining an acceptable rate of live birth as well as pregnancy and neonatal outcomes.

Should we still perform fresh embryo transfers in ART?

2019 ◽  
Vol 34 (12) ◽  
pp. 2319-2329 ◽  
Author(s):  
Christophe Blockeel ◽  
Alison Campbell ◽  
Giovanni Coticchio ◽  
John Esler ◽  
Juan A Garcia-Velasco ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Recent Trend ◽  
Scientific Evidence ◽  
Reproductive Technologies ◽  
Current Evidence ◽  
Embryo Cryopreservation ◽  
Fresh Embryo Transfer ◽  
Risks And Benefits ◽  
Randomised Controlled

Abstract An increasing number of researchers have alluded to the potential benefit of deferring the transfer of embryos produced during assisted reproductive technologies (ARTs) away from ovarian stimulation, using cryopreservation to enable this. The scientific evidence that may justify this recent trend in the use of the so-called ‘freeze-all strategy’ includes early, mostly small randomised controlled trials that have demonstrated an increase in live birth rates after elective embryo cryopreservation in certain patient populations, as well as evidence from cohort studies and retrospective analyses. What are the risks and benefits of freeze-all strategies in ART, who are the patients in whom it is likely to be advantageous, and does the current evidence allow us to identify situations when deciding that a fresh embryo transfer would be counter-productive? ART professionals are often faced with challenging clinical decisions regarding the best course of treatment for their patient. The purpose of this opinion paper is to provide a clinical guide for whether to perform a fresh embryo transfer or to opt for freezing all embryos in specific situations.

scholarly journals Perinatal outcomes of human singletons conceived naturally versus assisted reproductive technologies: analysis of the effect of stimulated IVF, modified natural IVF, and frozen embryo transfer

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Adhwaa Khudhari ◽  
Ali Mourad ◽  
Simon Phillips ◽  
Mohammad Zubair Alam ◽  
Robert Hemmings ◽  
...  
Keyword(s):  
Birth Weight ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Assisted Reproductive Technologies ◽  
Perinatal Outcomes ◽  
Reproductive Technologies ◽  
Primary Objective ◽  
Frozen Embryo Transfer ◽  
Significant Difference

Abstract Background Obstetrical outcomes in assisted reproduction techniques (ART) were compared with naturally conceived pregnancies and among each other in multiple reports. However, many important changes in the practice of in vitro fertilization (IVF) over the years, including single embryo transfers (sET) and the introduction of modified natural IVF (mnIVF), and the advances in the frozen embryo transfer (FET) might have impacted the outcomes. Our study is the first to our knowledge to assess four different groups, including spontaneous pregnancies, mnIVF, stimulated IVF (sIVF), and FET altogether in a head-to-head comparison. This is a retrospective study on perinatal outcomes of singleton babies conceived naturally or using three different ART protocols between 2011 and 2014. The primary objective was the comparison of gestational age and birth weight between spontaneously conceived pregnancies (NAT, n= 15,770), mnIVF (n=235), sIVF (n=389), and FET (n=222). Results Our results show a significant difference in favor of naturally conceived pregnancies over ART in term of gestational age. In fact, the gestational age of babies in the NAT group was statistically higher compared to each one of the ART groups alone. Regarding the birth weight, the mean was significantly higher in the FET group compared to the other categories. Conclusion Differences in perinatal outcomes are still found among babies born after different modes of conception. However, there is still need for well-designed high-quality trials assessing perinatal outcomes between naturally conceived pregnancies and different ART protocols based on different maternal and treatment characteristics.

scholarly journals An EPIC predictor of gestational age and its application to newborns conceived by assisted reproductive technologies

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Kristine L. Haftorn ◽  
Yunsung Lee ◽  
William R. P. Denault ◽  
Christian M. Page ◽  
Haakon E. Nustad ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Robust Regression ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Lasso Regression ◽  
Accurate Predictor ◽  
Prediction And Prevention ◽  
Precision And Accuracy

Abstract Background Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART). Methods We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)—a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study—a prospective pregnancy cohort of Finnish women. Results Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R2 = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R2 = 0.767, MAD = 3.7 days). Conclusions We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.

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