In Vitro Fertilization Singleton Pregnancies Research Articles

The impact of fresh versus frozen-thawed embryos on maternal serum analyte levels in IVF singleton and twin pregnancies.

To determine whether embryo cryopreservation is associated with a difference in maternal serum analyte levels in singleton and twin pregnancies conceived via in vitro fertilization (IVF). This was a retrospective cohort study of singleton and twin pregnancies conceived via IVF from a university health system from 01/2014 to 09/2019. Patients with available first and second trimester serum analyte data were included and analyzed separately. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A, alpha-fetoprotein (AFP), Inhibin A, and unconjugated estriol (uE3) were compared between two groups: pregnancies conceived after the transfer of fresh embryos versus pregnancies conceived after the transfer of frozen-thawed embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. For singletons, fresh embryos were associated with a lower median first trimester free β-hCG (1.00 MoM vs. 1.14 MoM; parameter estimate [PE] 0.90, 95% CI 0.82-0.99, p = .03) compared to frozen-thawed embryos. Fresh embryos were also associated with a lower median second trimester uE3 (0.93 MoM vs. 1.05 MoM; PE 0.88, CI 0.83-0.95, p = .0004) and AFP (1.02 MoM vs. 1.19 MoM; PE 0.91, CI 0.84-0.99, p = .02) compared to frozen-thawed embryos in singletons. There were no significant differences between median first and second trimester serum analytes in twin pregnancies compared between the two groups. Singleton pregnancies derived from fresh embryos had lower first (free β-hCG) and second (uE3 and AFP) trimester analytes compared to frozen-thawed embryos. Twin pregnancies demonstrated no difference between the groups.

The impact of preimplantation genetic testing on first- and second-trimester maternal serum analyte levels

Objective To determine whether preimplantation genetic testing (PGT) is associated with a change in maternal serum analyte levels in pregnancies conceived via in vitro fertilization (IVF). Methods Retrospective cohort of singleton and twin IVF pregnancies with available first- or second-trimester serum analyte data from 01/2014 to 09/2019. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol, were compared between two groups: pregnancies conceived after transfer of PGT screened euploid embryos vs. those conceived after transfer of untested embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Results Nine hundred and sixty-two singleton and 165 twin IVF pregnancies with serum analyte data available for analysis were included. PGT was associated with a higher median first- and second-trimester AFP compared to no PGT in singletons (1.23 MoM vs. 1.13 MoM; parameter estimate [PE] 1.08, 95% CI 1.00–1.17, p= .04, and 1.21 MoM vs. 1.07 MoM; PE 1.07, 95% CI 1.01–1.13, p= .01, respectively). PGT was also associated with a lower median PAPP-A compared to no PGT in twins (0.75 MoM vs. 1.18 MoM, PE 0.74, 95% CI 0.60–0.92, p= .006). Conclusions Our data suggest that PGT is associated with higher maternal serum levels of second-trimester AFP in singleton and lower levels of first-trimester PAPP-A in twin pregnancies conceived via IVF.

P-356 Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization

Abstract Study question Is there a correspondence between ultrasound estimation of gestational age (GAUS) and its calculation based on embryo transfer date (GAIVF), in in-vitro fertilization (IVF) pregnancies? Summary answer GAUS and GAIVF are not overlapping, being the first mildly greater than the latter, maybe due to anticipated ovulation and fertilization or accelerated embryo development. What is known already In IVF pregnancies the precise date of conception is known. However, it is possible that some factors (such as a time delay between conception and implantation, an early in-vitro embryo development, and the maternal environment itself with its altered hormonal milieu) may influence the early stages of embryonic development. Data regarding first-trimester fetal development in IVF pregnancies are in fact conflicting and both underestimation and overestimation of the true GA were reported when traditional charts were used for ultrasound pregnancy dating. Study design, size, duration A retrospective study was performed, including all singleton IVF pregnancies who underwent the first-trimester ultrasound scan for the screening of aneuploidies between January 2014 and June 2019. For each pregnancy GA was determined using two alternative methods: one based on the date of embryo transfer (GAIVF), and one based on ultrasound measurement of crown-rump length (CRL) (GAUS). GA were compared to search for any discrepancy. The impact of pregnancy dating on obstetric outcome was evaluated. Participants/materials, setting, methods All women with singleton pregnancies conceived by conventional IVF or intracytoplasmic sperm injection (ICSI), who performed first-trimester ultrasound scan for the screening of aneuploidies at the Department of Obstetrics and Gynecology ‘L. Mangiagalli', Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, were included. Exclusion criteria were as follows: multiple pregnancy (i.e., the evidence of more than one gestational sac at the first ultrasound scan), abnormal karyotype and/or congenital malformations detected either in pre- or postnatal period. Main results and the role of chance Overall, 249 women were selected: 111 pregnancies (45%) by conventional IVF, and 138 (55%) by ICSI. Among the included women, 127 (51%) pregnancies resulted from frozen-thawed embryo transfer. At first trimester ultrasound scan, the discrepancy in days between GAUS and GAIVF was ≥ 4 days in 32 cases (13%, 95%CI: 9-18%). It ranged within 2 and 3 days in 100 cases (40%, 95%CI: 34-47%). In 117 cases (47%, 95%CI: 41-53%) GAUS and GAIVF overlapped or showed a discrepancy of ± 1 day. Comparing GAUS and GAIVF at first trimester ultrasound scan, the median values of GA were 88 [86 - 91] days and 87 [85 - 90] days, respectively (p < 0.001). The median difference was 1 [0 - 2] days, with GAUS systematically higher than GAIVF. This discrepancy persisted when subgroups were analyzed comparing different IVF procedures (conventional IVF versus ICSI, cleavage versus blastocyst transfer, frozen versus fresh transfer). The overall duration of pregnancy differed, with median values of 274 [269 - 281] days in GAUS group and 273 [268 - 280] days in GAIVF group, (p > 0.001). No impact of the dating method on obstetric outcomes was observed, being no differences in the rate of preterm birth or abnormal fetal growth. Limitations, reasons for caution This is a retrospective study and thus exposed to the inaccuracies of this study design. Moreover, being a single-centre study, the sample size is relatively small. Finally, ultrasound evaluations were performed by multiple operators: although they are all certified, there is some inter-individual variability that may impact on the results. Wider implications of the findings Despite a known date of conception, it is difficult to assume that the oocyte retrieval date precisely resembles the date of natural ovulation and conception. IVF seems to anticipate fertilization. On these bases, it would be advisable to date IVF pregnancies using GAUS to realign them to natural pregnancies. Trial registration number Not Applicable

Pregnancy outcomes after in vitro fertilization for moderate and severe endometriosis. A case-control study

IntroductionPrevious international studies showed that endometriosis could have a link with obstetrical complications, as an increased risk of preterm birth, gestational diabetes mellitus, and cesarean section. However, the results are difficult to interpret because biases are common, such as heterogeneity in the severity of the endometriosis cases included. That's why some complications as risk of miscarriage and post-partum hemorrhage are still debated. Our objective was to study pregnancy outcome after In Vitro Fertilization (IVF) in women suffering from rAFS stage III and IV endometriosis. MethodsWe conducted a case-control study between 2009 and 2019. We compared pregnancy outcomes after IVF in two groups of women matched by age, body mass index and smoking in two hospital centers. Group A was constituted by singleton pregnancies following ART for moderate and severe endometriosis (rAFS stage III and IV endometriosis). Group B was composed of singleton pregnancies in women with no endometriosis following ART for another reproductive disease. All women achieved pregnancy after 22 weeks. ResultsA total of 240 pregnant women were included: 80 singleton IVF pregnancies (group A) were compared with 160 singleton IVF pregnancies (group B). We observed an increased risk of placenta previa (12.5% Vs 1.9%; p = 0,001), and cesarean section (49.4% (n = 39) Vs 29.6% (n = 47) p = 0,004). Rate of postpartum hemorrhage was not significantly different in endometriosis group (11.2% Vs 7.5% p = 0.47). ConclusionDespite conflicting results in literature due to a lot of confounding variables, the impact of endometriosis on pregnancy is still debated in women suffering from rAFS III and IV endometriosis. In our study, we observed statistically higher rates of placenta previa and cesarean section but not an increased risk of postpartum hemorrhage. Further larger series are needed to confirm our findings and a possible link with other obstetrical complications. However, we think that an ART pregnancy in a context of severe endometriosis should be considered at risk of adverse obstetrical outcomes.

The impact of preimplantation genetic testing for aneuploidy on prenatal screening.

To determine whether preimplantation genetic testing for aneuploidy (PGT-A) is associated with a reduced risk of abnormal conventional prenatal screening results in singleton pregnancies conceived using in vitro fertilization (IVF). This was a retrospective cohort study of singleton IVF pregnancies conceived from a single tertiary care center between January 2014 and September 2019. Exclusion criteria included mosaic embryo transfers, vanishing twin pregnancies, and cycles with missing outcome data. Two cases of prenatally diagnosed aneuploidy that resulted in early voluntary terminations were also excluded. The primary outcome of abnormal first or second-trimester combined screening results was compared between two groups: pregnancy conceived after transfer of a euploid embryo by PGT-A vs. transfer of an untested embryo. Multivariable backwards-stepwise logistic regression with Firth method was used to adjust for potential confounders. Of the 419 pregnancies included, 208 (49.6%) were conceived after transfer of a euploid embryo by PGT-A, and 211 (50.4%) were conceived after transfer of an untested embryo. PGT-A was not associated with a lower likelihood of abnormal first-trimester (adjusted OR 1.64, 95% CI 0.82-3.39) or second-trimester screening results (adjusted OR 0.96, 95% CI 0.56-1.64). The incidences of cell-free DNA testing, fetal sonographic abnormalities, genetic counseling, and invasive prenatal diagnostic testing were similar between the two groups. Our data suggest that PGT-A is not associated with a change in the likelihood of abnormal prenatal screening results or utilization of invasive prenatal diagnostic testing. Counseling this patient population regarding the importance of prenatal screening and prenatal diagnostic testing, where appropriate, remains essential.

PRETERM BIRTH AND LOW BIRTH WEIGHT IN SINGLETON PREGNANCIES AFTER IN VITRO FERTILIZATION- INFLUENCE OF INFERTILITY AND METHOD OF FERTILIZATION

The aim of our study was to determine the effect of infertility and the method of fertilization on the frequency of preterm birth and low birth weight in singleton pregnancies achieved by in vitro fertilization (IVF). The study was conducted in the period 01.2013 - 12.2017 and included 286 patients with births from singleton IVF pregnancies. Classical IVF received 107 patients (group A1) and ICSI fertilization - 148 (group A2). Cases with tubal infertility were 81 (group B1), and 85 were with male infertility (group B2). In group A1, birth prior to 37 weeks of gestation (w.g.) was found in 33 (30.8%) cases, compared to 26 (17.6%) in group A2 (p=0.029).In group A1, birth weight <2500 g was observed in 27 (25.3%) of cases, and in group A2 - in 17 (11.5%) of cases (p=0.015). In group B1, birth prior to 37 w.g. was established in 26 (32.1%) of the cases, compared to 9 (10.6%) in group B2 (p=0.003). In group B1 there was birth weight <2500 g in 19 (23.5%) of patients, compared to 6 (7.1%) in group B2 (p = 0.009). The average weight of the newborn and average duration of pregnancy was lower in groups with IVF fertilization and tubal infertility compared to ICSI fertilization and male infertility. Tubal infertility and classical IVF fertilization are independent risk factors that increase the frequency of preterm birth and low birth weight in IVF singleton pregnancies.

Does the etiology of infertility have any effect on perinatal outcomes?

Objective Pregnancies after in vitro fertilization (IVF) are associated with a less favorable outcome compared to natural conception as consistently shown in various studies. However, etiologic factors behind this issue remain to be elucidated. We aimed to demonstrate whether the etiology of infertility has a role on poor pregnancy outcomes in IVF pregnancies. Methods In this retrospective case control study; IVF and spontaneous singleton pregnancies were investigated. The infertile patients were divided into six groups according to the etiology of their infertility (anovulation, male factor, tubal factor, endometriosis, unexplained infertility and poor ovarian reserve). The incidence of preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, preterm birth and birth weight discrepancies was examined between the groups and subgroups. After adjusting the confounding variables for each infertility subgroup such as demographic data, embryo stage in transfer (blastocyst against cleavage stage) and fresh and frozen embryo transfer status, the effect on pregnancy outcomes was investigated using multinomial logistic regression analysis. Results The study included 934 patients in the IVF group and 1009 patients in the control group. While adverse pregnancy outcomes were more frequent in the general infertility group in comparison to the control group, after elimination of the confounding variables, the direct effect of the etiology of infertility on these outcomes could not be shown. Conclusion In the IVF pregnancies, most of the increased risk of poor pregnancy outcomes appeared to be explained by maternal characteristics (such as age, body mass index) and by treatment protocols rather than infertility etiology. Physicians should consider these risks while counselling patients.

Malpresentation of the Fetus in Singleton Pregnancies after In Vitro Fertilization

BACKGROUND: There are some data in the literature that show an increased incidence of breech presentation and other non-cephalic presentations in vitro fertilization (IVF) singleton pregnancies compared to spontaneous ones. AIM: The purpose of our study was to compare IVF and spontaneous singleton pregnancies in terms of frequency of breech presentation and its impact on the mode of delivery. Furthermore, we wanted to study the rate of transverse and oblique lie in both groups. MATERIALS AND METHODS: We conducted a prospective and retrospective study at “Maichin Dom” University Hospital in Sofia, Bulgaria for the period from January 2013 to December 2017 and analyzed 402 singleton IVF pregnancies and compared them with 523 spontaneous singleton pregnancies. The primary outcome was a breech presentation of the fetus. RESULTS: We found a significantly higher rate of breech presentation in IVF compared to spontaneous pregnancies (p < 0.001). According to gestational age, the difference between the groups persisted when the pregnancy was at least the 32nd week of gestation. We found no difference in the frequency of vaginal birth in the two groups when the fetus was in breech presentation CONCLUSION: IVF singleton pregnancies are associated with a higher risk of breech presentation. Further research is needed to determine the factors contributing to the higher incidence of breech presentation among patients undergoing IVF.

Obstetrical outcomes of ART pregnancies in patients with male factor infertility.

Pregnancies conceived by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are associated with an increased incidence of obstetrical and neonatal complications. With the growing rate of male factor infertility, which is unique by not involving the maternal milieu, we aimed to assess whether obstetrical outcomes differed between IVF/ICSI pregnancies due to male factor infertility and those not due to male factor infertility. A retrospective cohort study of women receiving IVF/ICSI treatments at a single hospital over a five-year period was involved in the study. Inclusion criteria were women with a viable pregnancy that delivered at the same hospital. Pregnancies were divided into male factor only related and non-male factor-related infertility. The groups were compared for several maternal and neonatal complications. In total, 225 patients met the study criteria, with 94 and 131 pregnancies belonging to the male factor and non-male factor groups, respectively. Demographic and clinical characteristics were comparable, except for younger maternal age and higher incidence of twin pregnancies in the male factor group. A sub-analysis for singleton pregnancies revealed a less likelihood of cesarean delivery, preterm birth, and male gender offspring in the male factor group (p < 0.05). These differences were not observed in the sub-analysis for twin pregnancies. Other outcome measures were similar in both groups, both for singleton and twin pregnancies. Singleton IVF pregnancies due to male factor infertility are associated with a reduced incidence of some adverse outcomes, likely due to lack of underlying maternal medical conditions or laboratory conditions related to ICSI. Our findings require validation by further studies on larger samples.

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study.

In Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM. In this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated. GDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007). GDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.

918 The impact of preimplantation genetic testing for aneuploidy on prenatal screening

The clinical utility of preimplantation genetic testing for aneuploidy (PGT-A) is well established. However, data is limited on the residual risk for abnormal prenatal screening in PGT-A screened embryos. We investigated whether PGT-A is associated with a reduced risk of abnormal prenatal screening in singleton pregnancies conceived using in vitro fertilization (IVF). Retrospective cohort of singleton IVF pregnancies conceived from a single center from 01/2014 to 09/2019. Exclusion criteria included transfer of mosaic embryos, vanishing twins, and missing data. Two cases of prenatally diagnosed aneuploidy that resulted in early voluntary terminations were also excluded. Maternal age was adjusted for donor egg age where indicated. The primary outcome of abnormal first or second trimester serum screening was compared between two groups: pregnancy after transfer of a euploid embryo by PGT-A (n = 208) versus transfer of an untested embryo (n = 211). Secondary outcomes included other prenatal screening modalities and rate of invasive prenatal diagnostic testing. Multivariate backwards-stepwise logistic regression with Firth method was used to adjust for potential confounders. Baseline characteristics compared between the two groups are displayed in Table 1. PGT-A was not associated with a reduced risk of abnormal first-trimester (adjusted OR 1.64, 95% CI 0.82-3.39) or second-trimester screening (adjusted OR 0.96, 95% CI 0.56-1.64) (Table 2). The likelihood of cell free DNA testing, soft sonographic markers, major fetal structural malformations, genetic counseling and invasive prenatal diagnostic testing were also similar between the two groups (Table 2). Our data illustrate that PGT-A is not associated with a reduced rate of abnormal prenatal screening, or likelihood of invasive prenatal diagnostic testing. Nevertheless, counseling this patient population regarding the importance of prenatal screening and prenatal diagnostic testing where appropriate remains essential.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Single Embryo Transfer Versus Double Embryo Transfer: A Cost-Effectiveness Analysis in a Non-IVF Insurance Mandated System.

Because of increased morbidity seen in multiple gestations, the American Society of Reproductive Medicine recommends transfer of blastocysts one at a time for most patients. While cost-effectiveness models have compared single embryo transfer (SET) versus double embryo transfer (DET), few incorporate maternal and neonatal morbidity, and none have been performed in U.S. Military facilities. The purpose of this study was to determine the cost effectiveness of sequential SET versus DET in a U.S. Military treatment facility. A cost-effectiveness model was created based on 250 patients between the ages of 20-44 who previously underwent in vitro fertilization (IVF) at our facility. The model consisted of patients pursuing either SET or DET with two total embryos. Cycle outcomes were determined using the published SARTCORS success calculator. Neonatal and obstetrical outcomes were simulated based on singleton and twin IVF pregnancies. Neonatal and obstetrical cost estimates were based on internal data as well. If 250 model patients pursue SET, 140 live births would occur, with total cost of $5.7 million, and cost per delivery of $40,500. If the model patients pursued DET, 117 live births would occur, with total cost of $9.2 million and a cost per delivery of $77.700. DET would lead to more total infants (207 vs. 143 in SET cohort). Personal costs are higher in SET versus DET cohorts ($23,036 vs. $20,535). SET in a system with no infertility coverage saves approximately $3.5 million per 250 patients. Higher personal costs as seen with SET may incentivize patients to seek DET. The total savings should encourage alteration to practice patterns with the U.S Military Healthcare System.

Vanishing Twins Conceived Through Fresh In Vitro Fertilization: Obstetric Outcomes and Placental Pathology.

To characterize the obstetric outcomes and placental pathology in live births arising from vanishing twin pregnancies compared with nonreduced in vitro fertilization (IVF) pregnancies. This is a retrospective cohort study of live births resulting from fresh embryo transfers after IVF cycles with autologous oocytes from 2004 through 2017 at a large academic fertility center. Clinical information and pathology reports were reviewed. Placental diagnoses were coded using established nosology by expert placental pathologists. Analysis of variance, Kruskal-Wallis, Pearson's χ, and Fisher exact tests were used, as appropriate, to compare pathology categories between pregnancy outcomes. Mixed effects logistic regression models were generated to reveal the association between pregnancy outcome and placenta pathology, controlling for pregnancies arising in the same woman and various suspected confounders. Of 905 fresh autologous IVF cycles with placental pathology available for review, we identified 73 vanishing twin pregnancies (8.1%), 556 singleton pregnancies (61.4%), and 276 twin pregnancies (30.5%). Vanishing twin syndrome was not associated with preterm delivery, route of delivery, growth restriction or other obstetric outcomes as compared with IVF singleton pregnancies. However, vanishing twin syndrome pregnancies showed distinctive placental pathologies including an increased rate of small placentas (less than the 10th percentile by weight), with more anatomical abnormalities than IVF singleton pregnancies (odds ratio 1.73, 95% CI 0.94-3.19; adjusted odds ratio 2.15, 95% CI 1.08-4.28). The frequency of placental vascular and inflammatory pathologies associated with IVF vanishing twin syndrome pregnancies were similar to that of IVF singleton pregnancies. Loss of a twin after 8 weeks of gestation was not associated with greater risks of placental pathologies. In vitro fertilization pregnancies affected by vanishing twin syndrome did not have significant differences in obstetric or perinatal outcomes as compared with twin or singleton gestations. However, early twin loss was potentially associated with differences in placental development associated with a higher rate of small placentas and other anatomic pathologies.

In Vitro Fertilization Technology and Child Health

Just under 3% of children in Germany, and approximately 6% of children in some other countries, such as Denmark, are now being conceived with the aid of in vitro fertilization (IVF) technology. Alongside the increased risk of organ malformation, there is now evidence for functional abnormalities due to epigenetic modifications. This review is based on pertinent publications retrieved by a literature search on currently known associations of IVF therapy with malformations and functional abnormalities. The potential implications for the treatment of infertility are discussed. The risk of congenital malformations is approximately one-third higher in children conceived with the aid of IVF technology than in other children; specifically, there is an odds ratio (OR) of 1.29 (95% confidence interval, [1.03; 1.60]) for cardiac malformations, and there is a relative risk (RR) of 1.35 ([1.12; 1.64]) for musculo- skeletal malformations and 1.58 ([1.28; 1.94]) for genitourinary malformations. The risks of preterm birth and low birth weight are, respectively, 1.7 and 1.5 times higher in IVF singleton pregnancies than in non-IVF pregnancies. Cardiovascular changes are the main type of functional disturbance. Some of the risks associated with IVF have decreased in recent years. An association has been revealed between cardiovascular abnormalities and epigenetic modifications; the causes are thought to include not only maternal and paternal factors, but also the IVF techniques that are used. A modification of IVF therapies might lower the risks, but might also lower the success rate. For the well-being of the children to be conceived, IVF therapy should hat cannot be treated by any other means, as the precise causes of the risks of IVF to child health are unclear.

Free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels – late markers of abnormal implantation and placentation. Comparison between spontaneous and IVF singleton pregnancies

Background. During the late first trimester, between 11-13 weeks of gestation, it is recommended for all pregnant women to have a screening for Down syndrome and for other chromosomal abnormalities like trisomy 13 or 18, because it estimates the potential risk and allows patients to make an informed choice about the continuation of pregnancy. The combined test analyzes three markers along with the maternal age: maternal serum beta-human chorionic gonadotropin (beta-hCG or free beta-hCG subunit), maternal serum pregnancy-associated plasma protein-A (PAPP-A) and an ultrasound measurement of nuchal translucency (NT). Objectives. To determine if there are differences regarding serum markers and pregnancy outcomes between spontaneous pregnancies and pregnancies obtained by assisted reproductive techniques (ART). Materials and method. We performed a literature review by searching MEDLINE and Cochrane databases using the keywords: beta-hCG, PAPP-A, screening, IVF, ICSI, ART, implantation. Results. Assisted reproduction techniques, such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), can alter serum markers levels and mimic the pattern associated with Down syndrome: maternal serum beta-hCG and inhibin A levels tend to be increased, while estradiol and PAPP-A levels are decreased. When comparing spontaneously conceived (SC) singleton pregnancies with in vitro fertilization/intracytoplasmic sperm injection, cohort studies confirm an increased risk of perinatal complications for the latter. The most frequent adverse outcomes are: preterm birth, intrauterine growth restriction, perinatal mortality, congenital malformations and higher risks for preeclampsia and placenta praevia. Conclusions. Overall, the risk of complications is significantly higher in ART pregnancies, but the reasons for this increase are still uncertain. The possible cause of this difference might be the increased maternal age and the particularities that occur during the implantation and placentation.

The impact of preimplantation genetic testing on prenatal diagnostic procedures

Objective In recent years, cell-free DNA screening has significantly reduced the number of invasive prenatal diagnostic testing in pregnancy. Preimplantation genetic testing for aneuploidies (PGT-A) is a commonly performed screening test in in vitro fertilization (IVF) pregnancies. Therefore, we aimed to determine the impact of PGT-A on subsequent utilization of prenatal diagnostic testing in IVF pregnancies. Methods Retrospective cohort of singleton and twin IVF pregnancies at a single center from January 2014 to December 2017. The rate of invasive diagnostic genetic testing (chorionic villus sampling (CVS) and/or amniocentesis) was compared between patients with pregnancies achieved after transfer of a euploid embryo by PGT-A (n = 71) and those with pregnancies achieved after transfer of an untested embryo (n = 38). Wilcoxon rank sum and Fisher’s exact tests were used for statistical analysis. Results There was no statistically significant difference in the number of prenatal diagnostic procedures (25.4% PGT-A euploid embryo versus 31.6% untested embryo, p = .51 and p = .32 for one-sided and two-sided analyses, respectively) between the two groups. Maternal age, nuchal translucency measurements and the rate of abnormal sonographic findings were similar between the two groups. Patients without PGT-A pregnancies had a higher BMI (mean 29.6, p = .01) and were ethnically different (p = .013) compared to those with PGT-A. Conclusion The implementation of PGT-A in IVF patients did not reduce the number of invasive diagnostic tests performed at our institution.

Spontaneous and in vitro fertilization pregnancies have comparable first trimester screening profiles for Down syndrome

Objective:We aimed to compare the first trimester screening profiles of spontaneous (n=972) and in in vitro fertilization (IVF) pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, body mass index, and ethnicity.Material and Methods:A non-interventional analysis of retrospective cohort data and review of the literature.Results:All IVF pregnancies were achieved via intracytoplasmic sperm injection using the same ovarian stimulation protocol with recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of pregnancy-associated plasma protein-A (PAPP-A) were slightly lower in the fresh (1.19±0.6 vs 1.33±0.7, respectively; p=0.056) and frozen embryo transfer (1.03±0.5 vs 1.33±0.7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and beta-human chorionic gonadotrophin (β-hCG), and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of β-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies.Conclusion:These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous onceptions.

Perinatal outcome of in vitro fertilization singletons - 10 years' experience of one center.

IntroductionIn vitro fertilization (IVF) singletons have a worse perinatal outcome than spontaneously conceived singletons, especially in terms of preterm birth and its complications.Material and methodsAn observational retrospective case control study was carried out. The study population consisted of 644 women in singleton pregnancies (336 IVF/intracytoplasmic sperm injection (ICSI); 308 controls) who delivered > 22 weeks of gestation at the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland, between 2004 and 2014. Controls were initially matched by age and parity and drawn from the group of deliveries following each IVF delivery. Collected data included maternal characteristics, incidence of pregnancy complications, time and mode of delivery, and neonatal outcome at delivery.ResultsThe two study groups were initially matched for age and parity and were also similar with regard to BMI and gestational weight gain. The IVF treatment increased the odds of having vaginal bleeding in the first trimester (OR = 1.68; 95% CI: 1.0–2.86), placenta previa (OR = 5.15; 95% CI: 1.1–33.9), preterm delivery (OR = 2.06; 95% CI: 1.16–3.68), newborn’s low birth weight (OR = 2.27; 95% CI: 1.19–4.36) and elective cesarean section (OR = 2.39; 95% CI: 1.7–3.4).ConclusionsThe IVF singleton pregnancies have an increased risk of adverse perinatal outcome, among which prematurity remains the greatest problem. Therefore, they should be managed as high risk not only due to psychological reasons.

Congenital Heart Defects in IVF/ICSI Pregnancy: Systematic Review and Meta-analysis

Objective There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. Methods A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: ‘IVF’, ‘IVF/ICSI’, ‘ART pregnancy’, ‘assisted conception’, ‘birth defect’, ‘congenital heart defects’ and ‘congenital malformation or abnormalities’. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. Results Forty-one studies were identified for review including six case–control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20–1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21–1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02; I2 = 0%; P = 0.43). Conclusion Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis.

There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: 'IVF', 'IVF/ICSI', 'ART pregnancy', 'assisted conception', 'birth defect', 'congenital heart defects' and 'congenital malformation or abnormalities'. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. Forty-one studies were identified for review including six case-control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20-1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21-1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03-1.60; P = 0.02; I2 = 0%; P = 0.43). Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.